Publications

2025
Balakrishnan A, Barmpounakis P, Demiris N, Andersson B, Brañes A, de Aretxabala X, Eilard MS, Gibbs P, Harper SJF, Huguet EL, et al. Assessment of nodal staging and risk factors for nodal involvement in gallbladder cancer. BJS Open. 2025;9(3).Abstract
BACKGROUND: Nodal assessment in gallbladder cancer remains challenging, particularly in incidental gallbladder cancer. This understages the number of patients with node-positive disease, resulting in prognostic inaccuracy and insufficient adjuvant treatment. This study aimed to identify risk factors for positive nodes in gallbladder cancer and to compare prognostic discrimination of available nodal staging parameters. METHODS: This international cohort study assessed gallbladder cancer resections undertaken between 1 January 2010 and 31 December 2020. Logistic regression was used to identify risk factors for node-positive status and develop a risk prediction score for positive nodes. Nodal staging models, including nodal site, number of positive nodes, and positive node ratio were compared for greatest prognostic discrimination in gallbladder cancer. RESULTS: A total of 3676 patients underwent gallbladder cancer resection across 133 centres in 41 countries. Tumour (T) stage (T2, P = 0.012; T3, P = 0.002; and T4, P < 0.001), lymphovascular and perineural infiltration (P < 0.001), and tumour differentiation (P < 0.001) carried the greatest risk of positive nodes. These three parameters comprised the OMEGA Node Positivity Prediction Score (OMEGA-NOPPS) with C-statistics of 0.81 (95% confidence interval 0.78 to 0.84) in the training data set and 0.79 (0.73 to 0.85) in the test data set for identification of node-positive status, highlighting a ≥ 20% increased risk of positive nodes in poorly differentiated tumours with lymphovascular and perineural infiltration despite T1 disease. CONCLUSION: Data from this large multicentre study confirmed that the number of positive nodes is the most discriminative prognostic model for nodal staging in gallbladder cancer. OMEGA-NOPPS provides three simple parameters to stratify nodal involvement according to risk. Incidental gallbladder cancer with lymphovascular and perineural infiltration and poorly differentiated tumours, including early T stages, should be considered for further treatment.
2024
Triantafillidis JK, Papakontantinou J, Antonakis P, Konstadoulakis MM, Papalois AE. Enteral Nutrition in Operated-On Gastric Cancer Patients: An Update. Nutrients. 2024;16(11).Abstract
It is well established that the preoperative nutritional status of gastric cancer (GC) patients significantly affects the prognosis of the operated patients, their overall survival, as well as the disease-specific survival. Existing data support that preoperative assessment of nutritional status and early correction of nutritional deficiencies exert a favorable effect on early postoperative outcomes. A variety of relevant indices are used to assess the nutritional status of GC patients who are candidates for surgery. The guidelines of almost all international organizations recommend the use of oral enteral nutrition (EN). Oncologically acceptable types of gastrectomy and methods of patient rehabilitation should take into account the expected postoperative nutritional status. The majority of data support that perioperative EN reduces complications and hospital stay, but not mortality. Oral EN in the postoperative period, albeit in small amounts, helps to reduce the weight loss that is a consequence of gastrectomy. Iron deficiency with or without anemia and low serum levels of vitamin B12 are common metabolic sequelae after gastrectomy and should be restored. EN also significantly helps patients undergoing neoadjuvant or adjuvant antineoplastic therapy. The occurrence of the so-called "postgastrectomy syndromes" requires dietary modifications and drug support. This review attempts to highlight the benefits of EN in GC patients undergoing gastrectomy and to emphasize the type of necessary nutritional management, based on current literature data.
Access to and quality of elective care: a prospective cohort study using hernia surgery as a tracer condition in 83 countries. Lancet Glob Health. 2024;12(7):e1094-e1103.Abstract
BACKGROUND: Timely and safe elective health care facilitates return to normal activities for patients and prevents emergency admissions. Surgery is a cornerstone of elective care and relies on complex pathways. This study aimed to take a whole-system approach to evaluating access to and quality of elective health care globally, using inguinal hernia as a tracer condition. METHODS: This was a prospective, international, cohort study conducted between Jan 30 and May 21, 2023, in which any hospital performing inguinal hernia repairs was eligible to take part. Consecutive patients of any age undergoing primary inguinal hernia repair were included. A measurement set mapped to the attributes of WHO's Health System Building Blocks was defined to evaluate access (emergency surgery rates, bowel resection rates, and waiting times) and quality (mesh use, day-case rates, and postoperative complications). These were compared across World Bank income groups (high-income, upper-middle-income, lower-middle-income, and low-income countries), adjusted for hospital and country. Factors associated with postoperative complications were explored with a three-level multilevel logistic regression model. FINDINGS: 18 058 patients from 640 hospitals in 83 countries were included, of whom 1287 (7·1%) underwent emergency surgery. Emergency surgery rates increased from high-income to low-income countries (6·8%, 9·7%, 11·4%, 14·2%), accompanied by an increase in bowel resection rates (1·2%, 1·4%, 2·3%, 4·2%). Overall waiting times for elective surgery were similar around the world (median 8·0 months from symptoms to surgery), largely because of delays between symptom onset and diagnosis rather than waiting for treatment. In 14 768 elective operations in adults, mesh use decreased from high-income to low-income countries (97·6%, 94·3%, 80·6%, 61·0%). In patients eligible for day-case surgery (n=12 658), day-case rates were low and variable (50·0%, 38·0%, 42·1%, 44·5%). Complications occurred in 2415 (13·4%) of 18 018 patients and were more common after emergency surgery (adjusted odds ratio 2·06, 95% CI 1·72-2·46) and bowel resection (1·85, 1·31-2·63), and less common after day-case surgery (0·39, 0·34-0·44). INTERPRETATION: This study demonstrates that elective health care is essential to preventing over-reliance on emergency systems. We identified actionable targets for system strengthening: clear referral pathways and increasing mesh repair in lower-income settings, and boosting day-case surgery in all income settings. These measures might strengthen non-surgical pathways too, reducing the burden on society and health services. FUNDING: NIHR Global Health Research Unit on Global Surgery and Portuguese Hernia and Abdominal Wall Society (Sociedade Portuguesa de Hernia e Parede Abdominal).
A prognostic model for use before elective surgery to estimate the risk of postoperative pulmonary complications (GSU-Pulmonary Score): a development and validation study in three international cohorts. Lancet Digit Health. 2024;6(7):e507-e519.Abstract
BACKGROUND: Pulmonary complications are the most common cause of death after surgery. This study aimed to derive and externally validate a novel prognostic model that can be used before elective surgery to estimate the risk of postoperative pulmonary complications and to support resource allocation and prioritisation during pandemic recovery. METHODS: Data from an international, prospective cohort study were used to develop a novel prognostic risk model for pulmonary complications after elective surgery in adult patients (aged ≥18 years) across all operation and disease types. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery, which was a composite of pneumonia, acute respiratory distress syndrome, and unexpected mechanical ventilation. Model development with candidate predictor variables was done in the GlobalSurg-CovidSurg Week dataset (global; October, 2020). Two structured machine learning techniques were explored (XGBoost and the least absolute shrinkage and selection operator [LASSO]), and the model with the best performance (GSU-Pulmonary Score) underwent internal validation using bootstrap resampling. The discrimination and calibration of the score were externally validated in two further prospective cohorts: CovidSurg-Cancer (worldwide; February to August, 2020, during the COVID-19 pandemic) and RECON (UK and Australasia; January to October, 2019, before the COVID-19 pandemic). The model was deployed as an online web application. The GlobalSurg-CovidSurg Week and CovidSurg-Cancer studies were registered with ClinicalTrials.gov, NCT04509986 and NCT04384926. FINDINGS: Prognostic models were developed from 13 candidate predictor variables in data from 86 231 patients (1158 hospitals in 114 countries). External validation included 30 492 patients from CovidSurg-Cancer (726 hospitals in 75 countries) and 6789 from RECON (150 hospitals in three countries). The overall rates of pulmonary complications were 2·0% in derivation data, and 3·9% (CovidSurg-Cancer) and 4·7% (RECON) in the validation datasets. Penalised regression using LASSO had similar discrimination to XGBoost (area under the receiver operating curve [AUROC] 0·786, 95% CI 0·774-0·798 vs 0·785, 0·772-0·797), was more explainable, and required fewer covariables. The final GSU-Pulmonary Score included ten predictor variables and showed good discrimination and calibration upon internal validation (AUROC 0·773, 95% CI 0·751-0·795; Brier score 0·020, calibration in the large [CITL] 0·034, slope 0·954). The model performance was acceptable on external validation in CovidSurg-Cancer (AUROC 0·746, 95% CI 0·733-0·760; Brier score 0·036, CITL 0·109, slope 1·056), but with some miscalibration in RECON data (AUROC 0·716, 95% CI 0·689-0·744; Brier score 0·045, CITL 1·040, slope 1·009). INTERPRETATION: This novel prognostic risk score uses simple predictor variables available at the time of a decision for elective surgery that can accurately stratify patients' risk of postoperative pulmonary complications, including during SARS-CoV-2 outbreaks. It could inform surgical consent, resource allocation, and hospital-level prioritisation as elective surgery is upscaled to address global backlogs. FUNDING: National Institute for Health Research.
2023
Balakrishnan A, Barmpounakis P, Demiris N, Jah A, Spiers HVM, Talukder S, Martin JL, Gibbs P, Harper SJF, Huguet EL, et al. Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study. EClinicalMedicine. 2023;59:101951.Abstract
BACKGROUND: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). METHODS: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. FINDINGS: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84-1.29], p = 0.711 and HR 1.18 [0.95-1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79-1.17], p = 0.67 and HR 1.48 [1.16-1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02-1.74], p = 0.037) and OS (HR 1.26 [1.03-1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3-3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62-3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55-5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02-1.37], p = 0.031) but not OS (HR 1.05 [0.91-1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. INTERPRETATION: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. FUNDING: Cambridge Hepatopancreatobiliary Department Research Fund.
Bramis K, Vouros D, Kotsarinis V, Frountzas M, Antonakis P, Memos N, Alexakis N, Konstadoulakis M, Toutouzas K. Completion Pancreatectomy as a Treatment Option for Complications Following Pancreatoduodenectomy. Am Surg. 2023;89(12):6348-6350.Abstract
Pancreatoduodenectomy remains a complex abdominal operation for hpb surgeons. Significant complications keep on occurring to many patients undergoing Whipple procedure. We present ten patients, who required completion pancreatectomy in the early postoperative period after Whipples procedure, due to postoperative complications. Indications for completion pancreatectomy included: Sepsis secondary to uncontrolled GRADE C postoperative pancreatic fistula, pancreatic leak and bleeding, postoperative hemorrhage, pancreatic leak with gastrointestinal anastomosis dehiscence, and hepaticojejunal anastomosis dehiscence combined with hemorrhage. Completion pancreatectomy was carried out at a mean interval of 9 days following Whipple procedure. Six patients (60%) survived the operation and discharged from the hospital, with a median survival of 21.3 months. Four patients (40%) died in the early post-operative period due to sepsis (10%) and multiple organ failure (30%). Completion pancreatectomy after pancreatoduodenectomy is rarely indicated and it can be considered as a salvage procedure in the management of severe life-threatening post pancreatic surgery complications.
Vouros D, Bramis K, Alexakis N, Kotsarinis V, Antonakis P, Memos N, Konstadoulakis M, Toutouzas K. Completion Pancreatectomy. Indications and Outcomes: A Systematic Review. Am Surg. 2023;89(12):6134-6146.Abstract
BACKGROUND/OBJECTIVE (S): Completion pancreatectomy (C.P.) is one acceptable treatment of choice in clinical scenarios such as management of post-pancreatectomy complications and recurrence in the pancreatic remnant. Studies referring to completion pancreatectomy as a distinct operation are limited, without emphasizing at the operation itself, rather reporting completion pancreatectomy as a possible option for treatment of various diseases. The identification of indications of CP in various pathologies and the clinical outcomes are therefore mandatory. METHODS: A systematic literature search was performed in the Pubmed and Scopus Databases (February 2020),guided by the PRISMA protocol, for all studies reporting CP as a surgical procedure with reference at indications for performing it combined with postoperative morbidity and/or mortality. RESULTS: Out of 1647 studies, 32 studies from 10 countries with 2775 patients in total, of whom 561 (20.2%) CPs met the inclusion criteria and were included in the analysis. Inclusion year ranged from 1964 to 2018 and were published from 1992 until 2019. 17 studies with a total number of 249 CPs were performed for post-pancreatectomy complications. Mortality rate was 44.5% (111 out of 249). Morbidity rate was (72.6%). 12 studies with 225 CPs were performed for isolated local recurrence after initial resection with a morbidity rate of 21.5% and 0% mortality rate in the early postoperative period. Two studies with a total number of 12 patients reported CP as a treatment option for recurrent neuroendocrine neoplasms. The mortality in those studies was 8% (1/12) and the mean morbidity rate was 58.3% (7/12). Finally, CP for refractory chronic pancreatitis was presented in one study with morbidity and mortality rates of 19% and 0%, respectively. CONCLUSION: Completion pancreatectomy is a distinct treatment option for various pathologies. Morbidity and mortality rates depend on the indications of performing CP, the status performance of the patients and whether the operation is performed electively or urgently
Georgiou K, Boyanov N, Antonakis P, Thanasas D, Sandblom G, Enochsson L. Validity of a virtual reality endoscopic retrograde cholangiopancreatography simulator: can it distinguish experts from novices?. Front Surg. 2023;10:1289197.Abstract
BACKGROUND: There is a lack of evidence regarding the effectiveness of virtual simulators as a means to acquire hands-on exposure to endoscopic retrograde cholangiopancreatography (ERCP). The present study aimed to assess the outcome and construct validity of virtual ERCP when training on the GI II Mentor simulator. METHODS: A group of seven experienced endoscopists were compared with 31 novices. After a short introduction, they were requested to carry out three virtual ERCP procedures: diagnosing and removing a common bile duct (CBD) stone; diagnosing and taking brush cytology from a hilar stenosis; and, finally, diagnosing and treating a cystic leakage with a BD stent. For each task, the total time required to complete the task, time required to correctly view the papilla, total time of irradiation, time to deep cannulation, time to define diagnosis, time to complete sphincterotomy, and time to complete the respective intervention were measured. Cannulation of the BD, correct diagnosis, sphincterotomy, and time to complete intervention were assessed by an assessor blinded to the status of the endoscopist who performed the virtual ERCP. RESULTS: The time required to visualize the papilla and to cannulate deeply when removing the BD stone was significantly shorter for the experts (both  < 0.05). The time to visualize the papilla, cannulate deeply, reach a diagnosis, complete sphincterotomy, and complete the intervention was significantly shorter for the experts when managing cystic leakage (all  < 0.05). In diagnosing and taking brush cytology from a hilar stenosis, there was only a trend toward the experts needing less time for the deep cannulation of the BD ( = 0.077). CONCLUSION: The performance differed between experts and novices, especially in the management of cystic leakage. This corroborates the construct validity of the GI II Mentor simulator.
2022
The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study. Colorectal Dis. 2022;24(6):708-26.Abstract
AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease.
SARS-CoV-2 infection and venous thromboembolism after surgery: an international prospective cohort study. Anaesthesia. 2022;77(1):28-39.Abstract
SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality (5.4 (95%CI 4.3-6.7)). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.
Elective surgery system strengthening: development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries. Lancet. 2022;400(10363):1607-1617.Abstract
BACKGROUND: The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs. METHODS: First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5, 2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score. FINDINGS: In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 clinicians (23 [33%] women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45·6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84·5 (95% CI 84·1-84·9), which varied between HIC (88·5 [89·0-88·0]), MIC (81·8 [82·5-81·1]), and LIC (66·8 [64·9-68·7]) settings. In the third phase, 1217 (74·6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51·4%) were from HIC, 538 (44·2%) from MIC, and 54 (4·4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3·6% (95% CI 3·0-4·1; p<0·0001) increase in SVR. This was consistent in HIC (4·8% [4·1-5·5]; p<0·0001), MIC (2·8 [2·0-3·7]; p<0·0001), and LIC (3·8 [1·3-6·7%]; p<0·0001) settings. INTERPRETATION: The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs. FUNDING: National Institute for Health Research (NIHR) Global Health Research Unit on Global Surgery, NIHR Academy, Association of Coloproctology of Great Britain and Ireland, Bowel Research UK, British Association of Surgical Oncology, British Gynaecological Cancer Society, and Medtronic.
Balakrishnan A, Jah A, Lesurtel M, Andersson B, Gibbs P, Harper SJF, Huguet EL, Kosmoliaptsis V, Liau SS, Praseedom RK, et al. Heterogeneity of management practices surrounding operable gallbladder cancer - results of the OMEGA-S international HPB surgical survey. HPB (Oxford). 2022;24(11):2006-2012.Abstract
BACKGROUND: Gallbladder cancer (GBC) is an aggressive, uncommon malignancy, with variation in operative approaches adopted across centres and few large-scale studies to guide practice. We aimed to identify the extent of heterogeneity in GBC internationally to better inform the need for future multicentre studies. METHODS: A 34-question online survey was disseminated to members of the European-African Hepatopancreatobiliary Association (EAHPBA), American Hepatopancreatobiliary Association (AHPBA) and Asia-Pacific Hepatopancreatobiliary Association (A-PHPBA) regarding practices around diagnostic workup, operative approach, utilization of neoadjuvant and adjuvant therapies and surveillance strategies. RESULTS: Two hundred and three surgeons responded from 51 countries. High liver resection volume units (>50 resections/year) organised HPB multidisciplinary team discussion of GBCs more commonly than those with low volumes (p < 0.0001). Management practices exhibited areas of heterogeneity, particularly around operative extent. Contrary to consensus guidelines, anatomical liver resections were favoured over non-anatomical resections for T3 tumours and above, lymphadenectomy extent was lower than recommended, and a minority of respondents still routinely excised the common bile duct or port sites. CONCLUSION: Our findings suggest some similarities in the management of GBC internationally, but also specific areas of practice which differed from published guidelines. Transcontinental collaborative studies on GBC are necessary to establish evidence-based practice to minimise variation and optimise outcomes.
2021
SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study. Br J Surg. 2021;108(9):1056-1063.Abstract
BACKGROUND: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. METHODS: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. RESULTS: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. CONCLUSION: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.
Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study. Lancet Oncol. 2021;22(11):1507-1517.Abstract
BACKGROUND: Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. METHODS: This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20-60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926. FINDINGS: Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16-30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77-0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50-0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80-0·88; p<0·001), and full lockdowns (0·57, 0·54-0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. INTERPRETATION: Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services. FUNDING: National Institute for Health Research Global Health Research Unit, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.
Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study. Anaesthesia. 2021;76(11):1454-1464.Abstract
We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or ≥ 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.
Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study. Anaesthesia. 2021;76(6):748-758.Abstract
Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
Preoperative nasopharyngeal swab testing and postoperative pulmonary complications in patients undergoing elective surgery during the SARS-CoV-2 pandemic. Br J Surg. 2021;108(1):88-96.Abstract
BACKGROUND: Surgical services are preparing to scale up in areas affected by COVID-19. This study aimed to evaluate the association between preoperative SARS-CoV-2 testing and postoperative pulmonary complications in patients undergoing elective cancer surgery. METHODS: This international cohort study included adult patients undergoing elective surgery for cancer in areas affected by SARS-CoV-2 up to 19 April 2020. Patients suspected of SARS-CoV-2 infection before operation were excluded. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery. Preoperative testing strategies were adjusted for confounding using mixed-effects models. RESULTS: Of 8784 patients (432 hospitals, 53 countries), 2303 patients (26.2 per cent) underwent preoperative testing: 1458 (16.6 per cent) had a swab test, 521 (5.9 per cent) CT only, and 324 (3.7 per cent) swab and CT. Pulmonary complications occurred in 3.9 per cent, whereas SARS-CoV-2 infection was confirmed in 2.6 per cent. After risk adjustment, having at least one negative preoperative nasopharyngeal swab test (adjusted odds ratio 0.68, 95 per cent confidence interval 0.68 to 0.98; P = 0.040) was associated with a lower rate of pulmonary complications. Swab testing was beneficial before major surgery and in areas with a high 14-day SARS-CoV-2 case notification rate, but not before minor surgery or in low-risk areas. To prevent one pulmonary complication, the number needed to swab test before major or minor surgery was 18 and 48 respectively in high-risk areas, and 73 and 387 in low-risk areas. CONCLUSION: Preoperative nasopharyngeal swab testing was beneficial before major surgery and in high SARS-CoV-2 risk areas. There was no proven benefit of swab testing before minor surgery in low-risk areas.
Glasbey JC, Nepogodiev D, Simoes JFF, Omar O, Li E, Venn ML, Venn ML, Abou Chaar MK, Capizzi V, Chaudhry D, et al. Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study. J Clin Oncol. 2021;39(1):66-78.Abstract
PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic. Br J Surg. 2021;108(12):1448-1464.Abstract
BACKGROUND: This study aimed to determine the impact of pulmonary complications on death after surgery both before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS: This was a patient-level, comparative analysis of two, international prospective cohort studies: one before the pandemic (January-October 2019) and the second during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Both included patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines. Patient selection and rates of 30-day postoperative pulmonary complications were compared. The primary outcome was 30-day postoperative mortality. Mediation analysis using a natural-effects model was used to estimate the proportion of deaths during the pandemic attributable to SARS-CoV-2 infection. RESULTS: This study included 7402 patients from 50 countries; 3031 (40.9 per cent) underwent surgery before and 4371 (59.1 per cent) during the pandemic. Overall, 4.3 per cent (187 of 4371) developed postoperative SARS-CoV-2 in the pandemic cohort. The pulmonary complication rate was similar (7.1 per cent (216 of 3031) versus 6.3 per cent (274 of 4371); P = 0.158) but the mortality rate was significantly higher (0.7 per cent (20 of 3031) versus 2.0 per cent (87 of 4371); P < 0.001) among patients who had surgery during the pandemic. The adjusted odds of death were higher during than before the pandemic (odds ratio (OR) 2.72, 95 per cent c.i. 1.58 to 4.67; P < 0.001). In mediation analysis, 54.8 per cent of excess postoperative deaths during the pandemic were estimated to be attributable to SARS-CoV-2 (OR 1.73, 1.40 to 2.13; P < 0.001). CONCLUSION: Although providers may have selected patients with a lower risk profile for surgery during the pandemic, this did not mitigate the likelihood of death through SARS-CoV-2 infection. Care providers must act urgently to protect surgical patients from SARS-CoV-2 infection.
2020
Delaying surgery for patients with a previous SARS-CoV-2 infection. Br J Surg. 2020;107(12):e601-e602.
Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic. Colorectal Dis. 2020;23(3):732-49.Abstract
AIM: This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic. METHOD: This was an international cohort study of patients undergoing elective resection of colon or rectal cancer without preoperative suspicion of SARS-CoV-2. Centres entered data from their first recorded case of COVID-19 until 19 April 2020. The primary outcome was 30-day mortality. Secondary outcomes included anastomotic leak, postoperative SARS-CoV-2 and a comparison with prepandemic European Society of Coloproctology cohort data. RESULTS: From 2073 patients in 40 countries, 1.3% (27/2073) had a defunctioning stoma and 3.0% (63/2073) had an end stoma instead of an anastomosis only. Thirty-day mortality was 1.8% (38/2073), the incidence of postoperative SARS-CoV-2 was 3.8% (78/2073) and the anastomotic leak rate was 4.9% (86/1738). Mortality was lowest in patients without a leak or SARS-CoV-2 (14/1601, 0.9%) and highest in patients with both a leak and SARS-CoV-2 (5/13, 38.5%). Mortality was independently associated with anastomotic leak (adjusted odds ratio 6.01, 95% confidence interval 2.58-14.06), postoperative SARS-CoV-2 (16.90, 7.86-36.38), male sex (2.46, 1.01-5.93), age >70 years (2.87, 1.32-6.20) and advanced cancer stage (3.43, 1.16-10.21). Compared with prepandemic data, there were fewer anastomotic leaks (4.9% versus 7.7%) and an overall shorter length of stay (6 versus 7 days) but higher mortality (1.7% versus 1.1%). CONCLUSION: Surgeons need to further mitigate against both SARS-CoV-2 and anastomotic leak when offering surgery during current and future COVID-19 waves based on patient, operative and organizational risks.
2019
Dragamestianos C, Messini CI, Antonakis PT, Zacharouli K, Kostopoulou E, Makrigiannakis A, Georgoulias P, Anifandis G, Dafopoulos K, Garas A, et al. The Effect of Metformin on the Endometrium of Women with Polycystic Ovary Syndrome. Gynecol Obstet Invest. 2019;84(1):35-44.Abstract
OBJECTIVES: To investigate the effect of metformin on endometrial receptivity in women with polycystic ovary syndrome (PCOS). METHODS: Twenty volunteer women with polycystic ovaries and oligomenorrhea were prospectively investigated. All women were treated with exogenous estradiol and progesterone to simulate a normal menstrual cycle (28-day duration) after GnRH-induced pituitary desensitization. Ten of the women received no other medication (group A, control), while the remaining 10 received metformin (group B, metformin). Endometrial biopsy was performed in all women on day 21 of the 2 simulated cycles. RESULTS: The expression of corticotropin - releasing hormone and urocortin in the endometrium was investigated. There was no significant difference between the 2 groups. A 3-day delay in the secretory maturation of the glandular epithelium relatively to the stroma was observed in 7 out of 10 women of group B (70%) as compared to only 1 out of 10 women of group A (10%, p = 0.02). CONCLUSIONS: It is shown for the first time that metformin administration to women with PCOS did not affect the expression of endometrial receptivity markers but delayed histological glandular maturation. It is suggested that metformin may have an impact on the function of the endometrium in PCOS.
2018
Kataki A, Karagiannidis I, Memos N, Koniaris E, Antonakis P, Papalois A, Zografos GC, Konstadoulakis MM. Host's Endogenous Caveolin-1 Expression is Downregulated in the Lung During Sepsis to Promote Cytoprotection. Shock. 2018;50(2):199-208.Abstract
The present study focuses on the profile of "endogeneous" caveolin-1 protein in septic lung (CLP model).Caveolin-1, CD25, pP38, pAkt, and 14-3-3b protein expression profiles were studied using flow cytometry and immunohistochemistry 6, 12, 24, 36, and 48 h after sepsis induction. Cell viability was determined by 7-AAD staining and fibrosis by Masson trichrome stain. The effect of protein C zymogen concentrate (PC) on caveolin-1 expression was also investigated given that PC, once dissociated from caveolin-1, elicits a PAR-1-mediated protective signaling by forming a complex with endothelial protein C receptor (EPCR).CLP treatment increased lung inflammation and cell apoptosis. Fibrosis was apparent in vessels and alveoli. Caveolin-1+ cells presented reduced protein expression, especially 12 h post-CLP (P = 0.002). Immunohistochemistry revealed caveolin-1 positive expression mainly in regions with strong inflammatory reaction. Early induction of pP38+ cell population (P = 0.014) and gradual increase of CD25+ cells were also observed. Alternations in 14-3-3b expression related to apoptosis were apparent and accompanied by increased AKT phosphorylation activity late during sepsis progression.After PC administration, cell apoptosis was reduced (P = 0.004) and both the percentile and expression intensity of caveolin-1 positive cells were compromised (P = 0.009 and P = 0.027, respectively). 14-3-3b, CD25, and pP38 protein expression were decreased (P = 0.014, P = 0.004, and P = 0.007, respectively), whereas pAkt expression was induced (P = 0.032).The observed decline of endogenous caveolin-1 protein expression during sepsis implies its involvement in host's cytoprotective reaction either directly, by controlling caveolae population to decrease bacterial burden, or indirectly via regulating 14-3-3b-dependent apoptosis and EPCR-PAR-1-dependent protective signaling.
2015
Antonakis PT, Ashrafian H, Martinez-Isla A. Pancreatic insulinomas: Laparoscopic management. World J Gastrointest Endosc. 2015;7(16):1197-207.Abstract
Insulinomas are rare pancreatic neuroendocrine tumors that are most commonly benign, solitary, and intrapancreatic. Uncontrolled insulin overproduction from the tumor produces neurological and adrenergic symptoms of hypoglycemia. Biochemical diagnosis is confirmed by the presence of Whipple's triad, along with corroborating measurements of blood glucose, insulin, proinsulin, C-peptide, β-hydroxybutyrate, and negative tests for hypoglycemic agents during a supervised fasting period. This is accompanied by accurate preoperative localization using both invasive and non-invasive imaging modalities. Following this, careful preoperative planning is required, with the ensuing procedure being preferably carried out laparoscopically. An integral part of the laparoscopic approach is the application of laparoscopic intraoperative ultrasound, which is indispensable for accurate intraoperative localization of the lesion in the pancreatic region. The extent of laparoscopic resection is dependent on preoperative and intraoperative findings, but most commonly involves tumor enucleation or distal pancreatectomy. When performed in an experienced surgical unit, laparoscopic resection is associated with minimal mortality and excellent long-term cure rates. Furthermore, this approach confers equivalent safety and efficacy rates to open resection, while improving cosmesis and reducing hospital stay. As such, laparoscopic resection should be considered in all cases of benign insulinoma where adequate surgical expertise is available.
Sigala F, Galyfos G, Coutelle AG, Antonakis P, Sigalas P, Bastounis E, Hepp W, Filis K. Open reconstructions for symptomatic atherosclerotic lesions of the supra-aortic vessels: thirty years results from two university hospitals. Ann Vasc Surg. 2015;29(3):404-10.Abstract
BACKGROUND: Atherosclerotic lesions at the origin of common carotid, subclavian, and innominate arteries are causes for brain and hand ischemic symptoms. Surgical reconstructions of symptomatic cases remain the golden standard treatment, although the endovascular approach has been promising as well. In this retrospective study, long-term results of open reconstructions from 2 University Hospitals are presented. METHODS: Through a 30-year period, prospective data of 107 patients, suffering from symptomatic atherosclerotic supra-aortic artery disease, were retrospectively reviewed and included in this study. Demographic data, arterial risk factors, presenting symptoms and signs, diagnostic evaluation, operative treatment and complications, resolution of symptoms, redo surgery, and overall mortality were analyzed. RESULTS: Eighty-one patients were operated on for subclavian, 14 for innominate, and 12 for common carotid severe lesions, through an extra-thoracic reconstruction (91 patients) or a transthoracic one (16 patients). Perioperative mortality was null although morbidity was 16.8%, and primary perioperative patency was 97.2% (secondary patency 100%). The cumulative primary patency was 95.3%, 90.7%, and 86.0% at 5, 10, and 15 years, respectively. The mean time of patency was 214.6 months (95% confidence interval = 198.5-230.6), with no difference between transthoracic and extrathoracic reconstructions (P = 0.278). CONCLUSIONS: Open reconstructions remain a therapeutic strategy with a considerably low perioperative morbidity/mortality offering excellent long-term results regarding patency of the reconstructions and clinical resolution of the symptoms. However, in the modern era of the endovascular techniques, we need more studies for establishing anatomic and clinical criteria regarding patient selection for endovascular angioplasty/stenting or open repair.
2014
Antonakis PT, Ashrafian H, Isla AM. Laparoscopic gastric surgery for cancer: where do we stand?. World J Gastroenterol. 2014;20(39):14280-91.Abstract
Gastric cancer poses a significant public health problem, especially in the Far East, due to its high incidence in these areas. Surgical treatment and guidelines have been markedly different in the West, but nowadays this debate is apparently coming to an end. Laparoscopic surgery has been employed in the surgical treatment of gastric cancer for two decades now, but with controversies about the extent of resection and lymphadenectomy. Despite these difficulties, the apparent advantages of the laparoscopic approach helped its implementation in early stage and distal gastric cancer, with an increase on the uptake for distal gastrectomy for more advanced disease and total gastrectomy. Nevertheless, there is no conclusive evidence about the laparoscopic approach yet. In this review article we present and analyse the current status of laparoscopic surgery in the treatment of gastric cancer.
2013
Papadima A, Gourgiotis S, Lagoudianakis E, Pappas A, Seretis C, Antonakis PT, Markogiannakis H, Makri I, Manouras A. Granisetron versus tropisetron in the prevention of postoperative nausea and vomiting after total thyroidectomy. Saudi J Anaesth. 2013;7(1):68-74.Abstract
BACKGROUND: Postoperative nausea and vomiting (PONV) are frequently encountered after thyroidectomy. For PONV prevention, selective serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are considered one of the first-line therapy. We report on the efficiency of granisetron and tropisetron, with that of placebo on the prevention of PONV in patients undergoing total thyroidectomy. METHODS: One hundred twenty-seven patients were divided into three groups and randomized to receive intravenously, prior to induction of anesthesia, tropisetron 5 mg, or granisetron 3 mg, or normal saline. All patients received additionally 0.625 mg droperidol. All episodes of postoperative PONV during the first 24 h after surgery were evaluated. RESULTS: Nausea visual analogue scale (VAS) score was lower in tropisetron and granisetron groups than the control group at all measurements (P<0.01) except for the 8-h measurement for tropisetron (P=0.075). Moreover, granisetron performed better than tropisetron (P<0.011 at 4 h and P<0.01 at all other points of time) apart from the 2-h measurement. Vomiting occurred in 22.2%, 27.5%, and 37.5% in granisetron, tropisetron, and control groups, respectively (P=0.43). CONCLUSIONS: The combination of the 5-HT3 antagonists with droperidol given before induction of anesthesia is well tolerated and superior to droperidol alone in preventing nausea but not vomiting after total thyroidectomy.
2011
Filis K, Kavantzas N, Isopoulos T, Antonakis P, Sigalas P, Vavouranakis E, Sigala F. Increased vein wall apoptosis in varicose vein disease is related to venous hypertension. Eur J Vasc Endovasc Surg. 2011;41(4):533-9.Abstract
OBJECTIVES: The study aimed to evaluate a wide range of apoptotic markers in the vein wall of patients with superficial chronic venous disease (SCVD) compared with normal veins. DESIGN: This was an observational study. METHODS: Vein specimens were obtained from 19 patients suffering from SCVD. From each patient, a specimen of the proximal part of the great saphenous vein (GSV), a specimen of the distal part of the vein and a specimen of a varicose tributary were obtained. Immunohistochemical analysis was used to localise the expression of BAX, p53, Caspase 3, BCL-2, BCL-6, BCL-xs, BCL-xl and Ki-67. Vein specimens from 10 healthy GSVs were used as controls. RESULTS: Saphenous vein specimens from patients with SCVD showed increased BAX, Caspase 3, BCL-xl and BCL-xs (p < 0.01 for all) and Ki-67 (p = 0.02) compared with healthy GSVs. In the venous disease group, GSV specimens from the distal ankle area showed increased BAX (p < 0.01) and BCL-xs (p = 0.031) compared with varicose tributaries specimens, which subsequently showed increased BAX (p = 0.044), Caspase 3 (p = 0.028) and BCL-xs (p = 0.037) compared with specimens from the proximal GSV. In addition, in the venous disease group, specimens from distal GSV showed increased BAX (p < 0.01), Caspase 3 (p = 0.019) and BCL-xs (p = 0.014) compared with the proximal GSV. CONCLUSION: Varicose veins exhibit increased apoptotic activity, by means of increased BAX, Caspase 3, BCL-xl and BCL-xs, compared with normal veins. Patients with varicose vein disease show increased apoptosis in the distal saphenous trunk compared with the proximal saphenous trunk, suggesting an association between chronic venous hypertension and apoptosis.
Papalambros A, Sigala F, Vouza EG, Hepp W, Antonakis P. Sister Mary Joseph's nodule as primary localized malignant mesothelioma. Report of a case. Zentralbl Chir. 2011;136(2):172-4.
2010
Pappas AV, Lagoudianakis EE, Dallianoudis IG, Kotzadimitriou KT, Koronakis NE, Chrysikos ID, Koukoutsi ID, Markogiannakis HE, Antonakis PT, Manouras AJ. Differences in colorectal cancer patterns between right and left sided colorectal cancer lesions. J BUON. 2010;15(3):509-13.Abstract
PURPOSE: Colorectal carcinomas that arise proximal (right) or distal (left) to the splenic flexure exhibit different clinical and biological characteristics. Although various hypotheses have been proposed to explain these differences, their origin remains unclear. In this study we investigated the clinicopathologic differences between left and right colon tumors and comment on the possible explanatory theories behind them. METHODS: This study included a total of 388 retrospectively collected cases of colorectal cancer, surgically treated from 1999 to 2004. Differences of patients' demographic data and tumor micro- and macroscopic characteristics between left and right-sided tumors were investigated and analysed. RESULTS: Patients with right-sided colon cancer were significantly older (mean age 70 vs. 68 years; p<0.05) and had more lymph nodes examined than patients with left colon tumors (mean number of nodes 18.9 vs. 12.6; p<0.05). There was a lower proportion of T1 stage right-sided tumors (3.1 vs. 5%) and a higher proportion of stage T2-4 (96.9 vs. 95%) compared with left-sided tumors (p<0.001 for x2 test of all T stages). Furthermore, right-sided tumors had a higher mean width and depth (4.3 vs. 3.8 cm and 1.8 vs. 1.6 cm, respectively; p<0.05). Finally, there was a higher percentage of poorly differentiated right colon tumors (41.4 vs. 17.5%; p<0.001). CONCLUSION: Right-sided colon tumors affect older patients and are diagnosed at more advanced disease stages. The underlying mechanisms that provoke these differences remain unclear. Further studies are needed in order to better understand the true nature of these differences and their possible clinical implications.
2009
Papadima A, Lagoudianakis EE, Antonakis P, Filis K, Makri I, Markogiannakis H, Katergiannakis V, Manouras A. Repeated intraperitoneal instillation of levobupivacaine for the management of pain after laparoscopic cholecystectomy. Surgery. 2009;146(3):475-82.Abstract
BACKGROUND: Laparoscopic cholecystectomy is the treatment of choice for symptomatic cholelithiasis. Postoperative pain, however, can prolong hospital stay and lead to increased morbidity. In the context of a multimodal approach to analgesia, intraperitoneal local anesthetic administration optimizes analgesia and facilitates early postoperative recovery, and it may be associated with a decreased risk of side effects. METHODS: A total of 71 patients was randomized to receive either intraperitoneal analgesic (IPA group) or not (controls). At the completion of cholecystectomy, 10 mL of levobupivacaine 0.5% were infused intraperitoneally in the IPA group and 8 h postoperatively, whereas in the controls, 10 mL of 0.9% NaCl were administered in the corresponding points of time. Differences in pain scores between groups were the primary endpoints. Opioid consumption and adverse effects were the secondary endpoints. RESULTS: The 2 groups were homogenous in respect to age, sex, body mass index (BMI), and duration of operation. No conversion, complication, or mortality was recorded. The IPA group had a lesser visual analog scale score at rest and at movement compared with controls at all points of time measured. Moreover, fentanyl consumption in the recovery room was significantly greater in the control group, and the consumption of meperidine and the percentage of the patients that requested rescue analgesia in the ward was significantly greater in the control group. Local analgesic intraperitoneal injection as well as parecoxib for postoperative analgesia had no significant adverse effects. CONCLUSION: Our study showed that 2 separate doses of intraperitoneally administered levobupivacaine significantly decreased postoperative pain and the need for opioids compared with placebo. This technique is simple, safe, and without adverse effects.
Leandros E, Antonakis PT, Gomatos I, Tsigris C, Konstadoulakis MM. Pelvic isolation with two Gore-tex dual-mesh pieces for a recurrent complicated enterovescicocervical fistula in a patient irradiated for cervical cancer. Am Surg. 2009;75(11):1146-8.
Lagoudianakis E, Pappas A, Koronakis N, Dallianoudis I, Kotzadimitriou K, Chrysikos J, Koukoutsis I, Antonakis P, Keramidaris D, Manouras A. Recurrent erythema multiforme after alcohol ingestion in a patient receiving ciprofloxacin: a case report. Cases J. 2009;2:7787.Abstract
The incidence of cutaneous adverse reactions to quinolones is low; moreover their development in patients with concomitant alcohol consumption is a phenomenon that has been scarcely reported. We present a case of 46-year-old male who developed erythema multiforme after ingestion of alcohol, while being treated with ciprofloxacin. The lesion was self-limiting and abstinence from alcohol permitted the completion of the course of therapy without any other adverse reaction.
Manouras A, Pararas N, Antonakis P, Lagoudiannakis EE, Papageorgiou G, Dalianoudis IG, Konstadoulakis MM. Management of major bile duct injury after laparoscopic cholecystectomy: a case report. J Med Case Rep. 2009;3:44.Abstract
INTRODUCTION: Bile duct injury is a severe and potentially life-threatening complication of laparoscopic cholecystectomy. Several series have described a 0.5% to 0.6% incidence of bile duct injury during laparoscopic cholecystectomy. The aim of this study was to analyze the presentation, characteristics, related investigation, and treatment results of major bile duct injuries after laparoscopic cholecystectomy. CASE PRESENTATION: A rare case of a 48-year-old Greek woman with a triple bile duct injury (right and left hepatic duct ligation and common bile duct cross-section) is presented. A Roux en Y hepaticojejunostomy was performed after repeated endoscopic retrograde cholangiopancreatographies, percutaneous transhepatic catheterization of the ducts and magnetic resonance cholangiographies to delineate the biliary anatomy and assess the level of injury. CONCLUSION: Early recognition and an adequate multidisciplinary approach are the cornerstones for the optimal final outcome. Suboptimal management of injuries often leads to more extensive damage to the biliary tree and its vasculature. Early referral to a tertiary care center with experienced hepatobiliary surgeons and skilled interventional radiologists would appear to be necessary to assure optimal results.
Konstadoulakis MM, Gomatos IP, Toufektzian L, Katsaragakis S, Koskinas J, Antonakis P, Nikiteas N, Leandros E, Tsigris C. Spontaneous intrahepatic echinococcal cyst rupture in a patient with chronic hepatitis C infection. Can J Surg. 2009;52(4):E120-E122.
2008
Markogiannakis H, Konstadoulakis M, Tzertzemelis D, Antonakis P, Gomatos I, Bramis C, Manouras A. Subclinical peritonitis due to perforated sigmoid diverticulitis 14 years after heart-lung transplantation. World J Gastroenterol. 2008;14(22):3583-6.Abstract
Acute complicated diverticulitis, particularly with colon perforation, is a rare but serious condition in transplant recipients with high morbidity and mortality. Neither acute diverticulitis nor colon perforation has been reported in young heart-lung grafted patients. A case of subclinical peritonitis due to perforated acute sigmoid diverticulitis 14 years after heart-lung transplantation is reported. A 26-year-old woman, who received heart-lung transplantation 14 years ago, presented with vague abdominal pain. Physical examination was normal. Blood tests revealed leukocytosis. Abdominal X-ray showed air-fluid levels while CT demonstrated peritonitis due to perforated sigmoid diverticulitis. Sigmoidectomy and end-colostomy (Hartmann's procedure) were performed. Histopathology confirmed perforated acute sigmoid diverticulitis. The patient was discharged on the 8th postoperative day after an uneventful postoperative course. This is the first report of acute diverticulitis resulting in colon perforation in a young heart-lung transplanted patient. Clinical presentation, even in peritonitis, may be atypical due to the masking effects of immunosuppression. A high index of suspicion, urgent aggressive diagnostic investigation of even vague abdominal symptoms, adjustment of immunosuppression, broad-spectrum antibiotics, and immediate surgical treatment are critical. Moreover, strategies to reduce the risk of this complication should be implemented. Pretransplantation colon screening, prophylactic pretransplantation sigmoid resection in patients with diverticulosis, and elective surgical intervention in patients with nonoperatively treated acute diverticulitis after transplantation deserve consideration and further studies.
Manouras A, Toutouzas KG, Markogiannakis H, Lagoudianakis E, Papadima A, Antonakis PT, Kafiri G, Bramis I. Intracystic hemorrhage in a mediastinal cystic adenoma causing parathyrotoxic crisis. Head Neck. 2008;30(1):127-31.Abstract
BACKGROUND: We report a case of intracystic hemorrhage in a mediastinal cystic parathyroid adenoma causing parathyrotoxic crisis. METHODS AND RESULTS: A 30-year-old man presented with a large neck mass, dyspnea, and abdominal pain. The patient's serum calcium and parathormone levels were elevated. Radiography showed a right tracheal deviation, ultrasonography identified a thyroid nodular goiter extending to the mediastinum with a large (4.0 cm x 5.6 cm) cystic mass adjacent to the lower left thyroid pole. After IV fluid, pamidronate, and furosemide were administered, the patient underwent total thyroidectomy, and excision of the cyst and a small mass (2 cm x 2 cm) adjacent to the upper right thyroid lobe. Histopathologic examination revealed a double parathyroid adenoma and identified the mediastinal lesion as a cystic adenoma with intracystic hemorrhage. CONCLUSIONS: Intracystic hemorrhage in a functional mediastinal cystic parathyroid adenoma is an extremely rare cause of parathyrotoxic crisis. Aggressive medical treatment should be immediately instituted, and surgery should be performed as soon as hypercalcemia is controlled.
Manouras A, Markogiannakis H, Koutras AS, Antonakis PT, Drimousis P, Lagoudianakis EE, Kekis P, Genetzakis M, Koutsoumanis K, Bramis I. Thyroid surgery: comparison between the electrothermal bipolar vessel sealing system, harmonic scalpel, and classic suture ligation. Am J Surg. 2008;195(1):48-52.Abstract
BACKGROUND: This study was conducted to compare the outcome of total thyroidectomy using the electrothermal bipolar vessel sealing system, the harmonic scalpel, and the classic suture ligation technique. METHODS: This was a retrospective study of prospectively collected data from 382 consecutive total thyroidectomies from September 2004 to August 2006. Patients were divided into 3 groups: group SL patients (n = 90) underwent total thyroidectomy with the classic suture ligation technique, group L (n = 148) with the electrothermal bipolar vessel sealer, and group U (n = 144) with the harmonic scalpel. The main outcomes measured were surgical and hospitalization time, intraoperative and postoperative bleeding, postoperative hypocalcemia, and superior and inferior laryngeal nerves injuries. RESULTS: The 3 groups were similar in terms of demographics, thyroid gland weight and pathology, perioperative complications, and hospital stay. Compared with the classic technique, surgical time was reduced significantly by about 20% when the bipolar vessel sealer or harmonic scalpel was used (93.3 +/- 12.5 vs 74.3 +/- 14.2 and 73.8 +/- 13.8 min, P = .001, and P = .001, respectively). CONCLUSIONS: Both the bipolar vessel sealer and harmonic scalpel are safe, useful, and time-saving alternatives to the traditional suture ligation technique for thyroid surgery. Because no differences were observed regarding these 2 devices, the choice should be made based on the surgeon's preferences and experience.
Manouras A, Markogiannakis H, Lagoudianakis E, Antonakis P, Genetzakis M, Papadima A, Konstantoulaki E, Papanikolaou D, Kekis P. Unintentional parathyroidectomy during total thyroidectomy. Head Neck. 2008;30(4):497-502.Abstract
BACKGROUND: Unintentional parathyroidectomy during thyroidectomy has been evaluated in a few studies. Moreover, the impact of the surgeon's experience and operative technique has not been evaluated. Our aim was to identify the incidence of unintentional parathyroidectomy during total thyroidectomy, its clinical consequences, and factors affecting its occurrence. METHODS: We reviewed all total thyroidectomies during a 2-year period. Patients were categorized into 2 groups: those with unintentional parathyroidectomy (parathyroidectomy group) and those without unintentional parathyroidectomy (no-parathyroidectomy group). RESULTS: Incidental parathyroidectomy occurred in 100 (19.7%) of the 508 patients. The groups were comparable in age, thyroid weight and pathology, operative time, surgeon experience (high/low volume), operative technique (suture-ligation, LigaSure, or Ultracision), postoperative calcium, and transient hypocalcemia. No permanent hypocalcemia occurred. However, 11% of the parathyroidectomy group was men compared with 22% of the no-parathyroidectomy group (p =.002). CONCLUSIONS: Unintentional parathyroidectomy, although common, has no clinical consequences. Unlike surgeon's experience and operative technique, patient sex was the only factor affecting its occurrence.
2007
Fotiadis C, Adamis S, Misiakos EP, Genetzakis M, Antonakis PT, Tsekouras DK, Gorgoulis VG, Zografos GC, Papalois A, Fotinou M, et al. The prophylactic effect of L-arginine in acute ischaemic colitis in a rat model of ischaemia/reperfusion injury. Acta Chir Belg. 2007;107(2):192-200.Abstract
BACKGROUND/AIMS: The decreased synthesis of nitric oxide (NO) during ischaemia/reperfusion (I/R) has been implicated as the major underlying mechanism for the pathogenesis of acute ischaemic colitis (A.I.C.). The aim of this study was to investigate the prophylactic effect of L-arginine, a NO donor, on tissue injury during intestinal I/R, and compare its efficacy with that of exogenous vasodilators (molsidomine) and inert nitrogen-containing molecules (casein). MATERIAL AND METHODS: One hundred forty four Wistar rats underwent occlusion of the superior mesentery artery for 30, 60 and 90 min for induction of intestinal ischaemia, followed by 90 min of reperfusion. The rats were randomly assigned to receive L-arginine, molsidomine, or casein hydrolysate. In all groups, apart of the histological study, we determined the levels of serum malondialdehyde (MDA), a reliable marker indicating the degree of the tissue damage after intestinal I/R. RESULTS: Serum MDA levels were significantly lower in the L-arginine group compared to the untreated animals or those that had received molsidomine or casein, after a period of ischaemia of 90 minutes (p < 0.0005), as well as after a period of ischaemia of 60 or 90 minutes followed by a 90 minutes reperfusion (p = 0.011, and p < 0.0005, respectively). In addition, lesser histopathological damage was noted after the use of L-arginine compared to that caused by the administration of molsidomine and casein. CONCLUSION: These findings support a prophylactic effect of L-arginine in experimentally induced intestinal ischaemia. In short, L-arginine attenuates the degree of tissue damage in intestinal ischaemia and promotes healing of intestinal mucosa.
Papadima A, Lagoudianakis EE, Antonakis PT, Pattas M, Kremastinou F, Katergiannakis V, Manouras A, Georgiou L. Parecoxib vs. lornoxicam in the treatment of postoperative pain after laparoscopic cholecystectomy: a prospective randomized placebo-controlled trial. Eur J Anaesthesiol. 2007;24(2):154-8.Abstract
BACKGROUND AND OBJECTIVE: Non-steroidal anti-inflammatory drugs are considered as an effective treatment of postoperative pain after laparoscopic cholecystectomy. COX-2 inhibitors are newer drugs having less adverse effects. Data supporting their efficacy postoperatively in comparison to older non-steroidal anti-inflammatory drugs are scarce. Our study is a prospective, randomized, double-blinded, placebo-controlled trial comparing the efficacy of lornoxicam vs. parecoxib for the management of pain after laparoscopic cholecystectomy. MATERIALS AND METHODS: We enrolled 76 patients, ASA I and II, scheduled for elective laparoscopic cholecystectomy. The patients were randomized to receive before induction parecoxib 40 mg i.v., lornoxicam 8 mg i.v. or placebo. Pain at rest and on movement was assessed using a visual analogue scale at 0, 6, 12 h postoperatively. Total meperidine consumption and adverse effects were also recorded. RESULTS: At 12 h, visual analogue scale scores at rest and on movement were significantly lower with parecoxib and lornoxicam compared with control ( P = 0.047). The percentage of patients needing meperidine and the average dose of meperidine administered was significantly lower with parecoxib and lornoxicam compared with control (P < 0.001 and P = 0.018). There was no difference between parecoxib and lornoxicam. One patient receiving lornoxicam vomited. CONCLUSIONS: Parecoxib 40 mg i.v. and lornoxicam 8 mg i.v. were equianalgesic and both were more efficacious than placebo for the management of pain after laparoscopic cholecystectomy.
Manouras A, Genetzakis M, Antonakis PT, Lagoudianakis E, Pattas M, Papadima A, Giannopoulos P, Menenakos E. Endoscopic management of a relapsing hepatic hydatid cyst with intrabiliary rupture: a case report and review of the literature. Can J Gastroenterol. 2007;21(4):249-53.Abstract
Hydatid disease, although endemic mostly in sheep-farming countries, remains a public health issue worldwide, involving mainly the liver. Intrabiliary rupture is the most frequent complication of the hepatic hydatid cyst. Endoscopy is advocated, preoperatively, to alleviate obstructive jaundice caused by intracystic materials after a frank rupture and is also a useful and well-established adjunct in locating postoperative biliary fistulas. Endoscopic retrograde cholangiography with sphincterotomy has been successful as the sole and definitive means of treatment of intrabiliary ruptured hydatid cysts. A case of an elderly woman with frank rupture is presented, where the rupture was definitively managed endoscopically in conjunction with sphincterotomy to remove the intrabiliary obstructive daughter cysts and to achieve decontamination of the biliary tree. Endoscopic retrograde cholangiography provided an excellent diagnostic and therapeutic modality in the present case and, thus, it should be considered as definitive treatment in similar cases especially if surgical risk is anticipated to be high.
Vassiliou S, Yapijakis C, Derka S, Papakosta V, Psyrri A, Antonakis P, Goutzanis L, Konstadoulakis M, Androulakis G, Vairaktaris E. Evaluation of apoptosis in nasal and buccal cells of septic patients. In Vivo. 2007;21(5):901-4.Abstract
BACKGROUND: Inhibition of lung cell apoptosis in the bronchoalveolar lavage (BAL) of septic patients may have a prognostic value for the severity of sepsis. The present study evaluated apoptosis in the nasal and buccal mucosa of septic patients as an alternative and less invasive approach for studying the cells involved in bronchial inflammation. PATIENTS AND METHODS: A prospective study was designed. Nasal and buccal mucosa brushings were obtained from 20 consecutive septic patients who were admitted to two intensive care units. Twenty-four patients scheduled to undergo surgery for colorectal cancer or laparascopic cholocystectomy were the control group. Apoptosis was evaluated using a TUNEL assay, while BCL-2 and BAX expression were evaluated by immunohistochemistry. RESULTS: Significantly reduced apoptosis in the nasal mucosa of septic patients compared to the control group (p=0.043) was detected only by the TUNEL assay. CONCLUSION: Reduced apoptosis was found during sepsis in the nasal mucosa in accordance with the reduced apoptosis in the lungs of septic patients. In contrast to septic lungs the underlying mechanism leading to apoptosis in the nasal mucosa was unrelated to the expression of two apoptosis-related genes BCL-2 and BAX.
2006
Konstadoulakis MM, Lagoudianakis E, Antonakis PT, Albanopoulos K, Gomatos I, Stamou KM, Leandros E, Manouras A. Laparoscopic versus open splenectomy in patients with beta thalassemia major. J Laparoendosc Adv Surg Tech A. 2006;16(1):5-8.Abstract
BACKGROUND: Laparoscopic splenectomy is considered the standard of care for the removal of the spleen in benign diseases. There are not sufficient data for the routine application of this technique in patients with beta thalassemia major. MATERIALS AND METHODS: Twenty-eight consecutive beta thalassemia major patients who underwent elective splenectomy were randomized for open and laparoscopic splenectomy. Patient demographics, operative time, intraoperative and postoperative complications, conversion rate, transfusions, and length of stay were recorded. RESULTS: There was no mortality in this series. There was no difference in complication rates between the two groups. Operative time was markedly increased in the group treated laparoscopically, as was the need for blood transfusions. Median hospital stay was decreased in the laparoscopic group (5 days) compared to the open group (6.5 days). CONCLUSIONS: Laparoscopic splenectomy in patients with beta thalassemia major is feasible; however, it is more time consuming and bleeding occurs more often.
Konstadoulakis MM, Gomatos IP, Antonakis PT, Manouras A, Albanopoulos K, Nikiteas N, Leandros E, Bramis J. Two-trocar laparoscopic-assisted appendectomy versus conventional laparoscopic appendectomy in patients with acute appendicitis. J Laparoendosc Adv Surg Tech A. 2006;16(1):27-32.Abstract
BACKGROUND: In order to reduce abdominal trauma and operative costs we have adopted a two-trocar laparoscopic-assisted appendectomy for patients with acute appendicitis. In the current study, the proposed technique is prospectively evaluated against conventional laparoscopic appendectomy with respect to feasibility, safety, and postoperative outcome. MATERIALS AND METHODS: Between July 2001 and July 2003, 83 consecutive patients were admitted with clinically diagnosed acute appendicitis and were randomly assigned to two-trocar laparoscopic-assisted appendectomy (n = 40, 48.2%) or conventional laparoscopic appendectomy (n = 43, 51.8%). RESULTS: Two-trocar laparoscopic-assisted appendectomy was successfully completed in 30 patients (80.1%). Four patients initially scheduled for two-trocar laparoscopic-assisted appendectomy (10.8%) were converted to laparotomy due to excessive body weight (BMI > or = 40), while an additional 5-mm infraumbilical trocar was inserted in another 3 patients (8.1%). The procedure was associated with decreased operative time and more rapid return to normal activity compared to laparoscopic appendectomy (P < 0.001 and P = 0.038, respectively). There was no statistically significant difference regarding the duration of hospitalization or the morbidity rate between the two groups. Conversion of the initial procedure was associated with increased wound infection rate and higher morbidity (P = 0.032 and P = 0.018, respectively). CONCLUSION: Two-trocar laparoscopic-assisted appendectomy represents a promising minimally invasive procedure for the treatment of acute appendicitis. It is fast and easy to perform, and it is expected to decrease the overall cost of laparoscopic appendectomy. Its only contraindication is excessive body weight; it remains to be evaluated in the setting of perforated appendicitis and retrocecally located appendices.
Filippakis GM, Lagoudianakis EE, Genetzakis M, Antonakis P, Papadima A, Boussiotou A, Katergiannakis V, Manouras A. Squamous cell carcinoma arising in a mature cystic teratoma of the ovary with synchronous invasive lobular breast cancer: case report. Eur J Gynaecol Oncol. 2006;27(5):537-40.Abstract
Malignant transformation of a mature ovarian cystic teratoma is the most serious complication of this relatively common neoplastic lesion. While any constituent tissue of the teratoma can undergo malignant transformation, squamous cell carcinoma represents approximately 80% of those malignancies. Furthermore, the synchronous occurrence of a second malignancy in that setting is extremely rare. Preoperative diagnosis of malignant transformation within a mature cystic teratoma is extremely difficult and poses a great challenge to current clinical surgical practice. The particularly aggressive behavior of this rare tumor, also poses significant surgical managing dilemmas. We present a case report of a premenopausal woman with an invasive squamous cell carcinoma arising in a mature cystic teratoma and a synchronous invasive lobular carcinoma of the breast.
2005
Konstadoulakis MM, Filippakis GM, Lagoudianakis E, Antonakis PT, Dervenis C, Bramis J. Intra-arterial bolus octreotide administration during Whipple procedure in patients with fragile pancreas: a novel technique for safer pancreaticojejunostomy. J Surg Oncol. 2005;89(4):268-72.Abstract
BACKGROUND AND OBJECTIVES: Leakage from the pancreaticojujenostomy is the most serious complication of Whipple. Pancreatic fistula rate is higher in cases of fragile pancreas often seen in duodenal carcinomas and carcinomas of the ampulla of Vater. Octreotide administration has been used for the prevention of fistula formation through the subcutaneous route. Due to its physiologic effects to the pancreatic parenchyma the intra-arterial administration of octreotide could provide tissue hardening that allows for a technically easier anastomosis while maintaining its protective role for fistula formation. METHODS: Octreotide was injected directly into the distal part of the gastroduodenal artery (GDA) in four patients undergoing Whipple for histologically proven periampullary cancer. RESULTS: Tissue hardening after octreotide administration was evident not only in surgeons' hands but in the intra-operative ultrasound as well. The three patients were discharged on day 9, 11, and 13; they had an uneventful postoperative course, while one patient had a minor bile leak from the choledojejunal anastomosis and was discharged on day 22. CONCLUSIONS: The intra-arterial administration of octreotide during Whipple is a safe procedure and provides tissue hardening thus making the performance of the anastomosis technically easier. The actual benefit in terms of morbidity, mortality, and fistula rate are to be further evaluated.
Leandros E, Antonakis PT, Karantzikos G, Gomatos IP, Lagoudianakis EE, Albanopoulos K, Konstadoulakis MM. Two-step treatment for complex cholecystocholedocholithiasis. Surgery. 2005;137(1):114-6.
Fotiadis C, Tsekouras D-K, Antonakis P, Sfiniadakis J, Genetzakis M, Zografos G-C. Gardner's syndrome: a case report and review of the literature. World J Gastroenterol. 2005;11(34):5408-11.Abstract
Gardner's syndrome is an autosomal dominant disease characterized by the presence of colonic polyposis, osteomas and a multitude of soft tissue tumors. The syndrome may present at any age from 2 mo to 70 years with a variety of symptoms, either colonic or extracolonic. We present a case of a 11-year-old female patient with Gardner's syndrome who presented with a lumbar area desmoid tumor and treated with resection of the desmoid, restorative proctocolectomy and ileal pouch anal anastomosis, A review of the current literature has been performed.
Manouras A, Lagoudianakis EE, Antonakis PT, Filippakis GM, Markogiannakis H, Kekis PB. Electrothermal bipolar vessel sealing system is a safe and time-saving alternative to classic suture ligation in total thyroidectomy. Head Neck. 2005;27(11):959-62.Abstract
BACKGROUND: Total thyroidectomy is associated with minimal morbidity. The electrothermal bipolar vessel sealing system is an adjunct to the surgical technique, recently made available to thyroid surgery. METHODS: This is a prospective randomized trial of total thyroidectomies performed in single unit from July 2003 to May 2004. Patients were randomly assigned in two groups: group A (n = 90), total thyroidectomy with the classic suture ligation technique; and group B (n = 94), total thyroidectomy with the use of the electrothermal bipolar vessel sealing system. RESULTS: Operative time was significantly reduced in group B by 14 minutes (mean difference, 14.3 +/- 4.2 minutes, 95% CI, 5.88-22.6 minutes). No statistically significant differences were found in postoperative complications, postoperative serum calcium measurements, or hospital stay between the two groups. CONCLUSIONS: The electrothermal bipolar vessel sealing system is a safe and useful, time-saving adjunct for total thyroidectomy.
Fotiadis C, Xekouki P, Papalois AE, Antonakis PT, Sfiniadakis I, Flogeras D, Karampela E, Zografos G. Effects of mycophenolate mofetil vs cyclosporine administration on graft survival and function after islet allotransplantation in diabetic rats. World J Gastroenterol. 2005;11(18):2733-8.Abstract
AIM: To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. METHODS: Thirty-six male Wistar rats and 18 male Lewis rats were used as recipients and donors respectively. Diabetes was induced by the use of streptozotocin (60 mg/kg) intraperitoneally. Unpurified islets were isolated using the collagenase digestion technique and transplanted into the splenic parenchyma. The recipients were randomly assigned to one of the following three groups: group A (control group) had no immunosuppression; group B received cyclosporine (CsA) (5 mg/kg); group C received mycophenolate mofetil (MMF) (20 mg/kg). The animals were killed on the 12th d. Blood and grafted tissues were obtained for laboratory and histological assessment. RESULTS: Median allograft survival was significantly higher in the two therapy groups than that in the controls (10 and 12 d for CsA and MMF respectively vs 0 d for the control group, P<0.01). No difference in allograft survival between the CsA and MMF groups was found. However, MMF had less renal and hepatic toxicity and allowed weight gain. CONCLUSION: Monotherapy with MMF for immunosuppression was safe in an experimental model of islet allotransplantation and was equally effective with cyclosporine, with less toxicity.
Manouras A, Lagoudianakis EE, Antonakis PT, Romanos A. Endoscope entrapment in the choledochal duct during endoscopic retrograde cholangiography for choledocholithiasis. Endoscopy. 2005;37(8):785.
2004
Leandros E, Antonakis PT, Albanopoulos K, Dervenis C, Konstadoulakis MM. Somatostatin versus octreotide in the treatment of patients with gastrointestinal and pancreatic fistulas. Can J Gastroenterol. 2004;18(5):303-6.Abstract
BACKGROUND AND PURPOSE: Gastrointestinal and pancreatic fistulas are characterized as serious complications following abdominal surgery, with a reported incidence of up to 27% and 46%, respectively. Fistula formation results in prolonged hospitalization, increased morbidity/mortality and increased treatment costs. Conservative and surgical approaches are both employed in the management of these fistulas. The purpose of the present study was to assess, evaluate and compare the potential clinical benefit and cost effectiveness of pharmacotherapy (somatostatin versus its analogue octreotide) versus conventional therapy. PATIENTS AND METHODS: Fifty-one patients with gastrointestinal or pancreatic fistulas were randomized to three treatment groups: 19 patients received 6000 IU/day of somatostatin intravenously, 17 received 100 microg of octreotide three times daily subcutaneously and 15 patients received only standard medical treatment. RESULTS: The fistula closure rate was 84% in the somatostatin group, 65% in the octreotide group and 27% in the control group. These differences were of statistical significance (P=0.007). Overall mortality rate was less than 5% and statistically significant differences in mortality among the three groups could not be established. Overall, treatment with somatostatin and octreotide was more cost effective than conventional therapy (control group), and somatostatin was more cost effective than octreotide. The average hospital stay was 21.6 days, 27.0 and 31.5 days for the somatostatin, octreotide and control groups, respectively. CONCLUSIONS: Data suggest that pharmacotherapy reduces the costs involved in fistula management (by reducing hospitalization) and also offers increased spontaneous closure rate. Further prospective studies focusing on the above parameters are needed to demonstrate the clinicoeconomic benefits.
Messaris E, Antonakis PT, Memos N, Chatzigianni E, Leandros E, Konstadoulakis MM. Deferoxamine administration in septic animals: improved survival and altered apoptotic gene expression. Int Immunopharmacol. 2004;4(3):455-9.Abstract
BACKGROUND: Oxidative damage is one of the major factors that lead to cell damage, organ dysfunction and death in sepsis. Thus, an attractive candidate for the pharmacologic treatment of the septic syndrome is desferoxamine (DFX), an antioxidant iron chelator used for the removal of iron and a potential free radical scavenger. OBJECTIVE: The impact of DFX administration on the survival of septic animals. The effect on cell integrity and cycle of vital organs. METHODS: Sepsis was induced in 40 rats using the cecal ligation and puncture method (CLP) and 20 rats randomly received twice subcutaneously DFX (total dose: 40 mg/kg). Rats were monitored for 36 h and all vital organs were harvested for pathology examination and immunohistochemical detection of Bax, Bcl-2, cytochrome c and caspase-8 apoptosis regulating proteins. RESULTS: Mean survival in the DFX group was 34.2 h (median 36.0, S.D. 4.4) and 30.2 h (median 36.0, S.D. 9.1) in the control group (p=0.04), while 36 h after follow up 85% of the DFX-treated rats and 55% of placebo rats were alive (p=0.04). Expression of pro-apoptotic bax protein was significantly increased in the heart, liver and kidney of animals in the DFX group compared to the control group. CONCLUSIONS: Treatment with the polymeric iron chelator DFX significantly increases survival of septic subjects and alters the expression of bax, an apoptosis regulating protein in certain organs (heart, liver and kidney).
Konstadoulakis MM, Antonakis PT, Karatzikos G, Alexakis N, Leandros E. Intraoperative findings and postoperative complications in laparoscopic cholecystectomy: the Greek experience with 5,539 patients in a single center. J Laparoendosc Adv Surg Tech A. 2004;14(1):31-6.Abstract
BACKGROUND: This is a retrospective study presenting the experience of a teaching-oriented laparoendoscopic unit with laparoscopic cholecystectomy (LC) in order to add data to the international literature concerning issues such as epidemiology, intraoperative findings, conversion and complication rates. PATIENTS AND METHODS: In this study 5539 consecutive patients who underwent LC between 1990 and 2000 were included. Elective (n=4903) or emergent (n=636) LC was performed in all but 99 patients (who were converted to the open procedure). Conversion rate, complication rate, mortality, and length of stay were the main outcome parameters in this study. RESULTS: There was no intraoperative or in-hospital mortality in our series. The conversion rate was 1.8%. The complication rate was 2.92% (162 patients). The vast majority of our patients (92%) were discharged from the hospital on the first postoperative day. CONCLUSIONS: LC is a safe technique when up-to-date equipment and meticulous dissection techniques are employed. A specialized laparoscopic unit is important in a general surgery department, to have an experienced laparoscopic surgeon in all cases. In our opinion this is the only way to minimize common bile duct injuries and the rates of other major complications.
2003
Antonakis P, Alexakis N, Mylonaki D, Leandros E, M Konstadoulakis M, Zografos G, Androulakis G. Incidental finding of gallbladder carcinoma detected during or after laparoscopic cholecystectomy. Eur J Surg Oncol. 2003;29(4):358-60.Abstract
AIM: Carcinoma of the gallbladder is a rare neoplasm with a dismal prognosis. With the increase of cholecystectomies due to the wide acceptance of laparoscopic cholecystectomy, the incidental diagnosis of gallbladder carcinoma is more frequent. We report our experience with gallbladder cancer diagnosed during or after the performance of laparoscopic cholecystectomy. METHODS: We evaluated 11 patients with gallbladder cancer out of 5539 patients who underwent laparoscopic cholecystectomy. Patient clinical and demographic characteristics were reviewed. RESULTS: Intraoperatively in 297 patients there was the suspicion of adenocarcinoma and frozen sections were performed. In four of them the diagnosis of adenocarcinoma was confirmed. In two of them the procedure was converted to open with gallbladder liver bed resection and regional lymph node dissection while the other two were considered inoperable. Of the remaining 5242 patients, seven were diagnosed postoperatively at the pathologic examination. Of these, five patients refused to undergo a repeat operation. We did not observe port site metastasis in any of our patients. Survival was low and ranged from 3-14 months. CONCLUSION: Gallbladder cancer runs a short course, with a poor prognosis. The use of a meticulous laparoscopic technique seems to be important for the diagnosis and the avoidance of early complications of the disease.
2001
M Konstadoulakis M, Antonakis PT, Tsibloulis BG, Stathopoulos GP, Manouras AP, Mylonaki DB, Golematis BX. A phase II study of 9-nitrocamptothecin in patients with advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2001;48(5):417-20.Abstract
PURPOSE: Preclinical and phase I clinical data suggest that 9-nitrocamptothecin (9NC) is an agent with potential anticancer activity. A phase II study was undertaken in order to evaluate the potential benefit of oral 9NC administration in patients with advanced pancreatic cancer. This was the first clinical study of 9NC in Europe. METHODS: A total of 19 consecutive patients with locally advanced or metastatic adenocarcinoma were enrolled (8 males and 11 females, aged 37-73 years). The patients were given 9NC orally five times a week, once a day. The end-points of this study were toxicity, objective response rate, subjective response rate (i.e. pain control, performance status and body weight), and survival. RESULTS: An objective response was documented in 4 of the 14 evaluable patients (28.6%), while a subjective response was observed in 13 patients (92.9%). Overall median survival was 21 weeks (31 weeks in the group of 14 patients evaluable for response), and the 1-year survival was 16.7% and 23.1%, respectively. Toxicity leading to temporary discontinuation of 9NC was encountered in seven patients (36.8%), all related to a prior dose increase, while milder toxicity was observed in eight patients (42.1%). CONCLUSIONS: 9NC administered orally to patients with advanced pancreatic cancer gave promising results, while the toxicity of the therapy was mild and readily overcome. A larger scale clinical trial should be organized in order to establish the potential benefit of 9NC in patients with pancreatic adenocarcinoma.
Katsaragakis S, Antonakis P, M Konstadoulakis M, Androulakis G. Reconstruction of the pancreatic duct after pancreaticoduodenectomy: a modification of the Whipple procedure. J Surg Oncol. 2001;77(1):26-9; discussion 30.Abstract
BACKGROUND AND OBJECTIVES: Pancreaticoduodenectomy is still associated with high morbidity and mortality even though there has been significant progress in the field of pancreatic surgery and postoperative follow-up. The pancreatoenteric anastomosis, regardless of the technique used, is a major cause for both morbidity and mortality after Whipple procedure. To overcome all problems resulting from anastomotic leakage, we used external drainage of the pancreatic duct. METHODS: In 24 patients who underwent pancreaticoduodenectomy in our Department from 1986 to 1995, a modification to the standard Whipple procedure was performed. Instead of pancreaticoenteric anastomosis, external drainage of the pancreatic duct remnant was performed. The pancreatic duct was intubated with a silastic tube, the external end of which was sutured to the skin. All patients received substitution therapy with pancreatic enzymes. RESULTS: Mortality in our group of patients was 4%. No complications due to the external drainage of the pancreatic duct were reported, while no patient developed diabetes mellitus after surgery. CONCLUSIONS: External drainage of the pancreatic duct remnant can be used alternatively to pancreatoenteric anastomosis after pancreatoduodenectomy. The technique is safe and simple to perform and appears to reduce overall operative time. It may be an option for patients with significant comorbidity and/or intraoperative hemodynamic instability which mandates expeditious completion of the operation.
2000
Katsaragakis S, Papadimitropoulos K, Antonakis P, Strergiopoulos S, M Konstadoulakis M, Androulakis G. Comparison of Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) scoring systems in a single Greek intensive care unit. Crit Care Med. 2000;28(2):426-32.Abstract
OBJECTIVE: To evaluate Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II scoring systems in a single intensive care unit (ICU), independent from the ICUs of the developmental sample; and to compare the performance of APACHE II and SAPS II by means of statistical analyses in such a clinical setting. DESIGN: Prospective, cohort study. SETTING: A single ICU in a Greek university hospital. PATIENTS: In a time interval of 5 yrs, data for 681 patients admitted to our ICU were collected. The original exclusion criteria of both systems were employed. Patients <17 yrs of age were dropped from the study to keep compatibility with both systems. Eventually, a total of 661 patients were included in the analysis. INTERVENTIONS: Demographics, clinical parameters essential for the calculation of APACHE II and SAPS II scores, and risk of hospital death were recorded. Patient vital status was followed up to hospital discharge. MEASUREMENTS AND MAIN RESULTS: Both systems showed poor calibration and underestimated mortality but had good discriminative power, with SAPS II performing better than APACHE II. The evaluation of uniformity of fit in various subgroups for both systems confirmed the pattern of underprediction of mortality from both models and the better performance of APACHE II over our data sample. CONCLUSIONS: APACHE II and SAPS II failed to predict mortality in a population sample other than the one used for their development. APACHE II performed better than SAPS II. Validation in such a population is essential. Because there is a great variation in clinical and other patient characteristics among ICUs, it is doubtful that one system can be validated in all types of populations to be used for comparisons among different ICUs.
Haidopoulos D, M Konstadoulakis M, Antonakis PT, Alexiou DG, Manouras AM, Katsaragakis SM, Androulakis GF. Circulating anti-CEA antibodies in the sera of patients with breast cancer. Eur J Surg Oncol. 2000;26(8):742-6.Abstract
AIM: The aim of this study was to detect circulating anti-carcinoembryonic antigen antibodies (anti-CEA) in breast cancer patients and to evaluate their clinical and prognostic significance. METHODS: Fifty-two breast cancer patients and 28 controls were included in this study. Detection of anti-CEA antibodies was performed using a modified enzyme linked immunoassay (ELISA). Sensitivity, specificity and usefulness index of anti-CEA antibodies were compared to those of CEA. The correlation of anti-CEA antibodies with survival and recurrence-free survival was tested with univariate and multivariate analysis. RESULTS: Anti-CEA was present in 57% of breast cancer patients and in 11% of controls. The sensitivity and usefulness index of anti-CEA were significantly better than those of CEA. The specificity of anti-CEA antibodies was less than that of CEA, the difference not being statistically significant. Anti-CEA antibodies were an independent statistically significant, favourable factor in recurrence-free survival. CONCLUSION: Anti-CEA antibodies circulate in breast cancer patients. They could be used as a more sensitive tumour marker than CEA. Their presence is associated with improved recurrence-free survival. These results should be confirmed in a larger series.