Pure laparoscopic versus open donor hepatectomy for adult living donor liver transplantation - A systematic review and meta-analysis.

BACKGROUND: Pure laparoscopic donor hepatectomy (PLDH) for adult living donor liver transplantation (LDLT) remains controversial. The aim of this study was to undertake a systematic review and meta-analysis of donor outcomes following PLDH for adult LDLT. MATERIALS AND METHODS: Systematic review in line with the meta-analysis of observational studies in epidemiology guidelines. RESULTS: Eight studies were included in the systematic review and six in the meta-analysis. A total of 575 donors underwent PLDH for adult LDLT. The mean donor age was 32.8 years with a BMI of 23.4 kg/m2 and graft weight of 675 g. The mean operative time was 353 min and the conversion rate was 2.8% (n = 16). Overall morbidity was 10.8% with 1.6% major complications (Clavien-Dindo grade 3b), zero mortality and 9.0 days length of stay (LOS). The meta-analysis demonstrated that the operative time was significantly shorter for the open donor hepatectomy group (mean difference 29.15 min; P = 0.006) and the LOS was shorter for the PLDH group (mean difference -0.73 days; P = 0.02), with a trend towards lesser estimated blood loss in PLDH group. However, no difference between the two groups was noted in terms of overall morbidity or major complications. CONCLUSIONS: Perioperative outcomes of PLDH are similar to the standard open approach in highly specialised centers with trend towards lesser blood loss and overall shorter hospital stay. Careful donor selection and standardisation of the technique are imperative for the successful implementation and adoption of the procedure worldwide.

Margin ACcentuation for resectable Pancreatic cancer using Irreversible Electroporation - Results from the MACPIE-I study.

INTRODUCTION: Margin accentuation (MA) using Irreversible electroporation (IRE) offers an unique opportunity to reduce the R1 resections in resectable pancreatic cancer (RPC). This study aims to assess the rate of margin positivity using IRE for MA during pancreaticoduodenectomy (PD) for resectable pancreatic head tumours. MATERIALS AND METHODS: Following ethical approval, MA using IRE was carried out in 20 consecutive patients to posterior and superior mesenteric vein (SMV) margin, and the pancreatic neck, prior to the PD resection. The control group (non-IRE; n = 91) underwent PD without MA over the study period, March 2018 to March 2020. RESULTS: There was no difference between the two groups in terms of patients' age, gender, pre-op biliary drainage, site of malignancy or pre-operative TNM stage. The overall margin positive rate for IRE group was lesser (35.0%) when compared to non-IRE group (51.6%; p = 0.177), with significantly less posterior pancreatic margin positivity (5.0% vs. 25.3%; p = 0.046). When only treated margins (SMA margin excluded) were compared, the IRE group had significantly lower margin positive rates (20.0% vs. 51.6%; p = 0.013). There was no difference between the two groups in terms of intra- or post-operative complications. With a median follow-up of 15.6 months, the median DFS and OS for IRE and non-IRE groups were 17 and 18 months (p = 0.306) and 19 and 22 months (p = 0.227) respectively. CONCLUSION: Our pilot study confirms the safety of MA using IRE for RPC, with reduction in margin positivity. These results as a proof of concept are promising and need further validation with a randomised controlled trial.

Laparoscopic versus open right posterior sectionectomy: an international, multicenter, propensity score-matched evaluation.

BACKGROUND: Although laparoscopic liver resection has become the standard for minor resections, evidence is lacking for more complex resections such as the right posterior sectionectomy (RPS). We aimed to compare surgical outcomes between laparoscopic (LRPS) and open right posterior sectionectomy (ORPS). METHODS: An international multicenter retrospective study comparing patients undergoing LRPS or ORPS (January 2007-December 2018) was performed. Patients were matched based on propensity scores in a 1:1 ratio. Primary endpoint was major complication rate defined as Accordion ≥ 3 grade. Secondary endpoints included blood loss, length of hospital stay (LOS) and resection status. A sensitivity analysis was done excluding the first 10 LRPS patients of each center to correct for the learning curve. Additionally, possible risk factors were explored for operative time, blood loss and LOS. RESULTS: Overall, 399 patients were included from 9 centers from 6 European countries of which 150 LRPS could be matched to 150 ORPS. LRPS was associated with a shorter operative time [235 (195-285) vs. 247 min (195-315) p = 0.004], less blood loss [260 (188-400) vs. 400 mL (280-550) p = 0.009] and a shorter LOS [5 (4-7) vs. 8 days (6-10), p = 0.002]. Major complication rate [n = 8 (5.3%) vs. n = 9 (6.0%) p = 1.00] and R0 resection rate [144 (96.0%) vs. 141 (94.0%), p = 0.607] did not differ between LRPS and ORPS, respectively. The sensitivity analysis showed similar findings in the previous mentioned outcomes. In multivariable regression analysis blood loss was significantly associated with the open approach, higher ASA classification and malignancy as diagnosis. For LOS this was the open approach and a malignancy. CONCLUSION: This international multicenter propensity score-matched study showed an advantage in favor of LRPS in selected patients as compared to ORPS in terms of operative time, blood loss and LOS without differences in major complications and R0 resection rate.

Micro-RNA Expression Patterns Predict Metastatic Spread in Solid Pseudopapillary Neoplasms of the Pancreas.

Solid pseudopapillary neoplasm (SPN) of pancreas is a rare pancreatic neoplasm with a low metastatic potential. Up to 10% of patients with localized disease at presentation will develop systemic metastases, usually in the peritoneum or the liver. Due to the rarity of SPNs and the overall excellent prognosis, reliable prognostic factors to predict malignant biological behavior remain undetermined. Therefore, we aimed to define clinical, histological, and microRNA patterns that are associated with metastatic disease. We conducted a retrospective single center study on all patients operated for SPN of pancreas between 1995 and 2018. Clinical and pathological data were collected, and expression patterns of 2,578 human microRNAs were analyzed using microRNA array (Affimetrix 4.1) in normal pancreases (NPs), localized tumors (LTs), and metastatic tumors (MTs). The diagnosis of SPN was confirmed in 35 patients who included 28 females and 3 males, with a mean age of 33.8 ± 13.9 years. The only clinical factor associated with metastases was tumor size (mean tumor size 5.20 ± 3.78 in LT vs. 8.13± 1.03 in MT, p < 0.012). Microscopic features of malignancy were not associated with metastases, nor were immunohistochemical stains, including the proliferative index KI67. Higher expressions of miR-184, miR-10a, and miR-887, and lower expressions of miR-375, miR-217, and miR-200c were observed in metastatic tissues on microarray, and validated by real-time polymerase chain reaction. Hierarchal clustering demonstrated that the microRNA expression pattern of MTs was significantly different from that of LTs. The only clinical factor associated with metastases of SPN of pancreas was tumor size. Histological features and immunohistological staining were not predictive of metastases. A panel of six microRNAs was differentially expressed in MTs, and these findings could potentially be used to predict tumor behavior. Validation of these results is needed in larger series.

A Novel Technique for Pancreatic Stump Closure: Clip Ligation of the Duct and Associated Suturing of Pancreas.

Pancreatic fistula (PF) remains the primary source of morbidity after distal pancreatectomy (DP). There is currently no optimal stump closure technique to reduce PF rates. We present a novel technique for pancreatic stump closure using Clip Ligation of the duct and Associated Suturing of Pancreas (CLASP). Five patients (three females) with a median age of 65 years underwent DP and splenectomy for pancreatic body or tail tumour using the CLASP technique. Four of those operations were done laparoscopically. Only one patient developed grade A PF. No other postoperative complications were noticed. The mean length of stay was 5.4 days. The CLASP technique was applicable in both laparoscopic and open distal pancreatectomy. The key points include mobilisation of the pancreatic body from the retroperitoneum and division of the parenchyma with energy device. The technique of pancreatic stump closure involves the isolation of the pancreatic duct (PD), application of a double ligaclip on the proximal duct, division of the PD and finally suturing of the pancreatic stump. The CLASP technique is an effective and safe alternative technique to the current traditional methods of pancreatic stump closure.

The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced gallbladder cancer - A systematic review.

BACKGROUND: Neoadjuvant chemotherapy for advanced gallbladder cancer (GBC) has recently been proposed as an alternative to adjuvant chemotherapy, with potential increase in resectability rate and overall survival. AIM: To undertake a systematic review and critical appraisal of available literature on the use of neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) in the treatment of advanced GBC. METHODS: Systematic review carried out in line with the Meta-analysis Of Observational Studies in Epidemiology guidelines. Primary outcomes were clinical benefit rate (CBR) of neoadjuvant therapy, defined as percentage of complete response, partial response and stable disease, resectability rate and R0 resection. Secondary outcomes were overall and disease-free survival. RESULTS: 8 studies met the inclusion criteria (n = 474), of which 398 (84.0%) received NACT and 76 (16.0%) received NACRT. 133 of 434 patients (30.6%) had progressive disease despite NACT or NACRT. The CBR was 66.6%. 17% of the patients who responded to chemotherapy did not proceed to surgery. 50.4% of the patients were considered suitable for surgical resection, of which 191 (40.3%) underwent curative resection. The R0 rate for the whole cohort was 35.4%. Overall survival ranged from 18.5 to 50.1 months for those who underwent curative resection versus 5.0-10.8 months for non-resected group. CONCLUSIONS: There is insufficient data to support the routine use of NACT or NACRT in advanced GBC, as this has only benefited a third of whole cohort, who eventually achieved a R0 resection. Future studies should be in the form of randomized controlled trials to investigate the role of neoadjuvant therapy in advanced GBC.

Irreversible electroporation in borderline resectable pancreatic adenocarcinoma for margin accentuation.

Achieving clear microscopic resection margins following pancreaticoduodenectomy (PD) is challenging particularly in borderline resectable pancreatic carcinoma (BRPC). Positive resection margins has been identified as a major independent prognostic factor. Irreversible electroporation (IRE) has emerged as a promising non-thermal ablative method that could be used in the treatment of pancreatic cancer as an adjunct to chemotherapy and surgery. This case report describes the successful simultaneous intraoperative IRE and PD in a patient with BRPC, achieving clear microscopic resection margins. Technical aspects and histology showing the effect of IRE are presented. The role of IRE in the treatment of pancreatic adenocarcinoma should be further evaluated in prospective studies.

Breast cancer liver metastases in a UK tertiary centre: Outcomes following referral to tumour board meeting.

INTRODUCTION: To assess the outcomes from multidisciplinary board meetings (MDM) for patients with breast cancer liver metastases (BCLM) and identify prognostic factors for survival. MATERIALS AND METHODS: A retrospective review of MDM records for patients referred with BCLM to a tertiary centre between 2005 and 2016. Patient demographics, clinicopathological factors and intervention type were analysed to find predictive factors for overall survival. RESULTS: 61 patients with BCLM were referred to the MDM. Treatment pathways included surgical resection (n = 23), radiofrequency ablation (RFA, n = 11), or chemotherapy (n = 27). Surgical resection patients had an improved median overall survival compared to chemotherapy (49 v 20mo; p < 0.001). RFA showed comparable survival benefit (37 v 20mo; p = 0.011). Resection and RFA showed no significant difference in survival over one another (49 v 37mo; p = 0.854). Survival analysis identified that resection (p = 0.002) and RFA (p = 0.001) were associated with improved overall survival compared to chemotherapy. Multivariate analysis identified extrahepatic disease (HR = 14.21; p = 0.044) and R0 resection (HR = 0.068; p = 0.023) as prognostic factors. CONCLUSIONS: Surgical resection of BCLM may improve the overall survival in selected patient groups. This study identifies a cohort of patients, without extrahepatic disease and responsive to chemotherapy, who may particularly benefit from surgery.

Diagnosis and management of acute appendicitis. EAES consensus development conference 2015.

Unequivocal international guidelines regarding the diagnosis and management of patients with acute appendicitis are lacking. The aim of the consensus meeting 2015 of the EAES was to generate a European guideline based on best available evidence and expert opinions of a panel of EAES members. After a systematic review of the literature by an international group of surgical research fellows, an expert panel with extensive clinical experience in the management of appendicitis discussed statements and recommendations. Statements and recommendations with more than 70 % agreement by the experts were selected for a web survey and the consensus meeting of the EAES in Bucharest in June 2015. EAES members and attendees at the EAES meeting in Bucharest could vote on these statements and recommendations. In the case of more than 70 % agreement, the statement or recommendation was defined as supported by the scientific community. Results from both the web survey and the consensus meeting in Bucharest are presented as percentages. In total, 46 statements and recommendations were selected for the web survey and consensus meeting. More than 232 members and attendees voted on them. In 41 of 46 statements and recommendations, more than 70 % agreement was reached. All 46 statements and recommendations are presented in this paper. They comprise topics regarding the diagnostic work-up, treatment indications, procedural aspects and post-operative care. The consensus meeting produced 46 statements and recommendations on the diagnostic work-up and management of appendicitis. The majority of the EAES members supported these statements. These consensus proceedings provide additional guidance to surgeons and surgical residents providing care to patients with appendicitis.

Ancient Greek Terminology in Hepatopancreatobiliary Anatomy and Surgery.

Most of the terminology in medicine originates from Greek or Latin, revealing the impact of the ancient Greeks on modern medicine. However, the literature on the etymology of Greek words used routinely in medical practice is sparse. We provide a short guide to the etymology and meaning of Greek words currently used in the field of hepatopancreatobiliary (HPB) anatomy and surgery. Focusing on HPB medical literature, the etymology and origin of Greek words including suffixes and prefixes are shown and analyzed. For example, anatomy (anatomia) is a Greek word derived from the prefix ana- (on, upon) and the suffix -tomy from the verb temno meaning to cut. Surgery, however, is not a Greek word. The corresponding Greek word is chirourgiki derived from cheir (hand) and ergon (action, work) meaning the action made by hands. Understanding the root of Greek terminology leads to an accurate, precise and comprehensive scientific medical language, reflecting the need for a universal medical language as a standardized means of communication within the health care sector.

Visceral Fat Content Correlates with Retroperitoneal Soft Tissue Sarcoma (STS) Local Recurrence and Survival.

BACKGROUND: Our aim was to evaluate the association between visceral fat content with soft tissue sarcoma (STS) local recurrence and survival. METHODS: One hundred and one computed tomography imaging studies of primary STS patients who had complete macroscopic resection at our institution between 2002 and 2012 were reviewed, and retroperitoneal and circumferential fat contents were measured. Correlations between imaging findings and clinical data were analyzed. RESULTS: Fifty-seven STS tumors (56.4%) were retroperitoneal; of them, 65% were high grade, median size was 15 cm (range 3-49), and the most common histological subtype was high grade liposarcoma (31.6%). Median follow-up length for the entire cohort was 64 months (range 6-95). High visceral fat (VF) content≥15 versus <15 mm was identified as a risk factor for retroperitoneal STS local recurrence; 65.1 versus 26.7%, respectively (p=0.04); VF content did not correlate with distant metastasis. Median overall survival (OS) length of patients with VF≥15 versus <15 mm was 57 months (range 2-144) versus not reached, respectively (p=0.007). Multivariable analysis identified VF≥15 mm as an independent risk factor for decreased OS (HR: 4.2, 95% CI 1.07-16.67). In contrast, circumferential fat content did not correlate with retroperitoneal STS patient outcomes. CONCLUSION: High VF content is an independent adverse prognosticator associated with significantly higher rates of retroperitoneal STS local recurrence and decreased patients survival. Local tumor biology may be affected by the presence of adipose cells. Further clinical and molecular research is needed to establish this premise.

Contemporary surgical approach to hilar cholangiocarcinoma.

BACKGROUND: The diagnostic and therapeutic approach to hilar cholangiocarcinoma and thus the prognosis have changed significantly over the last two decades. Nonetheless, hilar cholangiocarcinoma presents a complex surgical challenge. OBJECTIVES: To assess the outcome of the radical approach for the management of types III and IV hilar cholangiocarcinoma. METHODS: We conducted a retrospective single-center study. Preoperative diagnosis was based on ultrasound, computed tomography and selective percutaneous cholangiography without tissue diagnosis. Surgery was radical and included en-bloc liver, extrahepatic biliary tree and hilar lymph nodes resection, followed by biliary reconstruction with hepaticojejunostomy. RESULTS: Fifteen patients (mean age 49 years, range 24-72) were managed accordingly. Anatomic classification of the biliary involvement was Bismuth-Corlette type IIIA (n=4), type IIIB (n=3) and type IV (n=8). The surgical procedures performed included four right hepatic lobectomies, five left hepatic lobectomies and six trisegmentectomies (all extended to the caudate lobe). Complete negative resection margins (RO) were accomplished in 12 cases (80%). Regional lymph node metastases were detected in five cases. There were two perioperative mortalities. Long-term follow-up (mean 30 months, range 6-72) revealed local recurrences in two cases, distant metastases in three, and both local and distant in two cases. Eleven patients are alive and 6 are without evidence of disease. The overall 2- and 5-year survival is 78% and 38% respectively. CONCLUSIONS: In selected patients the aggressive surgical approach to hilar cholangiocarcinoma is justified and can result in long-term survival.

Primary liver tumors: origin and target therapy.

BACKGROUND: The liver is the largest gland and chief metabolic organ of the human body possessing a unique ability to regenerate. The general interest of primary liver tumors is noteworthy because of their increasing worldwide incidence and mortality. Recent studies have focused on the ancestors of mature hepatocytes, which are capable of proliferating, differentiating and self-renewing. OBJECTIVE: To provide a brief and up-to-date review on the cellular origin of primary liver tumors and to examine the use of stem cells in potential future therapeutic attempts. METHODS: A review of relevant literature. RESULTS: It is clear that hepatic progenitor cells (HPCs) could be the basis of some hepatocellular carcinomas (HCC), cholangiocarcinomas (CHC), hepatocellular adenomas and hepatoblastomas. Cancer stem cell (CSC) theory emphasizes the role of hepatic stem cells in the development and progression of liver tumors. CONCLUSION: The expression of HPCs markers may be used as new independent prognostic factors in HCC. Conventional treatments for HCC do not seem to be beneficial for the majority of patients and new therapeutic approaches such as gene therapy and targeted drug therapy are of great clinical interest.