Ismail Labgaa

Cost–benefit analysis of an enhanced recovery protocol for pancreaticoduodenectomy

Enhanced recovery after surgery (ERAS) programmes have been shown to decrease complications and hospital stay. The cost‐effectiveness of such programmes has been demonstrated for colorectal surgery. This study aimed to assess the economic outcomes of a standard ERAS programme for pancreaticoduodenectomy.

Effect of Antecolic versus Retrocolic Gastroenteric Reconstruction after Pancreaticoduodenectomy on Delayed Gastric Emptying: A Meta-Analysis of Six Randomized Controlled Trials

Background: One of the most frequent complications of pancreaticoduodenectomy (PD) is delayed gastric emptying (DGE). The study aim was to evaluate the impact of the type of gastro/duodenojejunal reconstruction (antecolic vs. retrocolic) after PD on DGE incidence. Methods: A systematic review was made according to the PRISMA guidelines. Randomized controlled trials (RCTs) comparing antecolic vs. retrocolic reconstruction were included irrespective of the PD techniques. A meta-analysis was then performed. Results: Six RCTs were included for a total of 588 patients. The overall quality was good. General risk of bias was low. DGE was not statistically significantly different between the antecolic and retrocolic group (OR 0.6, 95% CI 0.31-1.16, p = 0.13). The other main surgery-related complications (pancreatic fistula, hemorrhage, intra-abdominal abscess, bile leak and wound infection) were not dependent on the reconstruction route (OR 0.84, 95% CI 0.41-1.70, p = 0.63). No statistically significant difference in terms of length of hospital stay was found between the 2 groups. There was also no difference of DGE incidence if only pylorus-preserving PD was considered and between the DGE grades A, B or C. Conclusion: This meta-analysis shows that antecolic reconstruction after PD is not superior to retrocolic reconstruction in terms of DGE.

The future of patient-derived tumor xenografts in cancer treatment

Over the last decades, major technological advancements have led to a better understanding of the molecular drivers of human malignancies. Nonetheless, this progress only marginally impacted the cancer therapeutic approach, probably due to the limited ability of experimental models to predict efficacy in clinical trials. In an effort to offset this limitation, there has been an increasing interest in the development of patient-derived xenograft (PDX) models where human tumors are xenotransplanted into immunocompromised mice. Considering their high resemblance to human tumors and their stability, PDX models are becoming the preferred translational tools in preclinical studies. Nonetheless, several limitations hamper a wider use of PDX models and tarnish the concept that they might represent the missing piece in the personalized medicine puzzle.

Giant extra-hepatic thrombosed portal vein aneurysm: a case report and review of the literature

BackgroundExtrahepatic Portal vein aneurysm (EPVA) is a rare finding that may be associated with different complications, e.g. thrombosis, rupture, portal hypertension and compression of adjacent structures. It is being diagnosed more frequently with the advent of modern cross-sectional imaging. Our review of the English literature disclosed 13 cases of thrombosed EPVA.Case presentationA 50-years-old woman presented with acute abdominal pain but no other symptom. She had no relevant medical history. Palpation of the right upper quadrant showed tenderness. Laboratory tests were unremarkable. A computed tomography showed portal vein aneurysm measuring 88 × 65 mm with thrombosis extending to the superior mesenteric and splenic vein. The patient was treated conservatively with anticoagulation therapy. She was released after two weeks and followed on an outpatient basis. At two months, she reported decreased abdominal pain and her physical examination was normal. A computed tomography was performed showing a decreased thrombosis size and extent, measuring 80 × 55 mm.ConclusionsAlthough rare, surgeons should be made aware of this entity. Complications are various. Conservative therapy should be chosen in first intent in most cases. We reported the case of the second largest thrombosed extra-hepatic PVA described in the literature, treated by anticoagulation therapy with a good clinical and radiological response.

Serum albumin is an early predictor of complications after liver surgery

BACKGROUND The morbidity associated with liver surgery remained substantially high despite considerable surgical and anesthetic improvements. The unmet need of accurate biomarkers to predict postoperative complications is widely accepted. AIMS This pilot study aimed to assess serum albumin as a surrogate marker of surgical stress and to test its potential predictive role for postoperative complications. METHODS This retrospective pilot study included 106 patients who underwent liver surgery between 2010 and 2014. Serum albumin levels were measured pre- and post-operatively. Maximal albumin decrease (AlbΔmin) was correlated with complications. RESULTS Serum albumin rapidly dropped after surgery. AlbΔmin was significantly increased in patients with complications (14.5±6.0g/L vs. 10.3±7.2, p=0.009). On multivariate analysis, ASA III/IV (p=0.016) and AlbΔmin (p=0.037) were the only predictors of overall complications. CONCLUSION Early postoperative drop of serum albumin reflects the intensity of the surgical stress and may predict complications after liver surgery. Serum albumin is a biomarker displaying precious features and deserving further prospective investigations.

A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma

Cellular components of solid tumors including DNA are released into the bloodstream, but data on circulating-free DNA (cfDNA) in hepatocellular carcinoma (HCC) are still scarce. This study aimed at analyzing mutations in cfDNA and their correlation with tissue mutations in patients with HCC. We included 8 HCC patients treated with surgical resection for whom we collected paired tissue and plasma/serum samples. We analyzed 45 specimens, including multiregional tumor tissue sampling (n = 24), peripheral blood mononuclear cells (PMBC, n = 8), plasma (n = 8) and serum (n = 5). Ultra-deep sequencing (5500× coverage) of all exons was performed in a targeted panel of 58 genes, including frequent HCC driver genes and druggable mutations. Mutations detected in plasma included known HCC oncogenes and tumor suppressors (e.g., TERT promoter, TP53, and NTRK3) as well as a candidate druggable mutation (JAK1). This approach increased the detection rates previously reported for mutations in plasma of HCC patients. A thorough characterization of cis mutations found in plasma confirmed their tumoral origin, which provides definitive evidence of the release of HCC-derived DNA fragments into the bloodstream. This study demonstrates that ultra-deep sequencing of cfDNA is feasible and can confidently detect somatic mutations found in tissue; these data reinforce the role of plasma DNA as a promising minimally invasive tool to interrogate HCC genetics.

Is postoperative decrease of serum albumin an early predictor of complications after major abdominal surgery? A prospective cohort study in a European centre

Objective To test postoperative serum albumin drop (ΔAlb) as a marker of surgical stress response and early predictor of clinical outcomes. Design Prospective cohort study (NCT02356484). Albumin was prospectively measured in 138 patients undergoing major abdominal surgery. Blood samples were collected before surgery and on postoperative days 0, 1 2 and 3. ΔAlb was compared to the modified estimation of physiologic ability and surgical stress (mE-PASS) score and correlated to the performances of C reactive protein (CRP), procalcitonin (PCT) and lactate (LCT). Postoperative outcomes were postoperative complications according to Clavien classification and Comprehensive Complication Index (CCI), and length of hospital stay (LoS). Setting Department of abdominal surgery in a European tertiary centre. Participants Adult patients undergoing elective major abdominal surgery, with anticipated duration ≥2 hours. Patients on immunosuppressive or antibiotic treatments before surgery were excluded. Results The level of serum albumin rapidly dropped after surgery. ΔAlb correlated to the mE-PASS score (r=0.275, p=0.01) and to CRP increase (r=0.536, p<0.001). ΔAlb also correlated to overall complications (r=0.485, p<0.001), CCI (r=0.383, p<0.001) and LoS (r=0.468, p<0.001). A ΔAlb ≥10 g/L yielded a sensitivity of 77.1% and a specificity of 67.2% (AUC: 78.3%) to predict complications. Patients with ΔAlb ≥10 g/L on POD 1 showed a threefold increased risk of overall postoperative complications. Conclusions Early postoperative decrease of serum albumin correlated with the extent of surgery, its metabolic response and with adverse outcomes such as complications and length of stay. A decreased concentration of serum albumin ≥10 g/L on POD 1 was associated with a threefold increased risk of overall postoperative complications and may thus be used to identify patients at risk.

Lymphoepithelioma-Like Carcinoma in Liver

Liver cancer, primarily encompassing hepatocellular carcinoma and intrahepatic cholangiocarcinoma, has become the second leading cause of worldwide cancer-related death during the past two decades. Lymphoepithelioma-like carcinomas (LELCs) are defined as tumors composed of undifferentiated epithelial cells with a prominent lymphoid infiltrate, and can arise in the liver as hepatocellular or cholangiocarcinoma forms. Patients with liver LELC display distinctive demographics and tumor characteristics. LELCs also appear to be associated with strikingly better outcomes compared to typical liver cancers, with 5-year survival rates of 57% to 100% versus 12% to 68%, respectively. Liver LELCs represent a unique model of immune response in liver cancer. Data on LELCs of the liver remain limited, and future comprehensive studies are needed to further elucidate this disease, which could ultimately offer precious insights for immunotherapeutic strategies in liver cancer.

Lymphoepithelioma-Like Cholangiocarcinoma: A Rare Finding With Good Outcomes.

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Inflammatory Response and Toxicity After Pressurized IntraPeritoneal Aerosol Chemotherapy

Background: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel mode of intraperitoneal (IP) drug delivery claiming high IP tissue concentrations with low systemic uptake. The aim was to study inflammatory response and systemic toxicity after PIPAC. Methods: Retrospective monocentric analysis of a consecutive cohort of PIPAC patients between January 2015 and April 2016. Detailed hematological and biochemical analysis was performed the day before surgery and once daily until discharge. Comparative statistics were performed using Mann-Whitney U test and Wilcoxon signed ranked test. Results: Fourty-two consecutive patients underwent a total of 91 PIPAC procedures. Twenty patients received oxaliplatin and 22 cisplatin+doxorubicin (37 vs. 54 procedures). Creatinine, AST and ALT were not significantly altered after PIPAC (p=0.095, p= p=0.153 and p=0.351) and not different between oxaliplatin and cisplatin+doxorubicin regimens (p=0.371, p=0.251 and p=0.288). C-reactive protein (CRP) and procalcitonin (PCT) increased on post-operative day (POD) 2: ∆max 29±5 mg/L (p<0.001) and ∆max 0.05±0.01 μg/L (p=0.005), respectively. Leucocytes increased at POD 1: ∆max 2.2±0.3 G/L (p<0.001). Albumin decreased at POD 2: ∆max -6.0±0.5 g/L (p<0.001). CRP increase correlated positively with Peritoneal Cancer Index (tumor load) (ρ =0.521, p<0.001). Conclusion: PIPAC was followed by a modest and transitory inflammatory response that was commensurate to the disease extent. No hematological, renal or hepatic toxicity was observed even after repetitive administration.