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Purpose To assess technical feasibility, safety, and efficacy of the liver venous deprivation (LVD) technique that combines both portal and hepatic vein embolization during the same procedure for liver preparation before major hepatectomy. Materials and methods Seven patients (mean age:63.6y[42-77y]) underwent trans-hepatic LVD for liver metastases (n = 2), hepatocellular carcinoma (n = 1), intrahepatic cholangiocarcinoma (n = 3) and Klatskin tumour (n = 1). Assessment of future remnant liver (FRL) volume, liver enzymes and histology was performed. Results Technical success was 100 %. No complication occurred before surgery. Resection was performed in 6/7 patients. CT-scan revealed hepatic congestion in the venous-deprived area (6/7 patients). A mean of 3 days (range: 1–8 days) after LVD, transaminases increased (AST: from 42 ± 24U/L to 103 ± 118U/L, ALT: from 45 ± 25U/L to 163 ± 205U/L). Twenty-three days (range: 13–30 days) after LVD, FRL increased from 28.2 % (range: 22.4–33.3 %) to 40.9 % (range: 33.6–59.3 %). During the first 7 days, venous-deprived liver volume increased (+13.4 %) probably reflecting vascular congestion, whereas it strongly decreased (-21.3 %) at 3-4 weeks. Histology (embolized lobe) revealed sinusoidal dilatation, hepatocyte necrosis and important atrophy in all patients. Conclusion Trans-hepatic LVD technique is feasible, well tolerated and provides fast and important hypertrophy of the FRL. This new technique needs to be further evaluated and compared to portal vein embolization. Key Points • Twenty-three days after LVD, FRL increased from 28.2 % (range:22.4-33.3 %) to 40.9 % (range:33.6–59.3 %) • During the first 7 days, venous-deprived liver volume increased (+13.4 %) • Venous-deprived liver volume strongly decreased (mean atrophy:229 cc; -21.3 %) at 3-4 weeks • Histology of venous - deprived liver revealed sinusoidal dilatation , hepatocyte necrosis and important atrophy

The incidence and number of circulating tumor cells (CTCs) in the peripheral blood of colorectal cancer patients are lower than in other cancer types, which may point to a particular biology of colorectal cancer affecting CTC detection. We detected CTCs in the peripheral and mesenteric blood of colorectal cancer patients by use of 2 independent technologies on the basis of different biological properties of colon cancer cells. Seventy-five patients diagnosed with localized (M0, n = 60) and metastatic (M1, n = 15) colorectal cancer were included. Peripheral and mesenteric blood samples were collected before tumor resection. We performed CTC enumeration with an EpCAM-independent enrichment method followed by the Epispot assay that detected only viable CK19-releasing CTCs. In parallel, we used the FDA-cleared EpCAM-dependent CellSearch® as the reference method. The enumeration of CK19-releasing cells by the CK19-Epispot assay revealed viable CTCs in 27 of 41 (65.9%) and 41 of 74 (55.4%) (P = 0.04) patients in mesenteric and peripheral blood, respectively, whereas CellSearch detected CTCs in 19 of 34 (55.9%) and 20 of 69 (29.0%) (P = 0.0046) patients. In mesenteric blood, medians of 4 (range 0-247) and 2.7 CTCs (range 0-286) were found with Epispot and CellSearch (P = 0.2), respectively, whereas in peripheral blood, Epispot and CellSearch detected a median of 1.2 (range 0-92) and 0 CTCs (range 0-147) (P = 0.002). A considerable portion of viable CTCs detectable by the Epispot assay are trapped in the liver as the first filter organ in CRC patients.

Background Introduced more than 20 years ago, laparoscopic pancreatic surgery (LAPS) has not reached a uniform acceptance among HPB surgeons. As a result, there is no consensus regarding its use in patients with pancreatic neoplasms. This study, organized by the European Association for Endoscopic Surgery (EAES), aimed to develop consensus statements and clinical recommendations on the application of LAPS in these patients. Methods An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreatic surgery. Each panelist performed a critical appraisal of the literature and prepared evidence-based statements assessed by other panelists during Delphi process. The statements were further discussed during a one-day face-to-face meeting followed by the second round of Delphi. Modified statements were presented at the plenary session of the 24th International Congress of the EAES in Amsterdam and in a web-based survey. Results LAPS included laparoscopic distal pancreatectomy (LDP), pancreatoduodenectomy (LPD), enucleation, central pancreatectomy, and ultrasound. In general, LAPS was found to be safe, especially in experienced hands, and also advantageous over an open approach in terms of intraoperative blood loss, postoperative recovery, and quality of life. Eighty-five percent or higher proportion of responders agreed with the majority (69.5%) of statements. However, the evidence is predominantly based on retrospective case–control studies and systematic reviews of these studies, clearly affected by selection bias. Furthermore, no randomized controlled trials (RCTs) have been published to date, although four RCTs are currently underway in Europe. Conclusions LAPS is currently in its development and exploration stages, as defined by the international IDEAL framework for surgical innovation. LDP is feasible and safe, performed in many centers, while LPD is limited to few centers. RCTs and registry studies are essential to proceed with the assessment of LAPS.

The aim of this study is to evaluate the effectiveness of TachoSil sponge on distal pancreatectomy remnant stump in reducing the rate and severity of postoperative pancreatic fistula (POPF). All consecutive patients requiring distal pancreatectomy were randomized in 45 centers. The principal end point was onset of “clinically relevant” POPF. Univariate and multivariate analyses were searched for predictive factors. Of the 270 patients randomized (134 with TachoSil; 136 without), 150 (55.6%) patients sustained a POPF [74 clinically relevant and 76 clinically silent (27.4% and 28.1%), respectively]: no statistically significant difference was found between patients sustaining clinically relevant POPF [41 (30.6%) with vs 33 (24.3%) without TachoSil (P = .276)], or overall POPF [73 (54.5%) with vs 77 (56.6%) without TachoSil, (P = .807)], but there were more clinically relevant POPF after hand-sewn (32.3%) versus mechanical closure (19.8%) (P = .025) and, in case of splenic preservation, after splenic vessel ligation (15/32, 46.9%) versus vascular preservation (17/72, 23.6%) (P = .024). Hand-sewn pancreatic remnant closure (P = .023) and splenic vessel ligation in splenic preservation (P = .035) were independent predictive factors for the onset of clinically relevant POPF. TachoSil sponge reinforcement of the proximal remnant after distal pancreatectomy reduced neither the rate nor the severity of POPF. •Several procedures have been proposed to reduce the rate and/or severity of POPF.•This multicenter controlled randomized trial evaluated the usefulness of TachoSil sponge on remnant stump in reducing the rate and severity of POPF.•TachoSil sponge on the proximal remnant after distal pancreatectomy reduced neither the rate nor the severity of POPF.•Hand-sewn pancreatic remnant closure and splenic vessel ligation in splenic preservation were independent predictive factors for the onset of clinically patent POPF.•Negative studies must be published to avoid publication and reporting bias before drawing methodologically sound conclusions as to the usefulness or futility of therapeutic decisions.

Recurrence after resection of intrahepatic cholangiocarcinoma (ICC) remains common. The present study sought to evaluate risk factors for recurrence and the results of repeat liver resection (RLR) for recurrent ICC. Between 1997 and 2012, clinical data and outcomes of 125 consecutive patients undergoing liver resection for ICC were retrospectively analyzed. The rate of R0 resection was 89% (n = 110). Overall median survival was 35 months, and 1-, 3-, and 5-year actuarial survival rates were 80%, 48%, and 28%, respectively. Recurrence occurred in 76 patients (63.5%) and was intrahepatic only for 39 patients (51%). Tumor size greater than 5 cm was identified as an independent risk factor for recurrence (P ≤ .0001). RLR for recurrent ICC was feasible in 10 patients (25%) with a median survival after recurrence of 25 months (16 to 76). Tumor size more than 5 cm represents an independent risk factor for recurrence after resection of ICC. RLR in case of recurrent ICC, when feasible, is associated with longer overall survival. •Recurrence after resection of intrahepatic cholangiocarcinoma (ICC) is common.•Recent studies showed that cure after resection of ICC seems to be an elusive goal.•Tumor size greater than 5 cm is an independent risk factor for recurrence.•Recurrence after resection of ICC is often beyond the limits of resectability.•A repeat liver resection (RLR) was feasible in only 25% of patients.•A RLR was associated with prolonged overall survival.

Molecular and phylogeographic studies have led to the definition within the Mycobacterium tuberculosis complex (MTBC) of a number of geotypes and ecotypes showing a preferential geographic location or host preference. The MTBC is thought to have emerged in Africa, most likely the Horn of Africa, and to have spread worldwide with human migrations. Under this assumption, there is a possibility that unknown deep branching lineages are present in this region. We genotyped by spoligotyping and multiple locus variable number of tandem repeats (VNTR) analysis (MLVA) 435 MTBC isolates recovered from patients. Four hundred and eleven isolates were collected in the Republic of Djibouti over a 12 year period, with the other 24 isolates originating from neighbouring countries. All major M. tuberculosis lineages were identified, with only two M. africanum and one M. bovis isolates. Upon comparison with typing data of worldwide origin we observed that several isolates showed clustering characteristics compatible with new deep branching. Whole genome sequencing (WGS) of seven isolates and comparison with available WGS data from 38 genomes distributed in the different lineages confirms the identification of ancestral nodes for several clades and most importantly of one new lineage, here referred to as lineage 7. Investigation of specific deletions confirms the novelty of this lineage, and analysis of its precise phylogenetic position indicates that the other three superlineages constituting the MTBC emerged independently but within a relatively short timeframe from the Horn of Africa. The availability of such strains compared to the predominant lineages and sharing very ancient ancestry will open new avenues for identifying some of the genetic factors responsible for the success of the modern lineages. Additional deep branching lineages may be readily and efficiently identified by large-scale MLVA screening of isolates from sub-Saharan African countries followed by WGS analysis of a few selected isolates.

The highly successful human pathogen Mycobacterium tuberculosis has an extremely low level of genetic variation, which suggests that the entire population resulted from clonal expansion following an evolutionary bottleneck around 35,000 y ago. Here, we show that this population constitutes just the visible tip of a much broader progenitor species, whose extant representatives are human isolates of tubercle bacilli from East Africa. In these isolates, we detected incongruence among gene phylogenies as well as mosaic gene sequences, whose individual elements are retrieved in classical M. tuberculosis. Therefore, despite its apparent homogeneity, the M. tuberculosis genome appears to be a composite assembly resulting from horizontal gene transfer events predating clonal expansion. The amount of synonymous nucleotide variation in housekeeping genes suggests that tubercle bacilli were contemporaneous with early hominids in East Africa, and have thus been coevolving with their human host much longer than previously thought. These results open novel perspectives for unraveling the molecular bases of M. tuberculosis evolutionary success.

The aim of this work is to explain how, starting from the orthogonality expression of two polynomials, we deduce the Schrödinger equation and the solution of the N-body problem including two-body correlations as well as the existence of shells. Generated by the behaviour of kinetic energy for a two-body interaction. The quantification of matters is obtained by the application of the weight function algorithm to the statement that two states are independents when their product integrated over the whole space is null leading to a two variables second order differential equation. The Nuclear Shell Model is a consequence of the kinetic energy behaviour for increasing number of nucleons in ground state. It leaves the mean field theory useless.

BackgroundNearly 20% of patients who undergo hiatal hernia (HH) repair and anti-reflux surgery (ARS) report recurrent HH at long-term follow-up and may be candidates for redo surgery. Current literature on redo-ARS has limitations due to small sample sizes or single center experiences. This type of redo surgery is challenging due to rare but severe complications. Furthermore, the optimal technique for redo-ARS remains debatable. The purpose of the current multicenter study was to review the outcomes of redo-fundoplication and to identify the best ARS repair technique for recurrent HH and gastroesophageal reflux disease (GERD).MethodsData on 975 consecutive patients undergoing hiatal hernia and GERD repair were retrospectively collected in five European high-volume centers. Patient data included demographics, BMI, techniques of the first and redo surgeries (mesh/type of ARS), perioperative morbidity, perioperative complications, duration of hospitalization, time to recurrence, and follow-up. We analyzed the independent risk factors associated with recurrent symptoms and complications during the last ARS. Statistical analysis was performed using GraphPad Prism® and R software®.ResultsSeventy-three (7.49%) patients underwent redo-ARS during the last decade; 71 (98%) of the surgeries were performed using a minimally invasive approach. Forty-two (57.5%) had conversion from Nissen to Toupet. In 17 (23.3%) patients, the initial Nissen fundoplication was conserved. The initial Toupet fundoplication was conserved in 9 (12.3%) patients, and 5 (6.9%) had conversion of Toupet to Nissen. Out of the 73 patients, 10 (13%) underwent more than one redo-ARS. At 8.5 (1–107) months of follow-up, patients who underwent reoperation with Toupet ARS were less symptomatic during the postoperative period compared to those who underwent Nissen fundoplication (p = 0.005, OR 0.038). Patients undergoing mesh repair during the redo-fundoplication (21%) were less symptomatic during the postoperative period (p = 0.020, OR 0.010). The overall rate of complications (Clavien-Dindo classification) after redo surgery was 11%. Multivariate analysis showed that the open approach (p = 0.036, OR 1.721), drain placement (p = 0.0388, OR 9.308), recurrence of dysphagia (p = 0.049, OR 8.411), and patient age (p = 0.0619, OR 1.111) were independent risk factors for complications during the last ARS.ConclusionsFailure of ARS rarely occurs in the hands of experienced surgeons. Redo-ARS is feasible using a minimally invasive approach. According to our study, in terms of recurrence of symptoms, Toupet fundoplication is a superior ARS technique compared to Nissen for redo-fundoplication. Therefore, Toupet fundoplication should be considered in redo interventions for patients who initially underwent ARS with Nissen fundoplication. Furthermore, mesh repair in reoperations has a positive impact on reducing the recurrence of symptoms postoperatively.