The Prognosis for Unexpected Gallbladder Carcinoma with Bile Spillage during Laparoscopic Cholecystectomy

Here we review the prognosis of patients with unsuspected gallbladder carcinoma（GBC）, detected after laparoscopic cholecystectomy（LC）in a single institute. We reviewed the medical records of patients diagnosed with gallbladder stones on admission, who underwent LC. Carcinoma involving the gallbladder was found in 22 of 2,770 patients（0.9％）via postoperative pathological examination. This GBC group spanned 58-87 years of age（mean, 75 years; 13 females and 9 males）. The preoperative diagnosis was gallbladder stones with acute/chronic cholecystitis or adenomyomatosis of the gallbladder in all patients. We performed an additional surgery in 6 of 15 patients with pT2 and T3 disease; of these, 3 patients with pT2 disease and 1 with pT3 experienced bile spillage during the LC. The mean survival of patients with unexpected GBC was 21 months, with bile spillage occurring as a complication of LC identified as a potential risk factor for shorter survival（15.3 vs. 32.5 months）. We identified patients with pT2 and pT3 disease after LC, and two patients with pT2 and 1 with pT3 who had bile spillage during LC died of peritoneal dissemination within 28 months, despite additional surgery. Occasional seeding caused by bile spillage during LC should be carefully avoided to minimize the risk of developing unsuspected GBC after LC

The Surgical Benefits of Repeat Hepatectomy for Colorectal Liver Metastasis

The most common site of distant metastasis from colorectal cancer is the liver, and hepatectomy presents the best curative treatment for recurrence of colorectal liver metastasis （CRLM）. This study aimed to identify factors of prognostic value for repeat hepatectomy for CRLM and to determine whether a third such procedure could similarly produce favourable outcomes for CRLM. We analyzed data for 161 patients in our department with colorectal metastasis. Of these, 22 patients underwent repeat hepatectomy for recurrent metastasis, with 16 undergoing a second hepatectomy and 6 a third hepatectomy. We analyzed patient characteristics, tumor status, operation-related variables, and short- and long-term outcomes. Univariate analysis for repeat hepatectomy identified the following five prognostic risk factors: T factor （＞SE） of the primary cancer, number of tumors involved in the initial hepatectomy （＞5）, interval from first to second hepatectomy （＜1year）, number of tumors involved in second hepatectomy （＞3）, and post-operation time （＞30days）. By multivariate analysis, T factor （＞SE） of the primary cancer, number of tumors in the initial hepatectomy （＞5）, and number of tumors in the second hepatectomy （＞3） were independently associated with a worse survival after surgery for CRLM. Although surgical outcomes of the third hepatectomy were not compared with those of the first and second hepatectomy, there were no obvious differences, nor did the 1-, 3-, and 5-year survival rates differ significantly among the three groups. Repeat hepatectomy for CRLM could improve long-term survival. In addition, patients undergoing a third hepatectomy showed a similar survival benefit to those having one or two resections

TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2

Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia

Fast-track Surgery Protocol for Hepatectomy and the Rate of Surgical Site Infections: A Single-center Study

The fast-track surgery protocol, including perioperative immunonutritional management, is increasingly gaining attention for the prevention of surgical site infections （SSIs）. To analyze the association between the fast-track surgery protocol employed at a single center and outcomes, including SSIs and the length of hospital stays. This retrospective analysis included 217 patients who underwent hepatectomy at the study department between January 2009 and February 2014. Patients were divided into two groups: those managed by a conventional protocol （group C, n＝75） and those managed by the fast-track surgery protocol （group F, n＝142）. There were no significant differences in patient characteristics or factors between the two groups. However, serum albumin and total cholesterol levels before surgery were significantly higher in group F than in group C, and pre-hepatectomy C-reactive protein （CRP） levels were lower in group F than in group C. Moreover, serum albumin and CRP levels at postoperative day 7 were better in group F than in group C. The operations were longer in group F than in group C （312 vs. 286 min） and blood loss volume was less （385 g in group F vs. 428 g in group C）. SSI rates were significantly lower in group F （4.2％, n＝6） than in group C （13.3％, n＝10）, and the length of hospital stay was significantly shorter in group F （16.7 days） than in group C （25.8 days）. The fast-track surgery protocol as a perioperative management strategy may improve preoperative nutritional status and postoperative inflammation, with subsequent reductions in SSI rates and the length of hospital stay in patients undergoing hepatectomy

Feasibility of Precoagulation Without the Pringle Maneuver for Endoscopic Hepatectomy of Cirrhotic Liver

Various methods, devices, and techniques have been developed to improve safety during laparoscopic hepatectomy procedures. Among these, the Pringle maneuver （PM） is widely used to minimize blood loss during liver transections; however, the risk of ischemic injury associated with this technique is increased by poor hepatic reserve and regeneration dysfunction secondary to liver cirrhosis. This retrospective study evaluated the short-term outcomes and feasibility of precoagulation for endoscopic hepatectomy without PM in patients with liver cirrhosis. Eleven patients with liver cirrhosis who also underwent endoscopic hepatectomy for hepatocellular carcinoma were recruited to undergo either microwave tissue coagulation or radiofrequency ablation for precoagulation before liver transection. A wedge resection without the PM was performed in all patients, with seven patients selected for bipolar radiofrequency ablation and four patients for microwave coagulation therapy. The procedures included video-assisted thoracoscopic hepatectomy in two patients and laparoscopic hepatectomy in nine patients. One patient who underwent radiofrequency ablation developed postoperative bleeding （Clavien-Dindo grade Ⅲ）. In conclusion, precoagulation can help to minimize intraoperative blood loss without the PM, contributing to effective resection of liver tumors. We propose that precoagulation could serve as a standard technique for endoscopic hepatectomy in patients with cirrhosis

Efficacy and Safety of an Ultrasonically Activated Device for Sealing the Bile Ducts During Liver Resection

The use of ultrasonically activated devices (USADs) in hepatic resections may be associated with an increased rate of complications, such as postoperative bile leaks. Nonetheless, the safety of USADs for sealing bile ducts during liver surgery has not yet been established. The purpose of this study was to assess the efficacy of a USAD for sealing bile ducts. In animal experiments, the common bile duct of ten anesthetized dogs was individually occluded using a USAD. Additionally, using the prospective liver surgery database from a single institution, we identified 45 consecutive patients who underwent hepatic resection using a USAD (USAD group) and 45 similar patients who underwent hepatic resection without the use of a USAD (NUSAD group). In the occluded and harvested canine bile ducts, the mean burst pressure was 280mmHg, and the lumen of the bile duct was completely sealed morphologically. In the clinical study, there was no significant difference in postoperative mortality or complications between the two groups, and biliary leakage was observed in only one patient (0.7%) in the USAD group. These data demonstrate that the USAD is a safe, efficient, and practical instrument for use during liver surgery to achieve complete hemobiliary stasis

Development of a New Bioartificial Liver Support System Using a Radial-flow Bioreactor

There is an increasing number of patients with severe liver disease that requires whole organ transplantation or living-related split liver transplantation. This has resulted in a shortage of donor organs, which is particularly problematic and still awaits resolution. Bioartificial liver (BAL) support systems have been developed with the aim of supporting patients with life-threatening liver disease until their liver recovers. Here, we describe a high performance three-dimensional rat hepatocyte culture system using a radial-flow bioreactor (RFB) with a polyvinyl alcohol (PVA) membrane as a small-scale BAL support system. Hepatocytes from male Sprague-Dawley rat livers were isolated and divided into two groups as follows. Group A: isolated hepatocytes were maintained in culture medium as controls; and group B: isolated hepatocytes were injected into the medium chamber of the RFB-PVA culture system. Sampling was carried out every 48 h to analyze the concentrations of ammonia and albumin in the medium. Light and electron microscopic examination of hepatocytes explanted from the PVA membrane was also performed. Albumin production and urea synthesis by cells in group B were both significantly higher than in group A. Hematoxylin-Eosin staining of the cells in group B showed that three-dimensional cell masses were attached to the PVA membrane. It also showed that the cells were stably proliferating in the porous spaces of the PVA. Scanning electron microscopic images of group B also showed clusters of hepatocytes attached to the PVA membrane. Hepatocyte clusters growing in the RFB-PVA culture system retained their biological function and were stable in the porous spaces of the PVA membrane. This cell culture system may be useful for the development of new BAL support systems