Improvement in aged liver regeneration using cell transplantation with chemically induced liver progenitors.

BACKGROUND: A decrease in the regenerative capacity of age-damaged liver tissue has been reported. Liver progenitor cells may play an important role in the regeneration of injured livers. In the present study we aimed to investigate improvements in the regenerative capacity of age-damaged livers using chemically induced liver progenitors (CLiPs) derived from mature hepatocytes. METHODS: Old (>90 weeks) and young (<20 weeks) mice underwent 70% hepatectomy, with or without trans-splenic CLiP administration. The residual liver/bodyweight (LW/BW) ratio was measured on postoperative days 1 and 7, and changes in liver regeneration and histology were evaluated. RESULTS: At 7 days post-hepatectomy, LW/BW ratios were significantly better in CLiP-treated old mice than in untreated old mice (p = .02). By contrast, no effect of CLiP transplantation was observed in young mice (p = .62). Immunofluorescence staining of liver tissue after CLiP administration showed an increase in Ki67-positive cells (p < .01). Flow cytometry analysis of green fluorescent protein-labeled CLiPs indicated that transplanted CLiPs differentiated into mature hepatocytes and were present in the recipient liver. CONCLUSIONS: CLiP transplantation appears to ameliorate the age-related decline in liver regeneration in mice.

Ectopic Liver Tissue on the Gallbladder Wall Encountered During Laparoscopic Cholecystectomy.

Ectopic liver tissue is a rare developmental anomaly that is not directly connected to the liver. We encountered ectopic liver tissue on the surface of the gallbladder wall during laparoscopic cholecystectomy. It has vasculature arising from the liver parenchyma and is classified according to its branching pattern. Ectopic liver tissue has been reported to occur in a variety of locations, and when encountered in surgery, it is clinically important to identify ectopic liver tissue with vascular supply to prevent unexpected bleeding. Ectopic liver tissue should be resected and examined histologically for the potential for malignancy when detected during surgical intervention.

Evolution of Liver Transplantation Over the Last 2 Decades Based on a Single-Center Experience of 300 Cases.

BACKGROUND Over the past 2 decades, there have been many medical advances in the field of liver transplantation. We conducted this study to evaluate the changes in liver transplantation over the last 2 decades. MATERIAL AND METHODS Three hundred cases of liver transplantation encountered between 1997 and 2019 in Nagasaki University Hospital were divided into 3 groups: Era 1 (cases no. 1-100), Era 2 (cases no. 101-200), and Era 3 (cases no. 201-300). Several items were compared among the groups. RESULTS There were no cases of deceased-donor liver transplantation in Era 1, 1 case in Era 2, and 12 cases in Era 3. The proportion of virus-related disease was significantly lower in Era 3 compared to other eras. In contrast, the proportion of alcoholic liver cirrhosis was significantly higher in Era 3 (27%) than Era 1 (7%) and Era 2 (10%) (P<0.01). In Era 1, the right lobe was selected most frequently, but in Eras 2 and 3, the left lobe was more frequently selected. CONCLUSIONS The evolution of the treatment and the transplant system in Japan is clearly reflected in the indications and types of donors for liver transplantation, even at a single center in Japan.

Helicobacter bilis infection induces oxidative stress in and enhances the proliferation of human cholangiocytes.

BACKGROUND: Helicobacter bilis, an enterohepatic Helicobacter species, represents a carcinogenic risk factor for cholangiocytes owing to the prevalence of infections in patients with biliary tract cancer, cholecystitis, and pancreaticobiliary maljunction. However, the effect of H. bilis infection on cholangiocytes and the process and mechanism of carcinogenesis are not known. We aimed to determine the effects of H. bilis on cholangiocytes, focusing on inflammation and oxidative stress. MATERIALS AND METHODS: Helicobacter bilis and MMNK-1 cells were cocultured for 24 h and inflammatory cytokine secretion was evaluated. Furthermore, MMNK-1 cell proliferation, intracellular reactive oxidant species (ROS) production, and DNA damage caused by ROS were investigated. All factors were compared with and without H. bilis infection. RESULTS: Interleukin (IL)-6 and IL-8 secretion were significantly increased in MMNK-1 cocultures with H. bilis (IL-6, 24.3 ± 12.2 vs. 271.1 ± 286.4 pg/ml; IL-8, 167.6 ± 78.7 vs. 1085.1 ± 1047.1 pg/ml, p < .05). MMNK-1 proliferation was also significantly higher in H. bilis cocultures (1.05 ± 0.02 vs. 1.00-fold, respectively; p < .05). Coculturing enhanced the production of ROS in MMNK-1 cells depending on the cell concentration of H. bilis (1.0 vs. 1.17 ± 0.06, p < .05); however, DNA injury was not observed in cocultures with H. bilis (5.35 ± 0.87 vs. 6.08 ± 0.55 pg/µl, p = .06). CONCLUSIONS: Helicobacter bilis infection induced ROS production in and enhanced the proliferation of cholangiocytes.

Prognostic Impact of Relative Dose Intensity of Adjuvant Chemotherapy With S-1 on Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: Although adjuvant chemotherapy (AC) with S-1 is currently the standard treatment for pancreatic ductal adenocarcinoma (PDAC) in Japan, the associations between its relative dose intensity (RDI) and survival outcomes remain unclear. PATIENTS AND METHODS: We reviewed 310 patients with PDAC who had undergone pancreatectomy from January 2014 to June 2020 at three institutions. Of these, patients who had received adjuvant S-1 monotherapy were analyzed. Patients who had died or developed recurrences within 6 months, or received neoadjuvant chemotherapy, were excluded from the analyses. Possible predictors of overall survival (OS), including RDI, were analyzed using Cox regression. The cutoff value for RDI was determined by receiver operating characteristic analysis. RESULTS: Ninety-four patients with a median age of 69 years (range=39-84 years) were analyzed. In the high-RDI group (RDI≥72.3%, n=74), the OS rates were 98.5% and 80.8% at 1 and 3 years, respectively, whereas in the low-RDI group (RDI <72.3%, n=20) they were 88.9% and 51.6%, respectively (p=0.001). By multivariate analysis, lymph node metastasis [hazard ratio (HR)=3.06; p=0.020], low RDI (HR=2.95; p=0.020), and time interval from surgery to initiation of AC > 51 days (HR=2.50; p=0.046) were independently associated with inferior OS. The combination of the latter two factors clearly stratified both OS and recurrence-free survival (p<0.001 and p=0.017, respectively). CONCLUSION: Early initiation and maintenance of RDI of S-1 monotherapy after pancreatectomy may improve the OS of PDAC patients.

Evaluation of Preoperative Magnetic Resonance Cholangiopancreatography in Acute Cholecystitis to Predict Technical Difficulties in Laparoscopic Cholecystectomy.

Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive imaging technique that provides high-quality visualization of the biliary tree, including the gallbladder. This study aimed to evaluate the useful-ness of preoperative MRCP for acute cholecystitis in predicting technical difficulties during laparoscopic chole-cystectomy (LC). A total of 168 patients who underwent LC with preoperative MRCP were enrolled in this study. Patients were divided into two groups according to preoperative MRCP findings: the visualized group (n = 126), in which the entire gallbladder could be visualized; and the non-visualized group (n = 42), in which the entire gallbladder could not be visualized. The perioperative characteristics and postoperative complica-tions of the two groups were retrospectively analyzed. Operation time was longer in the non-visualized group (median 101.5 vs. 143.5 min; p < 0.001). The non-visualized group had significantly more intraoperative blood loss than the visualized group (median 5 vs. 10 g; p = 0.05). The rate of conversion to open cholecystectomy was significantly higher in the non-visualized group (1.6 vs. 9.5%; p = 0.03). In conclusion, patients in the non- visualized group showed higher difficulty in performance of LC. Our MRCP-based classification is a simple and effective means of predicting difficulties in performing LC for acute cholecystitis.

Wandering spleen with splenic arteriovenous torsion.

Splenic arteriovenous torsion causes splenomegaly and ischemic necrosis of the spleen. The recommended treatment for wandering spleen with hypersplenism is considered to be splenectomy.

Synchronous Total Occlusion of the Celiac Axis and Superior Mesenteric Artery: An Autopsy Case.

Acute mesenteric ischemia (AMI) is often caused by superior mesenteric artery (SMA) embolization. We report a rare case of synchronous celiac axis and SMA embolization in an elderly woman with initially mild abdominal pain. Ultimately, a second contrast-enhanced computed tomography revealed extensive necrosis from the stomach to the transverse colon together with liver ischemia due to hours of occlusion. Multiorgan failure made palliation the only option, and she died the following evening. Autopsy revealed a fragile atherosclerosis-asso-ciated thrombus. Careful examination and repeat diagnostic tests should be performed in patients with mild abdominal symptoms at risk for AMI.

A case of cystic duct syndrome.

In the diagnosis of gallbladder induced pain without gallstones, drip-infusion cholangiographic computed tomography, and endoscopic retrograde cholangiography are useful in differentiating cystic duct syndrome.

Aberrant common hepatic artery from the left gastric artery and with no connection to the gastroduodenal artery: Risky vascular anomaly in gastrectomy.

Knowledge of anatomical variations of the celiac axis is important in upper abdominal surgery. Aberrant common hepatic artery originating from the left gastric artery without connecting the gastroduodenal artery is extremely rare. Preoperative vascular anatomy assessment using reconstructions of CT images may be useful for safe surgical procedure.

Subcutaneous transplantation of engineered islet/adipose-derived mesenchymal stem cell sheets in diabetic pigs with total pancreatectomy.

INTRODUCTION: Intraportal islet transplantation is a promising therapeutic approach for patients with type 1 diabetes mellitus (T1DM). However, despite being minimally invasive, the method has some limitations, such as short-term graft loss, portal venous thrombosis, and difficulty in collecting adequate amounts of islets. Subcutaneous islet transplantation on adipose-derived mesenchymal stem cell (ADSC) sheets has been suggested to overcome these limitations, and in this study, we have examined its feasibility in T1DM pigs. METHODS: Inguinal subcutaneous fat was harvested from young pigs and then isolated and cultured adequate ADSCs to prepare sheets. Islets were isolated from the pancreases of mature pigs and seeded on the ADSC sheets. T1DM pigs were generated by total pancreatectomy, and ADSC sheets with transplanted islets were administered subcutaneously to the waist (n = 2). The effects of the islets on the ADSC sheets and on blood glucose levels were evaluated. Insulin secretion was measured by insulin stimulation index. RESULTS: Islet viability was higher on ADSCs compared to islets alone (91.8 ± 4.3 vs. 81.7 ± 4.1%). The insulin stimulation index revealed higher glucose sensitivity of islets on ADSC sheets compared to islets alone (2.8 ± 2.0 vs. 0.8 ± 0.3). After transplantation, the blood glucose levels of two pigs were within the normal range, and sensitive insulin secretion was confirmed by intravenous glucose tolerance tests. After graftectomy, decreased insulin secretion and hyperglycemia were observed. CONCLUSIONS: Subcutaneous islet transplantation using ADSC sheets can regulate the blood glucose levels of T1DM pigs.

Pancreaticoduodenectomy can be indicated for elderly patients: risk prediction using the estimation of physiologic ability and surgical stress (E-PASS) system.

BACKGROUND: Pancreaticobiliary malignant diseases are primarily treated by surgical resection. However, the surgical indications for elderly patients, especially for pancreaticoduodenectomy (PD), must be carefully considered due to patient compliance. Whether PD can contribute to better prognoses in elderly patients remains unclear. Therefore, we aimed to evaluate the complications, compliance, and survival of elderly and non-elderly patients who underwent PD in our department. METHODS: We retrospectively analyzed 282 patients who underwent PD from 2000 to 2017 and divided them into non-elderly (aged ≤ 79 years, n = 238) and elderly (aged ≥ 80 years, n = 44) groups. The estimation of physiologic ability and surgical stress (E-PASS) system was used to evaluate morbidity and mortality using preoperative risk score (PRS), surgical stress score (SSS), and comprehensive risk score (CRS). RESULTS: Preoperative risk score was higher in the elderly group than in the non-elderly group, although SSS and CRS were similar. No significant differences were detected in the occurrence of postoperative complications. In the elderly group, CRS was higher in patients with complications than in those without. Long-term outcomes evaluated by overall and disease-specific survival were not significantly different. CONCLUSIONS: In the elderly patients, E-PASS especially CRS can predict the occurrence of complications. The safety and prognoses of elderly patients after PD are comparable with those of non-elderly patients.

Nondegenerated cystic neuroendocrine tumor of the pancreas: a case report.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are typically solid neoplasms but, in very rare cases, present as cystic lesions. We describe a case of a cystic neuroendocrine tumor that developed as a small cystic lesion. CASE PRESENTATION: In 2011, a 66-year-old Japanese woman underwent computed tomography (CT) that revealed a cystic lesion in the tail of the pancreas measuring 9 mm. She did not have any symptoms. She underwent a CT scan every year thereafter. The cystic lesion gradually increased and was 40 mm in 2019; endoscopic retrograde pancreatography (ERP) was then performed. Cytological examination demonstrated class IIIb adenocarcinoma, and we conducted laparoscopic distal pancreatectomy. Pathological examination showed PNET. CONCLUSION: Although cystic change of PNET is generally caused by ischemia or necrosis inside the tumor, in our case, PNET occurred as a small cyst that increased without changing form.