The crucial role of SETDB1 in structural and functional transformation of epithelial cells during regeneration after intestinal ischemia reperfusion injury.

Su (var) 3-9, enhancer of seste, trithorax (SET)-domain bifurcated histone lysine methyltransferase (SETDB1) plays a crucial role in maintaining intestinal stem cell homeostasis; however, its physiological function in epithelial injury is largely unknown. In this study, we investigated the role of SETDB1 in epithelial regeneration using an intestinal ischemia/reperfusion injury (IRI) mouse model. Jejunum tissues were sampled after 75 min of ischemia followed by 3, 24, and 48 h of reperfusion. Morphological evaluations were performed using light microscopy and electron microscopy, and the involvement of SETDB1 in epithelial remodeling was investigated by immunohistochemistry. Expression of SETDB1 was increased following 24 h of reperfusion and localized in not only the crypt bottom but also in the transit amplifying zone and part of the villi. Changes in cell lineage, repression of cell adhesion molecule expression, and decreased histone H3 methylation status were detected in the crypts at the same time. Electron microscopy also revealed aberrant alignment of crypt nuclei and fusion of adjacent villi. Furthermore, increased SETDB1 expression and epithelial remodeling were confirmed with loss of stem cells, suggesting SETDB1 affects epithelial cell plasticity. In addition, crypt elongation and increased numbers of Ki-67 positive cells indicated active cell proliferation after IRI; however, the expression of PCNA was decreased compared to sham mouse jejunum. These morphological changes and the aberrant expression of proliferation markers were prevented by sinefungin, a histone methyltransferase inhibitor. In summary, SETDB1 plays a crucial role in changes in the epithelial structure after IRI-induced stem cell loss.

Clinical outcome and neurological development of patients with biliary atresia associated with a bleeding tendency: a single institution experience.

PURPOSE: We compared the clinical features of patients with biliary atresia (BA) associated with a bleeding tendency (BT) at the time of the diagnosis with those of patients without a bleeding tendency (NBT). METHODS: The patients' background characteristics, age in days at the first visit, Kasai portoenterostomy (KPE), and postoperative course were retrospectively analyzed. RESULTS: Nine of the 93 BA patients (9.7%) showed a BT, including 7 with intracranial hemorrhaging (ICH), 1 with gastrointestinal bleeding, and 1 with a prothrombin time (PT) of 0%. The age at the first visit was 62 ± 12 days old for BT patients and 53 ± 27 days old for NBT patients (p = 0.4); the age at KPE was 77 ± 9 days old for BT patients and 65 ± 24 days old for NBT patients (p = 0.2); the time from the first visit to surgery was 13 ± 7 days for BT patients and 11 ± 10 days for NBT patients (p = 0.5); and the native liver survival rate was 56% for BT patients and 58% for NBT patients (p = 1), with no significant difference in any of the parameters. The neurological outcomes of survivors of ICH were favorable. CONCLUSIONS: Appropriate BT correction allowed early KPE even after ICH, resulting in native liver survival rates comparable to those of NBT patients without significant neurological complications.

Efficacy of laparoscopic liver resection for small hepatocellular carcinoma located in the posterosuperior segments: A multi-institutional study using propensity score matching by the Kyushu Study Group of Liver Surgery.

AIM: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. METHODS: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. RESULTS: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. CONCLUSIONS: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS.

Measuring intraoperative anesthetic parameters during hepatectomy with inferior vena cava clamping.

PURPOSE: Uncontrollable bleeding remained problematic in anatomical hepatectomy exposing hepatic veins. Based on the inferior vena cava (IVC) anatomy, we attempted to analyze the hemodynamic and surgical effects of the combined IVC-partial clamp (PC) accompanied with the Trendelenburg position (TP). METHODS: We prospectively assessed 26 consecutive patients who underwent anatomical hepatectomies exposing HV trunks between 2020 and 2023. Patients were divided into three groups: use of IVC-PC (group 1), no use of IVC-PC (group 2), and use of IVC-PC accompanied with TP (group 3). In 10 of 26 patients (38%), hepatic venous pressure was examined using transhepatic catheter insertion. RESULTS: IVC-PC was performed in 15 patients (58%). Operating time and procedures did not significantly differ between groups. A direct hemostatic effect on hepatic veins was evaluated in 60% and 70% of patients in groups 1 and 3, respectively. Group 1 showed significantly more unstable vital status and vasopressor use (p < 0.01). Blood or fluid transfusion and urinary output were similar between groups. Group 2 had a significantly lower baseline central venous pressure (CVP), while group 3 showed a significant increase in CVP in TP. CVP under IVC-PC seemed lower than under TP; however, not significantly. Hepatic venous pressure did not significantly differ between groups. Systolic arterial blood pressure significantly decreased via IVC-PC in group 1 and to a similar extent in group 3. Heart rate significantly increased during IVC-PC (p < 0.05). CONCLUSION: IVC-PC combined with the TP may be an alternative procedure to control intrahepatic venous bleeding during anatomical hepatectomy exposing hepatic venous trunks.

Biliary atresia: graft-versus-host disease with maternal microchimerism as an etiopathogenesis.

Biliary atresia (BA) is an inflammatory disease of the biliary system in newborns and infants. The etiology is largely unknown. Approximately half of BA patients require liver transplantation by 20 years of age, even after surgical correction due to progressive fibrosis of the liver. Regarding the disease mechanism, there is circumstantial evidence to support the hypothesis of graft-versus-host disease because of the existence of maternal cells in the liver (maternal microchimerism, MMC), histopathological similarity of the liver and an intense maternal response to the BA patient with mixed lymphocyte culture. Immune dysregulation with decreased Treg and increased Th1 and Th17 cells are the pathogenic features of BA, which are homologous to the pathogenic features of GvHD. Further elucidation of the etiopathogenetic mechanism of BA is warranted for development of new therapeutic strategies for native liver survival.

Novel analysis using magnetic resonance cholangiography for patients with pancreaticobiliary maljunction.

PURPOSE: We used a novel diagnostic Fourier transform (FT) algorithm of the entire extrahepatic bile duct (EHBD) measured by magnetic resonance cholangiography (MRC) to evaluate subtle deformation of bile duct lumen, indicating the malignant potential of EHBD, in patients with pancreaticobiliary maljunction (PBMJ) and in a comparative group of controls without PBMJ. METHODS: From the workstation, the EHBD lumen was traced automatically and a 2D diagram cross section was measured at 0.5 mm-longitudinal intervals. The FT-based integrated power spectral density function value (FTPSDI) of the diameter or area (mm2 or mm4/Hz) and the phase value distribution entropy (PVDE) were also measured. RESULTS: There were 16 patients with undilated PBMJ and 7 with dilated PBMJ. The control group comprised 10 patients with a normal bile duct, 20 with bile duct carcinoma (BDC), and 1 with primary sclerosing cholangitis. Both the diameter and area of the dilated bile ducts and the ducts with early- or advanced-stage BDC were significantly greater than those of the normal duct (p < 0.05). The undilated type of PBMJ tended to have a larger FTPSDI diameter than a normal bile duct, which had a smaller diameter than the dilated type of PBMJ or BDC. BDC had a significantly larger FTPSDI diameter (p < 0.05) and the cutoff value for accuracy was 168 mm2 Hz-1. CONCLUSION: The novel mathematical FTPSDI is a promising indicator of whether preventive EHBD resection is necessary for patients with PBMJ, which can be widely applied in the early diagnosis of other biliary diseases.

Using indocyanine green fluorescence in laparoscopic surgery to identify and preserve rare branching of the right hepatic artery in pediatric congenital biliary dilatation.

We describe a laparoscopic surgical technique using indocyanine green (ICG) fluorescence to identify and preserve rare arterial branching associated with pediatric congenital biliary dilatation. Congenital biliary dilatation with pancreaticobiliary maljunction was diagnosed in a 9-year-old girl, who presented with upper abdominal pain. Abdominal enhanced computed tomography (CT) showed that the accessory right hepatic artery (aRHA) branched from the posterior superior pancreaticoduodenal artery (PSPDA) and flowed through the right aspect of the dilated common bile duct (CBD) directly into the right lobe of the liver. We performed laparoscopic dilated biliary duct resection and hepaticojejunostomy, administering ICG intravenously, at a dose of 0.6 mg/kg. The ICG fluorescence overlay mode showed an aRHA running along the right side of the dilated CBD. The aRHA was dissected from the CBD without injury. After finishing the anastomosis, the beating of the aRHA was preserved, confirming that blood flow had been maintained.

Endoscopic filling with polyglycolic acid sheets and fibrin glue of persistent fistula after esophagectomy.

BACKGROUND: Treatment of anastomotic leakage in reconstruction after esophagectomy remains challenging. This report presents a new endoscopic filling method for persistent fistula after failure of conservative treatment of leakage caused by anastomotic insufficiency. METHODS: 10 of 14 patients, in whom post-esophagectomy leakage had failed to resolve after 2 weeks of conservative treatment, underwent endoscopic filling with polyglycolic acid (PGA) sheet and fibrin glue into the anastomotic leakage site, using a delivery tube and endoscopic catheter, respectively. RESULTS: Each patient underwent jejunostomy, to secure nutrition. The leakage was resolved in all 10 patients. The mean number of PGA - fibrin glue procedures was 1.7. The mean period from the first application to the resumption of oral intake was 31.6 days, from the final application it was 14.7 days. CONCLUSIONS: The reported filling method offers a new endoscopic approach for persistent fistula after esophagectomy when conservative treatment of leakage has failed.

Current status of trauma surgery at a Japanese prefectural academic institute: improved organization in a regional prefecture.

PURPOSES: Balancing scheduled surgery and trauma surgery is difficult with a limited number of surgeons. To address the issues and systematize education, we analyzed the current situation and the effectiveness of having a trauma team in the ER of a regional hospital. METHODS: This retrospective study analyzed the demographics, traumatic variables, procedures, postoperative morbidities, and outcomes of 110 patients who underwent trauma surgery between 2012 and 2019. The trauma team was established in 2016 and our university hospital Emergency Room (ER) opened in 2012. RESULTS: Blunt trauma accounted for 82% of the trauma injuries and 39% of trauma victims were transported from local centers to our institute. The most frequently injured organs were in the digestive tract and about half of the interventions were for hemostatic surgery alone. Concomitant treatments for multiple organ injuries were performed in 31% of the patients. The rates of postoperative severe complications (over Clavien-Dindo IIIb) and mortality were 10% and 13%, respectively. Fourteen (12.7%) of 24 patients who underwent damage-control surgery died, with multiple organ injury being the predominant cause of death. CONCLUSION: Systematic education or training of medical students and general surgeons, as well as the co-operation of the team at the regional academic institute, are necessary to overcome the limited human resources and save trauma patients.

Relationship between hepatic venous anatomy and hepatic venous blood loss during hepatectomy.

PURPOSE: Predicting increased blood loss based on anatomical intervascular relationships is essential in major hepatectomy. METHODS: We assessed 63 consecutive patients undergoing anatomical hepatectomy exposing the hepatic vein (HV) trunk at two institutes. Correlations between anatomical alterations of the hepatic inferior vena cava (IVC), HV, hepatic IVC, or right atrium (RA) and the blood loss per standard weight (BLSW) or blood transfusion (n = 18) were analyzed. The results of IVC partial clamping (PC) were additionally examined. RESULTS: The BLSW in type V-up anatomical morphology was significantly higher than that in straight type (p < 0.05). The parameters associated with an increased BLSW (> 13.5 mL/kg) were tumor size (> 4 cm), prothrombin activity (< 87%), CVP (> 7 mmHg), area of suprahepatic IVC (< 360 mm2), IVC-RA gap (> 28 mm), longitudinal angle of IVC (< 160°), and axial angle of the MHV (< 55°). A multivariate analysis revealed that a high IVC-RA gap was a significant independent risk factor (odds ratio; 4.32, p < 0.05). Among 25 patients undergoing IVC-PC, only three showed a remarkable decrease in hepatic venous bleeding. No other statistically significant differences in the surgical records were observed in most cases. CONCLUSION: The IVC-RA gap might be a promising novel predictive parameter reflecting increased blood loss leading to blood transfusion in anatomical hepatectomy.