Background: Progression of chronic liver dysfunction influenced by long-term chemotherapy or repeated hepatectomy might be related to patient overall survival as well as tumor factors in colorectal liver metastasis (CLM) patients. Our aim of this study was to clarify the relationship between fibrotic liver damage and malignant behaviors of CLM malignancy or its long-term survivals by the retrospective cohort study. Methods: We examined the relationship between tumor-related factors or six liver fibrosis-associated parameters, including platelet count, hyaluronic acid (HA), mac-2 binding protein glycosylation isomer (M2BPGi), type IV collagen 7S (T4C7), aspartate aminotransferase-to-platelet ratio index (APRI), The fibrosis-4 (Fib-4) index, and clinicopathological parameters, surgical records, and postoperative patient survival in the 45 consecutive patients with CLM who underwent radical hepatectomy. Results: Fibrotic parameters were platelet count of 23.0 +/- 8.5 x10(4)/mu L, HA level of 68.9 +/- 82.3 ng/mL, M2BPGi of 0.87 +/- 0.48 ng/mL, and type IV collagen level of 5.74 +/- 3.76 ng/mL. Platelet count was significantly correlated with HA level (P<0.05) and tended to be correlated with M2BPGi levels (P=0.056). HA level was significantly associated with albumin level (P<0.05). Overall survival in this series showed five-year overall survivors after hepatectomy in 44 patients (98%), but cancer-related deaths were observed in only one patient. Patients with higher grades and increased bilirubin levels demonstrated significantly lower cancer-free survival (P<0.05), but fibrotic parameters were not associated with prognostic factors. Conclusions: Fibrotic markers indicating chemotherapy or repeated surgical liver injury were not significant predictive factors reflecting cancer malignant behaviors or patient overall survival, contrary to our hypothesis. The current overall survival status using various modalities for cancer recurrence is satisfactory under our present perioperative management.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a major health problem worldwide. Liver regeneration is crucial for restoring liver function, and is regulated by extraordinary complex process, involving numerous factors under both physiologic and pathologic conditions. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid synthesized by sphingosine kinase 1 (SphK1), plays an important role in liver function through S1P receptors (S1PRs)-expressing cells. In this study, we investigated the effect of lipid overload on hepatocyte proliferation in a mouse hepatic steatosis model induced by feeding a methionine- and choline-deficient (MCD) diet. After 50% partial hepatectomy (PHx), liver tissues were sampled at various timepoints and then analyzed by immunohistochemistry, oil Red-O staining, quantitative-polymerase chain reaction (qPCR), and flow cytometry. In mice fed the MCD-diet, significantly exacerbated hepatic steatosis and accelerated liver regeneration were observed. After PHx, hepatocyte proliferation peaked at 48 and 36 hr in the liver of chow- and MCD-diet fed mice, respectively. By contrast, increased expression of S1PR2 was observed in hepatic neutrophils and macrophages of MCD-diet fed mice. Flow cytometry and qPCR experiments demonstrated that levels of HGF and FGF2 released by neutrophils and macrophages were significantly higher in MCD-diet fed mice. In conclusion, hepatic lipid overload recruits Kupffer cells and neutrophils that release HGF and FGF2 via SphK1/S1PR2 activation to accelerate hepatocyte proliferation.

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.

Introduction Photodynamic therapy (PDT) is a salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Salvage PDT is the treatment available for vulnerable patients with various comorbidities at risk of salvage esophagectomy. This study assessed the impact of the Charlson comorbidity index (CCI) on the outcomes of salvage PDT using talaporfin sodium (TS) for esophageal cancer. Metohds Consecutive patients with esophageal cancer who underwent salvage TS-PDT from 2016 to 2022 were included in this retrospective study. We investigated the local complete response (L-CR), progression-free survival (PFS) and overall survival (OS) and evaluated the relationship between the CCI and therapeutic efficacy. Results In total, 25 patients were enrolled in this study. Overall, 12 patients (48%) achieved an L-CR, and the 2-year PFS and OS rates were 24.9% and 59.4%, respectively. In a multivariate analysis, a CCI ≥1 (p=0.041) and deeper invasion (p=0.048) were found to be significant independent risk factors for not achieving an L-CR. To evaluate the efficacy associated with comorbidities, we divided the patients into the CCI=0 group (n=11) and the CCI ≥1 group (n=14). The rate of an L-CR (p=0.035) and the 2-year PFS (p=0.029) and OS (p=0.018) rates in the CCI ≥1 group were significantly lower than those in the CCI=0 group. Conclusion This study found that the CCI was negatively associated with the efficacy of salvage TS-PDT for esophageal cancer.

BACKGROUND/AIM:Immune checkpoint inhibitors are effective in treating microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC). Pathological complete response to immune checkpoint inhibitors for MSI-H metastatic CRC have been described in several reports. Liver metastasis is known to predict resistance to ani-programmed death 1 (PD-1)/PD-1 ligand 1 (PD-L1) therapy in several cancers, including CRC. CASE REPORT:Herein, we report the case of a 23-year-old man with MSI-H colorectal liver metastasis who exhibited a pathological complete response to pembrolizumab following systemic chemotherapies. Pathological examination of the primary lesion revealed strong HLA-class I and HLA-DR expression in cancer cells. Elevated PD-L1 expression was observed in areas of increased CD8-postive T cell infiltration. Additional pathological study of regional lymph nodes showed increased PD-L1 and CD169 expression. CONCLUSION:A detailed pathological examination revealed PD-L1 expression not only in the primary CRC lesion but also in regional lymph nodes. Recent studies have highlighted the significance of regional lymph nodes in anti-cancer immune responses. Therefore, pathological studies using resected lymph nodes might be beneficial for predicting the response of anti-PD-1/PD-L1 therapy.

Purpose: To increase the number of medical students or residents who want to become surgeons, we must evaluate our program that recruits new young surgeons. Methods: We planned surgical training programs for medical students and residents that we named the MANGOU (Miyazaki Advanced New General surgery Of University) training project in the Department of Surgery, Miyazaki University, Japan. From January 2016 through December 2022, we asked trainees who attended this training to complete questionnaires to evaluate their interest in surgery, confidence in surgical skills, and training. Scoring of the questionnaire responses was based on a 5 -point Likert scale, and we evaluated this training prospectively. Results: Among the 109 trainees participating in this training, 61 answered the questionnaires. Two participants found the training boring, but 59 (96.7%) enjoyed it. All of them answered "Yes" to wanting to participate in the next training. Respective pre- and post -training scores were as follows: confidence in surgical skills, 2.2 +/- 1.0 and 3.0 +/- 1.0 (p < 0.0001); interest in surgery, 4.2 +/- 0.8 and 4.4 +/- 0.5 (p = 0.0011); and willingness to become surgeons, 3.9 +/- 0.7 and 4.1 +/- 0.6 (p = 0.0011). All scores rose after MANGOU training. Conclusion: We planned MANGOU surgical wet lab training for medical students and residents that aimed to educate and recruit new surgeons. After joining the MANGOU training, the trainees' anxiety about surgery was reduced, their confidence in performing surgical procedures improved, they showed more interest in surgery, and they increased their motivation to become surgeons.

OBJECTIVES:Educational simulation systems using virtual reality (VR) with head-mounted devices are spreading into the medical field. We developed an innovative training system whereby experienced ostomates can share their proficient stoma self-care techniques with novice ostomates through VR simulations, enabling anytime, anywhere learning. We examined the questionnaire study to assess the acceptance of VR simulation training for stoma care by healthcare providers. METHODS:This study was conducted for the participants, nurses, and doctors, at the 39th Kyushu Stoma Rehabilitation Research Meeting with the organizer's permission. We created two VR simulation prototypes from the perspective of ostomates and caregivers using modeled stomas. We conducted a qualitative study through a questionnaire with healthcare professionals regarding their experiences of viewing VR videos. RESULTS:The study included 20 (52.6%) nurses certified in wound, ostomy, and continence (WOC) care, 16 (42.1%) non-WOC nurses, and two (5.3%) medical doctors. Over 90% of participants showed a positive inclination towards the practical application of the system in clinical settings for both scenarios. A significantly higher number of nurses in the non-WOC nurse group expressed a definite interest in using the imaging from the ostomate's perspective versus that in the WOC nurse group (81.3% vs. 40%, P=0.013). CONCLUSIONS:From this survey, we concluded that the respondents felt a VR training system was a positive experience, to say it is acceptable means that it was as good as the standard of care. ​​​​​​Particularly, non-WOC nurses, with fewer opportunities in stoma care compared to WOC nurses, showed stronger interest in practically implementing this innovative training system.

Liver regeneration is a well-orchestrated compensatory process that is regulated by multiple factors. We recently reported the importance of the chromatin protein, a high-mobility group box 2 (HMGB2) in mouse liver regeneration. However, the molecular mechanism remains unclear. In this study, we aimed to study how HMGB2 regulates hepatocyte proliferation during liver regeneration. Seventy-percent partial hepatectomy (PHx) was performed in wild-type (WT) and HMGB2-knockout (KO) mice, and the liver tissues were used for microarray, immunohistochemistry, quantitative polymerase chain reaction (qPCR), and Western blotting analyses. In the WT mice, HMGB2-positive hepatocytes colocalized with cell proliferation markers. In the HMGB2-KO mice, hepatocyte proliferation was significantly decreased. Oil Red O staining revealed the transient accumulation of lipid droplets at 12-24 hr after PHx in the WT mouse livers. In contrast, decreased amount of lipid droplets were found in HMGB2-KO mouse livers, and it was preserved until 36 hr. The microarray, immunohistochemistry, and qPCR results demonstrated that the expression of lipid metabolism-related genes was significantly decreased in the HMGB2-KO mouse livers. The in vitro experiments demonstrated that a decrease in the amount of lipid droplets correlated with decreased cell proliferation activity in HMGB2-knockdown cells. HMGB2 promotes de novo lipogenesis to accelerate hepatocyte proliferation during liver regeneration:

Objective The extracellular volume (ECV) calculated based on contrast-enhanced computed tomography (CT) has been reported as a novel imaging parameter reflecting the morphological change of fibrosis in several parenchymal organs. Our retrospective study assessed the validity of the ECV fraction for diagnosing pancreatic fibrosis and the appropriate imaging condition as the "equilibrium phase". Methods In 27 patients undergoing multiphasic CT and subsequent pancreaticoduodenectomy, we investigated pathological fibrotic changes related to the ECV fraction and conducted analyses using the value obtained by subtracting the equilibrium CT value of the portal vein from that of the abdominal aorta (Ao-PVequilibrium) to estimate eligibility of the equilibrium phase. Results In all patients, the ECV fraction showed a weak positive correlation with the collagenous compartment ratio (r=0.388, p=0.045). All patients were divided into two groups - the high-Ao-PVequilibrium group and low-Ao-PVequilibrium group - based on the median value. No significant correlation was found in the high-Ao-PVequilibrium group, whereas a significant correlation was observed in the low-Ao-PVequilibrium group (r=0.566, p=0.035). Conclusion The ECV fraction is a possible predictive factor for histopathological pancreatic fibrosis. In its clinical application, the eligibility of the "equilibrium phase" may affect the diagnostic capability. It will be necessary to verify the imaging conditions in order to improve the accuracy of the diagnosis.

Laparoscopic hepatectomy is safely performed with minimal invasiveness on patients with recurrent liver tumors after previous hepatectomy. However, it is still difficult to dissect and expose the operative field at the transected edge or plane after open right hepatectomy, even for limited resection by a laparoscopic approach, due to severe adhesion to the surrounding peritoneum or organs. We herein applied the retroperitoneal laparoscopic approach to limited resection of the dorsal surface at the transected edge of Couinaud's segment 6 after previous repeated hepatectomies in a patient with recurrent hepatocellular carcinoma (HCC) by avoiding severe intra-abdominal adhesion. We safely resected recurrent HCC via the retroperitoneal space. This approach is a useful and alternative option for laparoscopy which minimizes the dissecting time and avoids organ injury on the right side of the transected area of the liver after hepatectomy in patients with liver malignancies.

A 48-year-old woman underwent transcatheter arterial embolization (TAE) for a splenic artery aneurysm, which resulted in a partial splenic infarction in the middle lobe. Five years after TAE, a 20-mm diameter mass in the noninfarcted area of the spleen was detected on imaging, which grew to 25 mm in diameter after 6 months. MRI after gadolinium administration showed a 35 × 34 mm mass within the superior pole and 15 × 12 mm mass within the inferior pole. The patient underwent laparoscopic splenectomy and had an uneventful postoperative recovery. No evidence of recurrence was observed during the 2-year follow-up period after surgery. The mass was pathologically confirmed to be sclerosing angiomatoid nodular transformation (SANT) of the spleen. While some studies hypothesize that SANT is a response to vascular injury or trauma, to the best of our knowledge, there have been no previous reports of SANT occurring after procedures directly affecting splenic blood flow. Additionally, multifocal SANTs are reported to be very rare, accounting for only 4.7

We developed a prototype VR platform, VECTORS L&M ( VLM), aiming to enhance the understanding of digestive surgery for students, interns, and young surgeons by limiting costs. Its efficacy was assessed via questionnaires before implementation in surgical education. The VLM provides nine-minute VR views of surgeries, from both 180- and 360-degree angles. It was created with L.A.B. Co., Ltd. and incorporates surgery videos from biliary malignancy patients. Following VLM development, a survey was conducted among surgeons who had experienced it. Twenty-eight participants (32% of observers) responded to the survey. A majority (81%) reported positive experiences with the VR content and showed interest in VR video production, though some reported sickness. Most respondents were experienced surgeons, and nearly all believed VR was important for medical education with a mean score of 4.14 on a scale of up to 5. VR was preferred over 3D printed models due to its application versatility. Participants expressed the desire for future VR improvements, such as increased mobility, cloud connectivity, cost reduction, and better resolution. The VLM platform, coupled with this innovative teaching approach, offers experiential learning in intraabdominal surgery, effectively enriching the knowledge of students and surgeons ahead of surgical education and training.

A 15-year-old girl with recurrent upper abdominal pain was diagnosed with congenital biliary dilatation. Abdominal enhanced computed tomography (CT) showed the anterior segmental branch of the right hepatic artery (RHA) running across the ventral aspect of the dilated common hepatic duct (CHD). Laparoscopic extrahepatic dilated biliary duct excision and Roux-en-Y hepaticojejunostomy were planned. Intraoperatively, the dilated CHD was observed to bifurcate into the ventral and dorsal ducts, between which the anterior segmental branch of the RHA crossed through the CHD. The CHD rejoined on the distal side as one duct. We transected the CHD just above the cystic duct. The patency of the ventral and dorsal sides of the bifurcated CHD was confirmed. Laparoscopic hepaticojejunostomy was performed at the distal side of the rejoined CHD, without sacrificing the anterior segmental branch of the RHA. There was no postoperative blood flow impairment in the right hepatic lobe or anastomotic stenosis.

An amendment to this paper has been published and can be accessed via the original article.

Estrogen and its receptors are involved in the pathogenesis of gastrointestinal diseases such as colitis. However, the role of the membrane estrogen receptor G-protein-coupled receptor 30 (GPR30) in colitis is poorly understood. We therefore investigated the effect of estrogen in dextran sulfate sodium (DSS)-induced colitis. Male C57BL/6 mice were administered 1.5

Background Oxaliplatin (OX)-based chemotherapy induces sinusoidal obstruction syndrome (SOS) in the nontumorous liver parenchyma, which can increase the risk of liver resection due to colorectal liver metastasis (CRLM). The extracellular volume (ECV) calculated from contrast-enhanced computed tomography (CT) has been reported to reflect the morphological change of hepatic fibrosis. The present retrospective study aimed to evaluate the ECV fraction as a predictive factor for OX-induced SOS. Methods Our study included 26 patients who underwent liver resection for CRLM after OX-based chemotherapy with a preoperative dynamic CT of appropriate quality. We investigated the relationship between the pathological SOS grade and the ECV fraction. Results Overall, 26 specimens from the patients were graded with the SOS classification of Rubbia-Brandt et al. as follows: grade 0, n = 17 (65.4%); grade 1, n = 4 (15.4%); and grade 2, n = 5 (19.2%). No specimens showed grade 3 SOS. In a univariate analysis, the ECV fraction in grade 0 SOS was significantly lower than that in grade 1 + 2 SOS (26.3 ± 3.4% vs. 30.6 ± 7.0%; P = 0.025). The cutoff value and AUC value of the ECV fraction to distinguish between grades 0 and 1 + 2 were 27.5% and 0.771, respectively. Conclusions Measurement of the ECV fraction was found to be a potential noninvasive diagnostic method for determining early-stage histopathological sinusoidal injury induced by OX-based chemotherapy.

INTRODUCTION:In recent years, dome resection, which preserves the splenic immunological function, has been the primary technique used to treat splenic cysts. We herein report a surgical technique using a needle grasper and indocyanine green (ICG) fluorescence to perform dome resection of a huge nonparasitic splenic cyst in a pediatric patient.PATIENT AND SURGICAL TECHNIQUE:A 13-year-old girl was incidentally diagnosed with a splenic cyst during follow-up for scoliosis. Abdominal enhanced computed tomography (CT) showed a 17 × 14 × 14 cm unifocal cyst. Laparoscopic dome resection was planned. The intraoperative findings showed that the spleen was distended, but there was no apparent prominence of the thin cyst wall on the surface of the spleen. An ICG fluorescence camera overlay revealed poor coloration in the thinning area. We punctured the area and aspirated the cyst contents. We grasped the cyst wall with a percutaneous needle grasper and dissected the cyst wall with a vessel sealing system. We placed anti-adhesion agent at the dissection line to prevent recurrence.DISCUSSION:ICG fluorescence was useful for identifying the thinning area of a splenic cyst. The use of a percutaneous needle grasper facilitated the performance of dome resection of a huge splenic cyst in a pediatric patient with minimal invasiveness and an improved cosmetic outcome.

Background: To identify predictors of changes in hepatic volumes after portal vein embolization, we examined the relationship with preoperative nutritional and immunological parameters. Patients and Methods: Ninety-three patients who underwent portal vein embolization were included. The control group comprised 13 patients who underwent right hepatectomy without portal vein embolization. Computed to-mographic volumetric parameter was measured for changes in embolized and nonembolized liver. Correlation with various candidates of immunonutritional parameters was examined. Results: Difference in increased liver ratio was 9.1%. C-reactive protein levels significantly increased after portal vein embolization (P < .01), whereas albumin and total cholesterol levels significantly decreased, respectively (P < .01). The C-reactive protein/albumin ratio, prognostic nutritional index, Controlling Nutritional Status score, and modified Glasgow Prognostic Score were significantly different, respectively (P < .01). Prothrombin activity and total cholesterol level significantly correlated with the increased change in nonembolized liver (P < .05). The C-reactive protein and C-reactive protein/albumin ratio after portal vein embolization negatively cor-related with hypertrophic ratio (P < .05). By comparing posthepatectomy outcomes between 64 patients under-going portal vein embolization and 13 who did not, the prevalence of severe complications and mortality in the portal vein embolization group was not different from that in the non-portal vein embolization group. Liver ac-tivity at 15 minutes > 0.92 and increased liver volume >= 10% tended to correlate with lower prevalence of severe complications. Only increased intraoperative blood loss >= 1,500 mL was significantly associated with morbidity and mortality (P < .05). Conclusion: Contrary to our hypothesis, immunonutritional parameters, except C-reactive protein and C-reactive protein/albumin ratio, did not reflect hypertrophy after portal vein embolization. Although it is difficult to predict the hypertrophic degree, the strategy of scheduled hepatectomy should be switched in case of impaired inflam-matory status after portal vein embolization. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Abstract Background Ultrasonography using Sonazoid, a novel contrast agent containing microbubbles is a useful diagnostic modality for intrahepatic mass lesions by specific characteristics in two phases of contrast enhancement of early vascular perfusion and perfusion defect of the lesion in the late phase. To improve diagnostic accuracy of intraoperative ultrasonography (IOUS) in biliopancreatic neoplasms, we investigated the usefulness of Sonazoid contrast agent as a preliminary study. Methods We examined IOUS images in 24 patients with the biliopancreatic diseases. Sonazoid was administered intravenously, and the early arterial- and nenous-phase images of tumor were observed during laparotomy. Results Tumors included the localized type of adenomyomatosis in the fundus of gallbladder (GAM) in seven patients as a benign control, adenomatous diseases of biliopancreatic lesions in four, gallbladder carcinoma (GC) in 12, and papilla adenocarcinoma in one. Scanning by Sonazoid IOUS was accomplished in all patients with no adverse effects. Although GC showed high enhancement in 83% of the tumors, GAM and adenoma also showed enhancement in more than half of them, whereas the VA and an intrahepatic duct adenoma were not enhanced. Pseudo-positivity was observed in one case of hyperplastic polyp, and pseudo-negativity was observed in two patients. Cholesterol polyps and liver metastases were not enhanced by Sonazoid. Conclusion Sonazoid IOUS is an alternative useful diagnostic tool to detect vascularity indicating malignancy or tumor extent that allows adequate surgical resection to be performed.

Introduction and importance: Acinar cell carcinoma (ACC) of the pancreas is a rare pancreatic cancer subtype (incidence, 0.5-2%) with unclear epidemiology and prognosis. Sometimes, repeat resection including total pancreatectomy is required for recurrence. We report a case of ACC recurring in the remnant pancreatic head after distal pancreatectomy that was successfully cured by remnant pancreatic resection following combination therapy with nab-paclitaxel (nab-PTX) and gemcitabine (GEM). Case presentation: A 64-year-old woman was referred for pancreatic tumour treatment. CT revealed a 46-mm tumour in the pancreatic body, and endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) indicated ACC. Distal pancreatectomy was performed, and the final diagnosis was ACC. CT 18 months later showed a 34-mm tumour in the remnant pancreatic head revealed as ACC by EUS-FNA. Portal vein invasion was apparent, so neoadjuvant chemotherapy with nab-PTX and GEM was administered, and remnant pancreatic resection (total pancreatectomy) was performed. No recurrence or distant metastasis was present more than 6 months later. Clinical discussion: Mean survival time for ACC is 18-47 months, and prognosis is good compared with pancreatic ductal adenocarcinoma (PDAC). ACC tends to extend and grow along the main pancreatic duct, which increases the recurrence rate to 50-60%. EUS and EUS-FNA were useful for evaluating tumour extension and diagnosis. Repeat pancreatic resection that included total pancreatectomy was feasible and could be performed safely. Conclusion: ACC has a better prognosis than PDAC but with a higher recurrence rate. Aggressive surgical resection that included remnant total pancreatotomy with chemotherapy was useful in treating ACC.