佐田 尚宏

BACKGROUND: Neoadjuvant therapy has been increasingly adopted for resectable pancreatic ductal adenocarcinoma (PDAC) in Japan following the Prep-02/JSAP-05 trial. However, real-world evidence regarding effectiveness and underlying pathological mechanisms remains limited. This retrospective study evaluated neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) impacts on resectable PDAC patient oncological and pathological outcomes. METHODS: Consecutive resectable PDAC patients treated with NAC-GS (n = 60) or upfront surgery (UFS) (n = 101) between 2013 and 2023 were retrospectively analyzed (total diagnosed during the study period, n = 186). An intention-to-treat principle assessed overall survival (OS) and recurrence-free survival (RFS). Propensity score matching using six baseline variables (1:1) minimized selection bias. RESULTS: Fifty-four patients were included in each group. The NAC-GS group demonstrated significantly longer OS than the UFS group (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25-0.90; P = 0.023). Among resected cases, NAC-GS was associated with improved OS (HR, 0.42; 95% CI, 0.20-0.90; P = 0.026). Pathologically, the NAC-GS group showed significantly lower lymph node stage and less lymphatic invasion. Pathological complete response was observed in 4.0% of NAC-GS patients. DISCUSSION: Neoadjuvant chemotherapy with GS was associated with prolonged survival in resectable PDAC, potentially through lymphatic spread suppression. Pathological complete response was rare but may represent a clinically meaningful benefit of neoadjuvant treatment in selected patients.

BACKGROUND AND PURPOSE: The peritoneal cavity constitutes a unique immune microenvironment that critically influences the pathobiology of peritoneal metastasis (PM). This study aimed to clarify the mechanisms by which local immune alterations affect the efficacy of intraperitoneal (IP) chemotherapy for PM from gastric cancer (GC). METHOD: Peritoneal lavage or ascitic fluid was obtained from 42 patients with GC and PM treated with IP paclitaxel (PTX) in combination with systemic oxaliplatin and oral S-1. Serial samples from 31 patients were analyzed after 1-3 cycles of chemotherapy. Immune cell subsets were evaluated using multicolor flow cytometry with monoclonal antibodies, and the functional properties of peritoneal eosinophils were assessed using gene expression profiling and cytotoxicity assays. RESULTS: IP chemotherapy was associated with decreased CD4(+) T cells and increased CD11b(+) myeloid cells. Notably, many patients, particularly those with negative cytology (CY0), exhibited striking recruitment of CD66b(+) CD16(-) CD193(+) Siglec-F(+) eosinophils into the peritoneal cavity. Eosinophil expansion was correlated with improved clinical outcomes. Post-treatment eosinophils displayed an activated, partially degranulated phenotype with elevated CD11b and CD63 expression and distinct messenger RNA signatures compared with circulating eosinophils. Peritoneal eosinophils demonstrated the ability to induce apoptosis in GC cells. CONCLUSION: IP PTX promotes the recruitment and activation of eosinophils with potent antitumor activity in the peritoneal cavity. Early post-treatment abdominal eosinophilia is a robust prognostic biomarker and may represent a promising therapeutic target to enhance the efficacy of IP chemotherapy in patients with PM from GC.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. While curative resection offers the best chance for long-term survival, the high postoperative recurrence rate suggests a persistent need for effective perioperative therapies. We investigated a multimodal approach, combining sequential lenvatinib with transarterial chemoembolization (TACE), as a presurgical treatment (PST) for resectable HCC. METHODS: This retrospective study included 19 patients with technically resectable HCC who underwent the PST protocol followed by surgery between March 2022 and September 2024. The protocol involved four phases: Pre-TACE lenvatinib administration (Pre-LEN), TACE, Post-TACE lenvatinib administration, and surgery. We assessed the feasibility, safety, and pathological response of the protocol. Liver function was evaluated using the albumin-bilirubin (ALBI) score, modified ALBI (mALBI) grade, and tumor response was assessed using the Response Evaluation Criteria in Cancer of the Liver (RECICL). RESULTS: The PST protocol demonstrated high efficacy and safety. The median tumor reduction rate was 22.9%, and the median pathological tumor necrosis rate was 95%. The preoperative overall RECICL response was a complete response in 84.2% of patients. With a median follow-up of 22 months, the 2-year recurrence-free survival rate was 84.6%, and the overall survival rate was 100%. A significant association was found between mALBI grade and the decision to proceed with surgery at two time points: Pre-LEN (p = 0.023) and before surgery (p = 0.006). CONCLUSION: Presurgical sequential lenvatinib-TACE therapy is a feasible and safe strategy for resectable HCC. This protocol achieved a high pathological response and favorable survival outcomes, suggesting that it may mitigate the risk of early recurrence. Our findings highlight the importance of mALBI grade monitoring for patient selection and provide a rationale for larger, prospective studies.

PURPOSE: There is limited awareness of work-related musculoskeletal disorders (MSDs) in Japan, despite the high ergonomic risks for surgeons. We conducted this study to investigate the prevalence, characteristics, and impact of MSDs on Japanese general surgeons. METHODS: An electronic survey of 136 general surgeons at a Japanese university hospital network used a modified Nordic Musculoskeletal Questionnaire to assess demographics, work factors, MSD symptoms, psychological distress, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and their impact. RESULTS: Based on a 56.6% response rate, we found a high prevalence of chronic (37.7%) and acute (51.9%) MSDs. These disorders frequently impacted surgeons' work (30.0%) and daily life (39.0%), leading to time off (5.2%) and medical intervention (28.6%). Both MSD types correlated significantly with the use of NSAIDs and psychological distress. Notably, neck pain was strongly associated with the use of NSAIDs. The proportion of minimally invasive surgical procedures performed each week was associated significantly with acute, but not chronic, MSDs. CONCLUSIONS: MSDs are highly prevalent among Japanese surgeons, impacting their physical and psychological health. The high symptom prevalence and the strong association between neck pain and NSAID reliance underscore the urgent need for ergonomic interventions and preventive strategies in surgical practice to protect this essential workforce.

BACKGROUND: Perihilar cholangiocarcinoma with large hepatic resection is associated with high risk for morbidity and mortality. To improve outcomes, assessment of remnant liver function is crucial. METHODS: A total of 70 patients with perihilar cholangiocarcinoma were examined retrospectively. Liver function was evaluated <1 month preoperatively by hepatic clearance of remnant liver using 99mTc-galactosyl serum albumin (GAS) scintigraphy and computed tomography, and clinicopathological data and outcomes were analyzed in comparison GSA scintigraphy with liver function test based on computed tomography volumetry. RESULTS: There was no postoperative 90-day mortality, with 10 patients of posthepatectomy liver failure (PHLF) Grade A, 10 of Grade B, and 1 of Grade C. Area under the curve of receiver operating curve showed better prediction power for PHLF compared to remnant liver volume/body surface area or future liver remnant/body weight, especially in patients with incomplete change of liver function. In univariable analysis, <150 ml/min ml/min cutoff of hepatic clearance of remnant liver and >1750 ml intra-operative blood loss were significant risk factors for PHLF. In multivariable analysis, <150 ml/min cutoff was a significant risk factor for PHLF. The area under the curve of hepatic clearance of remnant liver indicated better predictivity in patients with incomplete change of liver function compared with complete change of liver function. CONCLUSIONS: The hepatic clearance of remnant liver may have predictive power in patients with incomplete changes in liver function compared to computed tomography-based methods. Preoperative measurement of hepatic clearance of remnant liver may assist in risk stratification for surgical management.

BACKGROUND: Abdominal binders are widely used to manage postoperative pain and improve mobility, but their clinical efficacy remains uncertain. Despite potential benefits, current guidelines do not recommend routine use due to insufficient high-quality evidence. The aim was to assess the efficacy and safety of abdominal binder after abdominal surgery. METHODS: We performed a random-effect meta-analysis to compare patients' clinical outcomes including postoperative pain, 6-min walk test, and surgical site infection in patients with or without abdominal binder after abdominal surgery. MEDLINE, Embase, CENTRAL, WHO-ICTRP, and ClinicalTrials.gov databases were searched from inception to December 2024. We used GRADE to evaluate the certainty. RESULTS: A total of 27 RCTs with 2741 participants. On postoperative day 1, abdominal binder reduced postoperative pain (21 RCTs: standard mean difference [SMD] ​= ​-0.66 [-1.12 to -0.19], moderate evidential certainty) and improved 6-min walk (5 RCTs: MD ​= ​8.9 ​m [4.72-13.01], high evidential certainty). On postoperative day 7, abdominal binder reduced postoperative pain (4 RCTs: SMD ​= ​-0.95 [-1.20 to -0.70], moderate evidential certainty) and increased 6-min walk (2 RCTs: MD ​= ​41.8m [27.1-56.5], moderate evidential certainty). Patients with abdominal binder had less surgical site infection (7 RCTs: risk difference ​= ​-0.08 [-0.12 to -0.04], moderate evidential certainty). CONCLUSIONS: This systematic review and meta-analysis suggested that abdominal binders improved postoperative pain, physical activities, and surgical site infection compared to non-abdominal binders. Based on these findings, patients, surgeons, and healthcare providers should consider recommending use of abdominal binders for patients recovering from abdominal surgery.

BACKGROUND: The usefulness of subcutaneous immunoglobulin (SCIG) for the treatment of hypogammaglobulinemia has been reported, but there are no reports in the field of pediatric liver transplantation (LT). We herein report the therapeutic efficacy of SCIG in the postoperative management after pediatric living donor LT (LDLT). METHODS: Subjects were 112 pediatric recipients who underwent LDLT between March 2012 and December 2021. SCIG administration was started in February 2017 and performed in 43 patients with hypogammaglobulinemia (< 870 mg/dL). Intravenous immunoglobulin (IVIG) administration was performed in 69 patients before January 2017. SCIG was administered subcutaneously at 130 (82-238) mg/kg/dose every week from postoperative day (POD) 2 until discharge. RESULTS: The preoperative serum IgG level in the SCIG group was 906 (249-1987) mg/dL, and the IgG level at the end of LDLT was 491 (246-823) mg/dL, showing a significant difference (p < 0.001). The median IgG levels in the SCIG group after LT were 697, 607, 579, 691, 665, and 795 mg/dL at 1, 2, 3, 4, and 5 weeks after surgery and after discharge, respectively. The incidence of bacteremia was significantly lower in the SCIG group than in the IVIG group (p = 0.025). The recipient's survival rate was not significantly different between the SCIG and IVIG groups (p = 0.080), but the recipient's survival rate in the SCIG group was 100%. The multivariate analysis revealed that the IVIG group and CMV viremia were a significant risk factors for bacteremia (p = 0.023 and 0.001, respectively). CONCLUSIONS: Postoperative SCIG administration effectively maintained serum IgG levels and was useful for preventing bacteremia.

BACKGROUND: The aim of this study was to elucidate the association of pancreatic fluid cytology with intrapancreatic recurrence of intraductal papillary mucinous neoplasms (IPMNs). MATERIALS AND METHODS: A total of 68 patients with IPMN who underwent pancreatectomy and obtained cytologic analysis of pancreatic fluid at Jichi Medical University Hospital were included in this study. Computed tomography scan and magnetic resonance cholangiopancreatography were performed preoperatively. Endoscopic retrograde cholangiopancreatography was used to obtain pancreatic fluid. The association of recurrence with variables was determined by logistic regression multivariate analysis. RESULTS: Class V cytology was found in 7/68 patients preoperatively. Metachronous intrapancreatic recurrences occurred in 6/68 patients, including one branched type, main pancreatic duct type in two and mixed pancreatic duct type in three. Four of seven patients with class V cytology developed intra-pancreatic recurrences as a new lesion. Class V cytology was significantly associated with intrapancreatic recurrence, compared to those with class IV or lower cytology. In univariate analysis, patients with pathological findings with high-grade dysplasia or adenocarcinoma (P = 0.0392, odds ratio (OR) 10.2, 95 % confidence interval (CI) 1.12-93.6) and class V pancreatic fluid cytology (P = 0.0005, OR 38.7, 95 % CI 4.94-302) were significant risk factors. In multivariate analysis, class V pancreatic fluid cytology was significantly associated with developing intrapancreatic recurrence (P = 0.0149, OR 22.7, 95 % CI 1.83-279). CONCLUSION: Preoperative class V pancreatic fluid cytology is associated with intra-pancreatic recurrence after resection of IPMN.

BACKGROUND: Patients with advanced gastric cancer (GC) with peritoneal involvement have a dismal prognosis. Recent clinical trials have shown that anti-Claudin18.2 (CLDN18.2) antibody (zolbetuximab) enhances survival in patients with GC expressing high levels of CLDN18.2. However, the effectiveness of the zolbetuximab in patients with peritoneal metastases (PMs) remains unclear. In this study, we aimed to evaluate the expression of CLDN18.2 in disseminated lesions to assess the clinical utility of zolbetuximab in the treatment of GC with PM. METHODS: In 42 patients diagnosed with stage IV GC with PM, biopsy samples from the primary tumors and peritoneal metastatic nodules were collected and immunostained using the specific antibody (43-14A, Ventana). The expression of CLDN18.2 was comparatively evaluated based on staining intensity and the proportion of positive cells. RESULTS: Positive immunoreactivity of CLDN18.2 was observed in 37 (88%) of the primary tumors. Specifically, CLDN18.2 positivity was identified in 26 (62%) or 12 (29%) patients based on moderate to strong membrane staining in at least 40% or 75% of tumor cells, respectively. In comparison, the staining intensity in tumor cells was consistently reduced in PM across all patients. CLDN18.2 expression was absent in PM of 29 (69%) patients, while 3 (7.1%) cases were determined to be CLDN18.2-positive based on a cutoff value of 40% for high staining. This trend was particularly pronounced in cases with undifferentiated type and human epidermal growth factor receptor 2 (HER-2) negative primary tumors. CONCLUSIONS: Although CLDN18.2 expression in PM mirrored that in primary lesions, the levels were generally reduced. When zolbetuximab is used for GC patients with peritoneal involvement, it is preferable to assess the expression of CLDN18.2 in the disseminated lesions.

INTRODUCTION: Acinar cell carcinomas are rare pancreatic neoplasms, accounting for approximately 1% of all exocrine pancreatic tumors. We describe a case of a cystic variant with intracystic hemorrhaging that was difficult to differentiate from a pseudocyst due to its morphology. CASE PRESENTATION: A 54-year-old man was admitted with severe left upper quadrant abdominal pain. Imaging studies showed a 7.0-cm internal heterogeneous cystic lesion with a splenic artery pseudoaneurysm near the lesion. Transarterial embolization of the splenic artery was performed, but rebleeding occurred 1 month later. Distal pancreatectomy with partial resection of the stomach revealed internal nodular lesions on the resected specimen. Microscopically, the cystic mass was composed of neoplastic tissue with papillary and tubular structures. The tumor was diagnosed as acinar cell carcinoma since immunohistochemical examination showed tumor cells positive for BCL10, lipase, and trypsin. The patient experienced local recurrence 6 months postoperatively, received chemotherapy with gemcitabine followed by S-1, underwent a 2nd resection at 18 months, and has remained recurrence-free for 15 years. CONCLUSIONS: Acinar cell carcinoma rarely presents with a cystic structure and may be accompanied by a pseudoaneurysm, which can complicate differentiation from a pancreatic pseudocyst, highlighting the importance of careful differential diagnosis for appropriate treatment.

BACKGROUND: This study aimed to elucidate the clinical impact of osteopenia on the recurrence of colon cancer liver metastases. METHODS: Patients with colon cancer liver metastases (N = 186) undergoing hepatectomy at Jichi Medical University Hospital between March 2006 and March 2020 were examined retrospectively. Computed tomography (CT) scans on the 11th vertebra within 3 months of surgery assessed bone mineral density (BMD). Age-adjusted BMD determined osteopenia presence. Kaplan-Meier method with a log-rank test estimated survival. Factors associated with survival were assessed using Cox's proportional hazards model after adjustment for confounders. RESULTS: Patients with osteopenia had shorter overall (p = 0.0001; 5-year overall survival, 51.8% vs 81.8%) and recurrence-free survival (p = 0.0008, 5-year recurrence-free survival: 26.3% vs 51.5%) than BMD-normal patients. In multivariable analysis, the risk factor for overall survival was osteopenia (Hazard ratio (HR) 3.79, 95% confidence interval (CI) 2.09-6.87, p = 0.001). Risk factors for recurrence were chemotherapy (HR 1.92, 95%CI 1.12-3.30, p = 0.002), tumor number (HR 1.51, 95%CI 1.02-2.27, p = 0.04), and osteopenia (HR 2.18, 95%CI 1.46-3.24 p = 0.001). Patients with osteopenia are more likely to develop lung metastases, and BMD-value reduction associated with KRAS mutation. CONCLUSION: Osteopenia may have prognostic significance in patients with liver metastases colorectal cancer.

INTRODUCTION: Neoadjuvant gemcitabine plus S-1 (GS) therapy for resectable pancreatic cancer has been shown to prolong overall survival significantly compared with upfront surgery. Herein, we report two opposite cases of patients with resectable pancreatic cancer who underwent distal pancreatectomy after neoadjuvant GS therapy. CASE PRESENTATION: In Case 1, a 49-year-old female with a 12 mm tumor in the pancreatic body (cT1N0M0, cStage IA, union for international cancer control [UICC] 8th edition) underwent two courses of neoadjuvant GS therapy followed by an open distal pancreatectomy. Pathological examination revealed no residual cancer and the patient was diagnosed with a pathological complete response (pCR) without recurrence 31 months after surgery. However, in Case 2, a 74-year-old male with a 12 mm tumor in the pancreatic body (cT1N0M0, cStage IA, UICC 8th edition) also underwent two courses of neoadjuvant GS therapy, and then a laparoscopic distal pancreatectomy was performed. Pathological examination showed invasive pancreatic ductal adenocarcinoma with a 20 mm tumor. The tumor exhibited invasion into the lumen of the splenic vein and retroperitoneal tissue (ypT1N0M0, ypStage IA, UICC 8th edition). Adjuvant chemotherapy with S-1 was started, but 4 months postoperatively, a significant rise in serum CA19-9 levels was observed with multiple hepatic metastases and portal venous tumor thrombus. Gemcitabine plus nab-paclitaxel (GnP) therapy was started, however, the tumor progressed rapidly. The patient died 6 months after surgery. CONCLUSIONS: Neoadjuvant GS therapy is potentially expected to have a significant therapeutic effect as the pCR. Nevertheless, even after surgical resection, some patients still exhibit extremely poor prognosis. Therefore, it is necessary to clarify their clinical characteristics.

INTRODUCTION: When a thrombus extends to the suprahepatic inferior vena cava (IVC) in patients with Budd-Chiari syndrome (BCS) requiring liver transplantation (LT), there is a risk of thrombus migration during hepatectomy that can potentially lead to pulmonary embolism. Intraoperative pulmonary embolism can be life-threatening and may necessitate urgent thrombectomy. However, preventive strategies for pulmonary embolism during LT in BCS cases with IVC thrombosis have seldom been discussed in the literature. We report a case involving a 51-year-old woman with BCS complicated by thrombi extending into the suprahepatic IVC who underwent deceased donor LT (DDLT) for acute liver failure (ALF). CASE PRESENTATION: A previously healthy 51-year-old woman with ALF secondary to BCS was admitted to our hospital. 19 days back, BCS was diagnosed at another hospital, where computed tomography revealed thrombi in the hepatic veins and IVC. She subsequently developed grade II hepatic encephalopathy and severe liver dysfunction. Conservative treatment was ineffective, and 4 days before the current admission, she experienced grade III hepatic encephalopathy and showed hepatofugal portal flow on ultrasonography. DDLT was performed on day 13 after admission. Median sternotomy was performed to clamp the suprahepatic IVC near the right atrium, mitigating the risk of thrombus migration during hepatectomy and allowing for urgent thrombectomy in case of pulmonary embolism. Additionally, because a large-for-size graft was being used, the median sternotomy enhanced visibility and provided adequate space, facilitating suprahepatic IVC anastomosis. Postoperatively, the patient experienced no complications related to the sternotomy and was discharged 58 days after surgery. CONCLUSIONS: This case report highlights the potential utility of median sternotomy during LT for BCS, particularly for cases with concerns regarding thrombus migration from the suprahepatic IVC, the need for rapid thrombectomy in the event of pulmonary embolism, and anticipated challenges in suprahepatic IVC anastomosis due to large-for-size grafts.

Portal cavernoma cholangiopathy (PCC) is a complex condition associated with portal hypertension, particularly in patients with extrahepatic portal vein obstruction (EHPVO). Herein, we present a case of liver failure with PCC in a 55-year-old male successfully treated with living-donor liver transplantation (LDLT). The patient had a history of gastrointestinal bleeding and recurrence of cholangitis. Imaging studies confirmed cavernous transformation and pericholedochal varices. Preoperative angiography verified hepatopetal flow in the pericholedochal varix, which facilitated successful anastomosis with the donor's portal vein during LDLT. Histological examination of the explanted liver confirmed vanishing bile duct syndrome (VBDS) and secondary bile stasis was considered to have caused liver failure. No postoperative complications were observed within 13 months of LDLT. We report the first case of VBDS in the PCC resulting from EHPVO that was successfully managed with LDLT. Careful management of similar cases should involve angiography and long-term postoperative monitoring of portal vein complications.

BACKGROUND: Globally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk. Mesenchymal stem cells-conditioned medium (MSC-CM) is considered a rich source of paracrine factors that can repair tissues and restore function of damaged organs. Meanwhile, hydrogels have been widely recognized to load MSC secretome and achieve sustained release. This study aimed to evaluate the therapeutic effect of hydrogel-encapsulated MSC-CM on liver regeneration following partial hepatectomy (PHx) in a rodent model of diet-induced hepatic steatosis. METHODS: Male Lewis rats were fed with a methionine and choline-deficient diet. After 3 weeks of feeding, PHx was performed and rats were randomly allocated into two groups that received hydrogel-encapsulated MSC-CM or vehicle via the intra-mesenteric space of the superior mesenteric vein (SMV). RESULTS: The regeneration of the remnant liver at 30 and 168 h after PHx was significantly accelerated, and the expressions of proliferating cell nuclear antigen were significantly enhanced in the MSC-CM group. MSC-CM treatment significantly increased hepatic ATP and β-hydroxybutyrate content at 168 h after PHx, indicating that MSC-CM fosters regeneration not only in volume but also in functionality. The number of each TUNEL- and cleaved caspase-3 positive nuclei in hepatocytes at 9 h after PHx were significantly decreased in the MSC-CM group, suggesting that MSC-CM suppressed apoptosis. MSC-CM increased serum immunoregulatory cytokine interleukin-10 and interleukin-13 at 30 h after PHx. Additionally, mitotic figures and cyclin D1 expression decreased and hepatocyte size increased in the MSC-CM group, implying that this mode of regeneration was mainly through cell hypertrophy rather than cell division. CONCLUSIONS: MSC-CM represents a novel therapeutic approach for patients with MASLD requiring PHx.

INTRODUCTION: Hepatic resection (HR) and radiofrequency ablation (RFA) are curative treatments for three or fewer hepatocellular carcinomas in Japan. The laparoscopic approach in both has been used in recent years; however, its treatment outcome in combination with HR with RFA is unclear. We aimed to gain insights into this combined treatment. CASE PRESENTATION: This was a retrospective study of nine patients with two to three hepatocellular carcinomas who had undergone laparoscopic HR combined with laparoscopic RFA between December 2014 and February 2022. Six patients tested positive for hepatitis C virus, two had alcoholic cirrhosis, and one had non-alcoholic steatohepatitis. All patients had a Child-Pugh score of 5 (A). All 22 lesions were treated as planned. Laparoscopic HR was performed on 12 and laparoscopic RFA was performed on 10 lesions. Postoperative hemorrhage occurred in one patient and was managed conservatively. The remaining eight patients were discharged without complications. Recurrence occurred in the residual liver in eight patients. However, no local recurrence at the treatment site was noted during the observation period (15-94 months). CONCLUSION: The treatment combining laparoscopic HR and RFA was feasible for the local control of two to three HCCs and may be useful for preserving residual liver function.

A 50-year-old man was diagnosed with type 1 autoimmune pancreatitis (AIP) following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and a histopathological examination. After six months of untreated follow-up, the serum IgG4 level decreased, and the diffuse pancreatic enlargement improved; however, a pancreatic head mass became apparent. EUS-FNA of this mass revealed pancreatic ductal adenocarcinoma (PDAC) with IgG4-positive plasma cells. In addition, the resected specimen revealed PDAC, without any features of AIP. After pancreatoduodenectomy, AIP did not recur. The development of AIP in this case could be related to paraneoplastic syndrome.

This study explores a novel therapeutic approach for peritoneal metastasis (PM) using AAV-mediated delivery of tumor suppressor microRNA-29b (miR-29b) to peritoneal mesothelial cells (PMC). AAV serotypes 2 and DJ demonstrate high transduction efficiency for human and murine PMC, respectively. In vitro analysis indicates that AAV vectors encoding miR-29b precursor successfully elevate miR-29b expression in PMC and their secreted small extracellular vesicle (sEV), thereby inhibiting mesothelial mesenchymal transition and reducing subsequent attachment of tumor cells. A single intraperitoneal (IP) administration of AAV-DJ-miR-29b demonstrates robust and sustained transgene expression, suppressing peritoneal fibrosis and inhibiting the development of PM from gastric and pancreatic cancers. Additionally, AAV-DJ-miR-29b enhances the efficacy of IP chemotherapy using paclitaxel, restraining the growth of established PM. While conventional gene therapy for cancer encounters challenges targeting tumor cells directly but delivering miRNA to the tumor stroma offers a straightforward and efficient means of altering the microenvironment, leading to substantial inhibition of tumor growth. AAV-mediated miR-29b delivery to peritoneum via IP route presents a simple, minimally invasive, and promising therapeutic strategy for refractory PM.

Despite advances in systemic chemotherapy, patients with gastric cancer (GC) and peritoneal metastases (PMs) continue to have poor prognoses. Intraperitoneal (IP) administration of Paclitaxel (PTX) combined with systemic chemotherapy shows promise in treating PMs from GC. However, methods of drug administration need to be optimized to maximize efficacy. In this study, we utilized a mouse model with PMs derived from a human GC cell line, administering PTX either IP or intravenously (IV), and Carboplatin (CBDCA) IV 0, 1, and 4 days after PTX administration. The PMs were resected 30 min later, and concentrations of PTX and CBDCA in resected tumors were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results indicated that PTX concentrations were higher with IP administration than with IV administration, with significant differences observed on days 0 and 1. CBDCA concentrations 4 days post-IP PTX administration were higher than with simultaneous IV PTX administration. These findings suggest that IP PTX administration enhances CBDCA concentration in peritoneal tumors. Therefore, sequential IV administration of anti-cancer drugs appears more effective than simultaneous administration with IP PTX, a strategy that may improve prognoses for patients with PMs.

PURPOSE: Low anterior resection syndrome (LARS) causes devastating symptoms and impairs the quality of life (QOL). This study investigated the incidence and risk factors of LARS and their association with the QOL in patients with lower rectal tumors. METHODS: Patients who underwent anus-preserving surgery for lower rectal tumors between 2014 and 2019 and who had anal defecation between 2020 and 2021 were surveyed. The LARS score measured severity, and the QOL was evaluated using the Japanese version of the Fecal Incontinence Quality-of-Life Scale (JFIQL). The primary endpoint was the incidence of Major LARS, and the secondary endpoints were risk factors and association with the JFIQL. RESULTS: Of 107 eligible patients, 82 (76.6%) completed the LARS survey. The incidence of Major LARS was 48%. Independent risk factors included neoadjuvant chemoradiotherapy (CRT) and a short interval (< 24 months after surgery; odds ratio, 4.6; 95% confidence interval: 1.1-19, both). The LARS score was moderately correlated with the JFIQL generic score (correlation coefficient: - 0.54). The JFIQL scores were significantly worse in the Minor and Major LARS groups than in the No LARS group. CONCLUSIONS: Major LARS was found in 48% of lower rectal tumors, and independent risk factors include neoadjuvant CRT and a short interval. The QOL was significantly impaired in patients with both Minor and Major LARS.