Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide, characterized by late diagnosis, rapid progression and resistance to conventional therapies. Cancer‑associated fibroblast (CAF)‑derived extracellular vesicles (EVs) contribute to PDAC progression, but their downstream molecular effectors remain unclear. In the present study, it was demonstrated that CAF‑derived EVs enhanced the proliferative, migratory and invasive capacity of PDAC cells across two independent cell lines, as assessed by Cell Counting Kit‑8 assays and Transwell migration and Matrigel invasion assays. RAP1B was identified as a prominently upregulated protein by label‑free proteomic profiling following EV exposure. High RAP1B expression, evaluated by immunohistochemistry, in a cohort of 77 resected PDAC specimens tended to be more frequent with advancing pathological stage and was associated with poorer overall survival. RAP1B knockdown using small interfering RNA suppressed proliferation and motility in PDAC cells and induced cytokinesis failure characterized by multinucleation and cytoskeletal abnormalities, as demonstrated by time‑lapse imaging and immunofluorescence staining. Proteomic profiling of RAP1B‑knockdown cells identified anillin (ANLN) as a downstream mediator; ANLN knockdown recapitulated these cytokinetic defects, whereas ANLN knockdown did not reciprocally affect RAP1B levels, establishing a unidirectional RAP1B/ANLN axis. Furthermore, RAP1B depletion sensitized PDAC cells to gemcitabine, showing additive growth inhibition. In conclusion, CAF‑derived EVs mediate PDAC progression via the RAP1B/ANLN axis, representing a novel and promising therapeutic target in PDAC.

BACKGROUND:Laparoscopic hepatectomy (Lap-H) is increasingly being performed in Japan, but the high cost and handling complexity of laparoscopic ultrasonographic (US) probes remain a barrier to its wider adoption. Intraoperative ultrasonography is essential for safe liver resection; however, specialized laparoscopic probes are expensive, have a limited field of view, and are difficult to manipulate. METHODS:To overcome these limitations, we developed a practical technique using an open-surgery-type microconvex US probe in Lap-H. The probe is inserted via an umbilical incision using a Lap Protector mini™ and EZ Access™, and probe manipulation is achieved through a cord-based control system. We applied this method in over 150 Lap-H cases before the introduction of a dedicated laparoscopic US system. RESULTS:This technique enabled the acquisition of axial and sagittal images with a wide and deep field of view, enhancing anatomical orientation and lesion visualization. There were no complications such as air leaks or equipment failure. The method allowed for the use of contrast-enhanced ultrasound and minimized interference with the operative field. CONCLUSIONS:The use of open-surgery-type US probes in Lap-H offers a cost-effective, safe, and practical alternative to expensive laparoscopic US systems. This innovation may lower the barrier for institutions initiating Lap-H programs and promote the broader adoption of high-quality intraoperative ultrasonography in minimally invasive liver surgery.

BACKGROUND Early postoperative edema and ascites after liver resection are common; however, the endocrine drivers of water retention are not fully defined. Arginine vasopressin (AVP) promotes antidiuresis via V2-mediated aquaporin trafficking, whereas the renin-angiotensin-aldosterone system primarily modulates sodium handling. Differences in postoperative trajectories and their relationship to early fluid retention have not been clarified in patients undergoing liver resection. AIM To examine postoperative changes in plasma AVP and plasma aldosterone concentration (PAC) after liver resection, and association with fluid retention. METHODS We conducted a prospective cohort study of adults undergoing elective liver resection at a tertiary center. Blood samples were collected preoperatively, immediately post-resection, and on postoperative days (POD) 1, 2, 3, and 5. The primary objective was characterizing postoperative dynamics of AVP and PAC. Secondary objectives evaluated their temporal alignment with early fluid retention (body weight, urine output during POD 1-3) and compared hormonal profiles between major and minor resections. Analyses used trajectory and time-based comparisons by resection extent. RESULTS AVP increased sharply immediately after resection and remained above the preoperative baseline through POD 3, showing the most pronounced and sustained elevation after major liver resection. In contrast, PAC showed a transient postoperative increase that returned to near-baseline levels by POD 2. The period of elevated AVP closely matched the time frame during which early postoperative fluid retention was most evident, as indicated by greater short-term weight gain and reduced urine output. These patterns were consistent across sensitivity analyses and showed similar directional trends in subgroup comparisons based on resection extent. CONCLUSION AVP remains elevated longer than aldosterone and coincides with early fluid retention, particularly after major resection. Vasopressin-driven antidiuresis may be important in postoperative water retention.

BACKGROUND Postoperative pancreatic fistula (POPF) is a major complication of distal pancreatectomy (DP). Although anatomical and surgical risk factors are known, the relationship between preoperative pancreatic exocrine function and POPF remains unclear. Plasma apolipoprotein A2 isoforms (apoA2-i) hold promise as potential biomarkers of pancreatic exocrine function. AIM To examine the association between incidence of POPF following DP and preoperative apoA2-i. METHODS This retrospective cohort study included 51 patients who underwent DP at Nippon Medical School Hospital between November 2021 and December 2024. Preoperative plasma apoA2-i (ATQ/ATQ and AT/AT) levels were measured using an enzyme-linked immunosorbent assay. The primary outcome was the occurrence of POPF, classified as grade BL or grade B/C according to the 2016 International Study Group of Pancreatic Surgery criteria. RESULTS Preoperative apoA2-AT/AT levels were significantly higher in patients who developed POPF (n = 30) than in those who did not (n = 21) (P < 0.001). Receiver operating characteristic curve analysis yielded an area under the curve of 0.802 [95% confidence interval (CI): 0.681-0.924] for predicting POPF. The optimal cutoff value calculated by Youden's index was 58.17 mu g/mL. Plasma apoA2-AT/AT levels >= 58.17 mu g/mL were significantly associated with POPF (P < 0.001) and remained an independent risk factor for POPF following DP in both univariate (odds ratio = 55.7; 95%CI: 6.58-7319.4; P < 0.001) and multivariate (odds ratio = 163.9; 95%CI: 10.50-35710.29; P < 0.001) logistic regression analyses. CONCLUSION Preoperative measurement of apoA2-i may serve as a useful predictor of POPF following DP. These findings support its use for preoperative risk stratification and individualized perioperative management.

BACKGROUND:Repeated application of the Pringle maneuver is a key obstacle to safe minimally invasive repeat liver resection (MISRLR). However, limited technical guidance is available. AIM:To study the utility of newly developed Pringle taping method guided by liver surface in MISRLR. METHODS:We retrospectively reviewed 72 cases of MISRLR performed by a single surgeon at two centers from August 2015 to July 2024. Beginning in October 2019, a liver surface-guided encirclement of hepatoduodenal ligament (LSEH) was used for repeat Pringle taping. Perioperative outcomes including Pringle taping success, operative time, blood loss, conversion rate, morbidity, and mortality were assessed. RESULTS:Laparoscopic and robotic approaches were used in 63 patients and 9 patients, respectively. The median operative time, blood loss, and hospital stay were 331.5 minutes, 70 mL, and 8 days, respectively. Open conversion occurred in two cases (2.8%) due to severe adhesions and right renal vein injury. Clavien-Dindo grade ≥ III complications occurred in 5.6% of cases with no mortality. Anti-adhesion barriers were used in 54 patients (75.0%). LSEH was attempted in 57 cases, improving Pringle taping success from 33.0% to 91.4% (P < 0.001). LSEH succeeded in all patients with prior open liver resection (n = 11). Among 6 patients in whom LSEH failed, 3 patients (50.0%) had undergone a third liver resection, and 1 patient had a history of distal gastrectomy with choledochoduodenostomy. CONCLUSION:The newly developed LSEH technique for Pringle taping in MISRLR was feasible, enhancing safety and reproducibility even in patients with a history of open liver resection.

Background:Development of new-onset steatotic liver disease (SLD) has been increasingly observed after pancreatectomy. However, the pathophysiology of post-operative SLD remains poorly understood. This study aimed to clarify the risk factors for new-onset SLD after pancreatectomy and verify the utility of monitoring plasma apolipoprotein A2-isoforms (apoA2-i) as a potentially promising biomarker for evaluating pancreatic exocrine function. Methods:In this retrospective study of 79 patients who underwent pancreatectomy [47 pancreaticoduodenectomies (PDs) and 32 distal pancreatectomies (DPs)] between March 2021 and March 2024, the plasma apoA2-i (AT/AT and ATQ/ATQ) levels were measured using enzyme-linked immunosorbent assay (ELISA) methods, and non-contrast-enhanced computed tomography (CT) images were manually reviewed for the diagnosis of SLD. Results:Comparing the minimum value of apoA2-AT/AT after surgery between the SLD (n=32) and non-SLD group (n=47), the apoA2-AT/AT value in the SLD group was significantly lower than that in the non-SLD group (P<0.001). The plasma apoA2-AT/AT levels <9.58 µg/mL (median of this cohort) was significantly associated with SLD (P<0.001) and an independent risk factor of SLD with both univariable [odds ratio (OR), 20.1; 95% confidence interval (CI): 6.59-74.5; P<0.001] and multivariable (OR, 13.6; 95% CI: 2.68-134.2; P=0.001) logistic regression analysis. Moreover, even when stratified by pre-onset pancrelipase administration, the cumulative incidence of SLD was significantly higher in patients with plasma apoA2-AT/AT levels <9.58 µg/mL (P<0.001). The point estimate of the area under the curve for detecting SLD of apoA2-AT/AT was 0.843. Conclusions:SLD associated with malnutrition following pancreatectomy can be predicted using plasma apoA2-i monitoring.

BACKGROUND In Japan, primary hepatocellular carcinoma (HCC) often develops in the setting of chronic hepatitis, such as persistent hepatitis B virus (HBV) or hepatitis C virus infection. Patients with HCC are commonly in their 50s or 60s, and the occurrence of HCC in individuals in their 40s or younger is extremely rare. The adolescent and young adult (AYA) population refers to individuals aged 15-39 years. Patients with cancer in the AYA population may present distinct clinical features and biological characteristics. AIM To evaluate the outcomes of hepatic resection for AYA patients with HCC at our institution. METHODS We retrospectively analyzed 885 patients who underwent hepatectomy at our institution between 1994 and 2024. Patients were categorized into two groups: the AYA group and the non-AYA group. Patient demographics, operative details, perioperative outcomes, pathological features, clinicopathological findings, overall survival (OS), and recurrence-free survival (RFS) were compared between the groups. RESULTS Nine patients (5 males and 4 females) were younger than 40 years. The incidence of AYA HCC was 1.0%. Six patients had a history of hepatitis B. The percentage of HBV-positive patients was significantly greater in the AYA group than in the non-AYA group, and the tumor diameter was significantly greater in the AYA group. There were no significant differences in tumor marker levels, vascular invasion, differentiation, OS rate, or RFS rate between the AYA and non-AYA groups. CONCLUSION The outcomes of hepatic resection for AYA patients with HCC are favorable. Early detection of AYA HCC and timely hepatectomy are recommended.

BACKGROUND:Refractory ascites severely impairs quality of life in patients with liver cirrhosis (LC) and cancer-related peritonitis. For individuals who are intolerant to medical therapy and require frequent large-volume paracentesis, a peritoneovenous shunt (PVS) offers a potential treatment option. However, PVS placement is associated with high complication rates, perioperative mortality, and lacks well-defined indications. AIM:To identify prognostic factors for PVS placement and develop a novel postoperative survival scoring model for LC with refractory ascites. METHODS:A total of 100 patients who underwent PVS placement for refractory ascites due to LC in our department between 1998 and 2024 were analyzed. Patients were stratified into two groups: Those who survived more than 180 days after PVS placement (L-group) and those who survived for less than 180 days (S-group). Prognostic factors were compared between groups, and four variables (sex, age, Child-Pugh score, and liver volume) were selected for the creation of a new scoring system. RESULTS:Significant differences between the S- and L-groups were observed for age, sex, Child-Pugh score and preoperative liver volume. Based on these variables, we developed a scoring system as follows: 1 point each for age ≥ 60 years, Child-Pugh score ≥ 10, female sex, and preoperative liver volume < 1057 mL. Patients scoring 0-2 points were classified as PVS grade A, and those scoring 3-4 points as PVS grade B. Survival analysis showed that overall survival was significantly higher in PVS grade A compared with PVS grade B. Multivariate analysis confirmed PVS grade as an independent prognostic factor. CONCLUSION:The proposed PVS scoring system may be a useful tool for predicting postoperative prognosis following PVS placement in patients with LC and refractory ascites.

Introduction: Pancreatic transection is a crucial step in pancreaticoduodenectomy for pancreatic head cancer, which often leads to concomitant pancreatitis. The aim of pancreatic transection is to dissect only the pancreatic parenchyma without damaging the common hepatic artery (CHA), splenic artery (SpA), portal vein, or splenic vein. We demonstrate that a hanging maneuver using two cotton tapes enables the safe and uniform transection of pancreatic head cancer with concomitant pancreatitis. Methods: This hanging maneuver has three steps. In the first step, the area around the SMA up to the celiac plexus must be dissected. In the second step, the CHA is dissected from beyond the bifurcation of the Celiac Axis to the SpA. The third step, involves passing two cotton tapes through the planned pancreatic cut line. These three steps make pancreatic transection safe and uniform. The hanging maneuver has been performed in 30 cases of pancreaticoduodenectomy for pancreatic head cancer with severe concomitant pancreatitis. Results: No significant differences were observed in any of the items between the hanging maneuver for concomitant pancreatitis group and the conventional pancreaticoduodenectomy without concomitant pancreatitis group. Conclusions: Pancreatic transection using the hanging maneuver is an effective and safe approach to pancreaticoduodenectomy with concomitant pancreatitis.

High blood flow and intravariceal pressure in pipeline esophageal varices (EVs) can cause refractory variceal bleeding that is difficult to control with endoscopic procedures and interventional radiology. We used combination therapy with Hassab's procedure (HP) and subsequent endoscopic variceal ligation (EVL) to successfully treat two patients with pipeline EVs.Case 1A woman in her 30s with recurrent hemorrhagic pipeline EVs caused by idiopathic portal hypertension was referred for surgery. Magnetic resonance imaging revealed a dilated left gastric vein (LGV) connected to EVs with no palisade zone. Esophagogastroduodenoscopy (EGD) identified high-risk EVs (Ls, F3, Cw, RC1) and gastric varices (GVs) (Lg-c, F2, Cw, RC0). Eradication of the esophagogastric varices was maintained 5 years after laparoscopic HP followed by EVL at 1, 6 and 16 months postoperatively.Case 2A woman in her 50s with cirrhosis (type B) and enlarged pipeline EVs was referred for prophylactic surgery. Computed tomography (CT) imaging revealed that the EVs were supplied by a dilated LGV without a palisade zone. EGD identified high-risk EVs (Lm, F3, Cb, RC2) and GVs (Lg-c, F3, Cw, RC1). Combination therapy with laparoscopic HP and EVL at 2, 4, and 6 months showed the eradication of esophagogastric varices 8 months after surgery. CT scanning performed 10 days postoperatively in case 2 revealed residual EVs supplied by gastric intramural blood flow, strongly supporting the need for additional EVL after HP. HP involves gastroesophageal devascularization and splenectomy, which reduce blood supply to EVs, facilitating subsequent EVL to eradicate pipeline EVs. This combination therapy appears to enhance outcomes and should be considered a viable option for treating refractory pipeline EVs.

Mucinous cystic neoplasms of the liver (MCNs-L) are rare cystic tumors characterized by multilocular cysts lined with a mucin-producing epithelium and supported by ovarian-like stroma. These tumors account for <5% of all cystic liver lesions and carry a potential risk of malignant transformation, necessitating early diagnosis and surgical resection. This report describes the successful laparoscopic partial liver resection of segments 4 and 5 for a large MCN-L in a woman in her 40s who presented with upper abdominal discomfort. Imaging studies revealed a multilocular cystic lesion measuring 11.9 × 8.5 × 13.0 cm in segments 4 and 5 of the liver. The primary challenges were the size of the lesion and the need to prevent cystic content spillage during surgery. Using meticulous techniques, including the use of a retrieval bag and controlled aspiration, we successfully excised the tumor laparoscopically and without contamination. Pathological analysis confirmed a diagnosis of mucinous cystic adenoma with no evidence of malignancy. The patient recovered uneventfully and was discharged on postoperative day 7. This case highlights the feasibility and safety of a laparoscopic approach for large MCNs-L. Furthermore, it underscores the importance of preoperative planning, precise surgical techniques, and measures to prevent cystic content dissemination. Minimally invasive surgery offers significant benefits, including reduced recovery time and improved cosmetic outcomes, and can be effectively applied to large hepatic cystic lesions by experienced surgical teams.

Collision tumors, characterized by the coexistence of two distinct malignancies within the same area, are extremely rare. Herein, we report a collision tumor that was difficult to diagnose preoperatively in a patient with gastric cancer and gastric-type duodenal cancer. An 82-year-old woman with a history of melena and anemia was diagnosed with progressive gastric cancer of the gastric antrum at the lesser curvature. Part of the tumor infiltrated the pyloric ring but was not detected in the duodenal bulb within the observable range. Enhanced computed tomography revealed wall thickening from the gastric antrum up to the pyloric ring, with swelling of the lesser curvature and a subpyloric lymph node. The patient underwent a distal gastrectomy and D2 lymph node dissection for gastric cancer. Pathological findings showed gastric cancer (papillary adenocarcinoma and moderately differentiated tubular adenocarcinoma) positive for mucin 5AC (MUC5AC), and duodenal cancer (solid-type poorly differentiated adenocarcinoma > non-solid-type poorly differentiated adenocarcinoma) positive for MUC5AC and mucin 6 (MUC6), with both tumors meeting at the pyloric ring. Lymph node metastasis from gastric and duodenal cancer was also detected. No previous reports of collision tumors involving both gastric-type duodenal cancer and gastric cancer exist. In patients with gastric cancer with duodenal invasion, the possibility of duodenal cancer complications and the extent of lymph node dissection should be considered.

INTRODUCTION:Hepatocellular carcinoma (HCC) presents as a hepatic mass and may involve vascular invasion or extrahepatic spread. However, intraductal growth within the intrahepatic bile duct is rare and is often associated with obstructive jaundice. HCCs confined to the intrahepatic bile duct without detectable hepatic mass or jaundice are rare, and diagnosis is often difficult due to clinical and radiological resemblance to perihilar cholangiocarcinoma. Moreover, such cases generally carry a poor prognosis. We report a rare case of HCC that developed exclusively within the intrahepatic bile ducts, without forming a detectable mass in the liver or causing jaundice. CASE PRESENTATION:A 70-year-old man presented with right hypochondriac pain. Imaging revealed dilation of the intrahepatic bile ducts in the anterior sector and intraductal filling defects, particularly in the intrahepatic bile duct branch of segment 8, without a detectable hepatic mass. Alpha-fetoprotein and Duke pancreatic monoclonal antigen type 2 levels were elevated, whereas prothrombin induced by vitamin K absence-II, carbohydrate antigen 19-9, and carcinoembryonic antigen levels were within normal limits. Perihilar cholangiocarcinoma was suspected based on imaging. Right hepatectomy with extrahepatic bile duct resection was performed after preoperative portal vein embolization. Intraoperative ultrasonography and gross examination revealed no parenchymal mass. Histopathology showed atypical hepatocyte-like cell clusters with pleomorphic nuclei proliferating within the Glisson's capsule and infiltrating the adjacent liver parenchyma in a trabecular pattern without fibrous capsule formation. Tumor infiltration into the bile duct epithelium was evident. Immunohistochemical staining was positive for HepPar1 and negative for cytokeratin 19, with a 40% Ki-67 labeling index, confirming HCC diagnosis. The patient remains recurrence-free at 2 years and 7 months postoperatively. CONCLUSIONS:This case highlights a rare presentation of HCC without a hepatic mass or jaundice, confined to the intrahepatic bile duct. Most patients present with obstructive jaundice. Only two other English-language cases have no prior history of primary HCC, no hepatic mass, no jaundice, and disease confined to the bile duct. Although bile duct-invading HCC is generally associated with poor prognosis, our case suggests that early surgical intervention may lead to favorable long-term outcomes in select patients.

Abstract Background In Japan, primary hepatocellular carcinoma (HCC) often develops against a background of chronic hepatitis, such as persistent hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with HCC are commonly in their 50s or 60s. It is extremely rare to find HCC patients in their 40s or younger. In Japan, such cases are reported to constitute only 0.23% of all cases. The adolescent and young adult (AYA) population refers to people aged 15–39 years. Patients with cancer in the AYA population may present special clinical features and biologic characteristics. In this study, we evaluated hepatic resection of AYA hepatocellular carcinoma at our facility. Materials and Methods We analyzed 978 patients who underwent hepatectomy at our institute between 1994 and 2022. We categorized the patients into two groups: the AYA group and the non-AYA group. Patient demographics, operative details, perioperative outcomes, pathologic details, clinicopathological findings, overall survival (OS) and recurrence-free survival (RFS) were compared. Results Eight patients—five males and three females—were less than 40 years old. The incidence of AYA hepatocellular carcinoma was 0.8%. Six patients had a history of hepatitis B. Four patients had a history of liver cirrhosis. Two patients experienced recurrent HCC. One patient died a year and a half after surgery. The percentage of HBV-positive patients was significantly greater in the AYA group than in the non-AYA group, and the tumor diameter was significantly greater in the AYA group. There were no significant differences in tumor marker levels, vascular invasion, differentiation, overall survival rate, or recurrence-free survival rate between the AYA group and the non-AYA group. Conclusion The outcome of resection for AYA HCC is good. Detection of AYA HCC in the early stage and hepatectomy are recommended.

Background: With the advent of effective chemotherapy, conversion surgery (CS) has been performed in patients who have responded to pretreatment, even for pancreatic cancer diagnosed as unresectable (UR) at the time of initial diagnosis. In CS, major arterial resection and reconstruction are necessary for complete radical resection. Methods: We discuss the key points for safely performing pancreatectomy with celiac axis (CA) resection combined with reconstruction, divided into resection and arterial reconstruction. The possibility of safe pancreatectomy concurrent with CA resection and reconstruction depends on the ability to create a "golden view" that provides an unimpaired view of the Abdominal Aorta, CA, Superior Mesenteric Artery, Inferior Vena Cava, and left renal vein from the ventral side. Pancreatectomy concurrent with CA resection requires arterial reconstruction. Postoperatively, arterial blood flow must be maintained. To achieve this, tension-free and short bypass should be observed. Results: From 2014 to 2024, sixteen URLA patients underwent CS, requiring major artery en bloc resection after pretreatment. We performed DP-CAR in eight patients, gastrectomy-distal pancreatectomy-splenectomy (Appleby procedure) procedure in one patient, PD-CHAR in two patients, PD-CAR in two patients, TP-CAR(spleen preserving) in one patient, and TP-CAR+TG in two patients. In total, five patients required surgery with CA reconstruction. Histopathologically, four of the five patients had T4 pancreatic cancer. The R0 surgical rate was 80%. Complication of Clavien-Dindo IIIa or higher was observed in one patient. There were no deaths. Conclusions: Parallel to the determination of pretreatment, surgeons must be prepared to safely and reliably perform pancreatectomies that require concurrent major arterial resection and reconstruction.

Extrahepatic portal vein obstruction (EHPVO) is a rare disease with myeloproliferative neoplasm (MPN) as the most common cause. We report that hypersplenic hematologic changes in EHPVO might be eliminated by MPN. Through experience with splenectomy for variceal control with EHPVO, we suspected that spleen might mask MPN-induced thrombocytosis, and that MPN might have a significant influence on excessive thrombocytosis after splenectomy. To clarify the influence of MPN and spleen on platelet trends, we conducted a retrospective hospital database analysis, evaluating 8 EHPVO patients with splenectomy (2 males, 6 females; from 17 years to 64 years, mean 38.3 years). Three (37.5%) of 8 were diagnosed as MPN by JAK2V617F mutation. The perioperative serum platelet counts in EHPVO without MPN were 10.5, 35.4, and 36.6 (x104/mu L) preoperatively, after 1 week and 3 weeks, respectively. The platelet counts in EHPVO with MPN were 34.2, 86.4, and 137.0 (x104/mu L), respectively. Splenectomy and MPN showed positive interaction on platelet increasing with statistical significance. We also examined the spleen volume index (SpVI: splenic volume (cm3) / body surface area (m2) and postoperative platelet elevations ratio (PER: 3-week postoperative platelet counts / preoperative platelet counts). However, both SpVI and PER showed no significant difference with or without MPN. Histological examination revealed splenic congestion in all 8 EHPVO cases, and splenic extramedullary hematopoiesis in 2 of 3 MPN. In EHPVO with MPN, hypersplenism causes feigned normalization of platelet count by masking MPN-induced thrombocytosis; however, splenectomy unveils postoperative thrombocytosis. Spleen in EHPVO with MPN also participates in extramedullary hematopoiesis.

AIM:Epithelial splicing regulatory protein 1 (ESRP1) regulates tumor progression and metastasis through the epithelial‒mesenchymal transition by interacting with zinc finger E-box binding 1 (ZEB1) and CD44 in cancers. However, the role of ESRP1 in intrahepatic cholangiocarcinoma (iCCA) remains unclear. METHODS:Three iCCA cell lines (HuCCT-1, SSP-25, and KKU-100) were analyzed using small interfering RNA to investigate the molecular biological functions of ESRP1 and ZEB1. The association between clinicopathological features and the expression of ESRP1 and ZEB1 in iCCA tissues was analyzed immunohistochemically. Proteomic analysis was performed to identify molecules related to ESRP1 expression. RESULTS:ESRP1 expression was upregulated in HuCCT-1 and SSP-25 cells. Cell migration and invasion were enhanced, and the expression of ZEB1 and CD44s (CD44 standard) isoforms were upregulated in the ESRP1 silencing cells. Moreover, ESRP1 silencing increased the expression of N-cadherin and vimentin, indicating the presence of mesenchymal properties. Conversely, ZEB1 silencing increased the expression of ESRP1 and CD44v (CD44 variant) isoforms. Immunohistochemical analysis revealed that a lower ESRP1-to-ZEB1 expression ratio was associated with poor recurrence-free survival in patients with iCCA. Flotillin 2, a lipid raft marker related to epithelial‒mesenchymal transition, was identified as a protein related to the interactive feedback loop in proteomic analysis. CONCLUSIONS:ESRP1 suppresses tumor progression in iCCA by interacting with ZEB1 and CD44 to regulate epithelial‒mesenchymal transition.