BACKGROUND:The relationship between the radiographic portal vein-superior mesenteric vein (PV-SMV) involvement and pathological PV-SMV (pPV) invasion has been established in upfront surgery cases of pancreatic cancer (PC); however, evidence remains limited for patients receiving neoadjuvant therapy (NAT). This study aimed to evaluate the association of radiographic findings with pPV invasion in patients treated with NAT, and to examine whether this association differs between patients treated with neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT). METHODS:We retrospectively analyzed patients with PC whose tumors contacted the PV-SMV on radiographic imaging before or after NAT. The relationship between radiographic findings and pPV invasion was evaluated in subgroups defined by pre- and post-NAT imaging findings. RESULTS:Tumor size, PV-SMV contact length, and contact angle were significantly reduced in post-NAT imaging. Radiographic PV-SMV involvement showed limited association with pPV invasion in the entire cohort. The overall pPV invasion rate was 15% and did not differ between the NAC and NACRT groups (17% vs. 13%, p = 0.790). Among patients with a pre-NAT tumor size of < 20 mm, the pPV invasion rate was significantly lower in the NACRT group than in the NAC group (29% vs. 0%, p = 0.007). This difference was not observed in patients with a pre-NAT tumor size ≥ 20 mm (12% vs. 19%, p = 0.438). Across other radiographic classifications, pPV invasion rates remained comparable between treatment groups. CONCLUSIONS:The association of radiographic findings with pPV invasion differs between patients treated with NAC and NACRT in patients with small tumors.

Circular RNAs (circRNAs) are associated with various biological features of cancer, including chemosensitivity and the structural characteristics of circRNAs indicate their potential as liquid biomarkers. Gemcitabine is a cornerstone treatment for pancreatic cancer (PC). A deeper understanding of gemcitabine sensitivity and the exploration of clinically valuable liquid biomarkers that are predictive of gemcitabine sensitivity may contribute to the development of improved‑tailored treatment strategies for PC. The aim of the present study was to identify a candidate circRNA associated with gemcitabine sensitivity, investigate its biological functions and evaluate its potential as a liquid biomarker in predicting gemcitabine sensitivity. circRNA sequencing analysis was conducted to identify candidate circRNAs and the function of a candidate circRNA in modulating gemcitabine sensitivity was investigated in vitro. Further, the potential of this circRNA in predicting gemcitabine sensitivity in patients with PC who received gemcitabine‑based neoadjuvant chemotherapy was evaluated using pre‑treatment serum samples. circ72309 was identified as the candidate circRNA and its overexpression in gemcitabine‑resistant PC cell lines increased gemcitabine‑induced apoptosis and markedly increased gemcitabine sensitivity in vitro. Furthermore, circ72309 decreased cytidine deaminase by increasing reactive oxygen species activity and increasing human equilibrative nucleoside transporter 1 expression via regulation of target miRNAs. Patients with high serum circ72309 had markedly improved progression‑free survival (PFS) and high serum circ72309 was an independent prognostic predictor of a favorable PFS in patients with PC. circ72309 affected multiple steps in the gemcitabine metabolic pathway and its overexpression resulted in markedly increased gemcitabine sensitivity. Therefore, circ72309 expression in the pre‑treatment serum samples may serve as a predictor of gemcitabine sensitivity in patients with PC. .

INTRODUCTION:Single-incision laparoscopic hepatectomy has been introduced to reduce surgical invasiveness, but its short-term and long-term outcomes in malignant cases have not been fully elucidated. This study aimed to evaluate its impact on short- and long-term outcomes of laparoscopic hepatectomy. METHODS:This retrospective study included patients who underwent laparoscopic partial hepatectomy or left lateral sectionectomy for tumors with diameters < 5 cm, located in segments 2-6, between July 2009 and April 2019. Single-incision and multi-port procedures were matched one-to-one based on clinical factors, and short-term outcomes were compared. Long-term outcomes were also analyzed for hepatocellular carcinoma cases. RESULTS:A total of 136 patients were included: 20 in the single-incision group (17 with hepatocellular carcinoma) and 116 in the multi-port group (69 with hepatocellular carcinoma). Within the matched cohort, compared to the multi-port group, the single-incision group showed comparable operative time (179 min in the single-incision group vs. 185 min in the multi-port group, p = 0.133) and blood loss (9 vs. 20 mL, p = 0.076). These groups did not significantly differ in postoperative hospital stay (12 vs. 12 days, p > 0.99) or complication rate (5.0% vs. 10.0%, p > 0.99). Among matched hepatocellular carcinoma cases, the two groups showed comparable 5-year disease-free survival (52.9% vs. 40.5%, p = 0.653) and overall survival (82.4% vs. 68.2%, p = 0.415). CONCLUSIONS:Compared with the multi-port approach, single-incision laparoscopic hepatectomy showed comparable and equivalent short- and long-term outcomes. This procedure can be considered a safe and effective option for selected cases.

Postoperative pancreatic fistula (POPF) is a serious complication following pancreaticoduodenectomy (PD). While numerous studies have investigated POPF incidence and risk factors, few have focused on POPF healing time (POPF-HT). Skeletal muscle mass has been increasingly recognized as an endocrine organ involved in interorgan communication. The aim of this study was to evaluate how skeletal muscle mass influenced the healing time of POPF after PD. This investigation included patients who developed POPF of grade B–C after PD with pancreaticojejunostomy during the study period. POPF-HT was defined as the duration from the date of PD to the removal of all drains placed for POPF treatment. Skeletal muscle mass was assessed based on preoperative computed tomography images. Clinical factors associated with POPF-HT were analyzed, including skeletal muscle index (SMI). The mean POPF-HT was 40 ± 15 days (median: 37 days; range: 21–105 days). Compared to those with high SMI, patients with low SMI had a significantly longer POPF-HT (46 ± 18 days vs. 37 ± 11 days, p = 0.0101). In univariate analysis, low SMI was significantly associated with prolonged POPF-HT (hazard ratio: 0.5655, 95

The presence of a soft tissue mass (STM) around the arteries is often observed after pancreatectomy. Although a STM frequently represents local recurrence, it can also reflect benign postoperative changes. However, the frequency of STMs and the factors determining whether its presence leads to local recurrence or remains benign have not been studied. This study aimed to determine the frequency of STM after pancreatectomy and to identify the clinical factors associated with the development of local recurrence. A total of 246 patients who underwent pancreatectomy at a single institution were analyzed retrospectively. The presence of a STM was assessed by follow-up computed tomography, and its association with local recurrence was evaluated. Among the 246 patients, 33 (13.4

BACKGROUND:We recently developed a novel flexible suction/coagulation probe to overcome the rigidity of conventional electrosurgical probes, enabling simultaneous suction and coagulation from the console in robotic surgery. Although feasible in robot-assisted gastrectomy, its performance remains unevaluated in robot-assisted hepatectomy, which requires frequent suction and reliable hemostasis. METHODS:This single-arm feasibility study included 12 consecutive patients undergoing robot-assisted hepatectomy using the probe, directly manipulated by the console surgeon for hemostasis during parenchymal transection. Surgical outcomes (operative time, estimated blood loss, device trouble, complications) were assessed. Surgeons completed a post-procedure questionnaire covering seven usability and performance domains on a 3-point Likert scale. RESULTS:Robotic procedures included left hepatectomy, segmentectomies, and partial resections. All procedures were completed successfully without conversion. Median operative time was 397.5 min (range, 256-678 min), and estimated blood loss was 110 mL (range, 0-320 mL). No device-related adverse events or complications occurred. Overall satisfaction was rated 'satisfactory' by 75% of surgeons, with 'unsatisfactory' ratings occurring only for suction efficiency (16.7%). CONCLUSIONS:The flexible suction/coagulation probe appears to be a practical and clinically feasible option for robot-assisted hepatectomy. Although the suction efficiency requires further improvement, the device enables direct console surgeon-controlled suction and hemostasis during hepatic parenchymal transection.

Postoperative pancreatic fistula (POPF) remains a critical complication following pancreatic resection. Standard fibrin sealants are frequently degraded by pancreatic proteases, limiting their efficacy, which is hypothesized to be due to rapid degradation by proteolytic enzymes in pancreatic juice. CK2-085-SP is a novel, synthetic self-assembling peptide (SPG-178) gel that retains its structural integrity in pancreatic juice, potentially providing more robust sealing than conventional biological sealants. We designed this exploratory, investigator-initiated trial to evaluate the safety and feasibility of CK2-085-SP. This study represents the first-in-human clinical application of the self-assembling peptide gel for pancreatic resection. This is a prospective, single-arm clinical trial (PepSeal-001) for which the Clinical Trial Notification has been accepted by the Pharmaceuticals and Medical Devices Agency. A total of 25 patients will be enrolled to ensure that CK2-085-SP is applied to at least 10 patients undergoing pancreaticoduodenectomy and 10 patients undergoing distal pancreatectomy. To ensure the evaluation of the device in high-risk cases, the study aims to include at least seven patients undergoing pancreaticoduodenectomy with a main pancreatic duct diameter ≤ 3 mm. The primary endpoints are the incidence and severity of adverse events and device malfunctions within 90 days postoperatively. Secondary endpoints include amylase levels in drainage fluid; the incidence of clinically relevant POPF; incidence of intra-abdominal abscess, delayed gastric emptying, postoperative hemorrhage, drainage tube reinsertion, reoperation, readmission, and postoperative mortality; duration of drain placement; length of postoperative hospital stay; and usability of the study device. The PepSeal-001 trial will evaluate the safety and feasibility of CK2-085-SP in pancreaticoduodenectomy and distal pancreatectomy. This study is expected to provide clinical evidence for the development of a novel synthetic peptide-based sealant to improve outcomes in pancreatectomy.

Despite advances in multimodal treatment, the long-term survival of patients with resectable pancreatic ductal adenocarcinoma (PDAC) remains poor. In Japan, neoadjuvant chemotherapy with gemcitabine and S-1 (GS) has demonstrated a survival benefit compared with upfront surgery. The addition of radiotherapy to chemotherapy may further improve outcomes by enhancing local tumor control and increasing R0 resection rates; however, no randomized trial has directly compared GS alone with GS plus radiotherapy (GS-RT) in patients with resectable PDAC. The CSGO-HBP-027 trial is a multicenter, randomized phase II/III study designed to evaluate whether neoadjuvant GS-RT improves survival compared with GS alone. This trial will enroll 200 patients with resectable PDAC, who will be randomized in a 1:1 ratio to receive either two cycles of GS or two cycles of GS with concurrent radiotherapy (50.4 Gy in 28 fractions), followed by surgery scheduled 3-8 weeks after completion of neoadjuvant therapy. The primary endpoint is overall survival, and secondary endpoints include resection rate, R0 resection rate, histological tumor response, progression-free survival, and safety. Overall survival will be compared between the two treatment arms using the stratified log-rank test, with adjusted hazard ratios estimated using the Cox proportional hazards model. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051250150). The CSGO-HBP-027 trial will provide evidence on whether neoadjuvant GS-RT improves survival in patients with resectable PDAC compared with GS alone. The results of this study are expected to clarify the optimal neoadjuvant treatment strategy for resectable PDAC and to provide high-quality evidence regarding the clinical value of adding radiotherapy to GS-based neoadjuvant therapy.

Postoperative pneumonia (POP) is a major complication of hepatobiliary and pancreatic surgery that significantly affects patient outcomes. However, the necessity of routine preoperative spirometry to assess the risk of POP remains uncertain. We therefore evaluated whether or not omitting routine preoperative spirometry affects the postoperative outcomes, particularly the incidence of POP. This retrospective study included 691 patients who underwent hepatobiliary and pancreatic surgeries at our institution. Patients were categorized into two groups: the pre-COVID-19 group (April 2018 to March 2020), wherein all patients underwent spirometry, and the COVID-19 group (April 2020 to March 2022), with limited spirometry. This study evaluated postoperative outcomes and risk factors for POP in both groups. No significant differences were observed in the incidence of POP between the pre-COVID-19 and COVID-19 era groups (2.9

This study aimed to identify exosomal microRNAs (exo-miRNAs) in portal vein blood (PVB) linked to liver metastasis in pancreatic cancer (PC) and elucidate the related molecular mechanisms. Exo-miRNAs were extracted from peripheral blood (PB) and PVB samples collected intraoperatively from patients with PC. Microarray analysis revealed that the exo-miRNA profiles associated with PC liver metastasis differed between PVB and PB. miR-4800-3p emerged as a potential exo-miRNA involved in liver metastasis and was highly expressed in PVB but not in PB. The overexpression (OE) of miR-4800-3p enhanced cell migration, invasion, and epithelial‒mesenchymal transition in vitro. mRNA sequencing revealed phospholipase A2 activating protein (PLAA) as a target mRNA regulated by miR-4800-3p. PLAA inhibits ubiquitination and prevents the degradation of methyltransferase like-3 protein, thereby enhancing the G protein-coupled receptor class C group 5 member A oncogene in vitro. In the in vivo PC liver metastasis model, the number of tumor nodules markedly increased in the miR-4800-3p OE group. Immunostaining of clinical samples revealed significantly lower PLAA expression in liver metastases than in lung metastases. These findings underscore the importance of PVB as a liquid sample for investigating liver metastasis-specific mechanisms that are undetectable using conventional PB analysis.

BACKGROUND:Postoperative pancreatic fistula (POPF) is a severe complication after pancreatectomy. The preoperative prediction of POPF would benefit patients by providing postoperative management tailored to each patient based on the risk for POPF. The Charlson Comorbidity Index (CCI), which assesses the severity of patient comorbidities, has been associated with postoperative complications in various surgeries. However, its relationship with POPF remains unclear. This study investigates the impact of CCI on the development of POPF. METHODS:This retrospective study reviewed 597 patients who underwent pancreatectomy from 2010 to 2020, of whom 219 underwent distal pancreatectomy (DP) and 378 underwent pancreaticoduodenectomy (PD). Significant factors were assessed in association with clinically relevant POPF (CR-POPF) using a logistic regression model. K-means clustering was employed based on the body mass index, pancreatic thickness, and CCI score to stratify patients by the risk for CR-POPF. RESULTS:Higher CCI scores were significantly associated with an increased incidence of CR-POPF, particularly in patients undergoing DP, whereas such association was not observed in patients undergoing PD. Multivariate analysis identified male sex, BMI > 25.95 kg/m2, pancreatic thickness > 9.01 mm, and CCI score > 4 as independent predictors of CR-POPF in the DP group. A predictive model incorporating these factors demonstrated moderate accuracy (AUC = 0.6750) in stratifying patients into high- and low-risk groups for CR-POPF. CONCLUSION:CCI is a significant predictor of CR-POPF, especially in patients undergoing DP. By integrating CCI with other factors, it was feasible to develop a predictive model with high diagnostic accuracy.

Aim: Laparoscopic liver resection (LLR) for intrahepatic cholangiocarcinoma (ICC) is not as widespread as LLR for hepatocellular carcinoma or liver metastasis, mainly because ICC may require a lymph node dissection (LND). However, small, solitary, peripheral-type ICC rarely have lymph node metastasis (LNM). The aim of the current study is to examine the usefulness of LLR for ICC and determine whether our criteria for applying LLR without LND to small, solitary, peripheral-type ICC was appropriate. Methods: We retrospectively selected 78 patients that underwent liver resections for ICC at Osaka University Hospital between 2003 and 2020. We compared LLR (n = 13) to open liver resection (OLR, n = 65) for short-term and long-term outcomes. We also analyzed a subgroup (n = 29) with small, solitary, peripheral-type ICC. Results: The LLR group had less blood loss (P < .001), shorter postoperative stays (P < .001), and significantly higher 5-year recurrence-free survival (RFS, 74.0%), compared to the OLR group (29.6%, P = .030). However, the OLR group included a higher proportion of patients with advanced ICC. Among patients with small, solitary, peripheral-type ICC, LLR (n = 10) was associated with less blood loss (P = .004) and shorter postoperative stays (P = .002), compared to OLR (n = 19). These groups had similar pathological findings, similar 5-year RFS (75.0% versus 56.8%; P = .433), and similar 5-year overall survival (75.0% versus 80.4%; P = .530). No patients that underwent LLR without LND for ICC experienced lymph node recurrence. Conclusions: Among patients with ICC, LLR provided better intraoperative and short-term outcomes than OLR, and comparable oncological outcomes. Furthermore, no patients that underwent LLR without LND for ICC experienced lymph node recurrence. LLR without LND for ICC can be performed safely and feasibly by selecting patients with small, solitary, peripheral-type ICC.