Published papers

Background: Neoadjuvant therapy is recommended for treating resectable pancreatic ductal adenocarcinoma (PDAC); however, its appropriate use in patients with resectable PDAC remains debatable. Objective: This study aimed to identify independent poor prognostic factors and evaluate the clinical significance of neoadjuvant therapy in patients with resectable PDAC. Methods: We retrospectively reviewed consecutive patients diagnosed with resectable PDAC at our institute between January 2003 and December 2022. We analyzed poor prognostic factors at the time of diagnosis in patients who underwent upfront surgery using the Cox proportional hazards model for overall survival (OS). The prognostic score was calculated by adding the individual prognostic factor scores. Results: Overall, 359 patients were included in this study, with 308 patients undergoing upfront surgery and the remaining 51 patients receiving neoadjuvant therapy. The R0 resection rate was significantly higher in the neoadjuvant therapy group (70.6%) than in the upfront surgery group (64.0%). Multivariate analysis in the upfront surgery group revealed the following independent poor prognostic factors: tumor size ≥ 35 mm, serum albumin level ≤.5 g/dL, neutrophil-to-lymphocyte ratio ≥ 3.5, carbohydrate antigen 19-9 level ≥ 250 U/mL, and Duke pancreatic monoclonal antigen type 2 level ≥ 750 U/mL. Among patients with prognostic scores of 0–1 (n = 263), the intention-to-treat OS did not significantly differ between the neoadjuvant therapy and upfront surgery groups. Among those patients with a prognostic score of ≥ 2 (n = 96), the neoadjuvant therapy group had significantly longer intention-to-treat OS than the upfront surgery group. Conclusions: Prognostic score-based stratification can help identify patients who could benefit from neoadjuvant therapy.

Background: Lymph node metastases beyond the hepatoduodenal ligament are sometimes encountered in locally limited T2 gallbladder cancer (GBCA). However, the incidence and impact on prognosis remain unclear. Methods: This was a retrospective multi-institutional study of patients who underwent surgical resection for GBCA from 2002 to 2022. The eighth edition of the Union for International Cancer Control staging was used for tumor-node-metastasis categorization. The lymph node location was classified as follows: (A) along the hepatoduodenal ligament and common hepatic artery; (B) posterior side of the pancreatic head; and (C) others. Metastasis to regions A, B, and C nodes was denoted as Na, Nb, and Nc, respectively. Results: Data for 379 patients (pT1, 29; pT2, 162: pT3, 141; and pT4, 47) were evaluated; none with pT1 GBCA had node metastasis. For N1/2 GBCA, the proportion of patients with N2 disease increased with increasing T grade (p =.001), while the proportions of patients with Na, Nb, and Nc disease were comparable between pT2 (61%, 26%, and 13%), pT3 (63%, 26%, and 12%), and pT4 (50%, 38%, and 12%) disease (p =.681), respectively. Overall survival for pT2N1/2 disease (5 years, 43.8%) was comparable to that for pT3/4N0 disease (5 years, 37.2%; p =.192). Among patients with node-positive pT2 disease, overall survival was comparable for Na, Nb, and Nc disease, with 5-year survivals of 46%, 43%, and 31%, respectively (p =.346). Conclusion: Region B or C node metastasis was not rare even in pT2 GBCA. Regarding survival outcomes, pT2 node-positive GBCA should be considered advanced disease irrespective of the extent of node metastasis.

Background: Optimal preoperative biliary drainage for patients with pancreatic cancer before pancreatoduodenectomy remains unclear. This study aimed to investigate the comparison of efficacy and safety between a metallic stent (MS) and a plastic stent (PS). Methods: Comparative studies on the use of MS and PS for pancreatic cancer before pancreatoduodenectomy were systematically searched using the MEDLINE and Web of Science databases. Pre- and postoperative data also were extracted. Random-effects meta-analyses were performed to compare post-endoscopic retrograde cholangiopancreatography (ERCP) complications as well as intra- and postoperative outcomes between the two arms of the study, and pooled odds ratios (ORs) or mean differences (MDs) were calculated with 95 percent confidence intervals (CIs). Results: The study analyzed 12 studies involving 683 patients. Insertion of MS was associated with a lower incidence of re-intervention (OR, 0.06; 95% CI 0.03–0.15; P < 0.001), increased post-ERCP adverse events (OR, 2.22; 95% CI 1.13–4.36; P = 0.02), and similar operation time (MD, 18.0 min; 95% CI –29.1 to 65.6 min; P = 0.46), amount of blood loss (MD, 43.0 ml; 95% CI –207.1 to 288.2 ml; P = 0.73), and surgical complication rate (OR, 0.78; 95% CI 0.53–1.15; P = 0.21). The cumulative stent patency rate after 3 months was higher in the MS group than in the PS group (70–100 % vs 30.0–45.0 %). Conclusion: For biliary drainage in patients with pancreatic cancer during this era of multidisciplinary treatment, MS use might be the first choice because MS provides a more durable biliary drainage and a similar risk of postoperative outcomes compared with PS.

Background/objectives: This study aimed to evaluate the safety, efficacy, and long-term outcomes of S-1-based neoadjuvant chemoradiotherapy (NACRT) in patients with resectable or borderline-resectable pancreatic ductal adenocarcinoma (PDAC). Methods: This retrospective study included patients with PDAC who underwent S-1-based NACRT at our institute between 2010 and 2017. Results: Forty patients were included in the study, including 15 (37.5%) with resectable PDAC and 25 (62.5%) with borderline-resectable PDAC. The NACRT completion and resection rates were 85.0% (n = 34) and 67.5% (n = 27), respectively. Several grade 3 adverse events were observed, including leukopenia (25.0%), anorexia (17.5%), neutropenia (10.0%), thrombocytopenia (7.5%), febrile neutropenia (2.5%), elevated aspartate aminotransferase/alanine aminotransferase (2.5%) levels, and hyponatremia (2.5%). The R0 resection rate was 70.4% (n = 19/27) in patients who underwent pancreatectomy. Grades 1, 2, and 3 according to the College of American Pathologists grading system were observed in 1 (3.7%), 12 (44.4%), and 14 (51.9%) patients, respectively. Over a median follow-up period of 32.9 months (interquartile range, 9.1–68.0), the 1-, 3-, and 5-year OS rates were 81.4%, 45.5%, and 30.3%, respectively, in the intention-to-treat analysis. In the curative-intent surgery cohort (n = 27), the 1-, 3-, and 5-year OS rates were 88.9%, 48.2%, and 37.0%, respectively. Conclusions: S-1-based NACRT is safe and yields acceptable long-term outcomes for patients with resectable or borderline-resectable PDAC.

Technique: Laparoscopic cholecystectomy (LC), widely performed for gallbladder (GB) diseases poses risks of severe complications. To minimize these risks, Tokyo Guidelines 2018 advocated for “safe steps in LC for acute cholecystitis (AC)” including “maintaining the plane of dissection on the GB surface throughout LC”. Moreover, the dissection along the inner layer of the subserosa (SS-inner) of GB helps surgeons avoid bile duct or vascular injury. This step occasionally becomes challenging when distinguishing the GB surface from adjacent fat. ICG, injected into biliary tract, illuminates in green under Infra-red (IR) mode and facilitates the identification of biliary tract. Otherwise, Yellow Enhance (YE) mode developed by Olympus Corporation, which highlights yellow-colored tissues by converting orange-yellow tissues to a clearer yellow, improves the contrast between anatomical structures. Results: In a case of AC following percutaneous transhepatic gallbladder drainage (PTGBD), we applied both ICG fluorescence and YE mode. The ICG injected from PTGBD illuminated the GB surface in green, while YE mode highlighted the fatty tissue in a clearer yellow, facilitating the distinction between these two tissues and the accurate dissection along the SS-inner. An additional advantage of injecting ICG from PTGBD, or from the cannulation tube intraoperatively inserted to GB, over intravenous administration is that the GB surface can be illuminated in cases of GB stone incarceration. Conclusion: The combination of ICG fluorescence and YE mode encourages surgeons to identify the boundary between the GB surface and the surrounding fatty tissues, which assists the accurate dissection along the SS-inner.

Introduction: Pancreatic cancer (PC) is highly malignant and metastatic; however, bone metastases are rare. Although the effectiveness of conversion surgery for distant metastases of PC has been reported in a few cases, there are no reports on surgical resection for bone metastases. Here, we report a case of long-term survival after resection of bone metastasis from PC. Patient concerns: A 60-year-old woman underwent pancreaticoduodenectomy after neoadjuvant chemoradiotherapy for pancreatic head cancer. At 28 months after surgery, multiple lung metastases from PC were diagnosed, and chemotherapy was administered. After 59 months, chemotherapy was terminated because all target lesions had disappeared on imaging. Diagnosis: At 77 months after the initial surgery, bone metastasis in the left 9thrib was detected by positron emission tomography/computed tomography, which was performed due to elevated carbohydrate antigen 19-9 levels. Interventions: Chemotherapy was readministered as the initial treatment. Subsequently, due to the long-term well-controlled status of the recurrence site and the absence of other metastases, thoracoscopic-assisted partial resection of the left 9thrib was performed 128 months following pancreaticoduodenectomy. Pathological examination revealed adenocarcinoma metastasis from PC. Outcomes: The patient is currently alive without recurrence 44 months after resection for bone metastasis and 172 months after the initial surgery. Conclusion: Surgical resection may be favorable in patients with bone metastasis of PC that is well-controlled with chemotherapy.

Positive peritoneal washing cytology is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC); however, its sensitivity is relatively low. This study evaluated the performance of peptide nucleic acid (PNA)-directed PCR clamping as a molecular-based peritoneal washing cytology for sensitive detection of KRAS mutation in PDAC. Intraoperative peritoneal washing fluid (IPWF) obtained from patients with PDAC who underwent surgery was analyzed. PNA-directed PCR clamping was performed on DNA extracted from IPWF. Among 54 patients enrolled, threshold cycle (Ct) was significantly lower in patients with positive peritoneal washing cytology than in those with negative peritoneal washing cytology (P < 0.001) and in patients with peritoneal dissemination than in those without peritoneal dissemination (P < 0.01). The optimal Ct cut-off to predict KRAS mutations in IPWF was 36.42 based on a receiver operating characteristic curve. The sensitivity, specificity, and accuracy for molecular diagnosis were 100%, 80.0%, and 85.2%, respectively. Peritoneal dissemination recurrence was significantly more frequent in patients with a positive molecular diagnosis than in those with a negative diagnosis (38.9 vs. 8.0%, P = 0.013). The genomic approach might be clinically valuable for a more precise tumor cell detection in IPWF.

Background: Despite recent medical advancements, surgery for hilar cholangiocarcinoma is associated with high complication and mortality rates. This may be partly attributed to the absence of established preoperative liver evaluation criteria for safe surgery. This study aimed to propose a reliable indicator for safe and well-planned management of major hepatectomy with extrahepatic bile duct resection. Methods: We included 150 patients who underwent major hepatectomy with extrahepatic bile duct resection between 2013 and 2021 in Japan. The risk factors for post-hepatectomy liver failure (PHLF) were retrospectively analyzed. Results: PHLF was observed in 24 (16.0 %) patients who underwent major hepatectomy with extrahepatic bile duct resection. In the multivariate analysis, the identified risk factors for PHLF were the ratio of future remnant liver volume to total liver volume (FRLV/TLV) ≤ 42 % and indocyanine green clearance fraction of the future remnant liver (ICGK-F) ≤ 0.07. Patients with these two factors were significantly associated with PHLF compared with those with either one or none of the risk factors (60.0 % vs 15.1 % and 8.1 %, respectively). Conclusion: The combinational use of ICGK-F and FRLV/TLV is useful for preoperative liver function assessment with a safety margin to avoid PHLF and postoperative mortality in hepatectomy for hilar cholangiocarcinoma.

The efficacy of next‑generation sequencing (NGS) of tumor‑derived DNA from intraoperative peritoneal washing fluid (IPWF) of patients with pancreatic ductal adenocar‑ cinoma (PDAC) who intend to undergo curative resection remains unclear. The aim of the present study was to evaluate whether genomic mutations in tumor‑derived DNA from IPWF samples of patients with PDAC who intend to undergo curative resection could be detected using NGS. A total of 12 such patients were included in this study. Cytology of IPWF (CY) was assessed and NGS of genomic tumor‑derived DNA from the IPWF was performed to determine whether genomic mutations could be detected in these patient samples. A total of 2 patients (16.7%) had a CY(+) status and 1 patient (8.3%) showed intraoperative macro‑peritoneal dissemination; 11 patients underwent radical surgery. Actionable gene altera‑ tions were detected in 8 (80.0%) out of the 10 patients with CY(‑) status based on NGS of IPWF samples, and 3 (37.5%) patients among those with actionable gene mutations identi‑ fied from IPWF samples underwent peritoneal dissemination after surgery within ~12 months. The most common genomic mutation was in KRAS (9 patients, 75.0%), followed by TP53 (3 patients, 25.0%), SMAD4 (1 patient, 8.3%) and CDKN2A (1 patient, 8.3%). These findings indicated that the genomic

Background: De novo malignancies (DNMs) after liver transplantation (LT) are a major cause of long-term mortality. However, no definitive screening protocol has been established due to their diversity. This study aimed to evaluate DNM diagnosis methods, screening protocols, and prognoses. Methods: This retrospective study included 231 adult LT recipients from April 1997 to March 2021. Disease-specific survival (DSS) was analyzed to assess the impact of screening on prognosis. Most recipients underwent serum tests every three months, annual gastrointestinal endoscopy, and chest-abdominal CT as part of routine surveillance. Results: Twenty-five DNMs were diagnosed in 22 patients, with median age of 61 years (range, 23–72), of whom 13 (59.1%) were female. The duration from transplantation to DNM diagnosis of DNM was 88 months (range, 4–195). DNM was diagnosed as follows: seven patients (31.8%) through screening (screening group) and 15 patients (68.2%) by other means (non-screening group). Curative treatment was achieved in all of the patients diagnosed by screening, whereas it was possible in only 60.0% of patients diagnosed by other means (p = 0.026). DSS in the screening group was significantly longer than that in the non-screening group (p = 0.024). Conclusions: While screening was associated with earlier-stage diagnosis and improved outcomes in some patients, the overall efficacy of the protocol requires further validation in larger studies.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy due to the difficulty in diagnosis and poor prognosis because of the high recurrence rate, necessitating reliable biomarkers to improve the diagnosis and prognosis. However, the existing markers have limitations. We previously identified extracellular vesicles (EVs) recognized by O-glycan-binding lectins (Amaranthus caudatus agglutinin [ACA]) as a novel diagnostic biomarker for PDAC using an EV-counting system (ExoCounter). This retrospective study analyzed changes in ACA-positive EVs in perioperative PDAC serum and its association with prognosis using ExoCounter. Absolute EV levels in the pre- and postoperative sera of 44 patients who underwent curative pancreatectomy for PDAC were quantified using ExoCounter. The carbohydrate antigen 19-9 levels declined in most samples postoperatively, and presented no correlation with poor prognosis. In contrast, ACA-positive EVs increased in serum at 7 days postoperatively in 27 of 44 patients (61.4%). We therefore divided participants with ACA-positive EVs before and after surgery into elevation and decline groups. The overall survival (OS) and recurrence-free survival (RFS) of patients with higher ACA-positive EVs were significantly shorter than those with lower ACA-positive EVs (26.1 months vs. not reached, P = 0.018; 11.9 vs. 38.6 months, P = 0.013). Multivariable analysis revealed that ACA-positive EV elevation in postoperative serum was an independent prognostic factor for poor OS (hazard ratio [HR] = 3.891, P = 0.023) and RFS (HR = 2.650, P = 0.024). The detection of ACA-positive EVs in perioperative serum may be used to predict the prognosis of PDAC in the early postoperative period.

Background: Hepatopancreatoduodenectomy (HPD) is one of the most challenging surgeries for perihilar cholangiocarcinoma. Postoperative pancreatic fistula (POPF) is a critical and fatal complication. The safety and efficacy of pancreaticogastrostomy (PG) for HPD compared to pancreaticojejunostomy (PJ) remain unclear. In this study, we aimed to investigate and compare the short-term outcomes of PG and PJ for HPD in terms of the POPF rate. Methods: Two groups of patients (PG group vs. PJ group) were retrospectively compared between January 2013 and January 2024. The reconstruction method was changed from PJ to PG in March 2021. Results: A total of 50 patients were enrolled in this study. The PG and PJ groups comprised 15 (30.0%) and 35 (70.0%) patients, respectively. In the PJ group, three (8.6%) patients died after surgery because of clinically relevant POPF (CR-POPF), intraabdominal bleeding, and post-hepatectomy liver failure. The operative time was longer in the PG group (909 min vs. 706 min, P = 0.020); however, the CR-POPF rate was lower in the PG group than in the PJ group (0 [0%] vs. 19 [54.3%], P < 0.001). Moreover, the number of patients who developed massive postoperative ascites (≥ 1,500 mL/day) was lower in the PG group than in the PJ group (3 [20.0%] vs. 16 [45.7%] patients, P = 0.028). Conclusions: Changing the method of pancreatic reconstruction for HPD from PJ to PG improved the short-term outcomes of patients at our institution. PG reconstruction is safe and effective for HPD as it reduces the incidence of CR-POPF.

Splenic metastases from solid tumors are rare, particularly when they occur after a long postsurgical interval. We report the case of a 69-year-old woman who developed a splenic metastasis from endometrial carcinoma, presenting as a hemorrhagic splenic cyst, 17 years after her initial surgery. Laparoscopic splenectomy achieving R0 resection was successfully performed; however, the patient subsequently developed multiple liver metastases. This case highlights the importance of periodic evaluation for recurrence, including monitoring for symptoms and elevated tumor markers, in patients with a history of endometrial carcinoma or other solid tumors.

Background: Postoperative pancreatic fistula (POPF) continues to be the most common complication after distal pancreatectomy (DP). Recent advancements in surgical techniques have established minimally invasive distal pancreatectomy (MIDP) as the standard treatment for various conditions, including pancreatic cancer. However, MIDP has not demonstrated a clear advantage over open DP in terms of POPF rates, indicating the need for additional strategies to prevent POPF in MIDP. This trial (WRAP study) aims to evaluate the efficacy of wrapping the pancreatic stump with polyglycolic acid (PGA) mesh and fibrin glue in preventing clinically relevant (CR-) POPF following MIDP. Methods: This multicenter, randomized controlled trial will include patients scheduled for laparoscopic or robotic DP for tumors in the pancreatic body and/or tail. Eligible participants will be centrally randomized into either the control group (Group A) or the intervention group (Group B), where the pancreatic stump will be reinforced by PGA mesh and fibrin glue. In both groups, pancreatic transection will be performed using a bioabsorbable reinforcement-attached stapler. A total of 172 patients will be enrolled across 14 high-volume centers in Japan. The primary endpoint is the incidence of CR-POPF (International Study Group of Pancreatic Surgery grade B/C). Discussion: The WRAP study will determine whether the reinforcement of the pancreatic stump with PGA mesh and fibrin glue, a technique whose utility has been previously debated, could become the best practice in the era of MIDP, thereby enhancing its safety. Trial registration: This trial was registered with the Japan Registry of Clinical Trials on June 15, 2024 (jRCTs032240120).

Background: The incidence of pancreatic neuroendocrine neoplasm (PNEN) has been increasing. Resection is typically indicated for PNEN, regardless of its size; however, the indications for its resection are controversial. This study aimed to evaluate the treatment results of surgical resection of PNEN at our institute. Methods: In this single-center, retrospective, case-control study, 87 patients who underwent PNEN resection and 17 patients with PNEN who did not undergo surgical resection between 1993 and 2020 were included in this study. Clinical characteristics and outcomes were reviewed and statistically compared. Survival was also estimated for the patients in each cohort. Results: Seventeen patients who underwent resection (20%) had lymph node metastasis. Tumors measuring ≥ 2.0 cm and multiple lesions were identified as independent predictors for lymph node metastasis (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.0–100.0, p = 0.001 and OR 8.7, 95% CI 1.5–52.0, p = 0.018, respectively). There was a significant difference in the survival curves depending on the presence or absence of lymph node metastasis (5-year overall survival 74.7% vs. 94.3%, p < 0.001; 5-year recurrence-free survival: 66.3% vs. 93.6%, p < 0.001). All 17 PNEN cases under observation with a median 8 mm (range 5–23) tumor size for a median of 34 (range 2.4–114) months showed slight morphological change with a median tumor growth rate of 0.15 mm (range 0–3.33) per year. Conclusion: Patients with tumors measuring ≥ 2.0 cm have a high probability of lymph node metastasis or recurrence, thereby requiring resection. PNEN measuring < 1.0 cm may be acceptable for observation.

Background: Pancreaticoduodenectomy with porto-mesenterico-splenic confluence resection can cause sinistral portal hypertension (SPH), which may lead to gastrointestinal bleeding. Nevertheless, it remains difficult to predict SPH development during surgery. The aim of this study is to assess the feasibility of measuring splenic vein (SV) pressure to predict SPH. Methods: The patients who underwent pancreaticoduodenectomy with porto-mesenterico-splenic confluence resection between January 2016 and December 2017 were included in this study. SV pressure was measured before SV clamping (SVP1) and after SV clamping (SVP2). SPH was defined as varicose vein formation detected by follow-up computed tomography. Incidence of SPH was assessed in patients who had no SV drainage after surgery. Results: SV pressure was measured in 41 patients. Among them, 24 had no SV drainage (13 patients had occluded SV reconstruction, and 11 had SV ligation without an attempt at reconstruction) and were included for the analysis. SPH was observed in 16 of 24 patients (67%). The median ΔSVP (SPV2-SVP1) in patients with SPH was higher than that in patients without SPH (13.5 mmHg versus 7.5 mmHg, P = 0.0237). Most patients with SVP2 >20 mmHg (12/14 [86%]) or ΔSVP >10 mmHg (10/11 [91%]) developed SPH. Conclusions: For the patients with SV resection, high SV pressure after clamping (≥20 mmHg) and a large SV pressure difference (≥10 mmHg) before and after clamping are feasible indication criteria for SV reconstruction to prevent SPH.

Biliary complications after hepatectomy in living donors have yet to be eradicated. We hypothesized that a standardized upfront Glissonean approach and liver hanging maneuver (GH) would prevent mechanical and thermal injuries to the hilar plate of the remnant liver by determining the point of bile duct division and the final destination of hepatectomy preceding liver parenchymal transection (safety) and facilitate liver transection deep within the parenchyma and allow maximum length of hilar structures (rationality). GH was implemented in 2016 and its incidence of bile leakage was retrospectively compared against the conventional technique. GH comprises six steps: (1) development of the retrohepatic avascular plane between the right hepatic vein (RHV) and the middle hepatic vein (MHV) and isolation of the hepatic vein(s); (2) isolation of the right or left Glissonean pedicle with the corresponding Glissonean pedicles of the caudate lobe; (3) for right liver grafts and left liver grafts with the caudate lobe, passage of the tape for the liver hanging maneuver along the retrohepatic avascular plane and above the hilar plate, and for left liver grafts without the caudate lobe and for left lateral section grafts, passage of the tape from between the RHV and the MHV, along the Arantius ligament, and to the right of the umbilical portion; (4) liver transection; (5) isolation of hilar structures; and (6) graft procurement. Until 2020, 62 consecutive living donors underwent GH (success rate, 100%). The incidence of bile leakage from the hepatic hilum (0%) was significantly lower than that among 59 donors who underwent the conventional technique in 2011-2015 (9%; p = 0.01). In conclusion, GH is highly effective in reducing bile leakage from the hepatic hilum in living donors.

Background: The optimal surgical strategy for pancreatic neuroendocrine tumors (PNETs) is unknown. However, current guidelines recommend a watch-and-wait strategy for small nonfunctional PNETs (NF-PNETs). The aim of this study is to investigate the risk stratification and prognostic significance of lymph node metastasis (LNM) of PNETs to guide decision-making for lymphadenectomy. Patients and Methods: The MEDLINE and Web of Science databases were systematically searched for studies reporting either risk factors of LNM in resected PNETs or survival of patients with LNM. The weighted average incidence of LNM was calculated according to tumor characteristics. Random-effects metaanalyses were performed, and pooled hazard ratios (HR) and their 95% confidence intervals (CI) were calculated to determine the impact of LNM on overall survival (OS). In subgroup analyses, NF-PNETs were assessed. Results: From a total of 5883 articles, 98 retrospective studies with 13,374 patients undergoing resection for PNET were included. In all PNETs, the weighted median rates of LNM were 11.5% for small (≤ 2 cm) PNETs and 15.8% for G1 PNETs. In NF-PNETs, the rates were 11.2% for small PNETs and 10.3% for G1 PNETs. LNM of all PNETs (HR 3.87, 95% CI 3.00–4.99, P < 0.001) and NF-PNETs (HR 4.98, 95% CI 2.81–8.83, P < 0.001) was associated with worse OS. Conclusions: LNM is potentially prevalent even in small and well-differentiated PNETs and is associated with worse prognosis. A watch-and-wait strategy for small NF-PNETs should be reappraised, and oncologic resection with lymphadenectomy can be considered. Prospective and controlled studies are needed in the future.

Objectives Some intraductal papillary mucinous neoplasms (IPMNs) have malignant potential and can become pancreatic cancer. The mechanism behind the malignant progression of IPMN remains unknown. We aimed to identify the risk factors and interactions between backgrounds for IPMN. Methods We retrospectively enrolled 980 patients of pancreatic cancer or suspected IPMN (sIPMN) who underwent endoscopic ultrasound or retrograde cholangiopancreatography. We classified them into pancreatic cancer, high-risk sIPMN, and low-risk sIPMN, and investigated the risk factors for high-risk sIPMN. Results Smoking habits (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.04-6.85; P < 0.001), serum carbohydrate antigen 19-9 ≥37 U/mL (OR, 6.30; 95% CI, 2.88-13.80; P < 0.001), and family history of cancers (OR, 2.38; 95% CI, 1.30-4.37; P = 0.005) were independent risk factors for high-risk suspected IPMN. Odds ratios of diabetes and neutrophil-to-lymphocyte ratio of 2.45 or greater were significantly higher in patients with a family history of cancer than those without a family history of cancer (OR, 3.28; 95% CI, 0.52-20.80 vs 1.85; 95% CI, 0.78-4.41; OR, 2.44; 95% CI, 0.81-7.34 vs 1.24; 95% CI, 0.67-2.30, respectively). Conclusions Understanding the interactions between background factors can effectively prevent IPMNs' malignant transformation.