Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

High Incidence of Diabetes Mellitus After Distal Pancreatectomy and Its Predictors: A Long-term Follow-up Study.

CONTEXT: Glucose tolerance worsens after distal pancreatectomy (DP); however, the long-term incidence and factors affecting interindividual variation in this worsening are unclear. OBJECTIVE: To investigate the changes in diabetes-related traits before and after DP and to clarify the incidence of diabetes and its predictors. METHODS: Among 493 registered patients, 117 underwent DP. Among these, 56 patients without diabetes before surgery were included in the study. Glucose and endocrine function were prospectively assessed using a 75-g oral glucose tolerance test preoperatively, 1 month after DP, and every 6 months thereafter for up to 36 months. Pancreatic volumetry was performed using multidetector row computed tomography before and after surgery. RESULTS: Insulin secretion decreased and blood glucose levels worsened after DP. Residual pancreatic volume was significantly associated with the reserve capacity of insulin secretion but not with blood glucose levels or the development of diabetes. Among 56 patients, 33 developed diabetes mellitus. The cumulative incidence of diabetes at 36 months after DP was 74.1%. Multivariate Cox regression analysis showed that impaired glucose tolerance as a preoperative factor as well as a decreased insulinogenic index and impaired glucose tolerance at 1 month postoperatively were identified as risk factors for diabetes following DP. CONCLUSION: Impaired glucose tolerance and reduced early-phase insulin response to glucose are involved in the development of new-onset diabetes after DP; the latter is an additional factor in the development of diabetes and becomes apparent when pancreatic beta cell mass is reduced after DP.

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial).

Background: Nab-paclitaxel plus gemcitabine is a standard treatment for metastatic/locally advanced pancreatic cancer. The effectiveness of neoadjuvant therapy with nab-paclitaxel plus gemcitabine (GnP-NAT) in patients with borderline resectable pancreatic cancer (BRPC) remains unclear. Patients and Methods: This single-arm phase II trial included 61 patients with BRPC that were treated with two cycles of GnP-NAT, (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2), on days 1, 8, and 15 over a 4-week period, which comprised one cycle. The primary endpoint was overall survival time. In the absence of disease progression, patients underwent planned pancreatectomy. Results: Median overall survival, the primary endpoint, was 25.2 months, and the median recurrence-free survival was 12.3 months. The overall rate of grade 3/4 events was 73.8%. One patient, who had a history of radiation therapy for past esophageal cancer, died from exacerbation via pneumonia. The overall resection rate was 73.8% (n = 45), and the R0 resection rate was 63.9% (n = 39). Overall, postoperative complications were found in 19 patients (42%) with 24 events, and nine patients (20%) with nine events ≥ grade IIIa, based on Dindo's classification. Conclusions: This protocol treatment is thought to be a feasible, safe, and promising treatment regimen, but we caution against its use in patients with a history of interstitial lung disease and/or prior pulmonary irradiation. The survival data from this study suggest the need for further investigations of GnP-NAT efficacy in patients with BRPC, as well as prospective evaluation of adverse events. Clinical Trial Registration: UMIN Clinical Trials Registry, UMIN000024154 and ClinicalTrials.gov, NCT02926183.

Randomized phase II trial of chemoradiotherapy with S-1 versus combination chemotherapy with gemcitabine and S-1 as neoadjuvant treatment for resectable pancreatic cancer (JASPAC 04).

OBJECTIVE: The aim of the present study was to investigate which treatment, neoadjuvant chemoradiotherapy (NAC-RT) with S-1 or combination neoadjuvant chemotherapy with gemcitabine and S-1 (NAC-GS), is more promising as neoadjuvant treatment (NAT) for resectable pancreatic cancer in terms of effectiveness and safety. METHODS: In the NAC-RT with S-1 group, the patients received a total radiation dose of 50.4 Gy in 28 fractions with oral S-1. In the NAC-GS group, the patients received intravenous gemcitabine at a dose of 1000 mg/m2 with oral S-1 for two cycles. The primary endpoint was the 2-year progression-free survival (PFS) rate. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. RESULTS: From April 2014 to April 2017, a total of 103 patients were enrolled. After exclusion of one patient because of ineligibility, 51 patients were included in the NAC-RT with S-1 group, and 51 patients were included in the NAC-GS group in the intention-to-treat analysis. The 2-year PFS rate was 45.0% (90% confidence interval [CI]: 33.3%-56.0%) in the NAC-RT with S-1 group and 54.9% (42.8%-65.5%) in the NAC-GS group (p = .350). The 2-year overall survival rate was 66.7% in the NAC-RT with S-1 group and 72.4% in the NAC-GS group (p = .300). Although leukopenia and neutropenia rates were significantly higher in the NAC-GS group than in the NAC-RT with S-1 group (p = .023 and p < .001), other adverse events of NAT and postoperative complications were comparable between the two groups. CONCLUSION: Both NAC-RT with S-1 and NAC-GS are considered promising treatments for resectable pancreatic cancer.

Impact of antithrombotic therapy on postpancreatectomy hemorrhage in 7116 patients: A project study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

BACKGROUND: We previously reported an association between antithrombotic therapy and an increased risk of postpancreatectomy hemorrhage (PPH). To validate our findings, we conducted a large-scale multicenter retrospective study from 63 high-volume centers in Japan. METHODS: Between 2015 and 2018, 7116 patients who underwent pancreatectomy were enrolled. The antithrombotic group consisted of 920 patients (12.9%) who received preoperative antithrombotic agents including aspirin, clopidogrel, ticlopidine, prasugrel, warfarin, and direct oral anticoagulants. RESULTS: PPH occurred in 235 (3.3%) of the patients. The incidence of PPH and mortality were significantly higher in the antithrombotic group than in the control group (5.7 vs. 3.0% and 2.2 vs. 0.9%, respectively; both p < .001). In multivariate analysis, a history of antithrombotic use was an independent risk factor for grade C PPH (p = .036). In the antithrombotic group, PPH tended to be delayed in the patients with restarting antithrombotic therapy. Notably, the occurrence of delayed PPH after restarting antithrombotic therapy was observed only when antithrombotic therapy was restarted within 10 days after pancreatectomy. CONCLUSIONS: This multicenter study demonstrated that a history of antithrombotic use was a significant risk factor for PPH and mortality. In particular, the resumption of antithrombotic therapy in the early postoperative period should be done with caution.

Is surgical resection justified for pancreatic ductal adenocarcinoma with distant abdominal organ metastasis? A position paper by experts in pancreatic surgery at the Joint Meeting of the International Association of Pancreatology (IAP) & the Japan Pancreas Society (JPS) 2022 in Kyoto.

Pancreatic ductal adenocarcinoma (PDAC) is a typical refractory malignancy, and many patients have distant organ metastases at diagnosis, such as liver metastasis and peritoneal dissemination. The standard treatment for unresectable PDAC with distant organ metastasis (UR-M) is chemotherapy, but the prognosis remained poor. However, with recent dramatic developments in chemotherapy, the prognosis has gradually improved, and some patients have experienced marked shrinkage or disappearance of their metastatic lesions. With this trend, attempts have been made to resect a small number of metastases (so-called oligometastases) in combination with the primary tumor or to resect the primary and metastatic tumor in patients with a favorable response to anti-cancer treatment after a certain period of time (so-called conversion surgery). An international consensus meeting on surgical treatment for UR-M PDAC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of the Japan Pancreas Society (JPS) in Kyoto in July 2022. The presenters showed their indications for and results of surgical treatment for UR-M PDAC and discussed their advantages and disadvantages with the experts. Although these reports were limited to a small number of patients, findings suggest that these surgical treatments for patients with UR-M PDAC who have had a significant response to chemotherapy may contribute to a prognosis of prolonged survival. We hope that this article summarizing the discussion and agreements at the meeting will serve as the basis for future trials and guidelines.

Insights from managing clinical issues in distal pancreatectomy with en bloc coeliac axis resection: experiences from 626 patients.

BACKGROUND: Distal pancreatectomy with en bloc coeliac axis resection (DP-CAR) for pancreatic body cancer has been reported increasingly. However, its large-scale outcomes remain undocumented. This study aimed to evaluate DP-CAR volume and mortality, preoperative arterial embolization for ischaemic gastropathy, the oncological benefit for resectable tumours close to the bifurcation of the splenic artery and coeliac artery using propensity score matching, and prognostic factors in DP-CAR. METHODS: In a multi-institutional analysis, 626 DP-CARs were analysed retrospectively and compared with 1325 distal pancreatectomies undertaken in the same interval. RESULTS: Ninety-day mortality was observed in 7 of 21 high-volume centres (1 or more DP-CARs per year) and 1 of 41 low-volume centres (OR 20.00, 95 per cent c.i. 2.26 to 177.26). The incidence of ischaemic gastropathy was 19.2 per cent in the embolization group and 7.9 per cent in the no-embolization group (OR 2.77, 1.48 to 5.19). Propensity score matching analysis showed that median overall survival was 33.5 (95 per cent c.i. 27.4 to 42.0) months in the DP-CAR and 37.9 (32.8 to 53.3) months in the DP group. Multivariable analysis identified age at least 67 years (HR 1.40, 95 per cent c.i. 1.12 to 1.75), preoperative tumour size 30 mm or more (HR 1.42, 1.12 to 1.80), and preoperative carbohydrate antigen 19-9 level over 37 units/ml (HR 1.43, 1.11 to 1.83) as adverse prognostic factors. CONCLUSION: DP-CAR can be performed safely in centres for general pancreatic surgery regardless of DP-CAR volume, and preoperative embolization may not be required. This procedure has no oncological advantage for resectable tumour close to the bifurcation of the splenic artery, and should be performed after appropriate patient selection.

"Conversion surgery" for locally advanced pancreatic cancer: A position paper by the study group at the joint meeting of the International Association of Pancreatology (IAP) & Japan Pancreas Society (JPS) 2022.

Locally advanced pancreatic cancer (LAPC), which progresses locally and surrounds major vessels, has historically been deemed unresectable. Surgery alone failed to provide curative resection and improve overall survival. With the advancements in treatment, reports have shown favorable results in LAPC after undergoing successful chemotherapy therapy or chemoradiation therapy followed by surgical resection, so-called "conversion surgery", at experienced high-volume centers. However, recognizing significant regional and institutional disparities in the management of LAPC, an international consensus meeting on conversion surgery for LAPC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of Japan Pancreas Society (JPS) in Kyoto in July 2022. During the meeting, presenters reported the current best multidisciplinary practices for LAPC, including preoperative modalities, best systemic treatment regimens and durations, procedures of conversion surgery with or without vascular resections, biomarkers, and genetic studies. It was unanimously agreed among the experts in this meeting that "cancer biology is surpassing locoregional anatomical resectability" in the era of effective multiagent treatment. The biology of pancreatic cancer has yet to be further elucidated, and we believe it is essential to improve the treatment outcomes of LAPC patients through continued efforts from each institution and more international collaboration. This article summarizes the agreement during the discussion amongst the experts in the meeting. We hope that this will serve as a foundation for future international collaboration and recommendations for future guidelines.

Transarterial chemoembolization for liver metastases of a pancreatic neuroendocrine neoplasm: a single-center experience.

Transarterial chemoembolization (TACE) is performed for pancreatic neuroendocrine tumor (PanNEN) liver metastases; however, the safety and efficacy of TACE procedures, especially for patients who have undergone previous pancreatic surgery, have not been established. We reviewed 48 TACE procedures (1-6 procedures/patient) performed on 11 patients with PanNEN liver metastases, including 16 TACE procedures (4-6 procedures/patient) for 3 patients with a history of biliary-enteric anastomosis. The overall tumor objective response rate was 94%. The incidence of Clavien‒Dindo grade ≥ 2 complications was 1/16 (6%) and 1/32 (3%), and the median time to untreatable progression was 31 (14-41) and 27 (2-60) months among patients with and without a history of biliary-enteric anastomosis, respectively. Although validation is needed in future studies, our experiences have shown that TACE treatment is a viable treatment option for PanNEN liver metastases, even after biliary-enteric anastomosis with experienced teams and careful patient follow-up.

Gastrectomy reduces pancreatic secretory function via pancreatic atrophy.

PURPOSE: Although reports suggest that the pancreatic volume decreases after gastrectomy for gastric cancer, the relationship between the pancreatic volume and secretory function after gastrectomy remains unclear. In this study, we examined the relationship between the pancreatic volume and exocrine and endocrine functions after total gastrectomy. METHODS: The pancreatic volumes of 18 distal gastrectomy and 15 total gastrectomy patients were retrospectively measured using computed tomography volumetry up to 5 years postoperatively. Ten low anterior resection patients were selected as controls. In addition, the pancreatic volume and exocrine function evaluated by fecal elastase and the insulin secretory function evaluated by glucagon tolerance testing were prospectively examined before and one year after surgery in nine cases of total gastrectomy. RESULTS: After low anterior resection, the pancreatic volume did not change, but after distal and total gastrectomy, the pancreatic volume decreased continuously until the fifth year. After total gastrectomy, fecal elastase decreased significantly from 865.8 µg/g to 603.2 µg/g in the first year (p = 0.0316), and the insulin secretion capacity also decreased significantly from 3.83 ng/mL to 2.26 ng/mL (p = 0.0019). CONCLUSIONS: The pancreatic volume decreases continuously after gastrectomy for gastric cancer, and the pancreatic exocrine and endocrine functions decrease along with pancreatic atrophy after total gastrectomy.

Reappraisal of Malignant Risk Assessment for Small (≤20 mm) Non-functioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: Optimal management of non-functioning pancreatic neuroendocrine tumors (PanNETs) ≤20 mm is controversial. The biological heterogeneity of these tumors poses challenges when deciding between resection and observation. METHODS: In this multicenter, retrospective cohort study, we analyzed all patients (n = 78) who underwent resection of non-functioning PanNETs ≤20 mm at three tertiary medical centers from 2004 to 2020 to assess the utility of preoperatively available radiological features and serological biomarkers of non-functioning PanNETs in choosing an optimal surgical indication. The radiological features included non-hyper-attenuation pattern on enhancement computed tomography (CT; hetero/hypo-attenuation) and main pancreatic duct (MPD) involvement, and serological biomarkers included elevation of serum elastase 1 and plasma chromogranin A (CgA) levels. RESULTS: Of all small non-functioning PanNETs, 5/78 (6%) had lymph node metastasis, 11/76 (14%) were WHO grade II, and 9/66 (14%) had microvascular invasion; 20/78 (26%) had at least one of these high-risk pathological factors. In the preoperative assessment, hetero/hypo-attenuation and MPD involvement were observed in 25/69 (36%) and 8/76 (11%), respectively. Elevated serum elastase 1 and plasma CgA levels were observed in 1/33 (3%) and 0/11 (0%) patients, respectively. On multivariate logistic regression analysis, hetero/hypo-attenuation (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.7-22.2) and MPD involvement (OR 16.8, 95% CI 1.6-174.3) were significantly associated with the high-risk pathological factors. The combination of the two radiological worrisome features correctly predicted non-functioning PanNETs with high-risk pathological factors, with about 75% sensitivity, 79% specificity, and 78% accuracy. CONCLUSIONS: This combination of radiological worrisome features can accurately predict non-functioning PanNETs that may require resection.

Gastrojejunostomy versus endoscopic duodenal stent placement for gastric outlet obstruction in patients with unresectable pancreatic cancer: a propensity score-matched analysis.

BACKGROUND: Treatments for patients with gastric outlet obstruction (GOO) due to unresectable pancreatic cancers (URPC) include gastrojejunostomy (GJJ) and endoscopic duodenal stent placement (EDSP). This study compared the efficacy and safety of GJJ and EDSP in patients with GOO due to URPC. METHODS: This study retrospectively evaluated consecutive patients with GOO due to URPC who underwent GJJ or EDSP between April 2016 and March 2020. The efficacy and safety of GJJ and EDSP were compared with propensity score analysis. Subgroup analyses of overall survival (OS) were compared after propensity matching. RESULTS: Data were obtained from 54 patients who underwent GJJ and from 73 who underwent EDSP at five tertiary care hospitals. After propensity matching, OS was significantly longer in patients who underwent GJJ than EDSP (110 vs. 63 days, respectively; p = 0.019). Evaluation of long-term adverse events showed that the frequency of cholangitis and obstructive jaundice was significantly lower in the matched GJJ than in the matched EDSP group (p = 0.012). Subgroup analyses showed that OS in patients with good performance status (PS; p = 0.041), biliary obstruction (p = 0.007), and duodenal obstruction near the papilla (p = 0.027), and those receiving chemotherapy (p = 0.010), was significantly longer in the matched GJJ group than in matched EDSP group. CONCLUSION: GJJ provides longer OS than EDSP for patients with GOO caused by URPC, especially for patients with good PS, biliary obstruction, and duodenal obstruction near the papilla, and those receiving chemotherapy.

Comparison of infectious complications after spleen preservation versus splenectomy during laparoscopic distal pancreatectomy for benign or low-grade malignant pancreatic tumors: A multicenter, propensity score-matched analysis.

BACKGROUND: Previous studies have reported contrasting results regarding the advantages of spleen preservation during laparoscopic distal pancreatectomy (LDP) for preventing infectious complications. METHODS: A total of 3787 patients who underwent LDP for benign or low-grade malignant pancreatic disease in 92 centers across Korea and Japan were included in this retrospective study. Postoperative infectious complications and other complications were compared between LDP with splenectomy (LDPS) and LDP with spleen preservation (LSPDP) by propensity score matching (PSM) analysis. RESULTS: After PSM, the LSPDP group had a lower rate of overall infectious complications (P = .079) and a significantly lower rate of intra-abdominal abscess (P = .014) compared with the LDPS group. Within the LSPDP group, the vessel preservation subgroup had a significantly higher rate of infectious complications (P = .002) compared with the vessel resection subgroup. Low-volume centers had a higher rate of intra-abdominal abscess than high-volume centers in the LSPDP group (P = .001) and the splenic vessel preservation subgroup (P = .003). CONCLUSIONS: Spleen preservation in LDP for benign or borderline malignant pancreatic diseases was advantageous in lowering the risk of infectious complications, specifically intra-abdominal abscess. However, the risk of intra-abdominal abscess may differ according to the level of surgeon's experience.

Clinicopathological variables and risk factors for lung recurrence after resection of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate even after curative resection. Lung recurrence may have better outcomes than other recurrences. However, its detailed clinicopathological features are unclear. We investigated the clinicopathological features and risk factors for lung recurrence after pancreatectomy for PDAC. METHODS: The study included 161 patients with potentially and borderline resectable PDAC who had undergone R0 or R1 pancreatectomy between January 2008 and December 2016. We retrospectively examined the prognosis and predictors for lung recurrence after curative resection. RESULTS: Seventeen patients (10.6%) had isolated lung recurrence. The median overall and recurrence-free survivals were 38.0 and 16.1 months, respectively. In multivariate analysis, para-aortic lymph node (PALN) metastasis (p = 0.006) and female sex (p = 0.027) were independent factors for lung recurrence. CONCLUSION: Lung recurrence had a better prognosis than other recurrences. PALN metastasis and female sex are independent risk factors for lung recurrence after curative resection for PDAC.

Development, validation, and comparison of a nomogram based on radiologic findings for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: An international multicenter study.

BACKGROUND: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms. METHODS: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients. RESULTS: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255). CONCLUSIONS: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Three-Year Observation of Glucose Metabolism After Pancreaticoduodenectomy: A Single-Center Prospective Study in Japan.

CONTEXT: The glucose tolerance of patients changes considerably from before to after pancreaticoduodenectomy wherein approximately half of the pancreas is resected. OBJECTIVE: The aim of this prospective study was to investigate the incidence of and risk factors for diabetes after pancreaticoduodenectomy. METHODS: This study is a part of an ongoing prospective study, the Kindai Prospective Study on Metabolism and Endocrinology after Pancreatectomy (KIP-MEP) study. Of the 457 patients enrolled to date, 96 patients without diabetes who underwent pancreaticoduodenectomy were investigated in this study. Preoperatively, 1 month post-pancreaticoduodenectomy, and every 6 months thereafter, the glucose metabolism and endocrine function were evaluated using the 75 g oral glucose tolerance test. Various other metabolic, endocrine, and exocrine indices were also examined over a period of up to 36 months. RESULTS: Of the 96 patients analyzed in this study, 33 were newly diagnosed with diabetes. The cumulative diabetes incidence at 36 months following pancreaticoduodenectomy was 53.8%. The preoperative insulinogenic index and ΔC-peptide in the glucagon stimulation test were significantly lower in the progressors to diabetes than in the nonprogressors. Multivariate Cox regression analysis demonstrated that the insulinogenic index was the only significant risk factor for new-onset diabetes. CONCLUSION: The majority of patients developed new-onset diabetes after pancreaticoduodenectomy, and a low value of the insulinogenic index was suggested to be a risk factor for diabetes. Preoperative assessment for the prediction of the onset of diabetes serves as useful information for patients and is important for postoperative glycemic control and diabetes management in patients who require pancreaticoduodenectomy.

Utility of contrast-enhanced harmonic EUS for diagnosis of portal vein invasion by pancreatic cancer.

Background: The value of contrast-enhanced harmonic EUS (CH-EUS) for diagnosis of portal vein invasion in patients with pancreatic cancer was evaluated. Patients and Methods: This single-center, retrospective study included consecutive patients with pancreatic cancer who underwent both surgical resection after preoperative EUS, CH-EUS, and contrast-enhanced computed tomography (CE-CT) examinations between April 2015 and August 2017. CH-EUS evaluation was performed during the late phase. Portal vein invasion on EUS and CH-EUS was defined as no continuity in the line of the vessel wall. Definition of portal vein invasion on CE-CT was based on the Loyer's criteria. The accuracy of three modalities for diagnosis of invasion into the portal vein was compared using the McNemar's test. Results: Eighty-eight patients (mean age: 71.0 years, ratio of male to female: 48:40) were eligible. Postoperative pathological results were as follows: seven cases of portal vein invasion; 81 cases without. Diagnostic accuracy of EUS, CH-EUS, and CE-CT for diagnosing invasion into the portal vein was 72.7%, 93.2%, and 81.8%, respectively. The differences between CH-EUS and CE-CT (P = 0.0094) and CH-EUS and EUS (P = 0.0022) were significant. EUS and CE-CT were comparable. Conclusion: CH-EUS is useful for diagnosis of portal vein invasion by pancreatic cancer.

Risk factors associated with hypoglycemic events after total pancreatectomy: A nationwide multicenter prospective study in Japan.

BACKGROUND: The number of total pancreatectomy cases have increased worldwide, expanding the need for new insulin products and high-titer pancrelipases. However, the current data that is focused on hypoglycemic events after a total pancreatectomy from large nationwide series are still lacking. This study is aimed to assess the risk factors associated with hypoglycemic events after a total pancreatectomy. METHODS: Data were prospectively collected from 216 consecutive patients who underwent total pancreatectomies between August 2015 and December 2017 from 68 Japanese centers. Of the 216 patients, 166 with a follow-up period of 1 year were analyzed. The risk factors for hypoglycemic events at 6 and 12 months (postoperative months 6 and 12) were investigated based on the results of a nationwide multicenter prospective study. RESULTS: Of the 166 patients, 57 (34%) and 70 (42%) experienced moderate or severe hypoglycemic events or hypoglycemia unawareness on a monthly basis at postoperative months 6 and 12, respectively. Multivariate analysis revealed that body weight loss after surgery ≥0.3 kg and total cholesterol level ≤136 mg/dL at postoperative month 6, and glycated hemoglobin level ≤8.9% and rapid-acting insulin use at postoperative month 12 were independent risk factors for hypoglycemic events after a total pancreatectomy. There were different independent risk factors depending on the postoperative period. CONCLUSION: Patients with body weight loss after surgery, low total cholesterol level, strict glycemic control, and using rapid-acting insulin should be aware of the occurrence of hypoglycemic events after their total pancreatectomy. In order to prevent hypoglycemic events after a total pancreatectomy, we need to consider optimal nutritional and glycemic control according to the postoperative period.

Longitudinal Pancreaticojejunostomy for Pancreaticodigestive Tract Anastomotic Stricture After Pancreaticoduodenectomy.

Aim: Pancreaticodigestive tract anastomotic stricture is a long-term complication of pancreticoduodenectomy (PD). However, optimal treatment has not yet been defined. We conducted longitudinal pancreaticojejunostomy (LPJ) in symptomatic patients with anastomotic stricture after PD. This study aimed to evaluate the efficacy of this procedure. Methods: Pancreticoduodenectomy was performed in 605 patients at our institution between January 2005 and April 2020. Of these, 15 patients (2.5%) developed symptomatic pancreaticodigestive tract anastomotic stricture after PD. Three patients were referred to our institution owing to recurrent pancreatitis with anastomotic stricture after PD. LPJ was indicated for these 18 patients, and they were enrolled in this study. Results: The median time from the initial operation to LPJ was 2.0 y. Preoperative clinical presentations included obstructive pancreatitis in 10 patients, a rapid deterioration of glucose tolerance in nine, and severe steatorrhea in two. Surgical morbidity ≥grade III defined by the Clavien-Dindo classification was not observed. After LPJ, preoperative symptoms improved in 16 patients (89%) during a median follow-up of 39 mo. Nine of the 10 patients with obstructive pancreatitis achieved complete pain relief. All nine patients with a rapid deterioration of glucose tolerance showed improved endocrine function. Daily insulin requirement was significantly decreased after LPJ (11.6 ± 3.3 vs 3.4 ± 4.3 units, P = .0239). Four of the seven patients who required insulin injections were free of insulin after LPJ. Conclusion: LPJ is a safe and effective surgical procedure for symptomatic patients with stricture of the pancreaticodigestive tract anastomosis after PD.