Short-term serial circulating tumor DNA assessment predicts therapeutic efficacy for patients with advanced pancreatic cancer.

PURPOSE: We investigated the potential clinical utility of short-term serial KRAS-mutated circulating cell-free tumor DNA (ctDNA) assessment for predicting therapeutic response in patients undergoing first-line chemotherapy for advanced pancreatic cancer. METHODS: We collected 144 blood samples from 18 patients with locally advanced or metastatic cancer that were undergoing initial first-line chemotherapy of gemcitabine plus nab-paclitaxel (GEM plus nab-PTX). Analysis of KRAS-mutated ctDNA was quantified by digital droplet polymerase chain reaction (ddPCR) as mutant allele frequency (MAF). This study investigated pretreatment KRAS-mutated ctDNA status and ctDNA kinetics every few days (days 1, 3, 5 and 7) after initiation of chemotherapy and their potential as predictive indicators. RESULTS: Of the 18 enrolled patients, an increase in KRAS-mutated ctDNA MAF values from day 0-7 after initiation of chemotherapy was significantly associated with disease progression (P < 0.001). Meanwhile, positive pretreatment ctDNA status (MAF ≥ 0.02%) (P = 0.585) and carbohydrate antigen 19-9 (CA19-9) values above the median (P = 0.266) were not associated with disease progression. In univariate analysis, this short-term increase in ctDNA MAF values (day 0-7) was found to be associated with significantly shorter progression free survival (PFS) (hazard ration [HR], 24.234; range, (2.761-212.686); P = 0.0002). CONCLUSION: This short-term ctDNA kinetics assessment may provide predictive information to reflect real-time therapeutic response and lead to effective refinement of regimen in patients with advanced pancreatic cancer undergoing systemic chemotherapy.

An easy-to-implement, non-invasive head restraint method for monkey fMRI.

Functional magnetic resonance imaging (fMRI) in behaving monkeys has a strong potential to bridge the gap between human neuroimaging and primate neurophysiology. In monkey fMRI, to restrain head movements, researchers usually surgically implant a plastic head-post on the skull. Although time-proven to be effective, this technique could create burdens for animals, including a risk of infection and discomfort. Furthermore, the presence of extraneous objects on the skull, such as bone screws and dental cement, adversely affects signals near the cortical surface. These side effects are undesirable in terms of both the practical aspect of efficient data collection and the spirit of "refinement" from the 3R's. Here, we demonstrate that a completely non-invasive fMRI scan in awake monkeys is possible by using a plastic head mask made to fit the skull of individual animals. In all of the three monkeys tested, longitudinal, quantitative assessment of head movements showed that the plastic mask has effectively suppressed head movements, and we were able to obtain reliable retinotopic BOLD signals in a standard retinotopic mapping task. The present, easy-to-make plastic mask has a strong potential to simplify fMRI experiments in awake monkeys, while giving data that is as good as or even better quality than that obtained with the conventional head-post method.

Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.

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.

Utility of contrast-enhanced harmonic endoscopic ultrasonography for prediction of pathological response after neoadjuvant chemotherapy in patients with pancreatic cancer.

OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) plays an important role in the diagnosis of pancreatic lesions. The aim of this study was to evaluate whether CH-EUS is useful for predicting the treatment efficacy of neoadjuvant chemotherapy (NAC) determined by pathological response. METHODS: Patients who underwent CH-EUS before chemotherapy and surgical resection were divided into two groups according to poor (group-P) or rich tumor vascularity (group-R) determined by enhancement pattern on early- and late-phase CH-EUS. The pathological response to chemotherapy was categorized according to Evans' classification. Pathological analysis showing tumor cell destruction (>50 %) defined a good response. RESULTS: Early-phase CH-EUS classified 44 patients into group-R and 50 into group-P, whereas late-phase CH-EUS classified 10 into group-R and 84 into group-P. Early-phase CH-EUS classification resulted in significantly higher numbers of patients with a good response in the rich group (n = 19) than in the poor group (n = 4; P = 0.0015). Multivariate analysis showed that assignment to the rich group was the strongest independent factor associated with chemosensitivity (P = 0.006, hazard ratio = 5.66, 95 % confidence interval: 1.17-19.27). In resectable patients, the enhancement pattern was the only independent factor associated with chemosensitivity (group-P vs. group-R, P = 0.003; HR [95 % CI], 14.59 [1.38-154.38]). Late-phase CH-EUS did not reveal a significant difference between group-P and group-R. CONCLUSIONS: Evaluation of vascular pattern on CH-EUS could be useful for predicting the efficacy of NAC in patients with pancreatic cancer. The enhancement pattern on CH-EUS could be a one of the useful features for determining NAC indications in resectable pancreatic cancer patients.

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.

Right posterior bile duct stricture after laparoscopic anterior sectionectomy with long right bile duct: A case report.

Right anterior liver sectionectomy (RAS) is a complicated procedure with high incidences of postoperative complications. We report a case of right posterior bile duct (RPBD) stricture after laparoscopic RAS with discussion of the anatomical aspects. A 69-year-old Japanese man had solitary colorectal liver metastasis. A tumor was located near the root of the right anterior Glissonean pedicle. On postoperative day 6, he had cholangitis and imaging studies showed RPBD stricture. Symptoms disappeared following a course of antibiotics and the patient was discharged on postoperative day 21. The RBPD anatomy type of this patient was a supra-portal pattern with a long (18 mm) right biliary duct, which would be close to the right anterior Glissonean bifurcation. A stapling device might have caused its deformation and resulted in its stricture. As the RPBD has variant anatomy, we had to notice that there may be hazardous types for postoperative RPBD stricture.

Radiographic duodenal invasion is associated with poor prognosis and early recurrence in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: The prognostic impact of radiographic duodenal invasion (rDI) of pancreatic ductal adenocarcinoma (PDAC) has yet to be fully elucidated. This retrospective study aimed to investigate the prognostic and clinicopathological significance of rDI in patients with PDAC after pancreatoduodenectomy (PD). MATERIALS AND METHODS: We retrospectively analyzed 223 consecutive patients with resectable (R) and borderline resectable (BR)-PDAC that underwent up-front PD between 2002 and 2018. rDI was assessed by preoperative multi-detector row computed tomography. RESULTS: Ninety-three (42%) patients with PDAC had rDI, and all of them had pathological DI (pDI). The rDI(+) group had larger tumor size, BR-PDAC was more common, there was higher serum CA19-9 level, and microscopic lymphovascular invasion was more common than in the rDI(-) group. rDI was associated with significant reduction in overall survival (OS) (P < 0.001) and recurrence-free survival (RFS) (P < 0.001). In multivariate analysis, rDI was an independent prognostic factor in OS [hazard ratio (HR) = 0.52; 95% confidence interval (CI) 0.38-0.73, P < 0.001] and RFS [HR = 0.56; 95% CI 0.40-0.78, P = 0.001]. rDI was also an independent risk factor for early recurrence within 12 months [odds ratio (OR) = 0.36; 95% CI 0.18-0.73, P = 0.005]. rDI had positive correlation with liver recurrence (P = 0.024). CONCLUSION: Biological aggressiveness of PDAC with rDI implies short OS and early recurrence with frequent liver metastasis. Aggressive perioperative chemotherapy is recommended to improve prognosis, especially for R-PDAC patients with rDI.

Radiological Shape of the Tumor Predicts Progression and Survival in Resected Extrahepatic Cholangiocarcinoma.

BACKGROUND: The histological features and radiological shape of extrahepatic cholangiocarcinoma (eCCA) have not been widely studied in relation to prognosis. Multi-detector computed tomography (MDCT) is thought to be useful in diagnosis of progress and tumor distribution; it can also show morphological differences (round, triangular, and square forms) at the tumoral obstruction sites. Histological types of eCCA may be revealed, with potential association with tumor growth and survival. METHODS: We examined the distribution of tumor radiological shape subtypes on MDCT. The surgical outcomes of consecutive patients with eCCA who underwent macroscopic curative resection were reviewed. RESULTS: CT subtypes in 109 patients were 62 triangular, 35 square, and 12 round. There were clear prognostic differences in long-term survival rates (P < 0.001); 5-year survival rates were 100% in round, 64% in triangular, and 19% in square types. There was no recurrence in any cases of round-type tumor at the site of obstruction. Depth of tumor invasion and rates of nodal involvement were significantly higher in triangular and square-type tumors than in round-type tumors. In papillary adenocarcinoma, radiological obstructions were round type in seven patients (78%) and triangular type in two patients (22%). In tubular adenocarcinoma, all round-type tumors were well differentiated, the ratio of square-type tumors increasing as the degree of differentiation decreased from "well" to "moderate," and "poor" respectively (23%, 39%, 57%; P = 0.033). CONCLUSIONS: Tumor radiological shape predicts tumor progression, histological type, and survival in eCCA. This information may be helpful in preoperative radiological staging on MDCT.

Positive drain fluid culture on postoperative day 1 predicts clinically relevant pancreatic fistula in early drain removal with higher drain fluid amylase after pancreaticoduodenectomy.

BACKGROUND: This study aimed to clarify the risk factors of clinically relevant pancreatic fistula after early drain removal with higher drain fluid amylase after pancreaticoduodenectomy. Clinical evaluation of early drain removal with a higher drain fluid amylase after pancreaticoduodenectomy has been controversial. The safety and effectiveness have not been sufficiently examined. METHODS: Between 2015 and 2020, prophylactic surgical drains were prospectively removed on postoperative day 4 regardless of drain fluid amylase level in 364 study-eligible patients who underwent pancreaticoduodenectomy. Patients were classified according to drain fluid amylase on postoperative day 1: 281 patients with drain fluid amylase <4,000 U/L, and 83 patients with drain fluid amylase ≥4,000 U/L. RESULTS: Clinically relevant pancreatic fistula occurred in 40 of 364 enrolled patients (11.0%). In the entire cohort, male, positive postoperative day 1 drain fluid culture, and postoperative day 1 drain fluid amylase ≥4,000 U/L were independent risk factors for clinically relevant pancreatic fistula after early drain removal. When stratifying by 4,000 U/L of postoperative day 1 drain fluid amylase, the rate of clinically relevant pancreatic fistula in postoperative day 1 drain fluid amylase <4,000 U/L was significantly lower than that in postoperative day 1 drain fluid amylase ≥4,000 U/L (4% vs 35%, P < .001) after early drain removal. Moreover, in postoperative day 1 drain fluid amylase <4,000 U/L, positive postoperative day 1 drain fluid culture did not develop clinically relevant pancreatic fistula after early drain removal. However, in postoperative day 1 drain fluid amylase ≥4,000 U/L, multivariate analysis clarified that positive postoperative day 1 drain fluid culture was the only independent risk factor of clinically relevant pancreatic fistula after early drain removal (odds ratio 26.27, 95% confidence interval 5.59-123.56, P = .001). CONCLUSION: Positive drain fluid culture on postoperative day 1 might predict clinically relevant pancreatic fistula in early drain removal with a higher drain fluid amylase.

Clinical practice guidelines for duodenal cancer 2021.

Duodenal cancer is considered to be a small intestinal carcinoma in terms of clinicopathology. In Japan, there are no established treatment guidelines based on sufficient scientific evidence; therefore, in daily clinical practice, treatment is based on the experience of individual physicians. However, with advances in diagnostic modalities, it is anticipated that opportunities for its detection will increase in future. We developed guidelines for duodenal cancer because this disease is considered to have a high medical need from both healthcare providers and patients for appropriate management. These guidelines were developed for use in actual clinical practice for patients suspected of having non-ampullary duodenal epithelial malignancy and for patients diagnosed with non-ampullary duodenal epithelial malignancy. In this study, a practice algorithm was developed in accordance with the Minds Practice Guideline Development Manual 2017, and Clinical Questions were set for each area of epidemiology and diagnosis, endoscopic treatment, surgical treatment, and chemotherapy. A draft recommendation was developed through a literature search and systematic review, followed by a vote on the recommendations. We made decisions based on actual clinical practice such that the level of evidence would not be the sole determinant of the recommendation. This guideline is the most standard guideline as of the time of preparation. It is important to decide how to handle each case in consultation with patients and their family, the treating physician, and other medical personnel, considering the actual situation at the facility (and the characteristics of the patient).

Supervised Exercise Therapy and Adjuvant Chemotherapy for Pancreatic Cancer: A Prospective, Single-Arm, Phase II Open-Label, Nonrandomized, Historically Controlled Study.

BACKGROUND: Improvement of the completion rate of postoperative adjuvant chemotherapy is a key to obtaining favorable prognosis in patients who undergo macroscopically curative pancreatectomy for pancreatic ductal adenocarcinoma. STUDY DESIGN: This study is a prospective single-center phase II trial that aimed to examine whether a supervised exercise therapy for pancreatic ductal adenocarcinoma improved the completion rate of S-1 adjuvant chemotherapy in the development of a tolerable and effective exercise plan for patients undergoing adjuvant therapy. RESULTS: Forty-three patients were included in the study. The completion rate of S-1 therapy, the primary endpoint, was 93%, which exceeded the threshold completion rate of 53% (p < 0.001). As secondary endpoints, the relative dose intensity of S-1 was 100.0 [95.9 to 100.0] (median [interquartile range]), the median recurrence-free survival was 20.4 months, and the median overall survival was not reached, confirming the safety of the protocol treatment. Regarding frailty status, there was significant decrease in the Kihon checklist score (p = 0.002) and significant increase in G8 questionnaire score (p < 0.001), indicating that exercise therapy reduced frailty. There were no incidences of serious adverse events except for 1 case of grade 3 febrile neutropenia. The differences between before/after therapy (between 6 months/baseline) of mean muscle mass, mean body fat mass, mean body fat percentage, and mean controlling nutrition status score were 1.52 (p < 0.001), -1.18 (p = 0.007), -2.47 (p < 0.001), and -0.59 (p = 0.006), respectively. CONCLUSIONS: Adjuvant chemotherapy combined with supervised exercise therapy for pancreatic ductal adenocarcinoma was confirmed to improve the completion rate of S-1 adjuvant chemotherapy.

Neural signals regulating motor synchronization in the primate deep cerebellar nuclei.

Movements synchronized with external rhythms are ubiquitous in our daily lives. Despite the involvement of the cerebellum, the underlying mechanism remains unclear. In monkeys performing synchronized saccades to periodically alternating visual stimuli, we found that neuronal activity in the cerebellar dentate nucleus correlated with the timing of the next saccade and the current temporal error. One-third of the neurons were active regardless of saccade direction and showed greater activity for synchronized than for reactive saccades. During the transition from reactive to predictive saccades in each trial, the activity of these neurons coincided with target onset, representing an internal model of rhythmic structure rather than a specific motor command. The behavioural changes induced by electrical stimulation were explained by activating different groups of neurons at various strengths, suggesting that the lateral cerebellum contains multiple functional modules for the acquisition of internal rhythms, predictive motor control, and error detection during synchronized movements.

Perioperative management for patient with congenital factor VII deficiency who underwent laparoscopic cholecystectomy: Case report.

INTRODUCTION AND IMPORTANCE: In patients with congenital factor VII (FVII) deficiency, perioperative bleeding events are concern, so recombinant activated factor VII (rFVIIa) is favorably used, but the optimal dosage regimen has not clearly established. We report management of a patient with congenital FVII deficiency who underwent laparoscopic cholecystectomy. CASE PRESENTATION: A 70-year-male with congenital FVII deficiency was diagnosed as acute cholecystitis, so we planned laparoscopic cholecystectomy. FVII activity and prothrombin time international normalized ratio (PT-INR) were intraoperatively monitored as scheduled. At the start of surgery, FVII activity was 3.1% (75-130%) and PT-INR was 3.37 (0.8-1.2), so 1 mg of rFVIIa was administered. Both of these values then improved to 325.0% and 0.73, respectively. Laparoscopic cholecystectomy was successfully completed without unexpected bleeding or oozing. When FVII activity and PT-INR was re-checked 6 h after the first administration of rFVIIa, these values were 23.9% and 1.53, respectively. Additional 1 mg of rFVIIa was used only once after the operation. The patient was discharged on the sixth day after surgery without postoperative complication. CLINICAL DISCUSSION: In this case, rFVIIa was used just twice and there were no bleeding events during the perioperative period. Previous reports suggested using 15-30 µg/kg of rFVIIa before surgery and subsequent every 4-6 h in the first 24 h, then increasing the interval to 8-12 h. It is necessary to evaluate optimal dose of rFVIIa based on the risk and surgical invasiveness for each case. CONCLUSION: Our patient with congenital FVII deficiency uneventfully underwent laparoscopic cholecystectomy.

Surgical results of non-ampullary duodenal cancer: a nationwide survey in Japan.

BACKGROUND: As non-ampullary duodenal cancer is relatively rare, the optimal treatment strategy, including the appropriate surgical procedure and efficacy of adjuvant chemotherapy, remains unclear. This nationwide survey aimed to clarify the actual lymph node spread pattern and determine the optimal treatment strategy for this disease, using a large-scale database. METHODS: We used a questionnaire and a retrospective registry of 1083 patients with non-ampullary duodenal cancer who had undergone surgery during 2008-2017 in 114 high-volume Japanese Society of Hepatobiliary and Pancreatic Surgery-certified training institutions. Propensity score-matched analyses were conducted to minimise background bias. Cox regression was performed to identify covariates associated with recurrence-free survival. There were distinct disparities in the nodal dissection rate according to the predominant tumor location and tumor invasion depth. Metastases were frequently observed in the peripancreatic nodes and those along the superior mesenteric artery, irrespective of tumor location. Their dissection seemed to be beneficial for improved survival. In the overall cohort, no survival benefit was observed in patients who received adjuvant chemotherapy when compared with that in patients who underwent surgery alone. Nevertheless, in the matched cohort, adjuvant chemotherapy for > 6 months was associated with a significant improvement in recurrence-free survival (median: 43.5 vs. 22.5 months, p = 0.016), particularly in patients with tumor invasion of the subserosa or deeper tumor invasion, lymph node metastasis, or elevated serum carbohydrate antigen 19-9 levels. CONCLUSION: Pancreatoduodenectomy should be the standard procedure for advanced non-ampullary duodenal cancer. Adjuvant chemotherapy for > 6 months, especially for advanced tumors, significantly improves survival.

Malignant potential and specific characteristics of pure main duct type intraductal papillary mucinous neoplasm.

BACKGROUND: As the malignant potential of main duct (MD-) type intraductal papillary mucinous neoplasm (IPMN) has been discussed together with Mixed-type in most previous studies, the malignant potential of pure MD-type IPMN remains unclear. This study evaluated the specific characteristics and predictors of high-grade dysplasia (HGD) and invasive intraductal papillary mucinous carcinoma (IPMC) for pure MD-type IPMN. METHODS: From 1,100 patients with IPMN, this study includes 387 patients that underwent surgery. We evaluated the specific characteristics of pure MD-type IPMN by comparing clinicopathological factors between MD-type (n = 79) and branch duct (BD-) type (n = 146) or Mixed-type IPMN (n = 162), and predictors of HGD/invasive IPMC in pure MD-type IPMN. RESULTS: The rate of HGD/invasive IPMC was significantly higher in MD-type than in BD-type (70.9 vs. 48.6%, P = 0.001), although there was no difference between MD-type and Mixed-type IPMNs (P = 0.343). Recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with MD-type were better than those of patients with Mixed-type (P = 0.008 and P = 0.009, respectively). There were no significant differences in RFS, overall survival, and DSS between patients with MD-type and patients with BD-type IPMNs. Multivariate analysis showed two independent predictors of HGD/invasive IPMC in MD-type IPMN; mural nodule height ≥5 mm (P = 0.025, odds ratio [OR]; 16.949) and carcinoembryonic antigen (CEA) level in the pancreatic juice obtained by preoperative endoscopic retrograde pancreatography ≥50 ng/ml (P = 0.039, OR; 9.091). CONCLUSIONS: Measurement of mural nodule height and CEA in the pancreatic juice might be useful in determining surgical indication for pure MD-type IPMN, although further studies for confirmation are essential.

Pancreatectomy With Artery En-bloc Resection for Pancreatic Neck/Body Cancer: A Single-arm Pilot Study.

BACKGROUND/AIM: The potential benefits of pancreatectomy with major arterial resection have been studied in the past, but findings remain controversial. Pancreatic neck/body cancer (PNBC) involving arteries frequently requires combined resection of the pancreas, artery and portal vein. PATIENTS AND METHODS: Nine prospectively-registered consecutive patients with PNBC were enrolled, all underwent pancreatoduodenectomy with common hepatic artery en-bloc resection (PD-CHAR). We investigated the safety of PD-CHAR by blood flow evaluation with intraoperative indocyanine green fluorescence imaging in reconstructed vessels/organs. RESULTS: Among patients who underwent PD-CHAR, there was no severe morbidity. Artery/portal vein combined resection and reconstruction was performed in all patients. Four (44%) patients had pathological positivity for cancer cell invasion into the nerve plexus of artery at the site of radiographic artery involvement, although one (11%) was diagnosed with pathological artery involvement. CONCLUSION: PD-CHAR following neoadjuvant therapy might be feasible for PNBC without severe postoperative complications. Survival benefits in PNBC should be confirmed in further studies.

Circulating Tumor DNA as a Potential Prognostic Marker in Patients with Borderline-Resectable Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy Followed by Pancreatectomy.

BACKGROUND: Circulating tumor DNA (ctDNA) might be a promising biomarker for pancreatic cancer in liquid biopsy. This study aimed to evaluate the usefulness of liquid biopsy for patients with borderline-resectable pancreatic cancer (BR-PC). METHODS: Patients with BR-PC according to the National Comprehensive Cancer Network guidelines (2017) and eligible for neoadjuvant chemotherapy (NAC) followed by pancreatectomy were recruited at Wakayama Medical University Hospital (UMIN000026647) between March 2017 and April 2020. The study enrolled 55 patients with locally advanced PC, and each patient consented to inclusion in the study. The study investigated the relationship between KRAS status in ctDNA and clinicopathologic features, analyzing ctDNA at three time points: pretreatment, post-NAC, and post-operation. RESULTS: Of the 55 enrolled patients with a diagnosis of BR-PC, 34 were scheduled to undergo pancreatectomy. From 27 patients with resected BR-PC, 81 blood samples were analyzed in triplicate for ctDNA. The patients with positive pretreatment and post-NAC ctDNA status had no significant decrease in median relapse-free survival (RFS) or overall survival (OS). However, the patients with positive postoperation ctDNA status had a significantly shorter median OS (723 days) than the patients with negative ctDNA results (not reached; P = 0.0148). A combined analysis of postoperative ctDNA and CA19-9 values showed the cumulative effect on both RFS (P = 0.0066) and OS (P = 0.0046). The adjusted hazard ratio for risk of survival computed for the patients carrying risk factors (either detectable ctDNA or CA19-9 > 37 U/ml) increased from 4.13-fold to 17.71-fold (both P = 0.0055) compared with the patients who had no risk factors. CONCLUSION: Positive ctDNA predicts poor survival for patients with BR-PC who undergo NAC followed by pancreatectomy.