A multi-institutional randomized phase III study comparing minimally invasive distal pancreatectomy versus open distal pancreatectomy for pancreatic cancer; Japan Clinical Oncology Group study JCOG2202 (LAPAN study).

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP), including laparoscopic and robotic distal pancreatectomy, has gained widespread acceptance over the last decade owing to its favorable short-term outcomes. However, evidence regarding its oncologic safety is insufficient. In March 2023, a randomized phase III study was launched in Japan to confirm the non-inferiority of overall survival in patients with resectable pancreatic cancer undergoing MIDP compared with that of patients undergoing open distal pancreatectomy (ODP). METHODS: This is a multi-institutional, randomized, phase III study. A total of 370 patients will be enrolled from 40 institutions within 4 years. The primary endpoint of this study is overall survival, and the secondary endpoints include relapse-free survival, proportion of patients undergoing radical resection, proportion of patients undergoing complete laparoscopic surgery, incidence of adverse surgical events, and length of postoperative hospital stay. Only a credentialed surgeon is eligible to perform both ODP and MIDP. All ODP and MIDP procedures will undergo centralized review using intraoperative photographs. The non-inferiority of MIDP to ODP in terms of overall survival will be statistically analyzed. Only if non-inferiority is confirmed will the analysis assess the superiority of MIDP over ODP. DISCUSSION: If our study demonstrates the non-inferiority of MIDP in terms of overall survival, it would validate its short-term advantages and establish its long-term clinical efficacy. TRIAL REGISTRATION: This trial is registered with the Japan Registry of Clinical Trials as jRCT 1,031,220,705 [ https://jrct.niph.go.jp/en-latest-detail/jRCT1031220705 ].

Subcutaneous emphysema associated with laparoscopic or robotic abdominal surgery: a retrospective single-center study.

BACKGROUND: Subcutaneous emphysema (SCE) is a common complication in laparoscopic surgery. However, its precise incidence and impact on the clinical course are partially known. In this study, the incidence and risk factors of SCE were retrospectively analyzed. METHODS: Patients who underwent laparoscopic/robotic abdominal surgery (e.g., gastrointestinal, hepatobiliary, gynecologic, and urologic surgery) between October 2019 and September 2022 were retrospectively analyzed. The presence of SCE was confirmed by either conclusive findings obtained through chest/abdominal X-ray examination immediately after operation, or intraoperative palpation conducted by nurses. X-ray examination was performed in the operation room before extubation. RESULTS: A total of 2503 patients treated with laparoscopic/robotic abdominal surgery between October 2019 and September 2022 were identified and all of them were included in the analysis. SCE was confirmed in 23.1% of the patients (i.e., 577/2503). SCE was identified by X-ray examination in 97.6% of the patients. Extubation failure was observed in 10 patients; however, pneumothorax was not observed. Female sex (odds ratio [OR]: 2.09; 95% confidence interval [95%CI]: 1.69-2.57), age ≥ 80 years (OR 1.63; 95%CI 1.19-2.22), body mass index < 20 (OR 1.32; 95%CI 1.06-1.65), operation time > 360 min (OR 1.97; 95%CI 1.53-2.54), robotic surgery (OR 2.54; 95%CI 1.91-3.38), maximum intraabdominal pressure with CO2 > 15 mmHg (OR 1.79; 95%CI 1.02-3.16), and endo-tidal CO2 > 50 mmHg (OR 1.32; 95%CI 1.08-1.62)were identified as independent factors of SCE. Regarding the extubation failure due to SCE, age (OR 5.84; 95%CI 1.27-26.8) and maximum intraabdominal pressure with CO2 (OR 21.7; 95%CI 4.76-99.3) were identified as risk factors. CONCLUSION: Although the presence of SCE is associated with a low risk of severe complications, monitoring of the perioperative intraabdominal pressure is essential for performing safe laparoscopic/robotic surgery, particularly in elderly patients.

Autophagy Inhibition Increased Sensitivity of Pancreatic Cancer Cells to Carbon Ion Radiotherapy.

BACKGROUND/AIMS: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer. METHODS: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone. RESULTS: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining. CONCLUSION: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.

Protocol of the RACB study: a multicenter, single-arm, prospective study to evaluate the efficacy of resection of initially unresectable hepatocellular carcinoma with atezolizumab combined with bevacizumab.

BACKGROUND: Although the standard therapy for advanced-stage hepatocellular carcinoma (HCC) is systemic chemotherapy, the combination of atezolizumab and bevacizumab (atezo + bev) with a high objective response rate may lead to conversion to resection in patients with initially unresectable HCC. This study aims to evaluate the efficacy of atezo + bev in achieving conversion surgery and prolonged progression-free survival (PFS) for initially unresectable HCC. METHODS: The RACB study is a prospective, single-arm, multicenter, phase II trial evaluating the efficacy of combination therapy with atezo + bev for conversion surgery in patients with technically and/or oncologically unresectable HCC. The main eligibility criteria are as follows: (1) unresectable HCC without a history of systemic chemotherapy, (2) at least one target lesion based on RECIST ver. 1.1, and (3) a Child‒Pugh score of 5-6. The definition of unresectable tumors in this study includes macroscopic vascular invasion and/or extrahepatic metastasis and massive distribution of intrahepatic tumors. Patients will be treated with atezolizumab (1200 mg/body weight) and bevacizumab (15 mg/kg) every 3 weeks. If the patient is considered resectable on radiological assessment 12 weeks after initial chemotherapy, the patient will be treated with atezolizumab monotherapy 3 weeks after combination chemotherapy followed by surgery 3 weeks after atezolizumab monotherapy. If the patient is considered unresectable, the patient will continue with atezo + bev and undergo a radiological assessment every 9 weeks until resectable or until disease progression. The primary endpoint is PFS, and the secondary endpoints are the overall response rate, overall survival, resection rate, curative resection rate, on-protocol resection rate, and ICG retention rate at 15 min after atezo + bev therapy. The assessments of safety and quality of life during the treatment course will also be evaluated. The number of patients has been set at 50 based on the threshold and the expected PFS rate at 6 months after enrollment of 40% and 60%, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods will be 2 and 1.5 years, respectively. DISCUSSION: This study will elucidate the efficacy of conversion surgery with atezo + bev for initially unresectable HCC. In addition, the conversion rate, safety and quality of life during the treatment course will also be demonstrated. TRIAL REGISTRATION: This study is registered in the Japan Registry of Clinical Trials (jRCTs051210148, January 7, 2022).

A comparative study between computed tomography and endoscopic ultrasound in the detection of a mural nodule in intraductal papillary mucinous neoplasm -Multicenter observational study in Japan.

BACKGROUND/OBJECTIVES: The detection of malignancy is a major concern in the management of intraductal papillary mucinous neoplasm (IPMN). The height of the mural nodule (MN), estimated using endoscopic ultrasound (EUS) and computed tomography (CT), has been considered crucial for predicting malignant IPMN. Currently, whether surveillance using CT or EUS alone is sufficient for detecting MNs remains unclear. This study aimed to compare the ability of CT and EUS to detect MNs in IPMN. METHODS: This multicenter, retrospective observational study was conducted in 11 Japanese tertiary institutions. Patients who underwent surgical resection of IPMN with MN after CT and EUS examinations were eligible to participate. The MN detection rates between CT and EUS were examined. RESULTS: Two-hundred-and-forty patients who underwent preoperative EUS and CT had pathologically confirmed MNs. The MN detection rates of EUS and CT were 83% and 53%, respectively (p < 0.001). Additionally, the MN detection rate of EUS was significantly higher than that of CT regardless of morphological type (76% vs. 47% in branch-duct-type IPMN; 90% vs. 54% in mixed IPMN; 98% vs. 56% in main-duct-type IPMN; p < 0.001). Further, pathologically confirmed MNs ≥5 mm were more frequently observed on EUS than on CT (95% vs. 76%, p < 0.001). CONCLUSIONS: EUS was superior to CT for the detection of MN in IPMN. EUS surveillance is essential for the detection of MNs.

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.

Radiographic Splenic Artery Involvement Is a Poor Prognostic Factor in Upfront Surgery for Patients with Resectable Pancreatic Body and Tail Cancer.

PURPOSE: The prognostic impact of radiographic splenic vessel involvement in pancreatic cancer remains unclear. We evaluate its oncological significance in resectable pancreatic body/tail cancer. PATIENTS AND METHODS: We retrospectively review 102 cases of resectable pancreatic cancer and 51 of borderline resectable pancreatic cancer (BRPC) who underwent pancreatectomy for pancreatic body/tail cancer. Resectable pancreatic body/tail cancer was classified into one of three categories based on radiographic splenic vessel involvement. RESULTS: Among 102 cases of resectable pancreatic cancer, 37 (36.3%), 35 (34.3%), and 30 cases (29.4%) were classified as no splenic vessel involvement (Rnone), splenic vein involvement (RV), and splenic artery involvement (RA), respectively. Disease-free survival (DFS) among patients with Rnone, RV, RA, and BRPC was 58.5, 18.4, 10.8, and 9.2 months, respectively. Patients with RV and RA had significantly poorer DFS than patients with Rnone (P = 0.010, P < 0.001, respectively). Median survival among Rnone, RV, RA, and BRPC was 80.6, 23.4, 15.1, and 21.3 months, respectively. Patients with RV and RA had significantly poorer survival than patients with Rnone (P = 0.001, P < 0.001, respectively) and had short survival similar to that of those with BRPC. Multivariate Cox proportional hazard analysis detected preoperative CA19-9 ≥ 37 IU/L, radiologic splenic vein involvement, radiologic splenic artery involvement, intraoperative bleeding ≥ 500 ml, transfusion, positive washing cytology, and noncompletion of adjuvant therapy as independent prognostic factors. CONCLUSIONS: Radiographic splenic artery involvement is a poor prognostic factor in resectable pancreatic body/tail cancer and may have a role in stratification of treatment strategy.

Division of the pancreas at the neck reduces postoperative pancreatic fistula in laparoscopic distal pancreatectomy: Comparison of pancreatic division at the body.

BACKGROUND: objectives: During laparoscopic distal pancreatectomy (LDP), the optimal site for pancreatic division with consideration of postoperative pancreatic fistula (POPF) is unclear. We evaluate which site of pancreatic division, neck or body, has better outcomes after LDP. METHODS: This was a retrospective, observational study. LDP was performed in 102 consecutive patients between December 2009 and May 2020. After excluding 14 patients with pancreatic division at tail, 88 patients (pancreatic division at neck n = 46, at body n = 42) were included in this study. Short- and long-term outcomes after LDP were compared between pancreatic division at neck and body. RESULTS: The pancreatic transection site was thicker at body than at neck (17.5 vs. 11.9 mm, P < 0.001), although there were no significant differences of pancreatic texture and pancreatic duct size. The Grade B/C POPF rate was significantly higher when the pancreas was divided at body than when divided at neck (21.4 vs. 6.5%, P = 0.042). We found no significant differences between pancreatic division at neck and body in residual pancreatic volume (34.0 vs. 34.8 ml, P = 0.855), incidence of new-onset or worsening diabetes mellitus more than six months after LDP (P = 0.218), or body weight change (six-month: P = 0.116, one-year: P = 0.108, two-year: P = 0.195, tree-year: P = 0.131, four-year: P = 0.608, five-year: P = 0.408). CONCLUSION: This study suggests that the pancreatic division at neck might reduce the Grade B/C POPF incidence after LDP, compared to division at body. A potential reason is that the pancreas at body is thicker than that at neck. However, further large-scale studies are necessary to confirm our results.

Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study.

OBJECTIVES: This single-center comparative randomized superiority study compared biliary stenting using fully covered self-expandable metal stents (FCSEMS) and biliary stenting using plastic stents (PS) in preoperative biliary drainage of patients with borderline resectable pancreatic cancer (BRPC) who are planned to undergo a single regimen of neo-adjuvant chemotherapy (NAC). METHODS: Twenty-two patients with BRPC who required preoperative biliary drainage before NAC (Gemcitabine plus Nab-paclitaxel) were randomly assigned 1:1 to the FCSEMS or PS group. The primary endpoint was the rate of stent dysfunction until surgery or tumor progression. Secondary endpoints were stent patency, number of re-interventions, adverse events of endoscopic retrograde biliary drainage (EBD), operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs. RESULTS: Eleven patients in each of the groups reached the primary endpoint. The FCSEMS group showed a significantly lower rate of stent dysfunction (18.2% vs. 72.8%, P = 0.015), longer stent patency (P = 0.02), and lower number of re-interventions for stent dysfunction (0.27 ± 0.65 vs. 1.27 ± 1.1, P = 0.001) than the PS group. The adverse events of EBD, operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs did not significantly differ between the two groups. CONCLUSIONS: In patients with BRPC for preoperative biliary drainage, stent dysfunction occurred less frequently with FCSEMSs than with PSs. In addition, FCSEMS and PS provided similar preoperative management of BRPC in terms of the safety of surgery and medical costs. (UMIN ID000030473).

New Model for Predicting Malignancy in Patients With Intraductal Papillary Mucinous Neoplasm.

OBJECTIVE: To create a simple, objective model to predict the presence of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN), which can be easily applied in daily practice and, importantly, adopted for any lesion types. BACKGROUND: No predictive model for malignant IPMN has been widely applied in clinical practice. METHODS: The clinical details of 466 patients with IPMN who underwent pancreatic resection at 3 hospitals were retrospectively analyzed for model development. Then, the model was validated in 664 surgically resected patients at 8 hospitals in Japan.In the preoperative examination, endoscopic ultrasonography (EUS) was considered to be essential to observe mural nodules in both the model development and external validation sets. Malignant IPMNs were defined as those with high-grade dysplasia and associated invasive carcinoma. RESULTS: Of the 466 patients, 258 (55%) had malignant IPMNs (158 high-grade dysplasia, 100 invasive carcinoma), and 208 (45%) had benign IPMNs. Logistic regression analysis resulted in 3 variables (mural nodule size, main pancreatic duct diameter, and cyst size) being selected to construct the model. The area under the receiver operating characteristic curve (AUC) for the model was 0.763. In external validation sets, the pathological diagnosis was malignant and benign IPMN in 351 (53%) and 313 (47%) cases, respectively. For the external validation, the malignancy prediction ability of the model corresponded to an AUC of 0.725. CONCLUSION: This predictive model provides important information for physicians and patients in assessing an individual's risk for malignancy and may help to identify patients who need surgery.

Propensity score-matched analysis of internal stent vs external stent for pancreatojejunostomy during pancreaticoduodenectomy: Japanese-Korean cooperative project.

BACKGROUND: Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402). RESULTS: After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P < 0.001). CONCLUSION: Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy.

Prognostic Analysis of Hepatocellular Carcinoma With Hepatitis C Virus Infection Using Epithelial-Mesenchymal Transition Gene Profiles.

BACKGROUND: Epithelial-mesenchymal transition genes have prognostic influence on hepatocellular carcinoma (HCC). Previously, the following four epithelial-mesenchymal transition-related genes were considered to be significantly influential: E-cadherin (CDH1), inhibitor of DNA binding 2 (ID2), matrix metalloproteinase 9 (MMP9), and transcription factor 3 (TCF3). A prognostic prediction model, NRISK4 = (-0.333 × [CDH1] - 0.400 × [ID2] + 0.339 × [MMP9] + 0.387 × [TCF3]) was constructed, but from patients with HCC with predominantly hepatitis B virus infection. We therefore aim to validate if this model also fits patients with HCC and hepatitis C virus (HCV) infection. METHODS: We collected HCC tissue samples from 67 patients with HCV infection. Discrimination of the NRISK4 was re-estimated using receiver operating curve analysis and we redefined the appropriate cutoff value. Using this cutoff value, patients were divided into two groups (high/low risk patients) and we compared their clinicopathological factors and prognosis. RESULTS: Area under the curve of NRISK4 prediction was 0.70 and an appropriate cutoff value was 3.19 in this cohort. Patients were divided into high- (n = 25) and low-risk (n = 42) patients for prognosis. There were no significant differences in tumor factors between the two groups. Cancer-specific survival rates at 5 y after surgery on high- and low-risk patients were 45% and 68%, respectively (P = 0.02). At 2 y after surgery, recurrence rates were 68% and 37% among high- and low-risk patients, respectively (P = 0.01). Aggressive recurrences were highly observed in the high-risk patients (P = 0.01). CONCLUSIONS: NRISK4 model could also successfully validate prognosis of patients with HCC with HCV infection similarly to in the previous report of patients with hepatitis B virus infection, especially in the early period after surgery.

Complete REtraction of the StomaCh using pEnrose draiN and liver reTractor (CRESCENT) during laparoscopic distal pancreatectomy.

PURPOSE: Laparoscopic distal pancreatectomy (LDP) is a well-accepted procedure for benign and malignant diseases of the pancreatic body and/or tail. To perform it safely, a wide operative field is crucial. For the maintenance of a good surgical field during LDP, we developed an original technique for stomach retraction: "Complete REtraction of the StomaCh using pEnrose draiN and liver reTractor, CRESCENT." METHODS: In CRESCENT technique, the body and antrum of the stomach are suspended by two Penrose drains, and the fundus and/or upper body of the stomach are retracted upward using a liver retractor. After complete retraction, the stomach is well attached to the abdominal wall and forms a crescent-like shape. Before we developed the CRESCENT technique, we pulled the antrum of the stomach laterally by suture and hanged the body of the stomach upward using a Penrose drain (control method). We evaluated perioperative outcomes of the 87 consecutive patients who underwent LDP and compared outcomes of CRESCENT technique (n = 24) and previously used technique as a control (n = 63). RESULTS: Operative time was significantly shorter in the CRESCENT technique than in control method (median, 234 vs. 303 min, P < 0.001). We found no significant differences in incidences of overall morbidity (16.7 vs. 20.6%, P = 0.677), including grade B/C postoperative pancreatic fistula (8.3 vs. 7.9%, P = 0.455), between CRESCENT technique and control method. There was no mortality by either method. CONCLUSIONS: Our original technique, CRESCENT, is a simple procedure in which the stomach is completely retracted during LDP.

Diffusion-weighted MRI predicts the histologic response for neoadjuvant therapy in patients with pancreatic cancer: a prospective study (DIFFERENT trial).

PURPOSE: Pre-operative prediction of histological response to neoadjuvant therapy aids decisions regarding surgical management of borderline resectable pancreatic cancer (BRPC). We elucidate correlation between pre-/post-treatment whole-tumor apparent diffusion coefficient (ADC) value and rate of tumor cell destruction. We newly verify whether post-treatment ADC value at the site of vascular contact predicts R0 resectability of BRPC. METHODS: We prospectively reviewed 28 patients with BRPC who underwent diffusion-weighted magnetic resonance imaging before neoadjuvant chemotherapy and surgery. Correlation between the percentage of tumor cell destruction and various parameters was analyzed. Strong parameters were assessed for their ability to predict therapeutic histological response and R0 resectability. RESULTS: Pre-/post-treatment whole-tumor ADC value correlated with tumor cell destruction rate by all parameters (R = 0.630/0.714, P < 0.001/< 0.0001). The post-treatment cutoff value of ADC at the site of vascular contact for discriminating histological response of tumor destruction of ≤ 50% and tumor destruction of > 50% was determined at 1.42 × 10-3 mm2/s. It predicts R0 with 88% sensitivity, 50% specificity, and 61% accuracy. For histological response, the post-treatment whole-tumor ADC cutoff value for discriminating between tumor destruction of ≤ 50% and tumor destruction of > 50% was determined at 1.40 × 10-3 mm2/s. It predicts histological response with 100% sensitivity, 81% specificity, and 89% accuracy. It predicts R0 with 88% sensitivity, 70% specificity, and 75% accuracy. CONCLUSIONS: Post-treatment whole-tumor ADC value may be a predictor of R0 resectability in patients with BRPC. Tumor cell destruction rate is indicated by the difference between pre-/post-treatment ADC values. This difference is strongly affected by the pre-treatment ADC value. The cutoff value of ADC at the site of vascular contact could not discriminate R0 resectability.

Preoperative In-Hospital Rehabilitation Improves Physical Function in Patients with Pancreatic Cancer Scheduled for Surgery.

Low preoperative physical function in cancer patients is associated with postoperative complications; however, there have been no reports on the benefits of in-hospital preoperative rehabilitation on preoperative physical function in patients with pancreatic cancer. Therefore, the aim of this study was to quantitatively determine the effects of preoperative in-hospital rehabilitation provided under the supervision of a physiotherapist, on preoperative physical function in patients with pancreatic cancer. The study subjects were 26 patients (15 males, 11 females; age 71.2 ± 8.5 years, range: 51-87 years), including four patients with preoperative chemotherapy, scheduled for surgery for pancreatic cancer. Muscle strengthening exercises and aerobic exercises were conducted 11.9 ± 5.1 days prior to surgery. Cardiopulmonary exercise testing, 6-minute walk distance, and the Functional Independence Measure score were measured before and after the rehabilitation program. We also investigated the relation between the rehabilitation program and incidence of postoperative complications. All 26 study patients completed the preoperative rehabilitation program and no adverse events were noted. Peak oxygen uptake during cardiopulmonary exercise testing and 6-minute walk distance increased significantly after the rehabilitation program. The Functional Independence Measure score remained constant throughout the intervention. No wound infection, delirium, deep vein thrombosis, or respiratory complications were encountered postoperatively. In-hospital preoperative rehabilitation under the supervision of a physiotherapist significantly improved physical function and maintained physical activity in patients with pancreatic cancer. Such improvements may contribute toward preventing serious postoperative complications, resulting in better outcomes.

Surgical strategy for intraductal papillary mucinous neoplasms of the pancreas.

The current treatment strategy for intraductal papillary mucinous neoplasms (IPMNs), based on the international consensus guideline, has been accepted widely. However, reported outcomes after surgical resection for IPMN show that once the tumor progresses to invasive intraductal papillary mucinous carcinoma (IPMC), recurrence is not uncommon. The surgical treatment for IPMN is invasive and sometimes followed by complications. Therefore, the best timing for resection might be at the point when high-grade dysplasia (HGD) is evident. According to previous reports, main duct type IPMN has a high malignant potential and its surgical resection is universally accepted, whereas, the incidence of HGD/invasive IPMC in branch duct and mixed type IPMNs is thought to be lower. In addition to mural nodules and a dilated main pancreatic duct, cytology and measurement of the carcinoembryonic antigen level in the pancreatic juice might be useful to differentiate HGD/invasive IPMC from low-grade dysplasia. The nomogram proposed recently to predict the risk of HGD/invasive IPMC in IPMN patients might help surgeons decide on the best treatment strategy, depending on the patient's age and general condition. Second resection for high-risk lesions in the remnant pancreas might improve the survival of IPMN patients.

Impact of Ninjin'Yoeito on Fatigue in Patients Receiving Nab-Paclitaxel Plus Gemcitabine Therapy: A Prospective, Single-Arm, Phase II Open Label, Nonrandomized, Historically-Controlled Study.

BACKGROUND: Ninjin'yoeito, a traditional Japanese herbal medicine, is used to prevent fatigue, loss of appetite, and coldness of limbs. Fatigue is an especially common issue during chemotherapy and can affect quality of life and the ability to complete scheduled treatment. OBJECTIVES: This prospective exploratory trial evaluates the efficacy of ninjin'yoeito for fatigue in patients undergoing nab-paclitaxel plus gemcitabine therapy for unresectable pancreatic cancer. The primary end point was evaluation of fatigue according to Functional Assessment of Chronic Illness Therapy-Fatigue score during 2 courses of nab-paclitaxel plus gemcitabine therapy. Secondary end points included evaluation of dose intensity, appetite loss using numerical rating scale, and peripheral neuropathy using a patient neurotoxicity questionnaire. METHODS: We compared data from this interventional trial with a prior observational trial without administration of ninjin'yoeito with identical definition of end points (UMIN000021758). Thirty patients were required by the study. RESULTS: Threshold mean of Functional Assessment of Chronic Illness Therapy-Fatigue score across 8 weeks during chemotherapy was under 5.3 (P = 0.002). Secondary end points did not reveal any specific patterns in appetite loss or degree of pain. No significant changes in patient neurotoxicity questionnaire concerning sensory/motor disorders were observed, but the mean (SD) incidence of patients with sensory disturbance was higher between the fifth and eighth weeks (8.8 [1.26]) than during the first and fourth weeks (4.8 [0.96]) (P = 0.003). Clinically significant adverse reactions of ninjin'yoeito were not observed. CONCLUSIONS: Ninjin'yoeito may be useful for improving the symptoms of fatigue caused by nab-paclitaxel plus gemcitabine in patients with unresectable pancreatic cancer. UMIN Clinical Trials Registry identifier: UMIN000025606. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Modified Blumgart Mattress Suture Versus Conventional Interrupted Suture in Pancreaticojejunostomy During Pancreaticoduodenectomy: Randomized Controlled Trial.

OBJECTIVE: This study used a randomized controlled trial (RCT) to evaluate whether mattress suture of pancreatic parenchyma and the seromuscular layer of jejunum (modified Blumgart method) during pancreaticojejunostomy (PJ) decreases the incidence of clinically relevant postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). BACKGROUND: Several studies reported that mattress suture of Blumgart anastomosis in PJ could reduce POPF rate. This, however, is the first RCT. METHODS: Between June, 2013 and May, 2017, 224 patients scheduled for PD were enrolled in this study in Wakayama Medical University Hospital. Enrolled patients were randomized to either interrupted suture or modified Blumgart mattress suture. The primary endpoint was the incidence of grade B/C POPF based on the International Study Group on Pancreatic Fistula criteria. This RCT was registered with ClinicalTrials.gov (NCT01898780). RESULTS: Patients were randomized to either interrupted suture (103 patients) or modified Blumgart mattress suture (107 patients) and were analyzed by intention-to-treat. Grade B/C POPF occurred in 7 patients (6.8%) in the interrupted suture group and 11 (10.3%) in the mattress suture group (P = 0.367). Mortality within 90 days was 0 in both groups. There were no significant differences in all postoperative complications between the interrupted suture group and the modified Blumgart mattress suture group. CONCLUSIONS: Mattress suture of pancreatic parenchyma and the jejunal seromuscular layer during PJ (modified Blumgart technique) did not reduce clinically relevant POPF compared with interrupted suture.

Indocyanine green fluorescence imaging techniques and interventional radiology during laparoscopic anatomical liver resection (with video).

BACKGROUND: To accomplish laparoscopic anatomical liver resection, intraoperative liver segmentation is necessary. Tattooing method or Glissonian approach will be used in a similar way to that in open liver resection. Moreover, in liver segment detection, the fluorescence of indocyanine green (ICG) means it has been recognized as a useful dye. In laparoscopy, however, there are technical difficulties in performing these conventional methods, so development of new techniques is necessary for liver segment identification. We report a pilot study using interventional radiology technique for laparoscopic intraoperative liver segmentation. METHODS: Just prior to liver parenchymal resection, angiography was performed using a hybrid operation room. A catheter was inserted from the right femoral artery into the targeted arterial branch. After confirming the perfusion area by arteriography, embolic solution containing ICG was injected, and the branch was embolized. ICG fluorescence was observed by PINPOINT, a near-infrared imaging system. RESULTS: Immediately after embolic solution injection, we were able to observe ICG fluorescence on the surface of the liver to be resected. This visual effect continued during liver parenchymal resection. We were able to confirm the intra-parenchymal boundary by observing ICG fluorescence on the cut surface of the resecting side and accomplished precise anatomical liver resection. CONCLUSIONS: Our novel technique provides advances in laparoscopic anatomical liver resection performance. As two-dimensional laparoscopy lacks depth perception, additional visual information, such as ICG fluorescence imagery, is helpful as a navigation tool for precise laparoscopic anatomical liver resection.

Ischemic gastropathy after distal pancreatectomy with en bloc celiac axis resection for pancreatic body cancer.

PURPOSE: Risk factors of ischemic gastropathy (IG) following distal pancreatectomy with en bloc celiac axis resection (DP-CAR) remain unclear. METHODS: Fifty consecutive patients with pancreatic cancer who underwent DP-CAR were retrospectively reviewed for possible risk factors for IG. This study was registered on the UMIN Clinical Trials Registry (UMIN 000028732). RESULTS: Complications higher than grade 3 were observed in 21 patients (42%) and mortality in 4 (8%). Left gastric artery (LGA) resection (P = 0.046) and a combination of left inferior phrenic artery (IPA) with LGA resection (P = 0.012) were risk factors of IG, and an elevated creatine kinase (CK) value ≥ 1005 IU/L (P = 0.025) was associated with IG. Among prognostic factors, IG (OR, 5.997; 95% CI, 1.543-23.309; P = 0.010), completion of adjuvant chemotherapy (OR, 0.282; 95% CI, 0.121-0.654; P = 0.003), longer operative time (OR, 2.261; 95% CI, 1.084-4.714; P = 0.030), and higher age (OR, 2.212; 95% CI, 1.081-4.524; P = 0.030) remained independent predictors of survival. Comparison at 2 and 3 months postoperatively showed nutritional values were higher in patients who underwent LGA-preserving DP-CAR than those with LGA-resecting DP-CAR: total protein (7.17 ± 0.56 vs 6.65 ± 0.66 g/dl, P = 0.007), albumin (4.04 ± 0.45 vs 3.43 ± 0.43 g/dl, P < 0.001), and total cholesterol (162.3 ± 34.7 vs 141.6 ± 27.2 mg/dl, P = 0.044). CONCLUSIONS: The poorer prognosis in patients who undergo DP-CAR may be related to more advanced tumors. A combination of left IPA and LGA resection was a significant risk factor for IG. IG, completion of adjuvant chemotherapy, longer operative time, and higher age remain good independent predictors of survival.