Pancreatobiliary Maljunction-associated Gallbladder Cancer Is as Common in the West, Shows Distinct Clinicopathologic Characteristics and Offers an Invaluable Model for Anatomy-induced Reflux-associated Physio-chemical Carcinogenesis.

OBJECTIVE: To determine the associations of pancreatobiliary maljunction (PBM) in the West. BACKGROUND: PBM (anomalous union of common bile duct and pancreatic duct) is mostly regarded as an Asian-only disorder, with 200X risk of gallbladder cancer (GBc), attributed to reflux of pancreatic enzymes. Methods: Radiologic images of 840 patients in the US who underwent pancreatobiliary resections were reviewed for PBM and contrasted with 171 GBC cases from Japan. RESULTS: Eight % of the US GBCs (24/300) had PBM (similar to Japan; 15/ 171, 8.8%), in addition to 1/42 bile duct carcinomas and 5/33 choledochal cysts. None of the 30 PBM cases from the US had been diagnosed as PBM in the original work-up. PBM was not found in other pancreatobiliary disorders. Clinicopathologic features of the 39 PBM-associated GBCs (US:24, Japan:15) were similar; however, comparison with non-PBM GBCs revealed that they occurred predominantly in females (F/M = 3); at younger (<50-year-old) age (21% vs 6.5% in non-PBM GBCs; P = 0.01); were uncommonly associated with gallstones (14% vs 58%; P < 0.001); had higher rate of tumor-infiltrating lymphocytes (69% vs 44%; P = 0.04); arose more often through adenoma-carcinoma sequence (31% vs 12%; P = 0.02); and had a higher proportion of nonconventional carcinomas (21% vs 7%; P = 0.03). Conclusions: PBM accounts for 8% of GBCs also in the West but is typically undiagnosed. PBM-GBCs tend to manifest in younger age and often through adenoma-carcinoma sequence, leading to unusual carcinoma types. If PBM is encountered, cholecystectomy and surveillance of bile ducts is warranted. PBM-associated GBCs offer an invaluable model for variant anatomy-induced chemical (reflux-related) carcinogenesis.

Clinical efficacy and safety of endoscopic ultrasound-guided gallbladder drainage replacement of percutaneous drainage: A multicenter retrospective study.

OBJECTIVES: Percutaneous transhepatic gallbladder drainage (PTGBD) is widely used for patients with acute cholecystitis. There are little data on the efficacy and safety of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) replacement of PTGBD in patients who cannot undergo cholecystectomy. METHODS: This multicenter retrospective study in Japan reviewed records of patients who underwent EUS-GBD to replace PTGBD between January 2010 and December 2017. Outcomes evaluated included technical success, defined as successful stent placement between the gastrointestinal lumen and the gallbladder; clinical success, defined as subsequent removal of the percutaneous catheter; adverse events; and stent patency. RESULTS: EUS-GBD was performed in 21 patients (14 women, mean age 77.5 ± 8.0 years) to replace PTGBD that had been instituted for acute cholecystitis (n = 19) or obstructive jaundice (n = 2). Technical success was achieved in 19 (90.5%). The median period from PTGBD placement to EUS-GBD was 11 days (range, 6-68 days). The mean procedure time was 19.5 ± 5.1 min. No early adverse events were observed. There were three late adverse events, distal stent migration in two cases and stent occlusion causing recurrent cholecystitis in one patient. Reintervention was required in two patients. The percutaneous catheter was removed after EUS-GBD in 17 patients at a median of 7 days (range, 2-20 days). The duration of stent patency was 139 days (range, 8-664 days). CONCLUSIONS: Where ongoing gallbladder drainage is required, conversion from PTGBD to EUS-GBD is a feasible, effective, and safe technique for patients who cannot undergo cholecystectomy.

Comparison of the efficacy and safety of endoscopic ultrasound-guided choledochoduodenostomy and hepaticogastrostomy for malignant distal biliary obstruction: Multicenter, randomized, clinical trial.

BACKGROUND AND AIM: Endoscopic ultrasound-guided biliary drainage (EUS-BD) can be carried out by two different approaches: choledochoduodenostomy (CDS) and hepaticogastrostomy (HGS). We compared the efficacy and safety of these approaches in malignant distal biliary obstruction (MDBO) patients using a prospective, randomized clinical trial. METHODS: Patients with malignant distal biliary obstruction after failed endoscopic retrograde cholangiopancreatography were randomly selected for either CDS or HGS. The procedures were carried out at nine tertiary centers from September 2013 to March 2016. Primary endpoint was technical success rate, and the noninferiority of HGS to CDS was examined with a one-sided significance level of 5%, where the noninferiority margin was set at 15%. Secondary endpoints were clinical success, adverse events (AE), stent patency, survival time, and overall technical success including alternative EUS-BD procedures. RESULTS: Forty-seven patients (HGS, 24; CDS, 23) were enrolled. Technical success rates were 87.5% and 82.6% in the HGS and CDS groups, respectively, where the lower limit of the 90% confidence interval of the risk difference was -12.2% (P = 0.0278). Clinical success rates were 100% and 94.7% in the HGS and CDS groups, respectively (P = 0.475). Overall AE rate, stent patency, and survival time did not differ between the groups. Overall technical success rates were 100% and 95.7% in the HGS and CDS groups, respectively (P = 0.983). CONCLUSIONS: This study suggests that HGS is not inferior to CDS in terms of technical success. When one procedure is particularly challenging, readily switching to the other could increase technical success.

Endoscopic Ultrasound-Guided Rendezvous Technique for Failed Biliary Cannulation in Benign and Resectable Malignant Biliary Disorders.

BACKGROUND: Endoscopic ultrasound-guided rendezvous technique (EUS-RV) has emerged as an effective salvage method for unsuccessful biliary cannulation. However, its application for benign and resectable malignant biliary disorders has not been fully evaluated. AIMS: To assess the efficacy and safety of EUS-RV for benign and resectable malignant biliary disorders. METHODS: This was a multicenter prospective study from 12 Japanese referral centers. Patients who underwent EUS-RV after failed biliary cannulation for biliary disorder were candidates for this study. Inclusion criteria were unsuccessful biliary cannulation for therapeutic endoscopic retrograde cholangiopancreatography with benign and potentially resectable malignant biliary obstruction. Exclusion criteria included unresectable malignant biliary obstruction, inaccessible papillae due to surgically altered upper gastrointestinal anatomy or duodenal stricture, and previous sphincterotomy and/or biliary stent placement. The primary outcome was the technical success rate of biliary cannulation; procedure time, adverse events, and clinical outcomes were secondary outcomes. RESULTS: Twenty patients were prospectively enrolled. The overall technical success rate and median procedure time were 85% and 33 min, respectively. Guidewire manipulation using a 4-Fr tapered tip catheter contributed to the success in advancing the guidewire into the duodenum. Adverse events were identified in 15% patients, including 2 with biliary peritonitis and 1 mild pancreatitis. EUS-RV did not affect surgical maneuvers or complications associated with surgery, or postoperative course. CONCLUSIONS: EUS-RV may be a safe and feasible salvage method for unsuccessful biliary cannulation for benign or resectable malignant biliary disorders. Use of a 4-Fr tapered tip catheter may improve the overall EUS-RV success rate.

Intraductal papillary neoplasm of the bile duct with metachronous development in the downstream bile duct after radical resection.

We report a case of intraductal papillary neoplasms of the bile duct (IPNB) that metachronously developed twice in the downstream bile duct after radical resection. The first lesion was located in the left intrahepatic bile duct, the second lesion in the perihilar bile duct, and the third lesion in the distal bile duct. All lesions were IPNBs with associated invasive carcinoma (pancreatobiliary type). The depth of invasion was to the Glisson's capsule in the first lesion, to the subserosa in the second lesion, and to the fibromuscular layer in the third lesion, without lympho-vascular/perineural invasion and lymph-node metastasis. These were resected radically and had no biliary intraepithelial neoplasia and hyperplasia in the surrounding mucosa. In immunohistochemical examination, each lesion showed a different pattern. Although the downstream occurrence suggests intrabiliary dissemination, the mechanism of these metachronous developments may be multicentric. A literature review revealed that most metachronous cholangiocarcinomas have a grossly papillary appearance and tend to arise downstream. Our findings suggest that IPNB may develop metachronously in the residual bile duct after radical surgery, which may assist in early detection.

Successful laparoscopic resection for giant mature cystic teratoma of the pancreas: a case report and surgical refinements.

BACKGROUND: Mature cystic teratomas or dermoid cysts of the pancreas complicate surgical approaches because of their anatomical position and ever-growing size. Herein, we report a case of a giant mature cystic teratoma of the pancreas that was successfully resected via complete laparoscopic distal pancreatectomy (LDP). CASE PRESENTATION: A 39-year-old female patient was referred to our hospital for the evaluation of a pancreatic tumor. Three years of follow-up revealed that the tumor had increased in size to 18 cm, with hyperintense solid components on diffusion-weighted magnetic resonance imaging. Considering the possibility of malignancy, we decided to perform an LDP. The capsule appeared solid enough to withstand the retraction of the endoscopic forceps. Tumor size made it difficult to dissect the dorsal side of the tumor from the caudal to the cranial side. Early transection of the pancreas and additional ports facilitated dissection of the dorsal side of the tumor. We completed the LDP without intraoperative cyst rupture. On pathological examination, the tumor was diagnosed as a mature cystic teratoma originating from the pancreatic tail. The patient was discharged on postoperative day 13 with no complications. CONCLUSION: LDP may be an option for surgical procedures in patients with large cystic lesions of the pancreatic body or tail. Intraoperative observation of the tumor and surgical refinement are necessary to complete the laparoscopic procedure without tumor rupture.

Endoscopic ultrasound-guided antegrade stone removal in a patient with pancreatic stones and anastomotic stricture after end-to-side pancreaticojejunostomy.

Pancreaticoenteric anastomotic stricture can occur as a late complication of pancreatic head resection and is difficult to manage. The surgically altered anatomies of patients that have undergone pancreatic head resection make it difficult to perform pancreatic duct drainage using conventional endoscopes, and it is especially difficult to endoscopically identify stenotic pancreaticojejunal anastomoses. A 40-year-old woman was referred to our department for the treatment of symptomatic multiple pancreatic stones and anastomotic stricture after end-to-side pancreaticojejunostomy. Endoscopic ultrasound-guided pancreaticogastrostomy was performed in an attempt to avoid re-surgery. At 18 days after the initial procedure, a guidewire was successfully placed in the jejunum through the anastomotic stricture. The anastomotic stricture was dilated using a dilation balloon, and all of the stones were pushed into the jejunum using a retrieval balloon. No complications were experienced during the procedure. At 22 months after the stone removal, the main pancreatic duct displayed a decreased diameter, and no stone recurrence was detected.

Ultrasonographic Features of Nonneoplastic Protrusions in Pancreatic Cysts by Contrast-Enhanced Endoscopic Ultrasound.

OBJECTIVES: Most of the pancreatic cyst protrusions detected by B-mode endoscopic ultrasound (BM-EUS) are nonneoplastic and are not enhanced by contrast-enhanced EUS (CE-EUS) using ultrasound contrast agent (USCA). This study aimed to identify useful findings for distinguishing between neoplastic and nonneoplastic pancreatic cyst protrusions on BM-EUS to facilitate efficient USCA use. MATERIALS AND METHODS: A total of 151 pancreatic cyst protrusions in 119 consecutive patients who underwent CE-EUS were analyzed. We focused on the echo level (hyperechoic/isoechoic/hypoechoic/anechoic), base type (sessile without a basal waist/sessile with a basal waist/pedunculated), surface type (smooth/irregular), and the presence/absence of a hyperechoic surface layer. Enhanced and unenhanced protrusions on CE-EUS were interpreted as neoplastic and nonneoplastic, respectively. RESULTS: Forty-five and 106 protrusions were enhanced and unenhanced, respectively, on CE-EUS performed using USCA. In univariable analysis of predictors of nonneoplastic protrusion on BM-EUS, the following factors were found to be significant: echo level (hypoechoic/anechoic), base type (sessile with a basal waist/pedunculated), a smooth surface, and a hyperechoic surface layer. Of these, only a hyperechoic surface layer remained significant in the multivariable analysis ( P < 0.0001; odds ratio, 40.74; 95% confidence interval, 7.07-387.49). CONCLUSIONS: Pancreatic cyst protrusions with a hyperechoic surface layer on BM-EUS are suggestive of nonneoplastic disease.

A resected case of focal autoimmune pancreatitis with pancreatic duct wall thickening representing periductal lymphoplasmacytic infiltrate.

This case revealed that branch pancreatic duct wall thickening by endoscopic ultrasonography represented periductal lymphoplasmacytic infiltrate as a characteristic histopathological finding of autoimmune pancreatitis, which may help in the diagnosis of autoimmune pancreatitis. An 80-year-old man was referred because fluorodeoxyglucose-positron emission tomography for lung cancer indicated abnormal uptake in the pancreatic head. Computed tomography showed an enhanced mass with cystic structures in the pancreatic head. Magnetic resonance cholangiopancreatography revealed mild dilatation of the main pancreatic duct in the pancreatic body with no strictures. Endoscopic ultrasonography demonstrated a lobulated heterogeneous hypoechoic mass in the pancreatic head. A branch pancreatic duct with wall thickening connected the mass to the main pancreatic duct. An intraductal neoplasm filling and spreading into the branch pancreatic duct was considered, and surgery was performed. Histopathologically, the mass consisted of marked inflammatory cell infiltration, storiform fibrosis, and obliterative phlebitis. The branch pancreatic duct with wall thickening revealed a band-like inflammatory cell infiltration with mainly lymphocytes and plasma cells beneath the normal pancreatic duct epithelium. Immunohistological staining revealed abundant IgG4-positive plasma cells (> 10 cells/HPF) in the inflammatory cell infiltration. The definite diagnosis was type 1 focal autoimmune pancreatitis.

An unusual reversible color change in a gastric lesion during real-time endoscopy.

During endoscopy, a light purple flat lesion suddenly appeared at the antrum and the lesion disappeared subsequently. This is an unusual reversible color change that is associated with blood flow, and that must be differentiated from neoplasia.

Mucinous cystadenoma of the pancreas with huge mural hematoma.

A 60-year-old woman was referred for evaluation of a cystic mass in the pancreatic body that extended to the tail. Transabdominal ultrasonography demonstrated an oval cystic mass 24 cm in diameter, filled with debris. On the cyst wall there was a wide-based, smooth-surfaced, heterogeneous high-echoic protrusion that was 5 cm in diameter. On CT the protrusion showed internal enhancement. Endoscopic pancreatography showed no intraductal mucin or communication with the cyst. A distal pancreatectomy was performed under the diagnosis of mucinous cystadenocarcinoma. Grossly there was a brownish, hemispherical protrusion into the thin monolocular cyst. The cut surface of the protrusion showed a peripheral yellow-brownish area and an internal wine-colored area. Histopathologically the cyst wall consisted of tall columnar cells without atypical nuclei, ovarian-type stroma beneath the epithelium, and fibrotic tissue with abundant capillary vessels, suggestive of a mucinous cystadenoma. The protrusion was composed of peripheral organized hematoma without a covering epithelium, and internal hemorrhage and many capillary vessels, with no evidence of tumor cell necrosis. These histopathological findings appear to be similar to those of chronic expanding hematoma. The formation of a huge mural hematoma in a mucinous cystic neoplasm can occur as a repair process after the breaking of intrawall vessels.

Long-term outcomes of EUS-guided transluminal stent deployment for benign biliary disease: Multicenter clinical experience (with videos).

BACKGROUND AND OBJECTIVES: Biliary drainage (BD) under EUS guidance is usually indicated for malignant biliary obstruction. Recently, EUS-guided transluminal treatment has been applied to benign biliary disease (BBD). This multicenter retrospective study evaluated the clinical impact of EUS-guided transluminal stent deployment for BBD with long-term follow-up. PATIENTS AND METHODS: This retrospective study investigated patients treated between September 2015 and October 2016 at participating hospitals in the therapeutic endoscopic group. The inclusion criteria comprised complications with BBD obstructive jaundice or cholangitis and failed endoscopic retrograde cholangiopancreatography or inaccessible ampulla of Vater. RESULTS: Twenty-six patients underwent EUS-guided transluminal stent deployment. Indications for EUS-guided transluminal stent deployment comprised anastomotic biliary stricture (n = 17), bile duct stones (n = 5), inflammatory biliary stricture (n = 3), and acute pancreatitis prevention (n = 1). Thirteen of these 26 patients underwent scheduled reintervention, with technical success achieved in all 13 patients. None of the deployed stents became dysfunctional. Among the 13 patients who underwent reintervention on demand, stents had become dysfunctional in six patients (stent patency: 48, 90, 172, 288, 289, and 608 days). Reintervention was successfully performed in all patients. During follow-up (median, 749 days), severe adverse events were not seen in any patients. CONCLUSION: We concluded that EUS-guided transluminal stent deployment for BBD is feasible and safe. Because metal stent dysfunction was more frequent when deployed on demand, such stents should be exchanged for plastic stents in a scheduled manner if a metal stent is used.

Growth process of small pancreatic carcinoma: a case report with imaging observation for 22 months.

This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the low-echoic mass as a benign intraductal mucinous-papillary neoplasm (IPMN) based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.

Inflammatory myofibroblastic tumor of the gallbladder: a case report and literature review.

A 50-year-old man had undergone chemotherapy and radiotherapy for malignant lymphoma 1 year earlier. Follow-up computed tomography revealed a gallbladder polyp. Transabdominal ultrasound demonstrated a 20-mm hypoechoic sessile polyp with basal waist in the gallbladder fundus; the surface was covered with a hyperechoic layer of non-uniform thickness. On contrast-enhanced computed tomography, the polyp showed an early uniform and sustained staining pattern. Magnetic resonance imaging revealed that the polyp had low and slightly high signal intensities on T1- and T2-weighted imaging, respectively. Gallbladder bed resection was performed with the diagnosis of special tumor. Histologically, the polyp comprised a proliferation of myofibroblast-like spindle cells with inflammatory cell infiltration, without muscularis propria or vascular invasion. Most of the polyp surface was covered with necrotic exudate, and part of the normal epithelium remained. Consequently, a diagnosis of inflammatory myofibroblastic tumor was made. The sessile shape with basal waist, epithelium shedding, and surface necrotic exudative matter may represent intraluminal expansive growth such as a subepithelial tumor. A surface with a hyperechoic layer of non-uniform thickness on gallbladder polyp can help in the diagnosis of a tumor with expansive growth directly under the epithelium with stretching/rupture of the epithelium.

Distribution of intraductal lesions in small invasive ductal carcinoma of the pancreas.

AIMS: To investigate the distribution of intraductal lesions in small invasive ductal carcinoma (IDC) of the pancreas. METHODS: In 21 cases with IDCs microscopically < or = 20 mm in diameter, the intraductal lesions around a mass were studied histologically and mapped according to the pancreatic intraepithelial neoplasia (PanIN) classification. RESULTS: PanIN-3, PanIN-2, PanIN-1B and PanIN-1A were found in 17, 10, 20 and 21 of 21 cases, respectively, and were divided into lesions in adjacent and distal areas, respectively defined as within and beyond 10 mm from the mass as follows: 100% (17/17), 100% (10/10), 95.0% (19/20) and 90.5% (19/21) in the former, while 23.5% (4/17), 50.0% (5/10), 90.0% (18/20) and 95.2% (20/21) in the latter. PanIN-3 lesions were predominantly found in the area adjacent to the mass. In some cases, significant PanIN-3 appeared to show a consecutive geographic extension around the mass via the main pancreatic duct (MPD). The distance of PanIN-3 spread was within 25 (mean 10.5) mm from the mass edge. PanIN-2 lesions were found in the area adjacent to the mass and discontinuous with the mass or PanIN-3 lesions. PanIN-1B and PanIN-1A tended mainly to exist sporadically throughout the entire pancreas. In the MPD, PanIN-3 was found in 14 (82.4%) of 17 cases and in 36 (32.1%) of 112 lesions, which was most frequent in intraductal lesions. CONCLUSIONS: PanIN-3 lesions might be an intraductal extension of the main tumor. The resection margin of 25 mm, at least longer than 11 mm, from the mass edge will be necessary.

Reflux-Associated Cholecystopathy: Analysis of 76 Gallbladders From Patients With Supra-Oddi Union of the Pancreatic Duct and Common Bile Duct (Pancreatobiliary Maljunction) Elucidates a Specific Diagnostic Pattern of Mucosal Hyperplasia as a Prelude to Carcinoma.

Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range: 14 to 81). Cholelithiasis was uncommon (16% vs. 80% in non-PBM, P<0.01) whereas cholesterolosis was more common (49% vs. 29%, P=0.02) suggesting an altered chemical milieu. There was a distinctive diffuse mucosal hyperplasia (82% vs. 42%, P<0.01) with markedly elongated folds (mean: 1.1 vs. 0.7 mm, P<0.01) composed of compact villoglandular proliferation, often showing broad-based pushing into muscle, accompanied by prominent and more complex Rokitansky-Aschoff sinus formation (2.0 vs. 1.0/cm, P<0.01) at the base. At the tips, this villiform hyperplasia displayed frequent horizontal bridging of the folds (68% vs. 47%, P=0.01), bulbous dilatation (52% vs. 21%, P<0.01) as well as deposition of a peculiar amyloid-like hyaline material (56% vs. 15%, P<0.01). Despite paucity of inflammation and gallstones, findings attributed to mucosal injury were common including: pyloric gland metaplasia (70% vs. 48%, P=0.01) and intestinal metaplasia (24% vs. 6%, P<0.01). Invasive gallbladder carcinoma was present in 22 (29%) of the cases with 6 of these (27%) arising in association with intracholecystic papillary tubular neoplasm. Five cases had bile duct carcinoma at the time of cholecystectomy and 1 developed it 4 years after. In conclusion, gallbladders with patients with PBM display a distinctive pattern of mucosal hyperplasia with distinguishing features, which in constellation render it a microscopically diagnosable specific entity. We propose to refer to this entity as "reflux-associated cholecystopathy." Recognition of the pathologic characteristics of this entity is important so that investigation for, as well as treatment and prevention of, PBM-associated complications (biliary tract cancers and pancreatitis) can be instituted. This group also offers a distinct model of carcinogenesis (chemical rather than inflammatory) in the gallbladder for cancer researchers to scrutinize.

[Survey of gemcitabine treatment for advanced pancreatic cancer in 20 hospitals of Nagano Prefecture].

To establish an effective therapy for pancreatic cancer, we made a retrospective survey of gemcitabine treatment performed at 20 hospitals in Nagano Prefecture. We analyzed data of 106 patients (64 men and 42 women, median age 66 years (33-83 years old)), half of whom had stage IV disease. Gemcitabine was administered for 3 consecutive weeks with one week rest in 57 patients, biweekly in 30 patients, initially for 3 weeks with 1 week rest and switched to biweekly schedule to 15 patients, and with another regimen to 4 patients. Analysis of the results of gemcitabine treatment between the 3 weeks with 1-week-rest regimen and the biweekly regimen revealed no differences between regimens in growth inhibition and symptom alleviation. However, we found less occurrence of blood toxicity in the biweekly regimen (40%) than in the 3 weeks with 1 week-rest regimen (59%). Median survival time for the biweekly regime was 9.7 months, only slightly longer than that of the 3 weeks with 1-week-rest regimen (8.5 months). The present study showed that a biweekly regimen for gemcitabine administration may be equivalent to the standard regime of 3 weeks with 1-week-rest regimen. Moreover, the biweekly regimen has advantages over the 3 weeks with 1-week rest regimen both economically and in terms of convenience for outpatient treatment. Therefore, the present results should be confirmed in future prospective studies, with the hope of developing a new standard treatment regimen for pancreatic cancer.