Pancreatic ductal adenocarcinomas concomitant with intraductal papillary mucinous neoplasms of the pancreas: A investigation of those clinicopathological features by analyzing 48 patients who underwent surgery for those lesions.

BACKGROUND: Differences between pancreatic ductal adenocarcinomas (PDACs) concomitant with intraductal papillary mucinous neoplasm (IPMN) (C-PDACs), those without IPMN (NC-PDACs) and invasive cancers derived from IPMN (IC-Ds) have not been fully clarified. METHODS: Forty-eight patients with C-PDAC were included to investigate the differences in 1) clinicopathological features and 2) post-operative courses among the three invasive cancer groups. RESULTS: 1) Characteristics of C-PDACs were mostly similar to those of NC-PDACs; whereas, between C-PDACs and IC-Ds, the rate of mucinous carcinoma (2%/25%, p = 0.003) and pathological stage (IA, 15%/36%, p = 0.033; III, 31%/4%, p = 0.015) significantly differed. Most C-PDACs coexisted with small, multifocal IPMNs without mural nodules. 2) Cumulative 5-year recurrence-free survival (RFS) rate related to extra-pancreatic recurrence was significantly worse in C-PDACs than in IC-Ds (35%/69%, p = 0.008) and was not significantly different between C-PDACs and NC-PDACs (35%/18%). This related to intra-pancreatic recurrence tended to be poor in the order of IC-Ds, C-PDACs, and NC-PDACs (69%/82%/93%). CONCLUSIONS: Because characteristics of IPMNs remarkably differed between C-PDACs and IC-Ds, another algorithm specific to the early detection of C-PDACs is necessary. Appropriate post-operative managements according to the two types of recurrences may contribute to the improvement in the prognoses of C-PDACs/IC-Ds.

Early and long-term clinical outcomes of endoscopic interventions for benign pancreatic duct stricture/obstruction-the possibility of additional clinical effects of endoscopic ultrasonography-guided pancreatic drainage.

OBJECTIVES: For benign pancreatic duct strictures/obstructions (BPDS/O), endoscopic ultrasonography-guided pancreatic drainage (EUS-PD) is performed when endoscopic transpapillary pancreatic drainage (ETPD) fails. We clarified the clinical outcomes for patients with BPDS/O who underwent endoscopic interventions through the era where EUS-PD was available. METHODS: Forty-five patients with BPDS/O who underwent ETPD/EUS-PD were included. We retrospectively investigated overall technical and clinical success rates for endoscopic interventions, adverse events, and clinical outcomes after successful endoscopic interventions. RESULTS: The technical success rates for ETPD and EUS-PD were 77% (35/45) and 80% (8/10), respectively, and the overall technical success rate using two drainage procedures was 91% (41/45). Among the 41 patients who underwent successful endoscopic procedures, the clinical success rates were 97% for the symptomatic patients (35/36). The rates of procedure-related pancreatitis after ETPD and EUS-PD were 13% and 30%, respectively. After successful endoscopic interventions, the cumulative 3-year rate of developing recurrent symptoms/pancreatitis was calculated to be 27%, and only two patients finally needed surgery. Continuous smoking after endoscopic interventions was shown to be a risk factor for developing recurrent symptoms/pancreatitis. CONCLUSIONS: By adding EUS-PD to ETPD, the technical success rate for endoscopic interventions for BPDS/O was more than 90%, and the clinical success rate was nearly 100%. Due to the low rate of surgery after endoscopic interventions, including EUS-PD, for patients with BPDS/O, EUS-PD may contribute to their good clinical courses as a salvage treatment for refractory BPDS/O.

[Endoscopic mucosal resection of localized plasmablastic lymphoma with early rectal cancer:a rare case report and literature review].

A 79-year-old male with a positive fecal occult blood test result underwent total colonoscopy, which revealed a 15-mm-semipedunculated polyp in the rectum. The polyp appeared to be an adenoma using narrow-band imaging observation in magnifying endoscopy, although a 3mm reddish segment with a different surface structure was identified adjacent to the base of the polyp. En-bloc endoscopic mucosal resection (EMR) was performed. From the pathological evaluation using the specimen, the polyp was mainly a tubular adenoma with an adenocarcinoma component within the lesion. Additionally, a tiny plasmablastic lymphoma (PBL) component, which was positive for CD45, CD79a, CD30, CD38, MUM1, and lambda light chain;negative for CD3, CD5, CD20, CD56, CD138, cyclin D1, PAX5, IgG, IgA, IgM, IgE, HHV8, and kappa light chain, coexisted near the stalk. The proliferation index using Ki-67 immunohistochemistry was approximately 80%. Furthermore, Epstein-Barr virus-encoded RNAs were identified in in-situ hybridization, although the human immunodeficiency virus was not detected. The patient received contrast-enhanced computed tomography (CT) and positron emission tomography-CT (PET-CT) follow-ups after treatment without recurrence for two years. This is the first report of gastrointestinal PBL that could be treated using EMR.

Cholangioscopy- versus fluoroscopy-guided transpapillary mapping biopsy for preoperative evaluation of extrahepatic cholangiocarcinoma: a prospective randomized crossover study.

BACKGROUND: To evaluate the lateral extent of extrahepatic cholangiocarcinoma, the value of cholangioscopy-guided mapping biopsy (CMB) compared with that of fluoroscopy-guided mapping biopsy (FMB) remains unknown. The aim of this study was to compare these two techniques. METHODS: In this prospective, randomized, crossover study, both CMB and FMB techniques were performed for all patients in a randomized order. Target sites for the mapping biopsy were determined based on resection lines of possible surgical procedures. At least two biopsy strokes were attempted at each target site. The primary outcome was the rate of site-based successful biopsies, which was defined as acquisition of epithelium-containing material appropriate for diagnosing benignancy/malignancy from each site, regardless of amount of materials obtained from the same site. RESULTS: Between September 2016 and October 2018, 28 patients (16 distal bile duct cancer and 12 perihilar bile duct cancer) were enrolled and divided into two groups of 14 patients: CMB first and FMB first. Although all 118 target sites could be approached using CMB, FMB forceps reached only 71% of them with significantly poor accessibility to the B2/3 confluence. Since several materials were too small and did not contain epithelium, the overall rates of site-based successful biopsies were 78% (92/118) using CMB and 64% (76/118) using FMB (P = 0.031). CONCLUSIONS: The rate of site-based successful biopsies using CMB was significantly higher than that using FMB when evaluated using specimens obtained from several biopsy strokes.

Value of repeated cytology for intraductal papillary mucinous neoplasms of the pancreas with high risk potential of malignancy: Is it a promising method for monitoring a malignant transformation?

OBJECTIVES: The efficacy of and indications for cytological reexamination to detect malignant changes in branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) have not been studied in detail. We conducted a retrospective study to evaluate the efficacy and indications of cytological reexamination by using pancreatic juice (repeated cytology) for BD-IPMNs. METHODS: Forty-five patients who underwent repeated cytology after a diagnosis of benignancy by using initial cytology were recruited for this study. RESULTS: Thirty-eight patients, excluding 7 patients with lack of surveillance period after the final cytology, were classified into Malignancy (n = 13) and Benignancy groups (n = 25) on the bases of the findings from resected specimens or changes in BD-IPMNs after repeated cytology. The sensitivity and specificity to detect malignant changes in BD-IPMNs by using repeated cytology were 62% and 100%, respectively. For the 12 patients with mural nodules (MNs) ≥ 5 mm (67% of them were malignant), the sensitivity was 50%, whereas, for the 26 patients without MNs ≥ 5 mm (19% of them were malignant), it was 80%. In addition, malignant changes in BD-IPMNs after initial cytology occurred in 62% of the patients with changes in the MNs and 27% of the patients with an increase in the cyst size. CONCLUSION: Repeated cytology can play a role in the determination for surgery even after a diagnosis of benignancy by using initial cytology, especially for BD-IPMNs without MNs ≥5 mm. In addition, changes in the MNs or cyst size may be appropriate indications for repeated cytology.

[Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma with MALT translocation gene 1 diagnosed using an endoscopic submucosal dissection specimen].

A 15-mm whitish, depressed lesion was observed in the stomach of a 39-year-old using screening esophagogastroduodenoscopy. The lesion had grown to a size of 40mm and had a cobblestone-like appearance at an 11-year endoscopic follow-up. Using endoscopic submucosal dissection (ESD) as a diagnostic therapy, gastric mucosa-associated lymphoid tissue (MALT) lymphoma with MALT translocation gene 1 without Helicobacter pylori infection was detected. Although the patient did not undergo additional treatments, he remained alive without for recurrence 5 years after ESD.

[Synchronous double primary cancers of a mixed adenoneuroendocrine carcinoma of the distal bile duct and a carcinoma in situ in the perihilar bile duct].

We report the rare case of a 69-year-old man who underwent resection of a mixed adenoneuroendocrine carcinoma (MANEC) of the distal bile duct and a carcinoma in situ in the perihilar bile duct. The patient was admitted to our hospital for obstructive jaundice. Imaging studies revealed a mass in the distal bile duct, and an abnormal epithelium was detected in the perihilar bile duct using peroral cholangioscopy. Bile cytology and transpapillary biopsy of the tumor revealed adenocarcinoma. We diagnosed this patient with distal cholangiocarcinoma with extensive intraepithelial progression toward the perihilar bile duct and performed a subtotal stomach-preserving pancreaticoduodenectomy and left hepatectomy. According to the histological examination of the resected specimens, we found a MANEC in the distal bile duct and a carcinoma in situ in the perihilar bile duct. Together, they were diagnosed as synchronous double primary cancers due to the lack of pathological transition between them.

Should we regard all main duct type intraductal papillary mucinous neoplasms of the pancreas (MD-IPMN) as an indication of surgery? -A retrospective study in 29 patients with MD-IPMN showing mural nodules.

PURPOSE: To elucidate predictive factors for malignant main duct type IPMN (MD-IPMN). METHODS: All 29 subjects had mural nodules (MNs) in the main pancreatic duct (MPD) on preoperative endoscopic ultrasonography and underwent surgery (19, malignant; 10, benign). Possible predictive factors for malignancy such as background, imaging, and histological factors including histological subtype (HS), were evaluated. RESULTS: Multivariate analysis revealed an MPD diameter of ≥12 mm (p = 0.042) and non-gastric type (p = 0.001) to be the statistically significant predictive factors for malignancy. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy to detect malignancy by using "an MPD diameter of ≥12 mm and/or non-gastric type" were 95%, 70%, 86%, 88%, and 86%, respectively. In 7 subjects in whom HS was preoperatively evaluated using pancreatic specimens obtained before surgery, the agreement rate of the preoperative HS with definitive HS evaluated using resected specimens was 86%. CONCLUSIONS: For MD-IPMNs with MNs, "an MPD diameter of ≥12 mm and/or non-gastric type" are indicated for surgery. On the other hand, careful surveillance without immediate pancreatic surgery may be an option for MD-IPMNs showing both an MPD diameter of <12 mm and gastric type.

[Detection of small pancreatic cancer during surveillance of the main pancreatic duct stenosis].

An 83-year-old man with main pancreatic duct (MPD) stenosis in the pancreatic body had undergone surveillance with semiannual imaging studies for 3 years. During surveillance, magnetic resonance cholangiopancreatography revealed gradual enlargement of a small cyst near the MPD stenosis and contrast-enhanced computed tomography revealed locally progressive atrophic parenchyma in the pancreatic body. On endoscopic retrograde pancreatography, the MPD stenosis was more severe than it had been at diagnosis 3 years earlier. Endoscopic ultrasonography (EUS) showed a 10-mm hypoechoic mass adjacent to the MPD stenosis. The mass was pathologically diagnosed as an adenocarcinoma using EUS-guided fine needle aspiration, and distal pancreatectomy was performed. On histopathological examination, the resected specimen was found to be a moderately differentiated 9-mm invasive ductal carcinoma. Additionally, multiple high-grade pancreatic intraepithelial neoplasms (i.e., carcinoma in situ) were detected in the MPD and branch ducts near the invasive carcinoma.

Pancreatic juice cytology with immunohistochemistry to detect malignancy and histologic subtypes in patients with branch duct type intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND AND AIMS: The aim of this study was to elucidate the efficacy of pancreatic juice cytology with the cell-block method (CB-PJC) for the determination of surgery in patients with branch duct intraductal papillary mucinous neoplasm (BD-IPMN). METHODS: In 138 patients with BD-IPMN from whom pancreatic juice was collected under ERCP for CB-PJC, we retrospectively evaluated the following: (1) the rate of successfully evaluated CB-PJC; (2) the ability of CB-PJC to diagnose malignancy and to identify pathologic subtypes in resected BD-IPMNs; (3) the rate of development into invasive cancer and progression of BD-IPMNs in patients with BD-IPMNs diagnosed as benignancy by CB-PJC; and (4) post-ERCP adverse events. RESULTS: (1) The success rate of CB-PJC was 89.9%. (2) The sensitivity and specificity of CB-PJC for preoperative diagnosis of malignancy were 50% and 100%, respectively, with only hematoxylin and eosin staining, whereas they were 79% and 100%, respectively, by adding immunohistologic staining. The agreement rate of the preoperative subtypes by CB-PJC with the subtypes of resected specimens was 93%. (3) The onset of invasive cancer was not detected at all on imaging studies, whereas the progression of IPMN was detected in 14 patients. Multivariate analysis revealed the risk factor of progression to be non-gastric type. The cumulative 5-year progression rate in this group was 89%. (4) Post-ERCP pancreatitis developed in 13 patients (7.7%). CONCLUSIONS: The diagnostic efficacy of preoperative CB-PJC for malignant BD-IPMN was excellent. The results may suggest the feasibility of applying preoperative subtyping by CB-PJC for decisions as to whether surgery is indicated.

Pancreaticobiliary Juice Reflux in Patients With a Morphologically Normal Ductal System: Assessment Using Unenhanced MRI With Spin Labeling.

OBJECTIVE: The purpose of this article is to evaluate pancreaticobiliary reflux and to assess its correlation with clinical findings in patients without morphologic pancreaticobiliary maljunction by using a new MRI technique. MATERIALS AND METHODS: A total of 320 consecutive patients with suspected pancreaticobiliary diseases underwent MRCP and flow analysis by MRI. MRI flow analysis, clinical, and laboratory findings of each patient were retrospectively reviewed. The visible pancreaticobiliary reflux was graded on a 5-point confidence scale. RESULTS: Among all 320 patients with pancreatic juice reflux, 14.1% had reflux scored as grades 4 and 5 combined, and 5.0% had reflux scored as grade 5. By univariate analysis and multivariate analysis, a relatively long common channel was found to be the only significant causal factor for pancreatic juice reflux. Of patients with pancreatic juice reflux of grade 4 or 5, 11.1% (5/45) also had biliary malignancies; 18.8% (3/16) of those with pancreatic juice reflux of grade 5 had biliary malignancies. Conversely, pancreatic juice reflux of grade 4 or 5 occurred in 35.7% (5/14) of patients with biliary malignancies, and reflux of grade 5 occurred in 21.4% (3/14) of those patients. CONCLUSION: It was possible to evaluate pancreaticobiliary reflux using an MRI technique that may be suitable as a screening tool. Our results revealed that pancreaticobiliary reflux is relatively frequent in individuals without pancreaticobiliary maljunction.

Endoscopic-ultrasonography-guided biliary drainage for repetitive acute cholangitis of the accessory hepatic duct obstructed by clipping during laparoscopic cholecystectomy.

An 88-year-old man who had been suffering from repetitive fever and abdominal pain every few months for several years was diagnosed with localized acute cholangitis and referred to our center. Various examinations, including computed tomography (CT) and endoscopic ultrasonography (EUS), revealed that the accessary hepatic duct was obstructed by clips used during laparoscopic cholecystectomy performed 7 years previously. It was not possible to approach the completely isolated duct via the transpapillary route. After obtaining fully informed consent, EUS-guided drainage of the occluded duct through the duodenal wall was performed with a self-expanding metal stent. No adverse events related to the procedure were observed, and his symptoms disappeared by the next day. EUS-guided drainage represents a therapeutic option in patients with an accessory hepatic duct, which is iatrogenically isolated by surgical clips.

[Mixed adenoneuroendocrine carcinoma of the gallbladder diagnosed by endoscopic transpapillary catheterization using bile cytology assessed by the cell block method].

A 65-year-old woman was suspected of having advanced gallbladder cancer based on imaging results. This was considered inoperable because it was accompanied by possible liver metastasis. To confirm the diagnosis prior to chemotherapy, endoscopic transpapillary catheterization in the gallbladder (ETCG) was performed. The bile cytology was analyzed by the cell block method, which revealed mixed adenoneuroendocrine carcinoma. Based on the cytological results, extended cholecystectomy and partial hepatectomy were performed for the metastatic lesions. Bile cytology by ETCG with the cell block method was useful for deciding the therapeutic strategy in this patient with metastatic gallbladder cancer.

Ampullary intervention for bile duct stones in patients with surgically altered anatomy.

Transpapillary endoscopic treatment is a standard technique for the treatment of bile duct stones. This technique includes biliary cannulation, ampullary interventions such as endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilation (EPBD), and stone removal. In patients with Roux-en-Y anastomosis, the transpapillary approach using an ordinary scope has been challenging. A recently developed single-/double-balloon enteroscope enables therapeutic endoscopic retrograde cholangiopancreatography to be carried out in such cases. EST using a balloon enteroscope is often difficult to carry out as a result of restriction of scope maneuverability or inadequate direction of the accessory. Although EPBD is easy to carry out for any anatomy, large or multiple stones are difficult to remove by EPBD only because of insufficient opening of Vater's papilla. Endoscopic papillary large-balloon dilation following EST is reported to be useful for the treatment of large and/or multiple stones. This technique is also useful for the treatment of bile duct stones in patients with Roux-en-Y anastomosis.

Clinical usefulness of double-guidewire technique for difficult biliary cannulation in endoscopic retrograde cholangiopancreatography.

BACKGROUND AND AIM: Although biliary cannulation with pancreatic guidewire placement (P-GW) is useful for difficult cases in endoscopic retrograde cholangiopancreatography (ERCP), the clinical significance of wire-guided cannulation with P-GW (double-guidewire technique: DGT) has not been clarified. The aim of the present study was to evaluate the usefulness of DGT for difficult biliary cannulation after unsuccessful biliary cannulation using a cannula/sphincterotome under guidance of injected contrast with P-GW (single-guidewire technique: SGT). METHODS: One-hundred and forty-six patients with difficult biliary cannulation who underwent SGT were included in this retrospective study. DGT was carried out if SGT was unsuccessful. Pancreatic duct (PD) stenting was attempted to prevent post-ERCP pancreatitis (PEP) in all patients. The success rate of cannulation and the risk factors for PEP were investigated. RESULTS: Biliary cannulation with SGT was achieved in 70%. DGT was carried out in 25 patients with unsuccessful SGT, biliary cannulation being successful in 72%. Of the 13 patients who underwent precut sphincterotomy, biliary cannulation was achieved in 46%. The incidence of PEP in patients who had undergone SGT, DGT, and precut sphincterotomy was 8% (12: mild, 8; moderate, 3; severe, 1), 4% (mild, 1), and 0%, respectively. PD stenting was successfully carried out in 86%. Multivariate analysis revealed unsuccessful PD stenting to be the only risk factor for PEP (OR 8.3, 95% CI 2.3-30). CONCLUSIONS: DGT may replace SGT or become the salvage procedure in cases of unsuccessful SGT as a result of its high success rate with an acceptable incidence of PEP. Failed pancreatic duct stenting in these techniques was frequently associated with PEP.

Small Barrett's adenocarcinoma, 3 mm in size, in long-segment Barrett's esophagus detected after 4 years of follow up.

We herein report a rare case of very small Barrett's adenocarcinoma. A 65-year-old man underwent surveillance esophagogastroduodenoscopy (EGD) 3 years after endoscopic submucosal dissection (ESD) for superficial Barrett's adenocarcinoma, which revealed a very small reddish area in the mucosa, 2 mm in diameter, in long-segment Barrett's esophagus. The EGD carried out 1 year later confirmed slight enlargement of the lesion, from 2 mm to 3 mm in diameter. Macroscopic type changed from flat type to slightly depressed type. On narrow-band imaging with magnifying endoscopy, an irregular microstructure and irregular microvasculature became recognizable. It was resected by ESD and diagnosed as mucosal adenocarcinoma with a diameter of only 3 mm.

Therapeutic endoscopic retrograde cholangiography using a single-balloon enteroscope in patients with Roux-en-Y anastomosis.

BACKGROUND: The aim of the present study was to evaluate the usefulness of a single-balloon enteroscope (SBE) including a newly developed short SBE (SIF-Y0004) for therapeutic endoscopic retrograde cholangiography (ERC) in patients with Roux-en-Y (R-Y) anastomosis. PATIENTS AND METHODS: Therapeutic ERC using a SBE was attempted in 19 cases (41 procedures) with R-Y anastomosis after gastrectomy. A standard SBE (working length of 200 cm, working channel of 2.8 mm) was used in 11 cases (Group L), and a short SBE (working length of 152 cm, working channel of 3.2 mm) was used in eight cases (Group S). RESULTS: Insertion of the scope up to the major papilla was achieved in 79% (15/19) of cases. Average insertion time was 37.0 ± 13.8 min (range, 19-62 min). Bile duct cannulation rate was 79% (11/14) after exclusion of the initial case in which scope exchange was unsuccessful. Average procedure time was78.8 ± 26.9 min (18-119 min). The scheduled therapeutic procedure was completed in 67% (10/15) of the cases (53% [10/19] on an intention-to-treat basis). Cardiorespiratory suppression due to sedative agents resulting in scope withdrawal developed in one procedure (2.4%; 1/41). Although there was no significant difference in therapeutic results between the two groups, the number of procedures was smaller (1.8 ± 1.3 vs 3.6 ± 3.1; P = 0.286) in Group S than in Group L. CONCLUSIONS: Therapeutic ERC using a SBE for patients with R-Y anastomosis is considered to be safe and effective. A short SBE appears to be promising for further improvement in therapeutic results.

Efficacy and safety of a WallFlex enteral stent for malignant gastric obstruction.

AIM: The aim of the present study was to investigate the efficacy and safety of a newly available enteral WallFlex stent for malignant gastric outlet obstruction (GOO). METHODS: Twenty-one consecutive patients with symptomatic (unable to take solids) malignant GOO treated by a WallFlex stent from April 2010 to February 2012 were included and analyzed retrospectively. Main outcome measurements were technical success, early complications, clinical response (elimination of the need for nasogastric tube drainage), clinical success (improvement of oral intake to a GOO score of 2 or 3), and duration of sustaining a GOO score of 2 or 3 after clinical success (median duration until reworsening of GOO score to <2 by the Kaplan-Meier method). A four-point GOO scoring system (0-3) was used for estimation of oral intake. RESULTS: Technical success rate was 100%. Bleeding and perforation after stent placement and stent dislocation/migration in the follow-up period did not occur in any patients, whereas one patient (5%) developed moderate post-procedural pancreatitis. Clinical response and clinical success was achieved in all patients and in 81% (17/21), respectively. In 17 patients whose GOO score had improved to 2 or 3 after stent placement, eight (47%) developed reworsening of the GOO score to <2 with a median time of 148 days (95% confidence interval [CI], 0-328; Kaplan-Meier method). Median survival time after the initial intervention was 61 days (95% CI, 40-82). CONCLUSION: Placement of an enteral WallFlex stent in patients with malignant GOO is safe and effective.