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.

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.

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.

Accurate endoscopic identification of the afferent limb at the Y anastomosis using the fold disruption sign after gastric resection with Roux-en-Y reconstruction.

In patients with Roux-en-Y (RY) reconstruction for gastric resection, the newly defined "fold disruption" (FD) sign can be useful to distinguish the afferent limb from the efferent limb at the Y anastomosis when balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is performed. The FD sign was defined as endoscopic findings of the internal folds disrupted toward the afferent limb and continued toward the efferent limb at the Y anastomosis. In this prospective observational study, the accuracy of the FD sign was evaluated for those who underwent BE-ERCP after gastric resection with RY reconstruction. Of 28 patients for whom the accuracy could be evaluated among 30 enrolled patients, the afferent limb was identified using the FD sign with 100% accuracy. For the other two patients, the scope could not reach the target lumen due to severe intestinal adhesion in one and reached the target lumen without recognition of the Y anastomosis in the other. There was no patient for whom the FD sign could not be judged for any reason, such as a blurred anastomosis line, unclear folds, sticky discharge and blood coating the surface, when the Y anastomosis was recognized. The FD sign was a highly accurate tool for distinguishing the afferent limb from the efferent limb in patients after gastric resection with RY reconstruction. This study was registered in UMIN (issued ID, UMIN000038326).

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.

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.

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.

Efficacy of EUS-guided celiac plexus neurolysis compared with medication alone for unresectable pancreatic cancer in the oxycodone/fentanyl era: a prospective randomized control study.

BACKGROUND AND AIMS: The efficacy of celiac plexus neurolysis (CPN) with EUS guidance (EUS-CPN) has not been confirmed in the era of developed opioids. The aim of this study was to evaluate the efficacy of EUS-CPN for patients with pancreatic cancer-associated pain to compare medication using oxycodone and/or fentanyl with and without EUS-CPN. METHODS: In this randomized control study involving patients who underwent EUS-CPN and those who did not, pain, quality of life (QOL), and opioid consumption were compared. Standard medicinal treatment using oxycodone and/or fentanyl was performed for both groups. The primary endpoint was defined as the pain evaluated by using a visual analog scale (VAS) rated from a 0 to 10, 4 weeks after the baseline. RESULTS: For 48 registered patients, the outcomes of 24 patients in the EUS-CPN group and 22 patients in the control group were analyzed. EUS-CPN was successfully performed and did not induce severe procedure-related adverse events for all patients in the EUS-CPN group. Although the average pain VAS scores for both groups significantly decreased in comparison with baseline, scores were not statistically different between the groups at week 4 (1.3 ± 1.3 for the EUS-CPN group vs 2.3 ± 2.3 for the control group, P = .10). There was no statistical difference or tendency in favor of EUS-CPN at evaluation points of weeks 1, 2, 8, and 12. Moreover, the average VAS scores for QOL and the average opioid consumption between the groups were not different at all evaluation points. CONCLUSIONS: EUS-CPN for patients with pancreatic cancer-associated pain did not appear to improve pain, QOL, or opioid consumption compared with those who did not undergo EUS-CPN and medicated with oxycodone/fentanyl. Although EUS-CPN can be an option, it was not found to have a large enough impact to be routinely performed for all patients with pain. (Clinical trial registration number: UMIN 000037172.).

[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.

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.