Suprapapillary placement of plastic versus metal stents for malignant biliary hilar obstructions: a multicenter, randomized trial.

BACKGROUND AND AIMS: The efficacy of the suprapapillary placement of inside plastic stents (iPSs) for unresectable malignant hilar biliary obstructions (MHOs) is unknown compared with that of uncovered inside metal stents (iMSs). This randomized controlled trial was designed to evaluate the outcomes of endoscopic placement of these stents for unresectable MHOs. METHODS: This open-label, randomized study was conducted at 12 Japanese institutions. The enrolled patients with unresectable MHOs were allocated to iPS and iMS groups. The primary outcome was defined as the time to recurrent biliary obstruction in patients for whom the intervention was both technically and clinically successful. RESULTS: Among 87 enrollments, 38 patients in the iPS group and 46 patients in the iMS group were analyzed. Technical success rates were 100% (38 of 38) and 96.6% (44 of 46), respectively (P = 1.00). After transferring 1 unsuccessful iMS-group patient to the iPS group (since iPSs were deployed), the clinical success rates were 90.0% (35 of 39) for the iPS group and 88.9% (40 of 45) for the iMS group from a per-protocol analysis (P = 1.00). Among the patients with clinical success, the median times to recurrent biliary obstruction were 250 (95% confidence interval, 85-415) and 361 (95% confidence interval, 107-615) days (log-rank test, P = .34). No differences were detected in rates of adverse events. CONCLUSIONS: This Phase II randomized trial did not show any statistically significant difference in stent patency between suprapapillary plastic versus metal stents. Considering the potential advantages of plastic stents for malignant hilar obstruction, these findings suggest that suprapapillary plastic stents could be a viable alternative to metal stents for this condition.

Quantitative monitoring of circulating tumor DNA in patients with advanced pancreatic cancer undergoing chemotherapy.

According to cancer genome sequences, more than 90% of cases of pancreatic ductal adenocarcinoma (PDAC) harbor active KRAS mutations. Digital PCR (dPCR) enables accurate detection and quantification of rare mutations. We assessed the dynamics of circulating tumor DNA (ct-DNA) in patients with advanced PDAC undergoing chemotherapy using dPCR. KRAS G12/13 mutation was assayed by dPCR in 47 paired tissue- and ct-DNA samples. The 21 patients were subjected to quantitative ct-DNA monitoring at 4 to 8-week intervals during chemotherapy. KRAS mutation was detected in 45 of those 47 patients using tissue DNA. In the KRAS mutation-negative cases, next-generation sequencing revealed KRAS Q61K and NRAS Q61R mutations. KRAS mutation was detected in 23/45 cases using ct-DNA (liver or lung metastasis, 18/19; mutation allele frequency [MAF], 0.1%-31.7%; peritoneal metastasis, 3/9 [0.1%], locally advanced, 2/17 [0.1%-0.2%]). In the ct-DNA monitoring, the MAF value changed in concordance with the disease state. In the 6 locally advanced cases, KRAS mutation appeared concurrently with liver metastasis. Among the 6 cases with liver metastasis, KRAS mutation disappeared during the duration of stable disease or a partial response, and reappeared at the time of progressive disease. The median progression-free survival was longer in cases in which KRAS mutation disappeared after an initial course of chemotherapy than in those in which it was continuously detected (248.5 vs 50 days, P < .001). Therefore, ct-DNA monitoring enables continuous assessment of disease state and could have prognostic utility during chemotherapy.

Can the location of the mural nodule indicate benign or malignant in branch duct-type intraductal papillary mucinous neoplasm of the pancreas?

BACKGROUND/OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are classified into main duct (MD)-type IPMNs, branch duct (BD)-type IPMNs, and mixed type IPMNs. While MD-type IPMN has a high risk of malignancy and should therefore be considered for resection if the patient is fit, BD-type IPMN needs to be carefully judged for surgical indication. The decision to resect BD-type IPMN is often based on international consensus Fukuoka guidelines 2017, but further investigation is required. In this study, we focused on whether the location of the mural nodule (MN) could be an indicator of malignancy. METHODS: We enrolled 17 cases who had been diagnosed BD-type IPMNs which were surgically resected from January 2016 to December 2019. These cases were classified into benign and malignant group. Subsequently, a clinicopathological study was conducted based on the localization of MN (MN-central type or MN-peripheral type). RESULTS: Although MN was found in 57% (4/11) in the benign group, 88% (7/8) was noted in the malignant group, indicating the presence of MN to be more common in the malignant group. Those with MN consisted of 6 cases of MN-central type and 5 cases of MN-peripheral type. All cases of central type were malignant compared to only one case of the peripheral group being confirmed on histology as cancer. CONCLUSION: BD-IPMN with central mural nodule should be considered high risk for malignancy.

Additive Effect of Magnifying Endoscopy with Narrow-Band Imaging for Diagnosing Mixed-Type Early Gastric Cancers.

BACKGROUND: Pretreatment biopsy may not correctly diagnose mixed-type early gastric cancers. Despite reports on the usefulness of magnifying endoscopy with narrow-band imaging in diagnosing early gastric cancers, no reports exist on differences in magnifying endoscopy with narrow-band imaging findings between differentiated-type-predominant mixed-type and undifferentiated-type-predominant mixed-type early gastric cancers. AIM: This study aimed to clarify differences in magnifying endoscopy with narrow-band imaging findings and investigate the additive effect of combining magnifying endoscopy with narrow-band imaging and biopsy findings for pretreatment histological-type diagnosis. METHODS: Patients undergoing endoscopic submucosal dissection as initial treatment between April 2005 and March 2017 participated in this retrospective study. There were 156 differentiated-type-predominant mixed-type and 36 undifferentiated-type-predominant mixed-type lesions. We extracted the most significant magnifying endoscopy with narrow-band imaging findings of differentiated-type-predominant mixed-type and undifferentiated-type-predominant mixed-type lesions using multivariate analysis and compared the accuracy, sensitivity, and specificity between pretreatment biopsy alone and a combination of biopsy and magnifying endoscopy with narrow-band imaging findings. RESULTS: Significant magnifying endoscopy with narrow-band imaging findings was fine network pattern in differentiated-type-predominant and corkscrew pattern in undifferentiated-type-predominant mixed-type lesions. Accuracy, sensitivity, and specificity were significantly higher with combined biopsy and magnifying endoscopy with narrow-band imaging findings than with pretreatment biopsy alone. CONCLUSIONS: The study results demonstrated the additive effect of magnifying endoscopy with narrow-band imaging with biopsy for diagnosing mixed-type early gastric cancers. This study may be beneficial in routine practice because it indicates a possibility of reducing additional surgery after endoscopic submucosal resection because of incorrect diagnosis of histological type.

[Six cases of anaplastic pancreatic carcinoma diagnosed by endoscopic ultrasound-guided fine needle aspiration].

Anaplastic pancreatic carcinoma is a rare form of pancreatic cancer with an extremely poor prognosis. Its diagnosis is often based on surgical specimens and few reports have described the use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for diagnosis. In this study, we examined six patients (mean age, 70.5 years;sex ratio, 1:1) who were diagnosed with anaplastic pancreatic carcinoma using EUS-FNA. The carcinomas were located in the pancreatic head, body, and tail in one, three, and two patients, respectively. The mean tumor diameter was 49.2mm. Five patients opted for best supportive care due to poor performance status and one underwent chemotherapy (GEM+nab-PTX). The median survival was 40.5 (14-98) days. The characteristic imaging findings of anaplastic pancreatic carcinoma, including central necrosis, marginal contrast enhancement, cystic findings, and internal calcification, were frequently observed in the patients. Anaplastic pancreatic carcinoma can also be diagnosed using biopsy tissue;however, a pathologist's consultation is required to differentiate the disease based on imaging findings for an accurate diagnosis.

Diagnostic accuracy of demarcation using magnifying endoscopy with narrow-band imaging for Helicobacter pylori-uninfected undifferentiated-type early gastric cancer.

BACKGROUND: It is unknown how the accuracy rate of diagnostic demarcation of undifferentiated-type early gastric cancers (UD-type EGCs) differs between patients uninfected with Helicobacter pylori (H. pylori) and patients with and without H. pylori eradication. This study assessed and compared the diagnostic accuracy rate in the H. pylori-uninfected group and the non-H. pylori eradication and H. pylori eradication groups. METHODS: Subjects were 81 patients with 81 lesions who underwent endoscopic submucosal dissection between January 2010 and January 2015. There were 21 lesions in the H. pylori-uninfected group, 27 in the H. pylori eradication group, and 33 in the non-H. pylori eradication group. The rate in the H. pylori-uninfected group was separately compared with the rates in the non-H. pylori eradication and H. pylori eradication groups, as was inflammatory cell infiltration. RESULTS: The diagnostic accuracy rates were 60.6% in the non-H. pylori eradication group, 92.2% in the H. pylori eradication group, and 100% in the H. pylori-uninfected group; the rate was significantly higher in the H. pylori-uninfected group than in the non-H. pylori eradication group, but no significant difference was observed between the H. pylori-uninfected group and the H. pylori eradication group. In addition, the H. pylori-uninfected and H. pylori eradication groups showed no significant differences in neutrophil infiltration and intestinal metaplasia, whereas the state in the H. pylori-uninfected group was significantly milder. CONCLUSIONS: Because neutrophil infiltration was classified as mild or none, the accuracy of diagnostic demarcation was high in the H. pylori-uninfected and H. pylori eradication groups.

Mixed poorly differentiated adenocarcinoma in undifferentiated-type early gastric cancer predicts endoscopic noncurative resection.

BACKGROUND: Comparisons between surgical cases of mixed poorly differentiated adenocarcinoma and pure signet ring cell carcinoma have revealed higher frequencies of lymph node metastasis and submucosal invasion in the former. However, this comparison has not been reported for endoscopically treated cases. Therefore, we compared cases of curative and noncurative resection in patients who underwent endoscopic submucosal dissection to determine what factors could influence the curative resection rate. METHODS: We analyzed 268 undifferentiated-type early gastric cancers in 264 patients treated with endoscopic submucosal dissection in our hospital between March 2005 and March 2017, involving 229 and 39 cases of curative and noncurative resection, respectively. Treatment results were compared between 129 lesions of pure signet ring cell carcinoma and 139 lesions of mixed poorly differentiated adenocarcinoma. RESULTS: The overall curative resection rate was 85.4% (229/268). On comparing noncurative and curative resection cases, after excluding factors that determine curative resection (e.g., tumor diameter), we found that the former was associated with older age and significantly more mixed poorly differentiated adenocarcinomas, with odds ratios of 1.052 [95% confidence interval (CI), 1.017-1.089] and 2.746 (95% CI, 1.162-6.485), respectively, on multivariate analysis. The curative resection rate was significantly higher in pure signet ring cell carcinoma than in mixed poorly differentiated adenocarcinoma (93.8% vs. 77.7%, respectively). CONCLUSION: Advanced age and mixed poorly differentiated adenocarcinoma predicted endoscopic noncurative resection.

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

BACKGROUND AND AIM: Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. METHODS: A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. RESULTS: Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. CONCLUSIONS: Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO.

Undifferentiated-type component mixed with differentiated-type early gastric cancer is a significant risk factor for endoscopic non-curative resection.

BACKGROUND AND AIM: Previous studies of surgical specimens have found that the presence of mixed histological components in differentiated-type early gastric cancer (EGC) is a risk factor for lymph node metastasis and indicates greater malignancy. As there have been no reports on its endoscopic treatment, we examined endoscopic curative resection in relation to differentiated-type-predominant mixed-type (MT). METHODS: This was a single-center, retrospective study. Subjects were 2585 differentiated-type EGC in 2551 patients treated with endoscopic submucosal dissection (ESD) in our hospital between March 2005 and January 2016. These lesions comprised 2231 cases of curative resection and 354 cases of non-curative resection. Histologically, 2339 lesions were pure differentiated-type (PDT) and 246 lesions were MT. Rates of curative resection were compared, according to tumor size, between different histological types. RESULTS: When curative and non-curative cases were compared using multivariate analysis among lesions measuring ≤20 mm for factors other than those determining curative resection, significant differences were obtained for tumor diameter, ulcer, and MT. Among lesions measuring 21-30 mm, ulcer and MT were associated with significant differences. Among lesions measuring >30 mm, upper region and MT were associated with significant differences. Curative resection rates, in relation to histological type among lesions measuring ≤20 mm, were 93.4% for PDT and 63.4% for MT, whereas corresponding rates were 85.1% and 60.0%, respectively, among lesions measuring 21-30 mm, and 55.3% and 30.2%, respectively, among lesions measuring >30 mm. CONCLUSION: We found that MT was a risk factor for non-curative resection irrespective of lesion size.

Study on Clinical Factors Involved in Helicobacter pylori-Uninfected, Undifferentiated-Type Early Gastric Cancer.

BACKGROUND: The factors associated with the pathogenesis of Helicobacter pylori-uninfected undifferentiated-type early gastric cancer (HPUGC) remain unclear. This study compared patient characteristics, including medical history and alcohol/tobacco use, of HPUGC patients with characteristics of patients with H. pylori-positive undifferentiated-type early gastric cancer (HPPGC) to clarify and gain understanding on those differences that could play a role in the pathogenesis. METHODS: This retrospective study included 282 patients who were treated endoscopically from March 2005 to March 2014. This cohort consisted of 232 patients with HPPGC (82.3%) and 50 patients with HPUGC (17.7%). Patient characteristics were analyzed by subgroups of HPUGC vs. HPPGC, with comparisons for age, gender, cancer history, comorbidity of lifestyle diseases requiring medication (hypertension, type 2 diabetes, and dyslipidemia), cumulative amount of alcohol consumption, and smoking history (Brinkman index [BI]). RESULTS: HPUGC patients were typically younger, had less frequent hypertension, and had higher BI values (p < 0.05 for all parameters). In a younger non-hypertensive subgroup, the OR for high BI (BI ≥340) in the HPUGC group vs. HPPGC group was 5.049 (95% CI 2.458-10.373, p < 0.0001). CONCLUSIONS: The investigation of clinical factors identified smoking history as being possibly contributing to the pathogenesis of HPUGC. Future research is necessary at the cellular and genetic levels.

A case of rectal neuroendocrine carcinoma in a patient with long-standing ulcerative colitis involving alterations of the p16-Rb pathway.

The patient was a 54-year-old male who had been suffering from extensive ulcerative colitis (UC) for 17 years. Colonoscopy revealed an elevated lesion in the affected rectum, and its biopsy demonstrated neuroendocrine carcinoma (NEC). The surgical specimen obtained on laparoscopic high anterior resection showed extensive active inflammatory and dysplastic lesions and three grossly visible multifocal malignant lesions: a polypoid fungating tumor of NEC (type 1, 20 mm in diameter, pT3) that had been preoperatively noticed, a polypoid fungating tumor of adenocarcinoma (type 1, 22 mm, pT2) and a protruded sessile polypoid tumor (0-Is, 5 mm, pTis) of adenocarcinoma. The NEC was adjacently accompanied by dysplasia-carcinoma sequential lesions and showed a diffuse immunohistochemical overexpression of p53 and p16 proteins and the loss of Rb with no abnormal immunohistochemical staining of microsatellite instability markers and no KRAS mutations. Fifteen months later, the patient showed liver metastasis from the NEC component, followed by bone and spinal metastasis; he died 22 months after the initial diagnosis. A rare case of lethal NEC arising from long-standing extensive UC was reported. The NEC appeared to be UC-related, not incidental, and complicated by progression from dysplasia to carcinoma involving alterations of the p16-Rb pathway.