Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis.

BACKGROUND/OBJECTIVES: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC. METHODS: We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions. RESULTS: Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38-1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively. CONCLUSIONS: This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.

Effect of ice water injection toward the duodenal papilla for preventing post-ERCP pancreatitis: study protocol for a multicenter, single-blinded, randomized controlled trial (EUTOPIA study).

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure in the diagnosis and treatment of biliopancreatic diseases. The most common adverse event of ERCP is post-ERCP pancreatitis (PEP), which can sometimes be severe. Our previous study suggested that injecting ice water at the end of ERCP suppressed PEP, and we decided to investigate this effect in a multicenter randomized controlled trial. METHODS: This study is being conducted at eight hospitals in Japan starting in April 2022. Patients undergoing ERCP will be randomized to ice water group and control group. In the ice water group, 250 ml of ice water is injected toward the papilla at the end of ERCP. The next morning, a physical examination and blood tests are performed to evaluate for the development of pancreatitis. The goal is to have 440 cases in each group. DISCUSSION: The main cause of PEP is thought to be papilla edema. Cooling the papilla, as everyone naturally does at the time of a burn, is expected to prevent its inflammation and edema. Various methods to suppress PEP have been reported, but so far none of them are reliable. The method we have devised is very simple, easy, and safe. We hope that our study will change the world's ERCP common practice. TRIAL REGISTRATION: UMIN000047528. Registered 20 April 2022, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053209.

Does second-look endoscopy reduce the bleeding after gastric endoscopic submucosal dissection for patients receiving antithrombotic therapy?

BACKGROUND: In patients with average risk of bleeding, second-look endoscopy does not reportedly reduce bleeding after gastric endoscopic submucosal dissection. However, effectiveness of second-look endoscopy for patients with a high risk of bleeding, such as those who are taking antithrombotic agents, is unclear. Hence, this study aims to clarify the effectiveness of second-look endoscopy for patients with antithrombotic therapy. METHODS: We studied 142 consecutive patients with 173 gastric epithelial neoplasms who were routinely taking antithrombotic agents and were treated by endoscopic submucosal dissection at Tonan Hospital between November 2013 and December 2019. They were classified into two groups: those with second-look endoscopy (SLE group, 69 patients with 85 lesions) and those without second-look endoscopy (non-SLE group, 73 patients with 88 lesions). The incidence of post-endoscopic submucosal dissection bleeding was compared between the SLE and non-SLE groups. RESULTS: There were no statistical differences in the rate of patients undergoing single antiplatelet therapy, single anticoagulant therapy, and multiple therapy between the SLE and non-SLE groups (SLE group vs. non-SLE group; 32 [46.4%], 16 [23.2%], and 21 [30.4%] patients vs. 37 [50.7%], 20 [27.4%], and 16 [21.9%] patients, respectively; p = 0.50). Post-endoscopic submucosal dissection bleeding incidence was 21.7% (15/69) and 21.9% (16/73) in the SLE and non-SLE groups, respectively, and did not significantly differ between the two groups (p = 0.98). CONCLUSIONS: For patients taking antithrombotic agents, the incidence of post-endoscopic submucosal dissection bleeding was not reduced by second-look endoscopy.

Comparison of clinicopathological features and long-term prognosis between mixed predominantly differentiated-type and pure differentiated-type early gastric cancer.

BACKGROUND: Recent studies have shown that mixed predominantly differentiated-type (MD) early gastric cancer (EGC) might have more malignant potential than pure differentiated-type (PD) EGC. However, no study has analyzed all differentiated-type EGC cases treated endoscopically and surgically. This study aimed to compare the differences in clinicopathological features and long-term prognosis between MD- and PD-EGC. METHODS: We evaluated all patients with differentiated-type EGCs who were treated endoscopically and surgically in our hospital between January 2010 and October 2014. The clinicopathological features and long-term prognosis of MD-EGC were compared with those of PD-EGC. RESULTS: A total of 459 patients with 459 lesions were evaluated in this study; of them, 409 (89.1%) and 50 (10.9%) were classified into the PD and MD groups, respectively. Submucosal invasion was found in 96 (23.5%) patients of the PD group and in 33 (66.0%) patients of the MD group (p < 0.01). The rates of positive lymphatic and vascular invasion and ulceration were significantly higher in the MD group than in the PD group (p < 0.01). The proportion of patients with lymph node metastasis was also significantly higher in the MD group than in the PD group (5 (10%) vs 6 (1.5%), p < 0.01). The 5-year overall and EGC-specific survival rates in the PD group were 88.3 and 99.5%, respectively, while they were 94.0 and 98.0% in the MD group, respectively. CONCLUSIONS: MD-EGC has more malignant potential than PD-EGC. However, the long-term prognosis of MD-EGC is good and is not significantly different from that of PD-EGC when treated appropriately.

Metachronous intraductal papillary mucinous neoplasms disseminate via the pancreatic duct following resection.

Metachronous development of intraductal papillary mucinous neoplasms in the remnant pancreas following resection is a significant clinical burden. Our aim was to characterize the clinicopathological and molecular features of the patients with metachronous tumor development to identify predictive factors and the possible route(s) of dissemination. Seventy-four patients who underwent resection of intraductal papillary mucinous neoplasms with no invasive compartment or associated carcinoma were retrospectively analyzed. In patients with metachronous tumor development, targeted sequencing of 18 genes associated with pancreatic tumorigenesis and immunohistochemical detection of four proteins (p53, SMAD4, p16, and ß-catenin) were performed on both primary and metachronous tumors. The distributions of microscopic neoplastic lesions were examined at surgical margins and in apparently normal tissue apart from the primary tumor. During the median follow-up period of 52 months, 9 patients (12%) developed metachronous tumors in the remnant pancreas. Primary tumors located in the body/tail of the pancreas (odds ratio, 15; 95% confidence interval, 1.6-131) and of the pancreatobiliary type (odds ratio, 6.1; 95% confidence interval, 1.1-35.7) were identified as significant risk factors for subsequent metachronous tumor development. Eight of the nine patients shared molecular aberrations between their primary and metachronous tumors, suggesting migrations from the primary tumor to the pancreatic duct as the cause of metachronous tumor development. Our data suggest that these post-resection metachronous tumors develop by skip dissemination of the primary tumor, potentially via the pancreatic duct. The development of strategies to better predict and prevent this form of tumor progression is necessary.

Endoscopic ultrasound-guided fine needle aspiration for diagnosing pancreatic mass in patients with surgically altered upper gastrointestinal anatomy.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been established as a safe and accurate method for diagnosing a pancreatic mass; however, EUS-FNA for patients with surgically altered upper gastrointestinal (UGI) anatomy has not yet been investigated sufficiently. Therefore, the feasibility and safety of EUS-FNA in these patients were retrospectively investigated. METHODS: Patients in whom EUS-FNA was performed between March 2008 and April 2017 were retrospectively investigated in terms of EUS-FNA technical success, procedure time, diagnostic accuracies of cytology and histology, and procedure-related adverse events. RESULTS: Twenty-five EUS-FNAs were performed for 15 pancreatic body-to-tail and 10 head lesions. All patients underwent EUS-FNA successfully; however, changing of the echoendoscope to a forward-viewing echoendoscope and preplacement of a nasobiliary catheter by balloon-assisted enteroscopy for guidance were needed in one and two cases, respectively. The median procedure time was 26 min (range, 16-70). The diagnostic accuracies were 76%, 84%, and 88% for cytology, histology, and combined use, respectively. Adverse events were not observed. CONCLUSIONS: Endoscopic ultrasound-guided FNA is a safe and efficient method for diagnosing a pancreatic mass even in patients with surgically altered UGI anatomy. Nevertheless, some sophisticated techniques are required for pancreatic head lesions if reaching the duodenum after passing through the jejunal limb is required for visualization of the pancreatic mass.

Non-negligible rate of needle tract seeding after endoscopic ultrasound-guided fine-needle aspiration for patients undergoing distal pancreatectomy for pancreatic cancer.

BACKGROUND AND AIMS: Needle tract seeding after preoperative endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic body and tail cancer has been reported. This study aimed to investigate the long-term outcomes, including the needle tract seeding ratio, of patients undergoing distal pancreatectomy for pancreatic body and tail cancer diagnosed preoperatively by EUS-FNA. METHODS: This retrospective, observational cohort study assessed patients from three university hospitals and 11 tertiary referral centers. All patients who underwent distal pancreatectomy for invasive cancer of the pancreatic body and tail between January 2006 and December 2015 were identified and reviewed. Needle tract seeding rate, recurrence-free survival (RFS), and overall survival (OS) were evaluated. RESULTS: Of the 301 total patients analyzed, 176 underwent preoperative EUS-FNA (EUS-FNA group) and 125 did not (non-EUS-FNA group). The median follow-up periods of the EUS-FNA group and non-EUS-FNA group were 32.8 and 30.1 months. Six patients (3.4%) in the EUS-FNA group were diagnosed as having needle tract seeding. The 5-year cumulative needle tract seeding rate estimated using Fine and Gray's method was 3.8% (95% CI 1.6-7.8%). The median RFS or OS was not significantly different between the EUS-FNA group and the non-EUS-FNA group (23.7 vs 16.9 months: P = 0.205; 48.0 vs 43.9 months: P = 0.392). CONCLUSION: Although preoperative EUS-FNA for pancreatic body and tail cancer has no negative effect on RFS or OS, needle tract seeding after EUS-FNA was observed to have a non-negligible rate. (UMIN000030719).

Surgery for Pancreatic Neuroendocrine Tumor G3 and Carcinoma G3 Should be Considered Separately.

BACKGROUND: The role of surgery in pancreatic neuroendocrine neoplasm grade 3 (pNEN-G3) treatment remains unclear. We aimed to clarify the role of surgery for pNEN-G3, which has recently been reclassified as pancreatic neuroendocrine tumor-G3 (pNET-G3) and pancreatic neuroendocrine carcinoma-G3 (pNEC-G3), with and without metastases, respectively. METHODS: We analyzed a subgroup of patients from the Japanese pancreatic NEC study, a Japanese multicenter case-series study of pNEN-G3. Pathologists subclassified 67 patients as having pNET-G3 or pNEC-G3 based on morphological features. We compared the overall survival (OS) rates among patients who were grouped according to whether they had undergone tumor-targeted surgery for tumors without (SwoM) or with (SwM) metastases, or non-surgical procedures (NS). RESULTS: Data from 21 patients with pNET-G3 (SwoM, n = 6; SwM, n = 5; NS, n = 10) and 46 patients with pNEC-G3 (SwoM, n = 8; SwM, n = 5; NS, n = 33) were analyzed. OS of patients with pNET-G3 was significantly longer after SwoM and SwM than with NS (p = 0.018 and p = 0.022). In contrast, OS did not significantly differ between either SwoM or SwM and NS (p = 0.093 and p = 0.489) among patients with pNEC-G3. CONCLUSION: The role of surgery should be considered separately for pNET-G3 and pNEC-G3. Although SwoM and SwM can be considered for pNET-G3, caution is advised before considering SwM and SwoM for pNEC-G3.

Short-type single-balloon enteroscope-assisted ERCP in postsurgical altered anatomy: potential factors affecting procedural failure.

Background and study aims Short-type single-balloon enteroscope (short SBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) is a promising alternative treatment in postsurgical altered anatomy. However, it is technically demanding, and factors affecting its technical difficulty have not yet been clarified. This study aimed to examine the procedural success rate of short SBE-assisted ERCP and the potential factors affecting procedural failure. Patients and methods A total of 117 consecutive patients (203 procedures) with surgically altered anatomy underwent ERCP using prototype short SBEs. The procedural success rate of short SBE-assisted ERCP and the potential factors affecting procedural failure were examined retrospectively. Results The enteroscopy success rate and procedural success rate were 92.6 % (95 % confidence interval [CI] 88.1 % - 95.8 %) and 81.8 % (95 %CI 75.8 % - 86.8 %), respectively. Multivariate analyses indicated that pancreatic indication (odds ratio [OR] 4.35, 95 %CI 1.67 - 11.4), first ERCP attempt (OR 6.03, 95 %CI 2.17 - 16.8), and no transparent hood (OR 4.61, 95 %CI 1.48 - 14.3) were potential risk factors for procedural failure. Conclusions Short SBE-assisted ERCP was effective in postsurgical altered anatomy. This large case series suggested the potential factors affecting procedural failure.

Balloon catheter versus basket catheter for endoscopic bile duct stone extraction: a multicenter randomized trial.

BACKGROUND AND STUDY AIMS: Endoscopic bile duct stone (BDS) removal is a well-established treatment; however, the preference for basket or balloon catheters for extraction is operator-dependent. We therefore conducted a multicenter prospective randomized trial to compare catheter performance. PATIENTS AND METHODS: We enrolled patients with a BDS diameter ≤ 10 mm and common bile duct diameter ≤ 15 mm. Participants were randomly assigned to groups that were treated with basket or balloon catheters between October 2013 and September 2014. The primary endpoint was the rate of complete clearance of the duct; the secondary endpoints were the rate and time to complete clearance in one endoscopic session. RESULTS: We initially enrolled 172 consecutive patients; 14 were excluded after randomization. The complete clearance rates were 92.3 % (72/78) in the balloon group and 80.0 % (64 /80) in the basket group. The difference in the rates between the two groups was 12.3 percentage points, indicating non-inferiority of the balloon method (non-inferiority limit -10 %; P < 0.001 for non-inferiority). Moreover, the balloon was superior to the basket (P = 0.037). The rate of complete clearance in one endoscopic session was 97.4 % using the balloon and 97.5 % using the basket (P = 1.00). The median times to complete clearance in one endoscopic session were 6.0 minutes (1 - 30) and 7.8 minutes (1 - 37) in the balloon and basket groups, respectively (P = 0.15). CONCLUSIONS: For extraction of BDSs ≤ 10 mm, complete endoscopic treatment with a single catheter is more likely when choosing a balloon catheter over a basket catheter.University Hospital Medical Information Network Trials Registry: UMIN000011887.

Diagnostic ability of EUS-FNA for pancreatic solid lesions with conventional 22-gauge needle using the slow pull technique: a prospective study.

OBJECTIVE: Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) using the slow pull technique (SP-FNA) has recently attracted attention as an effective tissue acquisition technique. However, efficacy of SP-FNA with a 22-gauge conventional needle remains unclear. The aim of this study is to evaluate the diagnostic ability of SP-FNA with a 22-gauge needle. MATERIAL AND METHODS: Patients with a pancreatic solid lesion were prospectively enrolled in this study. SP-FNA was performed at two needle passes with a 22-gauge needle. One dedicated pathologist evaluated the obtained samples in terms of quantity (Grade 0: scant; Grade 1: inadequate; Grade 2: adequate), quality (Grade 0: poor; Grade 1: moderate; Grade 2: good), and blood contamination (Grade 0: significant; Grade 1: moderate; Grade 2: low), and provided a pathological diagnosis. Additional EUS-FNA was performed by applying suction (SA-FNA). The evaluation points were as follows: diagnostic accuracy of SP-FNA compared with that of SA-FNA, and the quantity, quality, and blood contamination level of SP-FNA-obtained samples. RESULTS: We enrolled 40 cases. The diagnostic accuracy of SP-FNA was 90% (36/40). There was no significant difference in the accuracy between SP-FNA and SA-FNA (90% vs. 90%, p = 1.000). The samples obtained using SP-FNA were assessed as Grade 2 for quantity in 29 cases (73%), quality in 31 (78%), and blood contamination in 25 (63%). CONCLUSIONS: Adequate, high-quality, and unsubstantially blood-contaminated samples could be obtained using SP-FNA. The diagnostic ability of SP-FNA was 90%, which appeared to be similar to that of SA-FNA.

Spontaneous migration of a dedicated plastic stent after endoscopic ultrasound-guided hepaticogastrostomy in a patient with surgically altered anatomy: a case report.

Objective: We report a case of spontaneous migration of a dedicated plastic stent after endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) in a patient with surgically altered anatomy. Patient: The patient was a male in his 70s. He underwent EUS-HGS with the successful insertion of a dedicated plastic stent and had no obvious postprocedural complications. However, nine days after the procedure, the patient visited our hospital because of abdominal pain, fever, and stent excretion. We performed EUS-HGS with antegrade stenting, after which the patient had no further complications. Conclusion: Stent migration is considered a complication requiring caution when performing EUS-HGS in patients with surgically altered anatomy.

Reactivation of hepatitis B virus in patients with undetectable HBsAg undergoing chemotherapy for malignant lymphoma or multiple myeloma.

Despite increasing reports of hepatitis B virus (HBV) reactivation in hematological malignancies, its incidence, and risk factors are still obscure. The aim of this study was to clarify the frequency and risk factors of HBV reactivation in hepatitis B surface antigen (HBsAg) undetectable patients with malignant lymphoma or multiple myeloma, during or after chemotherapy. A total of 109 patients with undetectable HBsAg undergoing chemotherapy for malignant lymphoma or multiple myeloma were enrolled in this study. Anti-hepatitis B surface (anti-HBs) and anti-hepatitis B core (anti-HBc) were checked before treatment, and HBV DNA in sera was quantified monthly during and after chemotherapy. Out of 109 patients, 42 (38.5%) had anti-HBs and 59 (54.1%) had anti-HBc. Among the 59 anti-HBc positive patients, four patients (4/59, 6.8%) showed HBV reactivation during 20.5 median follow-up months. In all four patients with HBV reactivation, peripheral lymphocyte counts before chemotherapy were lower than those without HBV reactivation (P=0.033). HBV reactivation occurred during and after chemotherapy containing rituximab for non-Hodgkin lymphoma. Four patients, who had HBV reactivation, did not develop de novo hepatitis due to HBV reactivation and were able to undergo chemotherapy against malignant lymphoma as scheduled. Monitoring of HBV DNA in sera is useful for the early diagnosis of HBV reactivation, and preemptive therapy is an useful alternative to prevent hepatitis due to HBV reactivation. Patients must be monitored periodically for HBV-DNA levels during and after chemotherapy.

Factors predictive of adverse events associated with endoscopic ultrasound-guided fine needle aspiration of pancreatic solid lesions.

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) provides high diagnostic accuracy with a low incidence of procedural complications. However, it occasionally causes serious complications, and factors that increase the susceptibility to such adverse events remain unknown. AIMS: We aimed to examine post-procedural events and determine risk factors associated with EUS-FNA of pancreatic solid lesions. METHODS: This single-center retrospective study included 316 consecutive patients with pancreatic solid lesions who underwent 327 EUS-FNA procedures from April 2003 to September 2011. We registered all patients undergoing EUS-FNA in the database and retrospectively ascertained the presence/absence of post-procedural adverse events. RESULTS: The incidence of post-procedural adverse events, including moderate to mild pancreatitis, mild abdominal pain, and mild bleeding, was 3.4 %. Univariate analysis showed that the incidence of post-procedural events was significantly increased in patients with tumors less than or equal to 20 mm in diameter (P < 0.001), those with pancreatic neuroendocrine tumors (PNET) (P = 0.012), and patients who had intervening normal pancreas for accessing the lesion (P = 0.048). Multivariate analysis identified tumors measuring less than or equal to 20 mm in diameter (OR 18.48; 95 % CI 3.55-96.17) and case of PNETs (OR 36.50; 95 % CI 1.73-771.83) were an independent risk factors. CONCLUSIONS: EUS-FNA of pancreatic solid lesions is a safe procedure. However, pancreatic lesions with small diameters and pancreatic neuroendocrine tumors are important factors associated with adverse events after EUS-FNA.