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.

Effect of intramuscular lidocaine injection with physical therapy on camptocormia in patients with Parkinson's disease who had previously had deep brain stimulation.

[Purpose] We aimed to evaluate the effects of an intervention consisting of intramuscular lidocaine injection in combination with physical therapy on the standing posture, balance ability, and walking ability in patients with Parkinson's disease who had camptocormia after deep brain stimulation. [Participants and Methods] The participants were nine patients with Parkinson's disease who had previously undergone deep brain stimulation. The intervention comprised a lidocaine injection into the abdominal external oblique muscles for five days in combination with physical therapy, including body weight-supported treadmill training for two weeks. Before and after the intervention, the total and upper camptocormia angles were used to assess the standing posture; the Berg balance scale was used to assess the balancing ability; and maximum walking speed and stride length were used to assess the walking ability. [Results] The total and upper camptocormia angles, and Berg balance scale improved significantly more after the intervention than before. Before and after the intervention, there was no significant difference in maximum walking speed, but the stride length was significantly greater after the intervention than before. [Conclusion] The intervention was effective in alleviating camptocormia and improving the balance and walking abilities of patients with Parkinson's disease with camptocormia after deep brain stimulation.

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.

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.).

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.

Prophylactic endoscopic transpapillary gallbladder stenting to prevent acute cholecystitis induced after metallic stent placement for malignant biliary strictures: a retrospective study, Japan.

Background/Aims: Endoscopic biliary drainage using self-expandable metallic stents (SEMSs) for malignant biliary strictures occasionally induces acute cholecystitis (AC). This study evaluated the efficacy of prophylactic gallbladder stents (GBS) during SEMS placement. Methods: Among 158 patients who underwent SEMS placement for malignant biliary strictures between January 2018 and March 2023, 30 patients who attempted to undergo prophylactic GBS placement before SEMS placement were included. Results: Technical success was achieved in 21 cases (70.0%). The mean diameter of the cystic duct was more significant in the successful cases (6.5 mm vs. 3.7 mm, p<0.05). Adverse events occurred for 7 patients (23.3%: acute pancreatitis in 7; non-obstructive cholangitis in 1; perforation of the cystic duct in 1 with an overlap), all of which improved with conservative treatment. No patients developed AC when the GBS placement was successful, whereas 25 of the 128 patients (19.5%) without a prophylactic GBS developed AC during the median follow-up period of 357 days (p=0.043). In the multivariable analysis, GBS placement was a significant factor in preventing AC (hazard ratio, 0.61; 95% confidence interval, 0.37-0.99; p=0.045). Conclusions: GBS may contribute to the prevention of AC after SEMS placement for malignant biliary strictures.

Plain computed tomography for differentiating neoplastic and non-neoplastic pedunculated gallbladder polyps.

AIMS: Surgery is recommended for large pedunculated gallbladder polyps (PGPs), which measure 10 mm or more in size, because they tend to be neoplastic polyps (NPs), such as adenomas and adenocarcinomas. However, after resection, they are often found to be non-neoplastic polyps (non-NPs). This study aimed to evaluate the usefulness of plain CT in distinguishing NPs from non-NPs. METHODS: Of the 80 patients who underwent cholecystectomy for PGPs ( 10 mm between January 2008 and February 2021, 46 who underwent plain and contrast-enhanced CT (CE-CT) before resection were included in this study. We retrospectively assessed the polyp detection rate (PDR) using CT and calculated the difference in the CT values between PGPs and the surrounding bile. RESULTS: Twenty-one patients had NPs (12 adenomas, 5 carcinomas in adenoma, and 4 adenocarcinomas). The others were non-NPs (24 cholesterol polyps and one hyperplastic polyp). The PDR using plain CT was significantly higher in the NP group than in the non-NP group (38% (8/21) vs. 0% (0/25), p <0.01). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of NPs were 38%, 100%, 100%, 66%, and 72%, respectively. The difference in the CT values between PGPs and the surrounding bile was significantly larger in the NP group than in the non-NP group (14.12 ± 11.38 HU, 5.04 ± 6.15 HU, p <0.01). CONCLUSIONS: PGPs detected using plain CT had a high probability of being NPs. Plain CT is therefore considered to be useful for differentiating NPs from non-NPs.

INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors.

Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5-RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.

Functional roles of TGF-ß1 in intestinal epithelial cells through Smad-dependent and non-Smad pathways.

BACKGROUND AND AIMS: Transforming growth factor-ß1 (TGF-ß1) is one of the growth factors expressed in the gut, and has been shown to play an important role in intestinal mucosal healing. We investigated the effects of TGF-ß1 on the cellular functions of intestinal epithelial cells, and also evaluated its signaling pathways in these cells. METHODS: We used the rat IEC-6 intestinal epithelial cell line for these studies. The expression of TGF-ß1/Smad signaling molecules was examined. We evaluated the effect of TGF-ß1 on the proliferation and differentiation by the BrdU incorporation assay and real-time PCR. We manipulated the expression levels of Smad2 and Smad3 using an adenovirus system and small interfering RNA to examine the signaling pathways. The expression of Smad2 and Smad3 along the crypt-villus axis was also examined in the murine intestine. RESULTS: IEC-6 cells produced TGF-ß1 and expressed functional TGF-ß/Smad signaling molecules. The addition of TGF-ß1 in the culture medium suppressed the proliferation and increased the expression of a differentiation marker of enterocytes, in a dose-dependent manner. The adenovirus-mediated and small interfering RNA-mediated studies clearly showed that the growth inhibitory effect and the promotion of differentiation were exerted through a Smad3-dependent and a Smad2-dependent pathway, respectively. IEC-6 cells exhibited upregulated expression of an inhibitory Smad (Smad7) as a form of negative feedback via a non-Smad pathway. Smad2 was predominantly expressed in villi, and Smad3 in crypts. CONCLUSIONS: TGF-ß1 regulates the cellular functions of intestinal epithelial cells through both Smad-dependent and non-Smad pathways.

Prospective feasibility study on the efficacy and safety of a novel spiral dilator for endoscopic ultrasound-guided drainage.

Objectives: A difficult step in endoscopic ultrasound (EUS)-guided drainage procedures is dilation of the puncture tract before stent deployment. The efficacy and safety of a novel spiral dilator, Tornus ES, for EUS-guided drainage were investigated in this study. Methods: This study was conducted as a prospective, single-arm, observational study at Sendai City Medical center. Dilation of the puncture tract using a spiral dilator was attempted for all EUS-guided drainage cases. The primary outcome was the technical success rate which was defined as successful stent placement in the puncture tract. Secondary outcomes were the success rate of dilation using a spiral dilator, procedure time, and adverse events related to the procedures. Results: A total of 10 patients were enrolled between January and March 2022. Seven patients underwent EUS-guided biliary drainage (hepaticogastrostomy for six and hepaticojejunostomy for one), and the remaining three patients underwent EUS-guided gallbladder drainage. The technical success rate and the success rate of dilation using a spiral dilator were both 100%. The mean procedure time was 27 min. No adverse events related to the procedure occurred in all cases. Conclusions: Dilation of the puncture tract using a spiral dilator was effective and safe and might make it easier to perform EUS-guided drainage.

Treatment Strategy for Acute Cholecystitis Induced by a Metallic Stent Placed in Malignant Biliary Strictures: Role of Percutaneous Transhepatic Gallbladder Aspiration.

Objective The present study evaluated the strategic role of percutaneous transhepatic gallbladder aspiration (PTGBA) for acute cholecystitis (AC) induced by a metallic stent (MS) placed in a malignant biliary stricture in comparison with percutaneous transhepatic gallbladder drainage (PTGBD). Methods The treatment outcomes for 31 patients who underwent PTGBA as the initial intervention for MS-induced AC were evaluated and compared with those for 12 who underwent PTGBD. Results The technical success rate was 100% for both groups. PTGBA was ineffective for 11 patients, all of whom recovered with additional intervention, whereas PTGBD was effective for all patients except for 1 who died of sepsis (clinical success rate, 65% vs. 90%, p=0.16). Adverse events (AEs) were observed in only 1 case (3%) in the PTGBA group (mild bile peritonitis). Among the clinically effective cases, AC recurred in 20% of the PTGBA group and 33% of the PTGBD group (p=0.72). In the PTGBA group, the clinical success rate was significantly higher for patients without cancer invasion to a feeding artery of the gallbladder than in those with invasion (75% without invasion vs. 29% with invasion; p=0.036). According to the multivariate analysis, this factor was an independent factor for clinical success of PTGBA (odds ratio, 9.27; p=0.040). Conclusion Although the clinical success rate of PTGBA for MS-induced AC was lower than that of PTGBD, PTGBA remains a viable option because of its safety and procedural simplicity, especially for cases without tumor invasion to a feeding artery.

Pancreatic duct lavage cytology combined with a cell-block method for patients with possible pancreatic ductal adenocarcinomas, including pancreatic carcinoma in situ.

BACKGROUND/AIMS: This study aimed to clarify the efficacy and safety of pancreatic duct lavage cytology combined with a cell-block method (PLC-CB) for possible pancreatic ductal adenocarcinomas (PDACs). METHODS: This study included 41 patients with suspected PDACs who underwent PLC-CB mainly because they were unfit for undergoing endoscopic ultrasonography-guided fine needle aspiration. A 6-Fr double lumen catheter was mainly used to perform PLC-CB. Final diagnoses were obtained from the findings of resected specimens or clinical outcomes during surveillance after PLC-CB. RESULTS: Histocytological evaluations using PLC-CB were performed in 87.8% (36/41) of the patients. For 31 of the 36 patients, final diagnoses (invasive PDAC, 12; pancreatic carcinoma in situ, 5; benignancy, 14) were made, and the remaining five patients were excluded due to lack of surveillance periods after PLC-CB. For 31 patients, the sensitivity, specificity, and accuracy of PLC-CB for detecting malignancy were 94.1%, 100%, and 96.8%, respectively. In addition, they were 87.5%, 100%, and 94.1%, respectively, in 17 patients without pancreatic masses detectable using endoscopic ultrasonography. Four patients developed postprocedural pancreatitis, which improved with conservative therapy. CONCLUSION: PLC-CB has an excellent ability to detect malignancies in patients with possible PDACs, including pancreatic carcinoma in situ.

Diagnostic value of homogenous delayed enhancement in contrast-enhanced computed tomography images and endoscopic ultrasound-guided tissue acquisition for patients with focal autoimmune pancreatitis.

BACKGROUND/AIMS: We aimed to investigate (1) promising clinical findings for the recognition of focal type autoimmune pancreatitis (FAIP) and (2) the impact of endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-TA) on the diagnosis of FAIP. METHODS: Twenty-three patients with FAIP were involved in this study, and 44 patients with resected pancreatic ductal adenocarcinoma (PDAC) were included in the control group. RESULTS: (1) Multivariate analysis revealed that homogeneous delayed enhancement on contrast-enhanced computed tomography was a significant factor indicative of FAIP compared to PDAC (90% vs. 7%, p=0.015). (2) For 13 of 17 FAIP patients (76.5%) who underwent EUS-TA, EUS-TA aided the diagnostic confirmation of AIPs, and only one patient (5.9%) was found to have AIP after surgery. On the other hand, of the six patients who did not undergo EUS-TA, three (50.0%) underwent surgery for pancreatic lesions. CONCLUSION: Homogeneous delayed enhancement on contrast-enhanced computed tomography was the most useful clinical factor for discriminating FAIPs from PDACs. EUS-TA is mandatory for diagnostic confirmation of FAIP lesions and can contribute to a reduction in the rate of unnecessary surgery for patients with FAIP.

Mixed neuroendocrine-non-neuroendocrine neoplasm with mucinous adenocarcinoma and amphicrine carcinoma components in the bile duct: an autopsy case.

We report the first case of bile duct mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) that had a mucinous carcinoma component. An 88-year-old man with biliary obstruction was diagnosed as having distal bile duct cancer using imaging examinations and endoscopic biopsy. The patient received the best supportive care without surgical resection for 13 months until death. An autopsy revealed a bulky mass involving the distal bile duct and multiple metastases in intra-abdominal lymph nodes, the liver, and the lungs. The primary cancer was microscopically diagnosed as a MiNEN, which consisted of mucinous adenocarcinoma and large cell-type neuroendocrine carcinoma (NEC) components. Metastatic lesions in the liver and lungs were composed of only NEC with rich extracellular mucin without adenocarcinoma cells. Using electron microscopy and immunohistochemistry, it was proved that all NEC cells in both primary and metastatic lesions had amphicrine features. On the basis of pathological findings, we thought that the MiNEN was initially derived from a mucinous adenocarcinoma that dedifferentiated to amphicrine NEC cells with mucin production.