Therapeutic Outcome of Multidisciplinary Treatment in Unresectable Biliary Tract Cancer: A Multicenter Retrospective Analysis.

Background: There is little established evidence regarding treatment strategies for unresectable biliary tract cancer (BTC). This study aimed to clarify the situation of multidisciplinary treatment for unresectable BTC in the 2000s when there was no international standard first-line therapy. Methods: We retrospectively reviewed 315 consecutive patients with unresectable BTC who had been treated at seven tertiary institutions in Kanagawa Prefecture, Japan between 1999 and 2008. Results: The unresectable factors were as follows: locally advanced, 101 cases (32.1%); hematogenous metastases, 80 cases (25.4%); and peritoneal dissemination, 30 cases (9.5%). Chemotherapy or radiation therapy was administered to 218 patients (69.2%). The best supportive care was provided in 97 cases (30.8%). The most common regimen was gemcitabine monotherapy, followed by gemcitabine combination therapy and S-1 monotherapy. The 1- and 2-year survival rates of all patients were 34.6% and 12.2%, respectively. The median survival time (MST) was 8 months in all patients. The 1-year survival rate was 65%, and the MST was 12 months among the locally advanced patients, whereas patients with peritoneal dissemination had the worst outcome; the 1-year survival rate was 7%, and the MST was 5 months. Among treated 90 cases of perihilar cholangiocarcinoma, patients who received chemoradiotherapy (n = 24) had a significantly better outcome than those who received chemotherapy alone (MST: 20 vs. 11 months, P < 0.001). Conclusions: Unresectable BTC has heterogeneous treatment outcomes depending on the mode of tumor extension and location. Multidisciplinary treatment seems useful for patients with locally advanced BTC, whereas patients with metastatic disease still have a poor prognosis.

Differential Diagnosis of Solid Pancreatic Lesions Using Detective Flow Imaging Endoscopic Ultrasonography.

The differential diagnosis of solid pancreatic lesions (SPLs) using B-mode endoscopic ultrasonography (EUS) is challenging. Detective flow imaging (DFI) offers the potential for detecting low-flow vessels in the pancreas, thus enhancing diagnostic accuracy. This retrospective study aimed to investigate DFI-EUS findings of SPLs and analyze their differential diagnostic accuracy for pancreatic cancer. We included 104 patients with pathologically confirmed SPLs who underwent EUS between April 2021 and June 2023. Expert endosonographers, blinded to the patients' clinical data, evaluated images obtained through B-mode, eFLOW, and DFI-EUS. The frame rate and vessel detection sensitivity were compared between eFLOW and DFI, and the diagnostic criteria for pancreatic cancer were established. The visualization rate for vessels in SPLs was significantly higher with DFI-EUS (96%) compared to eFLOW (27%). Additionally, DFI showed a superior frame rate, sensitivity (99%), and accuracy (88%) for detecting pancreatic cancer, although with a modest specificity (43%). On DFI-EUS, characteristics such as hypovascularity, peritumoral vessel distribution, or spotty vessel form were suggestive of pancreatic cancer. DFI-EUS significantly improved the visualization of vascular structures within the SPLs, highlighting its efficacy as a diagnostic modality for pancreatic cancer.

Clinical course of small gastric subepithelial lesion less than 20 mm diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

BACKGROUND AND AIM: Gastrointestinal stromal tumors (GISTs) are treated as malignant gastric subepithelial lesions (SELs), and resection is recommended. However, small gastric SELs < 20 mm with no malignant features are monitored without histopathological examination, and the frequency of malignancy is unknown. This study aimed to clarify the clinicopathological findings and clinical course of gastric SELs < 20 mm measured by endoscopic ultrasound (EUS). METHODS: This retrospective cohort study included consecutive patients with small gastric SELs < 20 mm diagnosed using EUS at a tertiary referral center between 2009 and 2021. The clinical course after diagnosis using EUS-guided fine-needle aspiration (EUS-FNA) was reviewed. RESULTS: Among 333 patients with small gastric SELs, 104 patients with 105 lesions underwent EUS-FNA. The pathological diagnosis was confirmed in 87 patients. GISTs were the most common pathology (47%). Among the 87 patients, 43 underwent therapeutic interventions, including tumor resection and chemotherapy. In groups of tumor resection, the pathological tumor size on the resected specimen was significantly larger than the size measured by EUS (19.5 mm vs 15.0 mm, P < 0.001), and 37% of resected SELs were 20 mm or over. No recurrence was observed after tumor resection during a mean follow-up period of 40 months. CONCLUSIONS: Approximately 40% of small gastric SELs were malignant tumors, such as GIST, with most of them requiring treatment. Additionally, considering that the EUS measurement is 5 mm smaller than the pathological tumor diameter, further examinations, such as systematic EUS-FNA, may be required for SEL, including those smaller than 20 mm.

Novel 8-wire basket catheter is useful for endoscopic removal of common bile duct stones up to 10 mm: A multicenter prospective study.

BACKGROUND/PURPOSE: Endoscopic treatment of common bile duct (CBD) stones involves the use of basket or balloon catheters; however, what is the appropriate device remains controversial. In this study we aimed to prospectively evaluate the usefulness of a novel 8-wire helical basket (8WB) catheter made of Nitinol for the removal of CBD stones ≤10 mm. METHODS: We conducted a multicenter prospective trial. Patients with CBD stones ≤10 mm were enrolled. The primary endpoint was the rate of complete stone removal within 10 min using the 8WB. The number of cases was determined using a previous study of stone removal by a conventional basket catheter as a historical control. RESULTS: A total of 155 patients were enrolled and 139 were ultimately included in the analysis. Patients with a single stone were the most common (84 cases, 60.4%), with a median maximum stone diameter of 5 mm. The median stone removal time using the 8WB was 6 min. The complete stone removal rate was 95.0% (132/139). Adverse events were observed in 14 patients (10.1%). CONCLUSIONS: The novel 8WB catheter is useful in the treatment of CBD stones ≤10 mm, presenting a high complete stone removal rate in this study. TRIAL REGISTRATION NUMBER: jRCT1032200324.

Early Tumor Shrinkage and Depth of Response as Predictors of Survival for Advanced Biliary Tract Cancer: An Exploratory Analysis of JCOG1113.

BACKGROUND: Recent studies suggest that early tumor shrinkage (ETS) and depth of response (DpR) reflect outcomes of chemotherapy in various cancers. This study evaluated the association of ETS and DpR with clinical outcomes using data from JCOG1113, which demonstrated the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for chemotherapy-naïve advanced biliary tract cancer. MATERIAL AND METHODS: In total, 354 (289 with measurable target lesions) patients enrolled in JCOG1113 were divided into ETS-unachieved and ETS-achieved groups (≥20% tumor reduction at week 6) and DpR-low and DpR-high groups (≥40% maximum shrinkage) until 12 weeks after enrollment. The impact of ETS and DpR on survival outcome was evaluated using the multivariable Cox proportional hazard model. RESULTS: The proportions of patients in the ETS-achieved and DpR-high groups were similar between the 2 treatment arms. The hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for the ETS-achieved group were 0.70 (95% confidence interval (CI), 0.52-0.93) and 0.60 (95%CI, 0.44-0.81), respectively. The HRs of PFS and OS for the DpR-high group were 0.67 (95%CI, 0.48-0.94) and 0.64 (95%CI, 0.46-0.90), respectively. In the subpopulation treatment effect pattern plot analysis, most patients in the ETS-achieved group in the GC arm did not experience disease progression after 12 weeks from the landmark. CONCLUSION: As on-treatment markers, ETS and DpR were effective tools. ETS was clinically useful, because it can be used to evaluate the outcomes of treatment early at a specific time.

Novel peroral cholangioscopy-guided electrohydraulic lithotripsy for difficult stones.

Miwa and colleagues report on their experience with a newly developed peroral cholangioscope that is effective for the removal of difficult stones in the common bile duct and the cystic duct. The scope offers a large working channel and a high mobility bending section, increasing the efficacy of electrohydraulic lithotripsy.

Development of a nomogram to predict survival in advanced biliary tract cancer.

The prognosis of advanced biliary tract cancer (BTC) patients remains poor due to limited efficacy of chemotherapy and difficulties in management. Thus, prediction of survival is crucial for the clinical management of advanced BTC. The aim was to develop and validate a nomogram to predict 6-month and 12-month survival in advanced BTC patients treated with chemotherapy. A multivariable Cox regression model was used to construct a nomogram in a training set (JCOG1113, a phase III trial comparing gemcitabine plus S-1 [GS] and gemcitabine plus cisplatin, n = 351). External validity of the nomogram was assessed using a test set (JCOG0805, a randomized, phase II trial comparing GS and S-1 alone, n = 100). Predictive performance was assessed in terms of discrimination and calibration. The constructed nomogram included lymph node metastasis, liver metastasis, carbohydrate antigen 19-9, carcinoembryonic antigen, albumin, and C-reactive protein. Uno's concordance index was 0.661 (95% confidence interval [CI] 0.629-0.696) in the training set and 0.640 (95% CI 0.566-0.715) in the test set. The calibration plots for 6-month and 12-month survival showed good agreement in the two analysis sets. The present nomogram can facilitate prediction of the prognosis of advanced BTC patients treated with chemotherapy and help clinicians' prognosis-based decision-making.

Endoscopic Resection with One-Port Placement: A Newly Developed Technique for the Safe Management of Advanced Endoscopic Resection for Gastric Gastrointestinal Stromal Tumors.

INTRODUCTION: Endoscopic full-thickness resection (EFTR) without laparoscopic assistance (pure EFTR) is an emerging, less invasive treatment for gastrointestinal stromal tumors (GISTs). However, the technique has seldom been performed outside China because of concerns regarding pneumoperitoneum, maintenance of endoscopic view, and endoscopic suturing. This study aimed to evaluate the efficacy and safety of endoscopic resection with one-port placement (EROPP) for gastric GISTs. METHODS: This retrospective study included 17 patients with gastric GISTs originating from the muscularis propria who underwent EROPP between 2019 and 2022. One camera port was inserted in the umbilicus before initiating the endoscopic procedure to maintain intra-abdominal pressure, which was monitored and adjusted via this port. While allowing for conversion to laparoscopic surgery if needed, EFTR was performed as follows: (1) circumferential incision of the mucosal and submucosal layers around the lesion was performed by typical endoscopic submucosal dissection; (2) an intentional perforation and subsequent seromuscular resection was made using dental floss and an endo-clip for traction; and (3) closure of the gastric full-thickness defect was performed with an over-the-scope clip (OTSC) after peroral retrieval of the specimen. We retrospectively assessed the short-term outcomes and safety. RESULTS: All procedures were completed successfully without conversion to laparoscopic surgery. The median size of the resected tumors was 23 mm (range, 8-35 mm), the median resection time was 36 min (range, 22-95 min), and closure time was 18 min (range, 10-45 min). The rates of en bloc and complete resection were 100% and 88%, respectively. In 2 cases, another port was added to aspirate the leaking fluid or check the condition of the endoscopic closure. All gastric defects were endoscopically closed, mainly using OTSCs. The recovery course for all patients was uneventful, and no adverse events were reported. CONCLUSIONS: EROPP is a safe and minimally invasive treatment for gastric GISTs and appears to be suitable for introducing EFTR procedures.

Loop technique for guidewire manipulation during endoscopic ultrasound-guided hepaticogastrostomy.

Background and Aim: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is widely used in the management of biliary obstructions; however, literature on guidewire manipulation is lacking. This study aimed to assess the utility and optimal conditions of the loop technique for guidewire manipulation during EUS-HGS. Methods: Consecutive patients who underwent EUS-HGS between April 2015 and January 2022 were included in this study. Patient characteristics and procedural details were retrospectively analyzed. Guidewire manipulations were classified as conventional technique or loop technique, based on the shape of the guidewire tip. Results: A total of 52 patients (Median age: 73 years, 38 male and 14 female) underwent EUS-HGS. The median guidewire insertion time was 49 s and the median overall procedure time was 20.5 min. The initial guidewire direction was toward the peripheral side in 23 patients (44%). Technical success rate of the EUS-HGS was 100%. Twenty patients (38%) underwent the procedure using the loop technique and 32 (62%) with the conventional technique. In the logistic regression analysis, an angle between the bile duct and needle of >70° was independently associated with use of the loop technique (OR 9.84; 95% CI: 2.24-43.13; P <0.01). Conclusion: This study revealed the utility of the loop technique in EUS-HGS. This technique is recommended if the bile duct is punctured at an angle >70°.

Combination Therapy With Lenvatinib and Radiofrequency Ablation for Patients With Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child-Pugh Class A Liver function: A Pilot Study.

Background: The present study aimed to evaluate the efficacy and safety of combined lenvatinib (first-line systemic therapy) and radiofrequency ablation (RFA) therapy in patients with intermediate-stage hepatocellular carcinoma with beyond up-to-seven criteria and Child-Pugh Class A liver function (CP A B2-HCC). Methods: Twenty-two patients with CP A B2-HCC were enrolled in the study. The patients had no history of systemic treatment. For the initial lenvatinib administration in this study, all of the patients had an adequate course of treatment (no less than two weeks) and were administered the recommended dose. Of them, 13 were treated by means of lenvatinib monotherapy (monotherapy group), while the 9 patients with no contraindication to RFA operation and who had consented to RFA received initial lenvatinib plus subsequent RFA (combination group). The clinical outcomes that were considered to evaluate the treatments included tumor response, prognosis (recurrence and survivals), and possible adverse events (serum liver enzymes and clinically visible complications). Results: The combination group exhibited a higher object response rate (9/9, 100%) as best tumor response than the monotherapy group (10/13, 76.9%). Longer progression-free survival (PFS) (12.5 months) and overall survival (OS) (21.3) were demonstrated in the combination group than in the monotherapy group (PFS: 5.5 months; OS:17.1 months). The combination group achieved a higher PFS rate (1-year: 74.1%) and OS rate (2-year: 80%) than the monotherapy group (1-year PFS rate: 0%; 2-year OS rate: 25.6%; for PFS, p<0.001; for OS, p=0.022). The treatment strategy was the independent factor for PFS (HR: 18.215 for monotherapy, p =0.010), which was determined by Cox regression analysis, suggesting that a combination strategy may reduce tumor progression when compared to the use of lenvatinib alone. There were no statistically significant intergroup differences that were observed in terms of adverse events, with the exception of ALT elevation (p=0.007) in the combination group. Conclusion: Our newly proposed combination therapy may potentially be effective and safe for CP A B2-HCC beyond up-to-seven criteria. A larger scale, multicenter, prospective study is warranted to confirm our findings.

Novel clip device for prevention of bleeding after endoscopic papillectomy.

Objectives: Recently, a novel clip device, SureClip® (Micro-Tech Co. Ltd., Nanjing, China), has been developed, which improved rotation and reopening performance. We aimed to assess the efficacy of the SureClip® in prophylactic closure of the mucosal break after endoscopic papillectomy (EP) for ampullary neoplasm. Methods: We retrospectively reviewed the medical records of 40 patients who underwent EP for ampullary neoplasms between October 2009 and March 2020. Prophylactic closure after resection was performed using the conventional clip between 2014 and 2018, and with the SureClip® after 2019. The baseline characteristics, techniques, outcomes, and complications of EP were analyzed. Results: The median age of the patients (25 males and 15 females) was 70 years. The en block resection rate was 82.5% and the curative resection rate was 80.0%. Histologically, 11 (27.5%) patients had malignancy. Prophylactic closure was performed in 29 (72.5%) patients (17 conventional clips, 12 SureClip®). Complications occurred in 18 (45.0%) patients, including postprocedure bleeding in 9 (22.5%) patients. However, no postprocedure bleeding was observed in the patients who received prophylactic closure using the SureClip® (p = 0.038). All other factors were not significantly correlated with postprocedure bleeding. The duration of hospital stay after EP was significantly shorter in patients treated with the SureClip® compared to those treated with a conventional clip or without clips (p < 0.05). Conclusions: In the present study, prophylactic clipping of the mucosal break using the SureClip® was effective in preventing bleeding after EP.

Randomized Phase II Study of Gemcitabine Monotherapy vs. Gemcitabine with an EPA-Enriched Oral Supplement in Advanced Pancreatic Cancer.

BACKGROUND: Pancreatic cancer is often associated with cachexia. It had been reported that eicosapentaenoic acid (EPA) improve cachexia. This study aimed to evaluate the efficacy and safety of gemcitabine with an EPA-enriched oral supplement in patients with advanced pancreatic cancer. METHODS: This open-label phase II study consisted of patients (pts) who were randomly categorized into the EPA group (1,000 mg/m2 gemcitabine was administered on day 1, 8, and 15, every 4 weeks while an EPA-enriched oral supplement (prosure®, EPA 1.056 mg per pack) was taken daily at the maximum of two packs or the gemcitabine monotherapy group with an allocation ratio of 2:1. The primary endpoint was the evaluation of the 1-year survival estimating 10% addition. RESULTS: Randomized 68 pts were examined (EPA: 45, gemcitabine: 23). The 1-year survival probability of the EPA group was 35% while the gemcitabine group was 19%. The median survival times were 8.2 and 9.7 mo, respectively. The hazard ratio for EPA group was 0.79 [95% CI 0.46-1.37]; (P = 0.40). The toxicities were mild and insignificant in both groups. More beneficial effects of EPA in survival were observed in men, pancreatic body-tail and low C-reactive protein patients. CONCLUSION: An EPA-enriched oral supplement may be effective in advanced pancreatic cancer.