Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer

We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer

Utility of Endoscopic Ultrasound-Guided Fine Needle Aspiration in the Diagnosis of Local Recurrence of Pancreaticobiliary Cancer after Surgical Resection

Background/Aims: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA; EUS-FNA) allows for diagnostic tissue specimens from various regions to be analyzed. However, diagnosing recurrent pancreaticobiliary cancer after surgery is sometimes difficult. We evaluated the efficacy of EUS-FNA in the diagnosis of local recurrence of pancreaticobiliary cancer and analyzed the factors associated with falsenegative results. Methods: Fifty-one consecutive patients who underwent EUS-FNA due to suspected recurrence of pancreaticobiliary cancer after surgery in an academic center were retrospectively analyzed. The criteria for EUS-FNA were a resected margin or remnant pancreas mass, round swollen lymph node (≥10 mm in diameter), and soft-tissue enhancement around a major artery. Patients with suspected liver metastasis or malignant ascites were excluded. Results: Thirty-nine of the 51 patients had pancreatic cancer; the remaining 12 had biliary cancer. The target sites for EUS-FNA were the soft tissue around a major artery (n=22, 43%), the resected margin or remnant pancreas (n=12, 24%), and the lymph nodes (n=17, 33%). The median size of the suspected recurrent lesions was 15 mm (range, 8 to 40 mm). The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of recurrence was 84% (32/38), 100% (13/13), and 88% (45/51), respectively. FNA of the soft tissue around major arteries (odds ratio, 8.23; 95% confidence interval, 1.2 to 166.7; p=0.033) was significantly associated with a falsenegative diagnosis in the multivariate analysis. Conclusions: EUS-FNA is useful for diagnosing recurrent cancer, even after pancreaticobiliary surgery. The diagnoses of recurrence at soft-tissue sites should be interpreted with caution

Effect of molecular bending on the photodissociation of OCS

At 230 nm, the photodissociation of OCS via a hot band and a triplet state was investigated by selective probing of high rotational levels of product CO (Jϭ45-67) with photofragment imaging spectroscopy: . Additional two-photon IR excitation of the UV photoprepared OCS with intense 1.06 m laser pulses bleaches the UV processes listed above and induces a new excitation channel of OCS: OCS(vϭ0)ϩh(UV͒→OCS*, OCS*ϩ2h(IR͒→CO(X 1 ⌺ ϩ ,J ϳ74)ϩS( 1 S). The bending mode of OCS in the excited states plays a central role in the excitation and dissociation dynamics. Additionally, the alignment effect of OCS by nonresonant infrared laser pulse, which appears on the angular distribution of the photofragment, is discussed

Effectiveness, safety, and factors associated with the clinical success of endoscopic biliary drainage for patients with hepatocellular carcinoma: a retrospective multicenter study

Background Only a few reports have assessed the effectiveness of endoscopic biliary drainage (EBD) in hepatocellular carcinoma (HCC) patients with obstructive jaundice and liver dysfunction. Methods This was a retrospective study based on the clinical databases from the Okayama University Hospital and 10 affiliated hospitals. All patients received EBD for jaundice or liver dysfunction. The indication for EBD was aggravation of jaundice or liver dysfunction with intrahepatic bile duct (IHBD) dilation. The technical and clinical success rate, complications, factors associated with clinical failure, and survival duration were evaluated. Results A total of 107 patients were enrolled in this study. Technical success was achieved in 105 of 107 patients (98.1%). Clinical success was achieved in 85 of 105 patients (81%). Complications related to endoscopic retrograde cholangiography (ERC) occurred in 3 (2.8%) patients. Child–Pugh class C (odds ratio 3.90, 95% confidence interval [CI] 1.47–10.4, p = 0.0046) was the only factor associated with clinical failure, irrespective of successful drainage. The median survival duration was significantly longer in patients with clinical success than in those without clinical success (5.0 months vs. 0.93 months; hazard ratio [HR] 3.2, 95% CI 1.87–5.37). HCC Stage I/II/III (HR 0.57, CI 0.34–0.95, p = 0.032), absence of portal thrombosis (HR 0.52, CI 0.32–0.85, p = 0.0099), and clinical success (HR 0.39, CI 0.21–0.70, p = 0.0018) were significant factors associated with a long survival. Conclusions EBD for obstructive jaundice and liver dysfunction in patients with HCC can be performed safely with a high technical success rate. Clinical success can improve the survival duration, even in patients expected to have a poor prognosis

Outcomes of endoscopic treatment for malignant biliary obstruction in patients with surgically altered anatomy: analysis of risk factors for clinical failure

Background To evaluate the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary obstruction (MBO) using short-type double-balloon enteroscope (sDBE) in patients with surgically altered anatomy. Methods A total of 45 patients with surgically altered anatomy underwent ERCP using sDBE for the treatment of MBO between April 2011 and March 2019. We retrospectively evaluated the clinical and technical success (insertion and biliary intervention success), adverse events, and risk factors for clinical failure. Results The scope was successfully inserted in the target site in 82.2% of patients (37/45), and among them, biliary intervention success was achieved in 86.4% (32/37). The overall technical success rate was 71.1% (32/45) and clinical success rate was 68.9% (31/45), with an adverse event rate of 11.1%. In multivariate analysis, the presence of peritoneal dissemination (odds ratio, 7.3; 95% confidence interval, 1.5–43.5, p = 0.02) was as an independent risk factor for clinical failure. The clinical success rate was 38.5% in patients with peritoneal dissemination and 81.3% in those without peritoneal dissemination. Conclusion Endoscopic treatment using sDBE in patients without peritoneal dissemination provided favorable outcomes, and it can be an initial treatment for MBO in patients with surgically altered anatomy. Endoscopic biliary stent placement with endoscopic retrograde cholangiography (ERCP) for the treatment of malignant biliary obstruction (MBO) has been widely accepted as an effective drainage method because it is less invasive and safe and has a high success rate (1–3). However, MBO is treated using percutaneous transhepatic biliary drainage (PTBD) or surgical bypass because of difficulties related to endoscopic access to the bile duct following gastrointestinal reconstruction. However, these methods are associated with marked adverse event (AE) rates [1,2,3]. Recently, balloon-assisted endoscopy (BAE) facilitates ERCP in patients with surgically altered anatomy. As for a double-balloon enteroscope (DBE), a short-type DBE (sDBE) is especially useful because it allows the use of many standard ERCP accessories. The success rates of reaching the target site and ERCP-related interventions associated using these endoscopes range from 73–100% and 85–100%, respectively [4, 5]. We previously reported that the success rate of reaching the target site and biliary intervention was 93.8% and 95.7%, respectively, in patients with benign hepaticojejunostomy (HJ) anastomotic stricture [6]. However, inaccessibility of the target site may occur due to severe postoperative adhesions or a long insertion time (i.e., > 60 min). Furthermore, previous reports have shown that the success rate of BAE in MBO cases was significantly lower than that in benign biliary diseases [7, 8]. Few reports have investigated the outcome of BAE for MBO in patients with surgically altered anatomy. Additionally, the risk factors for clinical failure are not well-established. Thus, we retrospectively evaluated the outcomes of endoscopic treatment for MBO using sDBE in patients with surgically altered anatomy and identified risk factors for clinical failure

Optimal liver drainage rate for survival in patients with unresectable malignant hilar biliary obstruction using 3D-image volume analyzer

Background: Drainage exceeding 50% of total liver volume is a beneficial prognostic factor in patients with unresectable malignant hilar biliary obstruction (UMHBO). However, it is unclear what threshold percentage of total liver volume drained ('liver drainage rate') significantly improves survival in patients with UMHBO who received systemic chemotherapy. Objectives: We aimed to assess the optimal liver drainage rate that improves survival in patients with UMHBO receiving chemotherapy using a three-dimensional (3D)-image volume analyzer. Design: This study was a single-center retrospective cohort study. Methods: Data from 90 patients with UMHBO who received chemotherapy after endoscopic biliary drainage using metal stents at Okayama University Hospital from January 2003 to December 2020 were reviewed. The liver drainage rate was calculated by dividing the drained liver volume by the total liver volume using a 3D-image volume analyzer. The primary endpoint was overall survival by liver drainage rate. The secondary endpoints were time to recurrent biliary obstruction (TRBO) and prognostic factors. Results: The median total liver volume was 1172 (range: 673-2032) mL, and the median liver drainage rate was 83% (range: 50-100). Overall survival was 376 (95% CI: 271-450) days, and patients with >80% drainage (n = 67) had significantly longer survival than those with 80% liver drainage [hazard ratio (HR): 0.35, 95% CI: 0.20-0.62, p = 0.0003] and hilar cholangiocarcinoma (HR: 0.30, 95% CI: 0.17-0.50, p Conclusion: In patients with UMHBO scheduled for chemotherapy, >80% drainage is associated with improved survival. Further prospective multicenter studies are needed to verify the results of this study

Gastric linitis plastica with autoimmune pancreatitis diagnosed by an endoscopic ultrasonography-guided fine-needle biopsy: A case report

BACKGROUND Gastric linitis plastica (GLP) is a subset of gastric cancer with a poor prognosis. It is difficult to obtain a definitive diagnosis by endoscopic mucosal biopsies, and the usefulness of an endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) for GLP has been recently reported. Meanwhile, autoimmune diseases are occasionally known to coexist with malignant tumors as paraneoplastic syndrome. We herein report the usefulness of an EUS-FNB for detecting GLP and the possibility of paraneoplastic syndrome coexisting with GLP. CASE SUMMARY An 81-year-old man was admitted to our hospital for a 1-mo history of epigastric pain that increased after eating. His laboratory data revealed high levels of serum carbohydrate antigen 19-9 and immunoglobulin-G4. Endoscopic examinations showed giant gastric folds and reddish mucosa; however, no epithelial changes were observed. The gastric lumen was not distensible by air inflation, suggesting GLP. Computed tomography showed the thickened gastric wall, the diffuse enlargement of the pancreas, and the peripancreatic rim, which suggested autoimmune pancreatitis (AIP) coexisting with GLP. Because the pathological findings of the endoscopic biopsy showed no malignancy, he underwent an EUS-FNB and was diagnosed with GLP. He received chemotherapy for unresectable gastric cancer due to peritoneal metastasis, after which both the gastric wall thickening and diffuse enlargement of the pancreas were improved. CONCLUSION An EUS-FNB for GLP with a negative endoscopic biopsy is useful, and AIP may develop as a paraneoplastic syndrome

Efficacy of low dose rectal diclofenac for preventing post‐endoscopic retrograde cholangiopancreatography pancreatitis: Propensity score‐matched analysis

Background Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of non‐steroidal anti‐inflammatory drugs (NSAIDs) decreases the incidence of post‐ERCP pancreatitis (PEP). However, the efficacy of low dose rectal NSAIDs for preventing PEP remains controversial. Methods We performed a retrospective study of 301 patients with native papilla and a body weight of Results A total of 66 pairs of patients in each group were selected. The patients and procedural‐related factors were similar in both groups. In total, 15 patients (11.4%) developed PEP: 12.1% (8/66) in the NSAIDs group and 10.6% (7/66) in the control group (Odds ratio (OR) 1.2; 95% confidence interval (CI) 0.4–3.5; P = 0.78). There was no significant difference in incidence of other adverse events related to ERCP between the two groups. Conclusions Prophylactic administration of a 25 mg dose of rectal diclofenac did not reduce the incidence of PEP in patients with a native papilla and a body weight of <50 kg in this study and a certain dose of rectal NSAIDs, such as a 100‐mg dose, should be administered regardless of body weight to prevent PEP