Elastography used in endoscopic ultrasound (EUS)-elastography for pancreatic disease is roughly classified into strain elastography (SE) and shear wave elastography (SWE). Most of the previous ...studies have been performed using SE. Methods of interpreting the results of SE include recognizing the pattern of the image in the region of interest (ROI), using the SR (strain ratio) to compare the hardness of adipose tissue or connective tissue and the hardness of the lesion, and histogram analysis of the hardness distribution in the target lesion. The first two methods have poor reproducibility, require multiple evaluations, and require careful attention to interpretation of the results. These two methods have been used mainly for focal pancreatic diseases. Histogram analysis has excellent reproducibility and has been used for evaluation of chronic pancreatitis and for evaluating hardness distribution in similar lesions. Since the hardness of the pancreas increases with aging, it is necessary to consider the patientʼs age in the diagnosis of pancreatic disorders using EUS-elastography.
Background
The Japanese Society of Hepato‐Biliary‐Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ...ampullary cancer) in 2007, then published the 2nd version in 2014.
Methods
In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence‐based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.
Results
The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded.
Conclusions
This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.
Highlight
These guidelines are the English version of “Evidence‐based clinical practice guidelines for the management of biliary tract cancers, 3rd edition” published in Japanese by the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery in 2019. A total of 31 clinical questions covering six topics provide recommendations for important clinical aspects based on evidence.
Previous therapeutic attempts to deplete cancer-associated fibroblasts (CAFs) or inhibit their proliferation in pancreatic ductal adenocarcinoma (PDAC) were not successful in mice or patients. Thus, ...CAFs may be tumor suppressive or heterogeneous, with distinct cancer-restraining and -promoting CAFs (rCAFs and pCAFs, respectively). Here, we showed that induced expression of the glycosylphosphatidylinositol-anchored protein Meflin, a rCAF-specific marker, in CAFs by genetic and pharmacological approaches improved the chemosensitivity of mouse PDAC. A chemical library screen identified Am80, a synthetic, nonnatural retinoid, as a reagent that effectively induced Meflin expression in CAFs. Am80 administration improved the sensitivity of PDAC to chemotherapeutics, accompanied by increases in tumor vessel area and intratumoral drug delivery. Mechanistically, Meflin was involved in the suppression of tissue stiffening by interacting with lysyl oxidase to inhibit its collagen crosslinking activity. These data suggested that modulation of CAF heterogeneity may represent a strategy for PDAC treatment.
Background
Primary sclerosing cholangitis (PSC) is relatively rare disease and pathogenesis and methods of treatments were still not established. Then, we had conducted the making clinical guidelines ...to manage patients with PSC based on the literature review and expert opinions. These clinical guidelines were made for the medical doctors on the management of PSC, except child case of PSC.
Methods
We had employed modified Delphi method. The production committee decided guidelines, strength of recommendations and evidence level after reviewed literatures systematically, and The Expert panel evaluated those. The Scientific Committee of the Japan Biliary Association (JBA) evaluated revised guidelines, and the Public comments were collected on web site of JBA.
Results
We had made 16 guidelines about epidemiology/pathophysiology, diagnostics, therapy and prognosis. Also, we had made both diagnostic and therapeutic flow chart.
Conclusions
We hope that these guidelines will contribute to the improvement and development of the medical care of PSC.
Prognosis of pancreatic cancer is poor with a 5-year survival rate of only 7%. Although several new chemotherapy treatments have shown promising results, all patients will eventually progress, and we ...need to develop newer chemotherapy treatments to improve response rates and overall survival (OS). HF10 is a spontaneously mutated oncolytic virus derived from a herpes simplex virus-1, and it has potential to show strong antitumor effect against malignancies without damaging normal tissue. We aimed to evaluate the safety and anti-tumor effectiveness in phase I dose-escalation trial of direct injection of HF10 into unresectable locally advanced pancreatic cancer under endoscopic ultrasound (EUS)-guidance in combination with erlotinib and gemcitabine administration. The mid-term results have been previously reported and here we report the final results of our study.
This was a single arm, open-label Phase I trial. HF10 was injected once every 2 weeks and continued up to four times in total unless dose-limiting toxicity (DLT) appears. A total of nine subjects in three Cohorts with dose-escalation were planned to be enrolled in this trial. The primary endpoint was the safety assessment and the secondary endpoint was the efficacy assessment.
Twelve patients enrolled in this clinical trial, and ten subjects received this therapy. Five patients showed Grade III myelosuppression and two patients developed serious adverse events (AEs) (perforation of duodenum, hepatic dysfunction). However, all of these events were judged as AEs unrelated to HF10. Tumor responses were three partial responses (PR), four stable diseases (SD), and two progressive diseases (PD) out of nine subjects who completed the treatment. Target lesion responses were three PRs and six SDs. The median progression free survival (PFS) was 6.3 months, whereas the median OS was 15.5 months. Two subjects from Cohort 1 and 2 showed downstaging and finally achieved surgical complete response (CR).
HF10 direct injection under EUS-guidance in combination with erlotinib and gemcitabine was a safe treatment for locally advanced pancreatic cancer. Combination therapy of HF10 and chemotherapy should be explored further in large prospective studies.
This study was prospectively registered in UMIN-CTR (UMIN000010150) on March 4th, 2013.
Aim
This study aimed to investigate the clinical characteristics and outcomes of candidates for second‐line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma (HCC) ...after sorafenib treatment.
Methods
Of 122 patients, 103 were radiologically confirmed as progressive disease (PD) (sorafenib‐refractory group), and 19 discontinued sorafenib therapy due to adverse events prior to radiologic PD (sorafenib‐intolerant group). Patients in the sorafenib‐refractory group were divided into two subgroups each, according to their eligibility for second‐line treatment (second‐line‐in and ‐out group), regorafenib (RESORCE‐in and ‐out group), or ramucirumab (REACH‐2‐in and ‐out group).
Results
Patients included in the non‐candidate group were those with α‐fetoprotein level <400 ng/mL (n = 51, 49.5%), daily sorafenib dose <400 mg (n = 44, 42.7%), Child–Pugh B or C (n = 40, 38.8%), and Eastern Cooperative Oncology Group performance status score ≥2 (n = 24, 23.3%). The percentages of candidates were 57.3% for second‐line, 35.0% for regorafenib, and 23.3% for ramucirumab. The median post‐progression survival (PPS) was significantly longer for the second‐line‐in and the RESORCE‐in groups than in the non‐candidate groups (12.6 and 11.0 months vs. 3.0 and 6.1 months, respectively). The PPS was not significantly different between the REACH‐2‐in and ‐out groups. A significant predictor of candidates for second‐line treatment at sorafenib initiation was a Child–Pugh score of 5 (A5).
Conclusions
Not all patients refractory to sorafenib were candidates for second‐line therapy. A Child–Pugh score of A5 at sorafenib initiation was an important and favorable factor related to eligibility for second‐line therapy and good outcomes.
Background
The prognostic nutritional index (PNI) and Charlson comorbidity index (CCI) have been useful for predicting the prognosis based on nutritional condition and comorbidities in surgery and ...endoscopic mucosal dissection. The age-adjusted CCI (ACCI) has also been reported to be useful in surgery, but it has not been applied to endoscopic treatment. We therefore clarified the prognostic factors associated with ampullary tumors treated with endoscopic papillectomy (EP).
Methods
From January 2003 to December 2020, 236 patients who underwent EP for sporadic ampullary tumors at Nagoya University Hospital were included in this study. The 5-year survival and ability to predict the prognosis were evaluated in terms of the sex, PNI, ACCI, final pathological diagnosis, and intraductal extension.
Results
During a median follow-up period of 1558 days, 17 patients died. No patient died of the primary disease. The 5-year survival rate was 91.1%. In a univariate analysis, only a high ACCI (≥ 5) was extracted as a significant prognostic factor (Odds ratio, 12.2; 95% confidence interval, 3.81–39.3;
p
< 0.001). The 5-year survival rates for a low ACCI (≤ 4) and high ACCI were 96.6% and 73.5%, respectively (
p
< 0.001).
Conclusions
A high ACCI is an important prognostic factor associated with the 5-year survival and a risk of death from other illness. Ampullary tumors suitable for EP are less likely to be a prognostic factor, and treatment-free follow-up may be acceptable in patients with a high ACCI.
Background and Aims In the International Consensus Diagnostic Criteria (ICDC), autoimmune pancreatitis (AIP) is classified into types 1 and 2, and its definite histopathology diagnosis can be made ...based only on surgical or core biopsy specimens. Although EUS-guided FNA (EUS-FNA) biopsy is a safe technique for the collection of pancreatic tissue, no consensus viewpoint has been reached with regard to the role of EUS-FNA biopsy in the diagnosis of AIP. This study investigated the utility of pancreatic tissue collected by EUS-FNA biopsy by using a standard 22-gauge aspiration needle in the diagnosis of AIP. Methods Patients with suspected AIP were prospectively enrolled in Nagoya University Hospital and Nagoya University–affiliated institutions. Pancreatic tissue was collected from each by EUS-FNA biopsy with a standard 22-gauge aspiration needle. Results Fifty patients were registered, including 45 with a final diagnosis of AIP. Lymphoplasmacytic infiltration and abundant immunoglobulin G4 –positive plasmacyte infiltration (>10/high-power field) were detected in 36 (72%) and 27 (54%) patients, respectively. Obliterative phlebitis and storiform fibrosis were not detected in our study. Granulocytic epithelial lesions (GEL) were observed in 3 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNA biopsy to definitively diagnose AIP were 7.9% (3/38), 100% (12/12), 100% (3/3), and 25.5% (12/47), respectively. Pathology evaluation of pancreatic tissue collected by EUS-FNA biopsy improved the diagnostic accuracy in 8 (16%) of the 50 patients. Conclusions In this study, EUS-FNA biopsy by using a standard 22-gauge aspiration needle is not an effective diagnostic method for most patients with AIP. The combination of level 2 histology diagnosis of AIP with other findings specified in the ICDC slightly improved the diagnostic accuracy, although it still remains insufficiently accurate for routine clinical use.(Clinical trial registration number: 000006297.)
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