Clinical benefit of subsequent chemotherapy after drug-induced interstitial lung disease in pancreatic cancer patients: a multicenter retrospective study from Japan.

PURPOSE: Drug-induced interstitial lung disease (ILD) is not a rare adverse event in the current chemotherapy strategy for pancreatic ductal adenocarcinoma (PDAC). Thus, we aimed to find the optimal management for PDAC patients with a history of ILD induced by a gemcitabine-based regimen. METHODS: We conducted a multicenter retrospective study. The primary endpoint was the overall survival (OS) of patients who underwent either S-1 monotherapy or FOLFOX after the onset of ILD. Toxicity data was also analyzed in the 2 groups. RESULTS: Twenty-four patients were diagnosed with ILD and 17 patients who received subsequent chemotherapy were enrolled in the study. Among 17 patients who were managed with subsequent chemotherapy after recovering from ILD, we did not observe significant difference in OS between S-1 and FOLFOX (290.0 days vs. undefined, p = 0.39). Relapse of drug-induced ILD was not observed in all cases during the course. Overall, severe adverse events (CTCAE Grade 3 or 4) were observed in 3 patients (23.1%) in S-1 treatment group and 1 patient (25.0%) in FOLFOX treatment group (p = 0.93). CONCLUSIONS: S-1 monotherapy and FOLFOX are comparable as the subsequent chemotherapy after gemcitabine-based chemotherapy-induced ILD in unresectable PDAC.

Effects of anti-thrombotic drugs on all-cause mortality after upper gastrointestinal bleeding in Japan: A multicenter study with 2205 cases.

OBJECTS: Although anti-thrombotic use is recognized as a risk factor for upper gastrointestinal bleeding (UGIB), there has been no clear evidence that it worsens the outcomes after the bleeding. The aim of this study is to investigate the effects of anti-thrombotic agents on in-hospital mortality following UGIB. METHODS: Information on clinical parameters, including usage of anti-thrombotic agents, was retrospectively collected from consecutive patients with UGIB at 12 high-volume centers in Japan between 2011 and 2018. The all-cause in-hospital mortality rate was evaluated according to the usage of anti-thrombotic agents. RESULTS: Clinical data were collected from 2205 patients with endoscopically confirmed UGIB. Six hundred and forty-five (29.3%) patients used anti-thrombotic agents. The all-cause in-hospital mortality rate was 5.7% (125 deaths). After excluding 29 cases in which death occurred due to end-stage malignancy, 96 deaths (bleeding-related, n = 22 ; non-bleeding-related, n = 74) were considered "preventable." Overall, the "preventable" mortality rate in anti-thrombotic users was significantly higher than that in non-users (6.0% vs. 3.7%, P < 0.05). However, the "preventable" mortality of anti-thrombotic users showed a marked improvement over time; although the rate in users remained significantly higher than that in non-users until 2015 (7.3% vs. 4.2%, P < 0.05), after 2016, the difference was no longer statistically significant (4.8% vs. 3.5%). CONCLUSIONS: Although the usage of anti-thrombotic agents worsened the outcomes after UGIB, the situation has recently been improving. We speculate that the recent revision of the Japanese guidelines on the management of anti-thrombotic treatment after UGIB may have partly contributed to improving the survival of users of anti-thrombotic agents.

Nature and treatment outcomes of bleeding post-bulbar duodenal ulcers.

BACKGROUND: Although post-bulbar duodenal ulcers (PBDUs) could become a source of upper gastrointestinal bleeding, the whole picture of the disease is unknown. We compared the characteristic features and treatment outcomes after endoscopic hemostasis between PBDUs and bulbar duodenal ulcers (BDUs). METHODS: Data on duodenal ulcers with evidence of endoscopically-active bleeding were extracted from the data that were retrospectively collected from 12 institutes in Japan between 2011 and 2018. Rebleeding and in-hospital mortality were compared between patients with PBDUs and those with BDUs by logistic regression analyses. RESULTS: Among 468 consecutive patients with bleeding duodenal ulcers, 96 (20.5%) had endoscopically-confirmed PBDUs. PBDUs were more frequently observed in patients with a poor general condition in comparison to BDUs. The rates of rebleeding and in-hospital mortality in patients with PBDUs were approximately three times higher than those in patients with BDUs (PBDU vs. BDU: 29.2% vs. 10.2% [P < 0.0001] and 14.6% vs. 5.1% [P = 0.0029], respectively). Although the high in-hospital mortality in PBDUs could be explained, to a lesser extent, by the likelihood of rebleeding, and, to a greater extent, by the patients' poor general condition, the presence of a PBDU itself was largely responsible for the high rebleeding rates in PBDUs. CONCLUSION: This is the first study focusing on the nature and treatment outcomes of bleeding PBDUs. PBDUs were associated with much higher rebleeding and mortality rates in comparison to BDUs, and the likelihood of rebleeding may be derived from their unique anatomic location.

A Hepatitis B Virus Reactivation Case Potentially Triggered by the Onset of Diffuse Large B Cell Lymphoma.

An 81-year-old man underwent rituximab-containing chemotherapy for chronic lymphocytic leukemia (CLL). Thirteen years after his last chemotherapy, he was diagnosed with hepatitis B virus (HBV) reactivation. He was then treated with entecavir, and improvement was seen in his liver injury. He developed diffuse large B cell lymphoma (DLBCL) after improvement in his hepatitis. Despite chemotherapy, he contracted the coronavirus disease 2019 (COVID-19) and died of COVID-19. We suspect that HBV reactivation was triggered by DLBCL. When HBV reactivation occurs a long time after chemotherapy has concluded, the onset of DLBCL should be considered.

A multicenter comparative study of endoscopic ultrasound-guided fine-needle biopsy using a Franseen needle versus conventional endoscopic ultrasound-guided fine-needle aspiration to evaluate microsatellite instability in patients with unresectable pancreatic cancer.

BACKGROUND/AIMS: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. METHODS: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018-2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. RESULTS: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. CONCLUSION: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

Evaluation of the relationship between the spleen volume and the disease activity in ulcerative colitis and Crohn disease.

ABSTRACT: Inflammatory bowel disease (IBD) is caused by the activation of an abnormal immune response in the intestinal mucosa; the spleen is involved in the main immune response. Ulcerative colitis (UC) and Crohn disease (CD) have different inflammatory mechanisms; this study aimed to quantitatively measure and compare the spleen volumes between patients with UC and CD and examine the relationship between spleen volume and disease activity in both.We retrospectively analyzed 44 patients with IBD aged 30-60 years (UC group, n = 24; CD group, n = 20). The control group comprised 19 patients with pancreatic cysts that did not affect the spleen volume. All patients underwent computed tomography (CT) between April 2014 and March 2019. Using the Image J software, spleen volumes in the UC, CD, and control groups were measured accurately from the CT images and adjusted for the body weight.No significant differences in the sex, age, or body weight were noted between the UC and CD groups and the control group. The spleen volumes, adjusted for the body weight, were 2.2 ±â€Š1.0 cm3/kg, 2.0 ±â€Š1.0 cm3/kg, and 3.6 ±â€Š1.7 cm3/kg in the control, UC, and CD groups, respectively. The volumes differed significantly between the CD and control groups (P = .01), but not between the UC and control groups (P = .43). Furthermore, a significant strong correlation was found between the disease activity and the body weight-adjusted spleen volume in patients with CD (P < .01).The spleen volume, adjusted for the body weight, was significantly larger in patients with CD than in the controls and was also strongly correlated with the CD activity. These results suggest that the immune response in CD may affect the spleen volume.

ATP assay-guided chemosensitivity testing for gemcitabine with biopsy specimens obtained from unresectable pancreatic cancer using endoscopic ultrasonography-guided fine-needle aspiration.

OBJECTIVES: This study evaluates the feasibility of chemosensitivity testing by use of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) samples and determines the optimum cut-off value for gemcitabine. METHODS: Thirty-four consecutive patients with unresectable pancreatic cancer were enrolled. Chemosensitivity (treated/control ratio: T/C ratio) was calculated as the quantity of adenosine triphosphate for a tumor treated with gemcitabine as a percentage of that for the control. To identify the cut-off value sufficient to predict 180 days of progression-free survival (PFS), the receiver operating characteristic curve and the corresponding area under the curve (AUC) were calculated. RESULTS: The success of this assay was 88.2% (30/34); therefore, 30 patients were assessable and included in the population of analyzable patients.. The response was 6.7%. Median PFS was 96 days and median overall survival was 241 days, respectively. The cut-off value was determined as 74% (AUC, 0.745; p = 0.053; 95% CI 0.485-1.005). According to this cut-off value, we predicted 180 days PFS with a sensitivity and specificity of 71.4 and 91.3%, respectively. When patients were divided into two groups at T/C ratio 74%, a significant difference was found in PFS (median 77 vs. 205 days, p = 0.0036). Moreover, T/C ratio < 74% and decrease of CA19-9 were significant and independent prognostic factors by multivariate analysis. CONCLUSION: Chemosensitivity testing by use of EUS-FNA samples in patients with unresectable pancreatic cancer is feasible. This definition emphasizes the possibility of selecting patients for whom favorable results from gemcitabine treatment can be expected.

A simple prediction score for in-hospital mortality in patients with nonvariceal upper gastrointestinal bleeding.

BACKGROUND: No prediction scores for the mortality of both inpatients and outpatients who developed nonvariceal upper gastrointestinal bleeding (UGIB) without endoscopic findings have been established. We aimed to derive and validate a novel prediction score for in-hospital mortality. METHODS: We conducted a three-stage, multicenter retrospective study. In the derivation stage, patients with nonvariceal UGIB at six institutions were enrolled to derive the prediction score by logistic regression analysis. External validation of the score was performed to analyze discrimination by patients at six other institutions. Then the performance of this score was compared with that of four existing scores. RESULTS: We enrolled 1380 and 825 patients in the derivation and validation cohorts, respectively. A prediction score (CHAMPS-R Score) comprising seven variables (Charlson Comorbidity Index ≥ 2, in-hospital onset, albumin < 2.5 g/dL, altered mental status, Eastern Cooperative Oncology Group performance status ≥ 2, steroids, and rebleeding) with equal-weight scores was established, with high discriminative ability in both derivation and validation cohorts (c statistic, 0.91 and 0.80, respectively). When rebeeding was excluded from the score (an onset model; CHAMPS Score), this score also achieved high discriminative ability (c statistic, 0.90 and 0.81, respectively). The prediction scores had significantly higher discriminative ability than the Glasgow Blatchford Score, AIMS65, ABC Score, and clinical Rockall Score in both cohorts (all, p < 0.05). CONCLUSIONS: We derived and externally validated prediction scores for in-hospital mortality in patients with nonvariceal UGIB. The CHAMPS Score might be optimal for managing such patients. Its mobile application is freely available ( https://apps.apple.com/app/id1565716902 for iOS and https://play.google.com/store/apps/details?id=hatta.CHAMPS for Android).

Complete response of anaplastic pancreatic carcinoma to paclitaxel treatment selected by chemosensitivity testing.

A 58-year-old woman was admitted to our institute in June 2007 because of obstructive jaundice. A mass in the pancreatic head and multiple swollen lymph nodes surrounding the common hepatic artery were identified using computed tomography (CT). Subsequently, endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNA) was done. Histopathologic results revealed anaplastic carcinoma of the pancreas. Using specimens obtained with EUS-FNA, chemosensitivity testing with adenosine triphosphate assay was performed. Testing indicated high chemosensitivity to paclitaxel (PTX). According to this result, chemotherapy using PTX was performed, and the primary lesion and lymph node metastases disappeared completely on CT. The patient has been doing well with no recurrence for 1 year and 11 months since initial chemotherapy.

A case of gastric pseudoaneurysm following endoscopic submucosal dissection of early gastric cancer.

A woman in her 80s underwent endoscopic submucosal dissection (ESD) for a 20-mm-sized early gastric cancer lesion in the posterior wall of the upper gastric body. The lesion was resected en bloc with no adverse events. However, bleeding was observed in a post-ESD mucosal defect the day after ESD, so endoscopic hemostasis was performed. Moreover, hematemesis occurred 4 days after ESD, when the bleeding site showed a sign of pulsatile aneurysm. Therefore, endoscopic hemostasis was considered difficult, and angiographic treatment was chosen. Since angiography revealed a pseudoaneurysm in a portion of a branch of the left gastric artery, embolization with microcoils was performed. Thereafter, no bleeding occurred. To the best of our knowledge, there is no case report about the formation of a pseudoaneurysm in a post-gastric ESD mucosal defect. Thus, this case is being reported to document valuable information.

Endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic masses with rapid on-site cytological evaluation by endosonographers without attendance of cytopathologists.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with rapid on-site evaluation (ROSE) has been reported to provide a more accurate diagnosis than EUS-FNA without such evaluation. However, even endosonographers can evaluate ROSE regarding sample adequacy. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA with ROSE by endosonographers compared to ROSE by cytopathologists in patients with solid pancreatic masses. METHODS: Between September 2001 and October 2005, of the 73 EUS-FNA procedures with the final diagnoses, 38 procedures after the introduction of ROSE by endosonographers (September 2001-September 2003, period 1), and 35 procedures after the introduction of ROSE by cytopathologists (October 2003-October 2005, period 2) were included. The specimens were stained with Diff-Quik stain and assessed. When the on-site assessors (endosonographers or cytopathologists) indicated that the amounts of cell samples were adequate, the procedure was stopped. RESULTS: Results are presented with 95% confidence limits. The average numbers of needle passes were 4.0 +/- 1.6 and 3.4 +/- 1.5 in periods 1 and 2, respectively (P = 0.06). The specimen collection rates were 97.4 and 97.1% in periods 1 and 2, respectively (P = 0.51). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for malignancy and benign were 92.9, 100, 100, 83.3, and 94.7%, respectively, in period 1, and 93.1, 100, 100, 75.0, and 94.3%, respectively, in period 2 (P = 0.97, P = 1.0, P = 1.0, P = 0.65, P = 0.93, respectively). No complications were seen. CONCLUSIONS: For accurate diagnosis, ROSE should be performed during EUS-FNA by the endosonographer, if no cytopathologist is available.

Pancreatobiliary drainage using the EUS-FNA technique: EUS-BD and EUS-PD.

The recent progression of endoscopic ultrasonography (EUS) enables EUS-guided transmural drainage based on the EUS-guided fine-needle aspiration biopsy technique. Prior to the development of EUS-guided drainage procedures, the options for treating obstruction of the pancreatobiliary system included surgical drainage, percutaneous drainage using ultrasound and radiological guidance, and endoscopic (non EUS-guidance) transmural drainage. Today, using EUS guidance and dedicated accessories, it is possible to create bilio- or pancreato-digestive anastomosis, EUS-guided biliary drainage (EUS-BD), and EUS-guided pancreatic drainage (EUS-PD). The recent literature describes that EUS-BD and EUS-PD have acceptable success and complication rates. These procedures are anticipated for use as alternatives to surgery or percutaneous drainage when endoscopic transpapillary procedures fail.

Pancreatic lipoma diagnosed using EUS-FNA. A case report.

CONTEXT: Pancreatic mesenchymal tumors are rare, accounting for only 1-2% of pancreatic tumors. A pancreatic lipoma is an especially rare condition. This is only the second report of a pancreatic lipoma diagnosed before surgery using endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA). CASE REPORT: A 75-year-old woman with a round low-density lesion which had been detected by CT was referred to our hospital. EUS revealed an oval 49x32 mm homogeneous and almost isoechoic mass (as compared to normal pancreatic parenchyma) in the pancreatic head. Its outer margin was not clearly differentiated from the parenchyma. Although a benign pancreatic lipomatous lesion was deemed most probable from information obtained using CT/MRI, a mass with malignancy such as a liposarcoma could not be ruled out as a differential diagnosis. Therefore, EUS-FNA was performed for a definitive diagnosis. Two passes were performed with on-site pathology. The results obtained from the sample analysis indicated a pancreatic lipoma consisting of mature fat cells with no atypia. CONCLUSION: Although imaging modalities are useful for the diagnosis of pancreatic lipomatous lesions, it is sometimes difficult to diagnose lipomatous malignancies mimicking benign lipoma. This case demonstrates the usefulness of EUS-FNA for the differential diagnosis of pancreatic lipomatous lesions.

Interventional endoscopic ultrasonography: applications for cancer related treatment.

For tissue diagnosis in patients with abnormalities of various organs, endoscopic ultrasonography (EUS)-guided fine needle aspiration (EUS-FNA) has emerged as an effective technique. Subsequently, EUS-guided fine needle injection (EUS-FNI) has expanded the clinical utility of EUS. Several applications of EUS-FNI for anti-cancer efforts have included celiac nerve blocking and drug delivery into tumors, such as ablation, chemotherapy, gene therapy, and cytoimplantation. Furthermore, chemosensitivity tests with materials obtained using EUS-FNA are available to produce tailor-made medicines. Demonstrably, EUS-guided intervention has opened new and exciting clinical applications for the management of malignancies.

Analysis of prognostic factors in patients with gastric varices after endoscopic treatment.

BACKGROUND: The prognostic factors, including gastric variceal bleeding itself, in patients with gastric varices (GV) after endoscopic treatment remain unclear. The aim of this study was to analyze prognostic factors in patients with GV after endoscopic treatment as well as to evaluate safety and efficacy of our endoscopic treatment. PATIENTS AND METHODS: This study enrolled 115 patients who underwent endoscopic treatment for GV between October 1988 and December 2003 using cyanoacrylate and 5% ethanolamine oleate. Successful hemostasis, recurrence rates, rebleeding rates, survival rates, complications and prognostic factors after the treatment were retrospectively reviewed. RESULTS: Treatment sessions for GV were performed 3.4 +/- 2.5 times. All cases, including 14 emergency cases, were treated successfully. The cumulative recurrence rates at 1, 3 and 5 years after the treatment were 7.0%, 15.6% and 20.0%, respectively, and the cumulative rebleeding rates at 1, 3 and 5 years were 3.5%, 8.7% and 14.8%, respectively. The overall survival rates were 78.3%, 63.7% and 51.5% at 1, 3 and 5 years, respectively. Grade B or C in Child-Pugh classification, emergency or elective cases, and association with hepatocellular carcinoma were identified as significant negative prognostic factors after endoscopic treatment by multivariate analysis. Although several complications were observed, there was no mortality. CONCLUSIONS: Grade B or C in Child-Pugh classification, emergency or elective situation, and association with hepatocellular carcinoma are negative prognostic factors after endoscopic treatment.

Two cases of pancreatic abscess associated with penetration to the gastrointestinal tract during treatment using endoscopic ultrasound-guided drainage.

Of pancreatic pseudocysts, approximately 30% are complicated by abscess formation, perforation into the abdominal cavity, penetration to the gastrointestinal tract, or bleeding. We report two cases of pancreatic abscess complicating severe acute pancreatitis in which the abscess penetrated to the gastrointestinal tract during the course of treatment with endoscopic ultrasound (EUS)-guided pseudocyst drainage. In these cases, neither aggravation nor recurrence of the pancreatic abscess has been identified since the event occurred. The EUS-guided treatment was effective for improvement of severe inflammation of the pseudocyst as an initial treatment. However, drainage tube placement limitations pertained because the pseudocyst was present with multilocular infection. Penetrations eventually contributed to their resolution because the fistulas were used as wide drainage routes. It is important to understand the courses of these cases for preparation of therapeutic strategies to treat pancreatic pseudocyst/abscess.

A case of esophageal small cell carcinoma associated with hypercalcemia causing severe acute pancreatitis.

A 60-year-old woman was diagnosed with esophageal small cell carcinoma in October 2004 and received chemotherapy. However, the tumor grew gradually and multiple bone metastases occurred. Anorexia, nausea, emesis, numbness in both hands, and disturbed consciousness developed at the end of January 2006, and the patient was admitted to Fukushima Medical University Hospital. Abdominal pain, marked hypercalcemia and hyperamylasemia were noted and the patient was diagnosed with severe acute pancreatitis. Because the level of blood parathyroid hormone-related protein was elevated, we considered that esophageal small cell carcinoma caused human hypercalcemia of malignancy and that metastatic bone tumors caused local osteolytic hypercalcemia, eventually leading to severe acute pancreatitis. This is an extremely rare case of esophageal small cell carcinoma associated with hypercalcemia causing severe acute pancreatitis.

A case of transgastric gallbladder puncture as a complication during endoscopic ultrasound-guided drainage of a pancreatic pseudocyst.

A 43-year-old man, a regular drinker, developed a pseudocyst in the pancreatic tail as a result of acutely worsening chronic pancreatitis. Because the pseudocyst, 10 cm in diameter, did not disappear despite conservative treatment, an internal drainage stent was placed transgastrically under endoscopic ultrasound (EUS) guidance. However, cyst infection occurred, and EUS-guided drainage was performed, when the gallbladder was punctured inadvertently. Immediately a nasocystic drain was placed in the gallbladder. Owing to this timely measure, only mild and localized peritonitis developed. Conservative treatment with fasting and an antibiotic was administered, and peritonitis subsided quickly. On the same day, another nasocystic drain was placed for the pancreatic pseudocyst, and it disappeared. As far as we know, this is the first case in which gallbladder puncture was inadvertently performed during EUS-guided drainage of a pancreatic pseudocyst.

Echo-endoscopic analysis of variceal hemodynamics in patient with isolated gastric varices.

BACKGROUND: It is considered that gastric varices (GVs) which have the large form in endoscopic view should be treated because they are regarded as having high blood flow volume and the risky varices of hemorrhage. However, there is no data of the correlation among the endoscopic view, diameter of GV, and blood flow volume in GV. The aim of this study was to investigate whether GV diameter correlates to blood flow volume or not. In addition, the correlation between the endoscopic findings of GVs, patient status, and blood flow volume was assessed. MATERIALS AND METHODS: In this study, 24 patients were enrolled. Variceal form and its location were observed using flexible GI endoscopes. Assessment of variceal form and location was according to Japanese society of portal hypertension. Then, the GV diameter (the maximum short axis), the GV flow velocity, and the GV flow volume were measured by echo-endoscope with curved linear array or with electronic radial array. RESULTS: Nineteen of 24 enrolled patients were analyzed. There was strong correlation between the GV diameter and the GV flow volume (rs = 0.85, P < 0.01). No significant difference in the GV diameter and the GV flow volume was found between each location. However, there was no significant difference in the GV diameter between each variceal form. In addition, no significant difference was found among Child-Pugh classifications, and in cases associated with or without hepatocelluer carcinoma. CONCLUSIONS: Strong correlation was found between GV diameter and flow volume of GV, regardless of the location. However, since there was no significant difference in the GV diameter between each variceal form in endoscopic view, measuring GV diameter is important to understand its hemodynamics for further treatment.