Zinc supplementation for dysgeusia in patients with unresectable pancreatic cancer.

BACKGROUND: Although patients with advanced pancreatic cancer (PC) often experience dysgeusia with zinc deficiency during chemotherapy, data on zinc supplementation for dysgeusia and its effects on nutritional status are scarce. We aimed to examine the efficacy of zinc supplementation in patients with advanced PC. METHODS: Thirty-three patients with unresectable PC who presented with dysgeusia and zinc deficiency during chemotherapy and received zinc acetate hydrate between January 2018 and December 2022 were included. We evaluated the changes in serum zinc levels and the improvement in dysgeusia. Among the 26 patients who received zinc supplementation for 12 weeks, we also compared patient characteristics and changes in serum zinc and albumin levels between patients who showed improvement in dysgeusia (effective group) and those who did not (non-effective group). RESULTS: The serum zinc level increased significantly after zinc supplementation (median: 60 µg/dL at baseline, 99.5 µg/dL at 4 weeks, 101 µg/dL at 8 weeks and 101 µg/dL at 12 weeks). The rate of improvement in dysgeusia increased over time (18.2% at 4 weeks, 33.3% at 8 weeks, and 42.4% at 12 weeks). Comparing the effective group and non-effective group revealed that while the median serum albumin level of the effective group did not change, the non-effective group showed a significant decrease from baseline to 12 weeks (3.2 g/dL to 3.0 g/dL, p = 0.03). CONCLUSION: Zinc supplementation significantly increased serum zinc levels, improving dysgeusia. Zinc supplementation might also contribute to maintaining nutritional status in patients with unresectable PC.

Oil blotting paper for formalin fixation increases endoscopic ultrasound-guided tissue acquisition-collected sample volumes on glass slides.

OBJECTIVES: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is used for pathological diagnosis and obtaining samples for molecular testing, facilitating the initiation of targeted therapies in patients with pancreatic cancer. However, samples obtained via EUS-TA are often insufficient, requiring more efforts to improve sampling adequacy for molecular testing. Therefore, this study investigated the use of oil blotting paper for formalin fixation of samples obtained via EUS-TA. METHODS: This prospective study enrolled 42 patients who underwent EUS-TA for pancreatic cancer between September 2020 and February 2022 at the Osaka International Cancer Institute. After a portion of each sample obtained via EUS-TA was separated for routine histological evaluation, the residual samples were divided into filter paper and oil blotting paper groups for analysis. Accordingly, filter paper and oil blotting paper were used for the formalin fixation process. The total tissue, nuclear, and cytoplasm areas of each sample were quantitatively evaluated using virtual slides, and the specimen volume and histological diagnosis of each sample were evaluated by an expert pathologist. RESULTS: All cases were cytologically diagnosed as adenocarcinoma. The area ratios of the total tissue, nuclear, and cytoplasmic portions were significantly larger in the oil blotting paper group than in the filter paper group. The frequency of cases with large amount of tumor cells was significantly higher in the oil blotting paper group (33.3%) than in the filter paper group (11.9%) (p = 0.035). CONCLUSIONS: Oil blotting paper can increase the sample volume obtained via EUS-TA on glass slides and improve sampling adequacy for molecular testing.

Long-term survival after systemic chemotherapy, chemoradiotherapy, and maintenance therapy for an older adult patient with recurrent pancreatic acinar cell carcinoma.

Pancreatic acinar cell carcinoma (PACC) is a rare cancer with no specific treatment. The treatment and chemotherapy for PACC are selected according to pancreatic ductal adenocarcinoma (PDAC). Herein, we describe a recurrent PACC case of an older adult patient. The patient was treated with systemic chemotherapy, chemoradiotherapy, and maintenance therapy based on the pathologic germline BRCA2 variant, resulting in long-term survival. The pathogenic BRCA variant is detected more frequently in patients with PACC than in those with PDAC. The BRCA variant significantly impacts treatment selection and prognosis; therefore, early genomic analysis is recommended when treating PACC.

Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Portal Vein Aneurysm in a Patient with Cirrhosis Type C Controlled by Direct-Acting Antiviral Treatment.

Introduction: Portal vein aneurysm (PVA) is a rare saccular or fusiform portal vein dilatation. The management and optimal treatment of PVA remain unknown. Case Presentation: A 53-year-old man with hepatitis C virus (HCV) infection was diagnosed with PVA measuring 28 mm in diameter. Under observation, his liver fibrosis progressed, and the PVA diameter gradually increased to 52 mm. The patient was treated with elbasvir-grazoprevir for 12 weeks, and HCV disappeared. After achieving sustained virological response, liver fibrosis improved and the PVA progression ceased. Conclusion: HCV clearance by direct-acting antiviral treatment not only regressed liver fibrosis but may have also restrained the progression of PVA in a patient with cirrhosis type C and PVA.

Comprehensive review of pancreatic acinar cell carcinoma: epidemiology, diagnosis, molecular features and treatment.

Pancreatic acinar cell carcinoma is a rare form (0.2-4.3%) of pancreatic neoplasm with unique clinical and molecular characteristics, which largely differ from pancreatic ductal adenocarcinoma. Pancreatic acinar cell carcinoma occurs more frequently in males and can occur in children. Serum lipase is elevated in 24-58% of patients with pancreatic acinar cell carcinoma. Pancreatic acinar cell carcinomas tend to be large at diagnosis (median tumour size: ~5 cm) and are frequently located in the pancreas head. Radiologically, pancreatic acinar cell carcinoma generally exhibits a solid appearance; however, necrosis, cystic changes and intratumoral haemorrhage can occur in larger lesions. Immunostaining is essential for the definitive diagnosis of pancreatic acinar cell carcinoma. Compared with pancreatic ductal adenocarcinoma, pancreatic acinar cell carcinoma has a more favourable prognosis. Although radical surgery is recommended for patients with pancreatic acinar cell carcinoma who do not have distant metastases, the recurrence rate is high. The effectiveness of adjuvant therapy for pancreatic acinar cell carcinoma is unclear. The response to FOLFIRINOX is generally favourable, and some patients achieve a complete response. Pancreatic acinar cell carcinoma has a different genomic profile compared with pancreatic ductal adenocarcinoma. Although genomic analyses have shown that pancreatic acinar cell carcinoma rarely has KRAS, TP53 and CDKN2A mutations, it has a higher prevalence of homologous recombination-related genes, including BRCA1/2 and ATM, than pancreatic ductal adenocarcinoma, suggesting high sensitivity to platinum-containing regimens and PARP inhibitors. Targeted therapies for genomic alternations are beneficial. Therefore, genetic testing is important for patients with pancreatic acinar cell carcinoma to choose the optimal therapeutic strategy.

An age-group analysis on the efficacy of chemotherapy in older adult patients with metastatic biliary tract cancer: a Japanese cancer registry cohort study.

BACKGROUND: The effectiveness of chemotherapy in older adult patients with biliary tract cancer (BTC) remains to be established, despite the fact that the majority of patients diagnosed with BTC tend to be aged ≥ 70 years. In this study, we used three databases to examine the effectiveness of chemotherapy in a large patient population aged ≥ 70 years with metastatic BTC. METHODS: Using a large Japanese database that combined three data sources (Osaka Cancer Registry, Japan's Diagnosis Procedure Combination, the hospital-based cancer registry database), we extracted the data from patients pathologically diagnosed with metastatic BTC, between January 1, 2013, and December 31, 2015, in 30 designated cancer care hospitals (DCCHs). A cohort of patients with comparable backgrounds was identified using propensity score matching. The log-rank test was used to examine how chemotherapy affected overall survival (OS). RESULTS: Among 2,622 registered patients with BTC in 30 DCCHs, 207 older adult patients aged > 70 years with metastatic BTC were selected. Chemotherapy significantly improved the prognosis of older adult patients, according to propensity score matching (chemotherapy, 6.4 months vs. best supportive care, 1.8 months, P value < 0.001). The number of patients receiving chemotherapy tends to decrease with age. Gemcitabine plus cisplatin (GC) and gemcitabine plus S-1 (oral fluoropyrimidine) (GS) combination therapy were frequently performed in the chemotherapy group for patients under 80 years of age (70-74 years, 61.7%; 75-79 years, 62.8%). In contrast, monotherapy including GEM and S-1 was more frequently performed in age groups over 80 years (80-84 years, 56.2%; 85-89 years, 77.7%; ≥90 years, 100%). In the chemotherapy group among older adult patients aged < 85 years, the median OS was significantly longer according to age-group analysis of the 5-year age range following propensity score matching. CONCLUSIONS: In older adult patients with metastatic BTC who received chemotherapy, prolonged survival was observed. Chemotherapy may be a viable option for patients with metastatic BTC who are aged < 85 years.

Hospital volume and prognosis of patients with metastatic pancreatic cancer: A study using the Osaka Cancer Registry.

PURPOSE: Pancreatic cancer (PC) has one of the worst prognoses among all solid cancers. Hospital volume has been shown to be significantly associated with outcomes in patients with PC undergoing surgery. Nonetheless, the association between hospital volume and prognosis in patients with metastatic PC remains unclear. This study aimed to examine the association between hospital volume and prognosis in patients with metastatic PC using large-scale population-based cancer registry data. METHODS: This retrospective observational study was conducted using data from the Osaka Cancer Registry database. Data of patients with metastatic PC over 10 years (2009-2018) were obtained. Hospitals were categorized into high-volume hospitals (HVHs; ≥ 240 patients diagnosed with PC for 10 years), middle-volume hospitals (MVHs; 120-239 patients diagnosed with PC for 10 years), and low-volume hospitals (LVHs; < 120 patients diagnosed with PC for 10 years). Multivariate analysis was performed to identify factors associated with overall survival (OS). RESULTS: The analysis included 8,929 patients with metastatic PC. Median OS was significantly more favorable in HVHs than in MVHs and LVHs. Multivariate analysis adjusted for hospital volume, age, primary tumor site, year of diagnosis, chemotherapy, and radiotherapy revealed that hospital volume was an independent factor associated with OS (HVHs vs. MVHs: hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03-1.16; P = 0.003, HVHs vs. LVHs: HR, 1.20; 95% CI, 1.13-1.27; P < 0.001). CONCLUSION: Hospital volume is an independent prognostic factor in patients with metastatic PC, suggesting an association between hospital volume and treatment outcomes.

Parallel administration of nanoliposomal irinotecan and levo-leucovorin for pancreatic cancer.

BACKGROUND: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) was approved for unresectable pancreatic cancer (UR-PC) in March 2020 in Japan. Levo-LV is administered by intravenous infusion over 120 min following 90 min intravenous infusion of nal-IRI (conventional method), causing a significant burden on both patients and the outpatient chemotherapy room owing to the prolonged administration time. Thus, from July 2021, we introduced the simultaneous intravenous administration of nal-IRI and Levo-LV (parallel method) with the approval of the institutional regimen committee. METHODS: We retrospectively reviewed the data of 69 patients with UR-PC who received nal-IRI plus 5-FU/Levo-LV at our hospital between June 2020 and October 2021. We examined the safety of the parallel method and compared the treatment outcomes and administration times between the two methods. RESULTS: The median age was 66 years (54%, male). Disease statuses were locally advanced, metastatic, and postoperative recurrence after pancreatectomy in 7, 50, and 12 patients, respectively. Nal-IRI plus 5-FU/Levo-LV treatment was second and third-line or later in 35 and 34 patients, respectively. No intravenous line problems were observed during the parallel administration of nal-IRI and Levo-LV. Although there were no significant differences in response rates and adverse events between the two methods, the administration time was significantly shorter in the parallel method than in the conventional method. CONCLUSION: The parallel administration of nal-IRI and Levo-LV is clinically safe and not inferior in efficacy. Moreover, parallel administration may offer convenience to patients and healthcare workers by reducing administration time.

Occupational radiation exposure to the lens of the eyes and its protection during endoscopic retrograde cholangiopancreatography.

This study aimed to examine occupational radiation exposure to the lens of the eyes during endoscopic retrograde cholangiopancreatography (ERCP). In this multicenter, prospective, observational cohort study, we collected data regarding occupational radiation exposure to the lens of the eyes during ERCP. We measured radiation exposure of patients and examined its correlation with occupational exposure. In dosimetrically-measured ERCPs (n = 631), the median air kerma at the patient entrance reference point, air kerma-area product, and fluoroscopy time were 49.6 mGy, 13.5 Gycm2, and 10.9 min, respectively. The median estimated annual radiation dose to the lens of the eyes was 3.7, 2.2, and 2.4 mSv for operators, assistants, and nurses, respectively. Glass badge over lead aprons and eye dosimeter results were similar in operators but differed in assistants and nurses. A strong correlation was shown between eye dosimeter measurements and patients' radiation exposure. The shielding rates of the lead glasses were 44.6%, 66.3%, and 51.7% for operators, assistants, and nurses, respectively. This study revealed the actual occupational exposure dose for the lens of the eyes during ERCP and the efficacy of lead glass. Values of radiation exposure to patients can help estimate exposure to the lens of the eyes of medical staff.

Effect of systemic inflammatory response on induction chemotherapy followed by chemoradiotherapy for locally advanced pancreatic cancer: an exploratory subgroup analysis on systemic inflammatory response in JCOG1106.

OBJECTIVE: JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment. METHODS: All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil-lymphocyte ratio, at the baseline on overall survival. P values <0.1 for the interaction were regarded as denoting significant association. RESULTS: Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95% confidence interval, 0.82-2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95% confidence interval, 0.24-1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein >10 mg/L and/or albumin <35 g/L) (n = 7/15) (P-interaction = 0.06). C-reactive protein alone and albumin alone also showed significant treatment interactions for overall survival. CONCLUSIONS: Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy.

A case of multiple myeloma with pancreatic involvement diagnosed via endoscopic ultrasound-guided fine needle aspiration.

This report highlights the importance of considering multiple myeloma in the differential diagnosis of a pancreatic tumor with bone lesions. sampling not only from the pancreatic lesion but also from bone lesions may reach an accurate diagnosis.

Utility of Comprehensive Genomic Profiling Tests for Patients with Incurable Pancreatic Cancer in Clinical Practice.

Although comprehensive genomic profiling (CGP) tests have been covered under the Japanese national health insurance program since 2018, the utility and issues of CGP tests have not been clarified. We retrospectively reviewed 115 patients with incurable pancreatic cancer (IPC) who underwent CGP tests in a Japanese cancer referral center from November 2019 to August 2021. We evaluated the results of CGP tests, treatments based on CGP tests, and survival time. Eight cases (6.9%) were diagnosed as tumor mutation burden-high (TMB-H) and/or microsatellite instability-high (MSI-H). The gene mutation rates of KRAS/TP53/CDKN2A/SMAD4 were 93.0/83.0/53.0/25.2%, respectively. Twenty-five patients (21.7%) had homologous recombination deficiency (HRD)-related genetic mutations. Four patients (3.5%) having TMB-H and/or MSI-H were treated with pembrolizumab, and only two patients (1.7%) participated in the clinical trials. Patient characteristics were not significantly different between patients with and without HRD-related gene mutations. The median OS was significantly longer in the HRD (+) group than in the HRD (-) group (749 days vs. 519 days, p = 0.047). In multivariate analysis, HRD-related gene mutation was an independent prognostic factor associated with favorable OS. CGP tests for patients with IPC have the potential utility of detecting HRD-related gene mutations as prognostic factors as well as a therapeutic search.

Does endoscopic sphincterotomy contribute to the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis after endoscopic biliary stenting for malignant biliary obstruction? A multicenter prospective cohort study.

BACKGROUND: There is no consensus on the necessity of endoscopic sphincterotomy (ES) to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) after endoscopic stenting in patients with malignant biliary obstruction. We investigated the incidence of PEP after endoscopic biliary stenting for malignant biliary obstruction with or without ES in a multicenter prospective cohort study. METHODS: We enrolled 807 patients who underwent endoscopic biliary stenting for malignant biliary obstruction with a native papilla at 36 hospitals between April 2017 and March 2018. The incidence of PEP in patients with or without ES was compared for subgroups based on stent type, placement method, and patient background. Univariate and multivariate analysis was performed to investigate the incidence of PEP in all stenting patients. RESULTS: Plastic and metal stents (MS) were inserted in 598 and 209 patients, respectively. The incidence of PEP in patients with or without ES was 7.9% and 7.4%, respectively among all stenting patients. The incidences of PEP with or without ES in plastic stent insertion patients, patients with MS insertion, stent insertions across the papilla, stent insertions across the papilla in patients without main pancreatic duct obstruction, and fully covered MS insertions across the papilla were compared. There was no overall significant difference in the incidence of PEP between those with or without ES. Multivariate logistic regression analysis for the incidence of PEP in all stenting patients revealed obstruction of the main pancreatic duct at the pancreatic head and epinephrine spraying on the papilla were significant factors; there was no significant difference in the incidence of PEP between patients with or without ES. CONCLUSION: Endoscopic sphincterotomy may not contribute to the prevention of PEP after endoscopic biliary stenting for malignant biliary obstruction, even in cases of insertion with a fully covered MS across the papilla.

Metastatic undifferentiated pleomorphic sarcoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Pathological differentiation is important for suspected lesions of metastatic undifferentiated pleomorphic sarcoma (UPS) because no reliable imaging criteria exist for this entity yet. In the present case, transgastric endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the pancreatic tumor and transcolonic EUS-FNA for the intraabdominal tumor contributed to the definitive diagnosis of metastatic UPS, leading to appropriate treatment selection.

Chemotherapy effectiveness and age-group analysis of older adult patients with metastatic pancreatic cancer: A Japanese cancer registry cohort study.

INTRODUCTION: Although older adults aged ≥75 years comprise a substantial proportion of patients diagnosed with pancreatic cancer (PC), the effectiveness of chemotherapy in older adults with PC remains to be established. MATERIALS AND METHODS: This retrospective study examined the effectiveness of chemotherapy according to age in older adult patients with metastatic PC. We used a large database that combined three data sources (the hospital-based cancer registry database, Osaka Cancer Registry, and Japan's Diagnosis Procedure Combination) and extracted data from patients pathologically diagnosed with metastatic PC between 2013 and 2015 in 31 designated cancer care hospitals in Japan. Propensity score matching (PSM) was used to identify a cohort of patients with similar backgrounds. The effect of chemotherapy on overall survival (OS) was analyzed using the log-rank test. RESULTS: Compared with 687 younger patients (<75 years old), 276 older adult patients had significant impairments in activities of daily living and poorer prognoses (6.8 vs. 4.1 months, p < 0.001), with a lower frequency of chemotherapy (81.5% vs. 55.1%; p < 0.001). PSM of older adult patients showed that chemotherapy significantly contributed to a better prognosis (best supportive care, 2.6 months vs. chemotherapy, 5.8 months, p < 0.001). Age group analysis with PSM of five-year age ranges revealed that the median OS was significantly longer in the chemotherapy group among older adult patients aged <85 years. DISCUSSION: Chemotherapy provides a survival benefit in older adult patients with metastatic PC, and patients aged <85 years could be promising candidates for chemotherapy.

New Screening System Using Forward-Viewing Radial Endoscopic Ultrasound and Magnetic Resonance Imaging for High-Risk Individuals With Familial History of Pancreatic Cancer.

Background and Aims: Attention is increasingly being paid to family history of pancreatic cancer (PC) as a risk factor for developing PC. It is mandatory to develop a screening system for early detection of PC; however, the relationship between a family history of PC and the incidence of pancreatic abnormalities, such as pancreatic cyst and chronic pancreatitis (CP), in the Japanese population remains unknown. Patients and Methods: Individuals with a family history of PC were prospectively enrolled in a screening program using forward-viewing radial endoscopic ultrasound (FR-EUS) and magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) as the diagnostic modalities. Results: In total, forty-three individuals in 37 families were enrolled (mean age, 54 years). All individuals underwent FR-EUS and MRI with no complications. FR-EUS revealed resectable PC (n = 1, 2.3%), pancreatic cysts (n = 24, 55.8%), intraductal papillary mucinous neoplasm (IPMN; n = 13, 30.2%), and early CP-like appearance (n = 15, 34.9%). The detection rate of early CP-like appearance was significantly higher by EUS than by MRI. Pancreatic cysts and IPMN detected by FR-EUS were significantly correlated to age (≥60 years) and less correlated to men (hazard ratio [HR] 22.4; 95% confidence interval [CI], 2.10-236.0; p < 0.01 and HR 0.092; 95% CI, 0.01-0.83; p = 0.033, respectively). Early CP-like appearance detected by FR-EUS was significantly correlated with men and smoking (HR 5.0; 95% CI, 1.3-19.3; p = 0.02 and HR 4.02; 95% CI, 0.991-16.3; p = 0.05, respectively). Conclusion: A screening system using FR-EUS and MRI/MRCP for individuals with a family history of PC was useful for identifying curable PC and pancreatic abnormalities. The incidence of pancreatic cysts, such as IPMN and early CP-like appearance, was also high in the Japanese cohort.

Feasibility of immunotherapy in cancer patients with persistent or past hepatitis B or C virus infection.

Background and Aim: Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events in the liver. The risk of exacerbating liver injury is of concern in patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), as immunotherapy can damage liver function because of the immune response against viral antigens. We assessed the feasibility of immunotherapy in HBV- or HCV-infected patients. Methods: This retrospective study included 266 patients with persistent or past HBV infection, 26 patients seropositive for anti-HCV, and 820 patients with negative viral markers for HBV and HCV, who were treated with ICIs. ICI-induced liver injury and changes in virological markers were analyzed. Results: The occurrence rates of ICI-induced liver injury in the HBsAg-positive, anti-HBc-positive/anti-HBs-positive, and anti-HBc-positive/anti-HBs-negative groups were 12.5, 21.6, and 19.1%, respectively, which were comparable with those of the negative for HBV- and HCV-related markers group (20.9%). The frequency of any grade ICI-induced liver injury was different among the HCV RNA-positive (3/5; 60.0%), anti-HCV-positive/HCV RNA-negative (2/21; 9.5%), and negative for HBV- and HCV-related markers (171/820; 20.9%) groups (P = 0.045), with no significant difference in grade ≥2 ICI-induced liver injury. In patients with persistent infection, neither serum HBV DNA, HBsAg, nor HCV RNA level changed significantly during ICI treatment. One of five treatment-naïve HCV-infected patients required interruption of ICI treatment due to virus-related liver injury. Conclusion: Immunotherapy is feasible for most cancer patients with chronic HBV or HCV infection; however, liver function and virological markers should be carefully monitored in treatment-naïve patients, especially those with HCV infection, during ICI treatment.

5-Fluorouracil/L-Leucovorin Plus Oxaliplatin (FOLFOX) Regimen as Salvage Chemotherapy for Patients with Unresectable Pancreatic Cancer Receiving Gemcitabine and Nab-Paclitaxel and 5-Fluorouracil/L-Leucovorin Plus Nanoliposomal Irinotecan: Preliminary Results from Clinical Practice.

Salvage chemotherapy for patients with unresectable pancreatic cancer (UR-PC) who have been treated with gemcitabine and nab-paclitaxel (GnP), and 5-fluorouracil (5-FU)/l-leucovorin (LV) plus nanoliposomal irinotecan (nal-IRI), has not been fully established. We retrospectively reviewed data from 17 patients with UR-PC who initiated 5-FU/l-LV plus oxaliplatin (FOLFOX) as salvage chemotherapy at our hospital between June 2020 and August 2021, after treatment with GnP and 5-FU/LV plus nal-IRI. The primary endpoint was tumor response. The secondary endpoints were progression-free survival (PFS) and adverse events (AEs). The response and disease control rates were 5.9% (1/17) and 17.6% (3/17), respectively. The median PFS was 1.8 months (range: 0.4-5.2 months). Eight patients (47.1%) experienced grade 3 nonhematologic AEs, while none experienced grade 3 hematologic AEs. Two patients with controlled disease had homologous recombination deficiency (HRD)-associated gene mutations in cancer panel testing. The FOLFOX regimen benefit for UR-PC patients treated with GnP and 5-FU/LV plus nal-IRI may be limited to patients with HRD-associated gene mutations.

Early detection of venous thromboembolism after the initiation of chemotherapy predicts a poor prognosis in patients with unresectable metastatic pancreatic cancer who underwent first-line chemotherapy with gemcitabine plus nab-paclitaxel.

BACKGROUND: Pancreatic cancer is associated with a high thromboembolism risk. We investigated the significance of early venous thromboembolism (VTE) detection in patients with unresectable metastatic pancreatic cancer (UR-MPC) who received first-line chemotherapy with gemcitabine plus nab-paclitaxel (GnP). METHODS: This single-center retrospective study enrolled 174 patients with UR-MPC who underwent GnP as a first-line chemotherapy from April 2017 to March 2020. The early detection of VTE (deep venous thrombosis and pulmonary thromboembolism) was defined as diagnosis by the first follow-up CT scan after the initiation of chemotherapy. We compared the patients with early detection of VTE (VTE (+) group) with the others (VTE (-) group). We examined overall survival (OS), progress free survival (PFS), severe adverse events, and predictors associated with OS using the Cox proportional hazards model. RESULTS: Early detection of VTE was observed in 17 patients (9.8%). Thirteen patients were diagnosed with VTE at treatment initiation, and four patients were diagnosed after treatment initiation. The median time to diagnosis after treatment initiation was 55 days (range: 31-71 days). Only 3 patients were symptomatic. The VTE (+) group exhibited worse OS and PFS than the VTE (-) group (OS: 259 days vs. 400 days, P < 0.001; PFS: 120 days vs. 162 days, P = 0.008). The frequency of grade 3-4 adverse events was not significantly different. Although the performance status was poorer in the VTE (+) group, VTE was identified as a statistically significant independent predictor for OS in multivariate analyses (HR, 1.87; 95% CI, 1.02-3.44; P = 0.041). CONCLUSIONS: Early VTE detection is a predictor of a poor prognosis in UR-MPC patients who receive GnP as first-line chemotherapy, suggesting that screening VTE for patients with UR-MPC is crucial, even if patients are asymptomatic.