Mcl-1 expression is a predictive marker of response to gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer.

Antiapoptotic protein, including Mcl-1, expression is frequently observed in pancreatic cancer. Gemcitabine plus nabpaclitaxel (GnP) is the standard chemotherapy for metastatic pancreatic cancer (MPC); however, predictive markers for its efficacy remain unestablished. This study evaluated the association between GnP's therapeutic effects and Mcl-1 expression in tissue samples obtained using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumor or percutaneous ultrasound-guided biopsy for metastatic liver tumor. We retrospectively reviewed 38 patients with histologically diagnosed MPC who received GnP as the first-line chemotherapy at our institute between December 2014 and July 2018. Post-immunohistochemistry analysis for Mcl-1 expression detection, patients were divided to into two groups based on the cell proportion showing Mcl-1 immunoreactivity: positive (> 20%; 23 [60.5%] patients) and negative (≤ 20%; 15 [39.5%] patients) groups. Clinical characteristics did not differ between the two groups. The Mcl-1 positive group showed a significantly higher disease control rate (95.7% vs. 73.3%; P = 0.046), longer progressionfree survival (PFS) (7.2 months vs. 4.9 months; P = 0.018) and longer overall survival (OS) (14.9 months vs. 9.2 months; P = 0.008) than the Mcl-1 negative group. Multivariate analysis showed that Mcl-1 expression was an independent predictive marker for PFS and OS. Mcl-1 expression could be a predictive marker for favorable response to GnP.

Real-world assessment of comprehensive genome profiling impact on clinical outcomes: A single-institution study in Japan.

INTRODUCTION: Comprehensive genome profiling (CGP) has revolutionized healthcare by offering personalized medicine opportunities. However, its real-world utility and impact remain incompletely understood. This study examined the extent to which CGP leads to genomically matched therapy and its effectiveness. METHODS: We analyzed data from advanced solid tumor patients who underwent CGP panel between December 2019 and May 2023 at the Osaka International Cancer Institute. Patient demographics, specimen details, and expert panel assessments were collected. Turnaround time (TAT) and genomically matched therapy outcomes were analyzed. Gene alterations and their co-occurrence patterns were also assessed. RESULTS: Among 1437 patients, 1096 results were available for analysis. The median TAT was 63 [28-182] days. There were 667 (60.9%) cases wherein recommended clinical trials were presented and there were 12 (1.1%) cases that could be enrolled in the trial and 25 (2.3%) cases that could lead to therapies under insurance reimbursement. The median progression free survival of the trial treatment was 1.58 months (95% CI: 0.66-4.37) in clinical trials and 3.66 months (95% CI: 2.14-7.13) in treatment under insurance. Pathologic germline variants were confirmed in 15 patients (1.3%). Co-alteration of CDKN2A, CDKN2B, and MTAP was significantly observed in overall population. CONCLUSION: The effectiveness of the genomically matched therapy based on the CGP panel was unsatisfactory. Expansion of clinical trials and utilization of remote clinical trials are required to ensure that the results of the CGP panel can be fully returned to patients.

Clinical significance of germline breast cancer susceptibility gene (gBRCA) testing and olaparib as maintenance therapy for patients with pancreatic cancer.

BACKGROUND: Germline breast cancer susceptibility gene (gBRCA) mutation in patients with pancreatic cancer (PC) is not common in clinical practice. Therefore, factors that efficiently show gBRCA mutations and the real-world outcomes of olaparib maintenance therapy have not been fully established. In the present study, we clarified the indicators for the effective detection of gBRCA mutation and the efficacy and safety of olaparib as maintenance therapy. METHODS: We retrospectively analyzed 84 patients with PC who underwent gBRCA testing (BRACAnalysis, Myriad Genetics, Salt Lake City, UT, USA) at our institute between January 2021 and March 2022. For each patient, clinical data were extracted from medical records. RESULTS: The median patient age was 64 y (29-85 y), and 41 patients (48.8%) were male. The gBRCA mutations were identified in 10 (11.9%) patients; two patients had BRCA1 mutation and eight had BRCA2 mutation. All patients with gBRCA mutation had a family history of any cancer, and eight of them had a family history of Hereditary Breast and Ovarian Cancer syndrome (HBOC)-related cancer. The gBRCA mutation rate was higher for patients with PC with a family history of HBOC-related cancer compared to that in patients with PC having a family history of other cancers and no family history of cancer (22.9% vs. 4.1%; P = 0.014). In our study, eight out of 10 patients with gBRCA-positive PC received olaparib after platinum-based chemotherapy. The best responses to platinum-based chemotherapy included a complete response in one patient (12.5%) and a partial response in seven patients (87.5%). The median duration of treatment with platinum-based chemotherapy plus olaparib was 17.5 months (8-87 months), and the duration of treatment with olaparib maintenance therapy was 11 months (1-30 months). During olaparib maintenance therapy, three patients showed no disease progression. One of these three patients underwent conversion surgery after receiving olaparib for 12 months. CONCLUSIONS: The gBRCA testing should be considered proactively, especially in patients with PC with a family history of HBOC-related cancer.

Abscopal effect in a patient with advanced hepatocellular carcinoma upon resuming bevacizumab in combination with atezolizumab after radiotherapy.

Combining bevacizumab with atezolizumab enhances the antitumor effects of the treatment by activating an immune response. This combination is approved for the treatment of unresectable hepatocellular carcinoma (HCC). An abscopal effect is associated with an immune response triggered by radiation-induced immunogenic cell death, based on experimental models. Thus, combining radiotherapy and immunotherapy is expected to induce an abscopal effect. However, the clinical significance of immunotherapy in the abscopal effect remains unknown due to the rarity of clinical cases. Herein, we report a case of advanced HCC with lung and adrenal metastases. The antitumor efficacy of atezolizumab and bevacizumab (atezo/bev) was enhanced following stereotactic body radiotherapy (SBRT), although atezo/bev did not yield a sufficient therapeutic response pre-SBRT. Furthermore, an abscopal effect following SBRT was not observed during atezolizumab alone but was evoked after resuming bevacizumab in combination with atezolizumab, culminating in the patient achieving a complete response status. These findings suggest that immune activation following radiotherapy may be related to the induction of an abscopal effect in clinical practice as well as in experimental settings, and combining immunotherapy with bevacizumab post-radiotherapy could evoke an abscopal effect in a case of HCC, even though immune checkpoint inhibitor use alone may be insufficient.

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.

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.

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.

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.

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.

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.

Activation of p53 After Irradiation Impairs the Regenerative Capacity of the Mouse Liver.

Radiation therapy is one of the treatment methods for hepatocellular carcinoma. However, radiation tolerance of the liver is low, and the detailed effect of radiation on liver regeneration has not been clarified. C57BL/6J mice or hepatocyte-specific p53 knockout (KO) mice (albumin [Alb]-Cre Trp53flox/flox ) were irradiated with a single fraction of 10 Gy localized to the upper abdomen. We performed 70% partial hepatectomy (PHx) 24 hours after irradiation. Liver regeneration was assessed by proliferation cell nuclear antigen (PCNA)- and Ki-67-positive hepatocyte ratios and liver-to-body weight ratio after PHx. To establish a fibrosis model, CCl4 was orally administered for 8 weeks. The murine hepatocyte cell line BNL CL.2 (CL2) was irradiated with 10 Gy. Irradiation activated p53, induced downstream p21 in the liver, and delayed liver regeneration after PHx. While PHx increased hepatocyte growth factor (HGF) levels and activated Met with or without irradiation in the regenerative liver, it activated Akt and extracellular kinase 1 and 2 (Erk 1/2) less in irradiated mice than in nonirradiated mice. In CL2 cells cultured with HGF, irradiation suppressed cell growth by decreasing phosphorylated Akt and Erk 1/2 levels, which was abolished by small interfering RNA-mediated p53 knockdown but not by p21 knockdown. Hepatocyte-specific knockout of p53 in mice abolished the irradiation-induced suppression of both liver regeneration and Akt and Erk 1/2 activation after PHx. In the fibrotic mouse model, the survival rate after PHx of irradiated p53 KO mice was higher than that of wild-type mice. Conclusion: p53 but not p21 is involved in the impaired regenerative ability of the irradiated liver.

The Survival Benefit of Chemoradiotherapy following Induction Chemotherapy with Gemcitabine Plus Nab-Paclitaxel for Unresectable Locally Advanced Pancreatic Cancer.

An optimal therapeutic strategy for unresectable locally advanced pancreatic cancer (UR-LAPC) has not been established. This study investigated the therapeutic efficacy of chemoradiotherapy (CRT) following induction chemotherapy with gemcitabine plus nab-paclitaxel (GnP) (CRT group) compared with systemic chemotherapy alone (CTx group) in patients with UR-LAPC. This was a retrospective study of 63 consecutive patients with UR-LAPC treated at our department in a Japanese cancer referral center between February 2015 and July 2018. We excluded patients who underwent other regimens and those enrolled in another prospective study. The CRT group (n = 25) exhibited significantly better progression-free survival (PFS) and overall survival (OS) than the CTx group (n = 20, PFS 17.9 vs. 7.6 months, p = 0.044; OS 29.2 vs. 17.4 months, p < 0.001). In the multivariate analyses, CRT following induction chemotherapy was identified as an independent prognostic factor for OS. Seven (15.6%) patients underwent conversion surgery, all of whom were in the CRT group. The R0 resection rate was 85.7% (6/7). In summary, patients with UR-LAPC experienced favorable treatment outcomes after receiving GnP as the first-line chemotherapy, especially when receiving additional CRT. Thus, this treatment strategy represents a promising treatment option for selected patients with UR-LAPC.