Histopathological growth pattern and vessel co-option in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) exhibits different blood imaging features and prognosis depending on histology. To clarity histopathological growth patterns (HGPs) and vascularization processes of iCCA, we collected 145 surgical specimens and histologically classified them into large bile duct (LBD) (20 cases), small bile duct (SBD) (54), cholangiolocarcinoma (CLC) (35), combined SBD-CLC (cSBD-CLC) (26), and ductal plate malformation (DPM) (10) (sub)types. According to the invasive pattern at the interface between tumor and adjacent background liver, HGPs were classified into desmoplastic, pushing, and replacing HGPs. Desmoplastic HGP predominated in LBD type (55.5%), while replacing HGP was common in CLC (82.9%) and cSBD-CLC (84.6%) subtypes. Desmoplastic HGP reflected angiogenesis, while replacing HGP showed vessel co-option in addition to angiogenesis. By evaluating microvessel density (MVD) using vascular markers, ELTD1 identified vessel co-option and angiogenesis, and ELTD1-positive MVD at invasive margin in replacing HGP was significantly higher than those in desmoplastic and pushing HGPs. REDD1, an angiogenesis-related marker, demonstrated preferably higher MVD in the tumor center than in other areas. iCCA (sub)types and HGPs were closely related to vessel co-option and immune-related factors (lymphatic vessels, lymphocytes, and neutrophils). In conclusion, HGPs and vascular mechanisms characterize iCCA (sub)types and vessel co-option linked to the immune microenvironment.

Lenvatinib radiofrequency ablation sequential therapy offers survival benefits for patients with unresectable hepatocellular carcinoma at intermediate stage and the liver reserve of Child-Pugh A category: A multicenter study.

AIM: This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients. METHODS: One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy. RESULTS: After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin-bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186-0.782), 2.220 (95% CI, 1.410-3.493), and 0.982 (95% CI, 0.966-0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176-0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215-0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed. CONCLUSION: Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy.

Current status of the cost burden of first-line systemic treatment for patients with advanced hepatocellular carcinoma in Japan, 2021-22.

BACKGROUND: Although recent advances in systemic therapies for hepatocellular carcinoma (HCC) have led to prolonged patient survival, the high costs of the drugs place a heavy burden on both patients and society. The objectives of this study were to examine the treatment regimens used as first-line systemic treatment for patients with advanced HCC in Japan and to estimate the treatment costs per regimen. METHODS: For this study, we aggregated the data of patients who had received first-line systemic treatment for advanced HCC between July 2021 and June 2022. The treatment cost per month of each regimen was estimated based on standard usage, assuming an average weight of 60 kg for male patients. The data were categorized by the treatment regimen, and the treatments were categorized based on the cost into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month) and other (<500 000 JPY/month) treatments. RESULTS: Of the total of 552 patients from 24 institutions whose data were analyzed in this study, 439 (79.5%) received atezolizumab plus bevacizumab, 98 (17.8%) received lenvatinib and 15 (2.7%) received sorafenib as the first-line treatment. The treatment cost per month for each of the above regimens was as follows: atezolizumab plus bevacizumab, 1 176 284 JPY; lenvatinib, 362 295 JPY and sorafenib, 571 644 JPY. In total, 82.2% of patients received high-cost regimens, and the majority of these patients received a very high-cost regimen of atezolizumab plus bevacizumab. CONCLUSIONS: Advances in systemic therapies for HCC have led to prolonged patient survival. However, the treatment costs are also increasing, imposing a burden on both the patients and society.

Combined duplicate origin and early bifurcated middle cerebral artery diagnosed by magnetic resonance angiography.

PURPOSE: To describe a case of combined duplicate origin and early bifurcated middle cerebral artery (MCA) incidentally diagnosed using magnetic resonance (MR) angiography. METHODS: A 51-year-old woman with an unruptured left MCA aneurysm underwent cranial MR angiography with a 3-Tesla scanner for presurgical evaluation. MR angiography was performed using a standard 3-dimensional time-of-flight technique. RESULTS: An unruptured left MCA aneurysm at the M1-M2 junction was identified. The maximum aneurysm diameter was 9 mm. Two almost equally sized right MCAs arose from the terminal segment of the right internal carotid artery. These two channels soon anastomosed, and the temporal branch arose from the inferior channel. The aneurysm was successfully treated with coil embolization. CONCLUSION: We herein report a case of a combined duplicate origin and early bifurcated MCA. This variation can also be regarded as anastomosis between the main MCA and the duplicated MCA. This variation has been previously reported as segmental duplication of the MCA. This is the third case of this rare MCA variation reported in the relevant English-language literature. The term "segmental duplication" may be confused with duplicate origin of the MCA, in which only one artery is located distal to the fusion.

Oxidative stress in peroxisomes induced by androgen receptor inhibition through peroxisome proliferator-activated receptor promotes enzalutamide resistance in prostate cancer.

Androgen receptor (AR)-targeting therapy induces oxidative stress in prostate cancer. However, the mechanism of oxidative stress induction by AR-targeting therapy remains unclear. This study investigated the mechanism of oxidative stress induction by AR-targeting therapy, with the aim to develop novel therapeutics targeting oxidative stress induced by AR-targeting therapy. Intracellular reactive oxygen species (ROS) was examined by fluorescence microscopy and flow cytometry analysis. The effects of silencing gene expression and small molecule inhibitors on gene expression and cytotoxic effects were examined by quantitative real-time PCR and cell proliferation assay. ROS induced by androgen depletion co-localized with peroxisomes in prostate cancer cells. Among peroxisome-related genes, PPARA was commonly induced by AR inhibition and involved in ROS production via PKC signaling. Inhibition of PPARα by specific siRNA and a small molecule inhibitor suppressed cell proliferation and increased cellular sensitivity to the antiandrogen enzalutamide in prostate cancer cells. This study revealed a novel pathway by which AR inhibition induced intracellular ROS mainly in peroxisomes through PPARα activation in prostate cancer. This pathway is a promising target for the development of novel therapeutics for prostate cancer in combination with AR-targeting therapy such as antiandrogen enzalutamide.

The correlation between immune-related adverse events and efficacy of immune checkpoint inhibitors.

Immune checkpoint inhibitors have revolutionized cancer treatment by targeting the cytotoxic T lymphocyte antigen-4 and programmed death-1/ligand-1. Although immune checkpoint inhibitors show promising therapeutic efficacy, they often cause immune-related adverse events. Immune-related adverse events differ from the side effects of conventional chemotherapy and require vigilant monitoring. These events predominantly affect organs, such as the colon, liver, lungs, pituitary gland, thyroid and skin, with rare cases affecting the heart, nervous system and other tissues. As immune-related adverse events result from immune activation, indicating the reinvigoration of exhausted immune cells that attack both tumors and normal tissues, it is theoretically possible that immune-related adverse events may signal a better response to immune checkpoint inhibitor therapy. Recent retrospective studies have explored the link between immune-related adverse event development and clinical efficacy; however, the predictive value of immune-related adverse events in the immune checkpoint inhibitor response remains unclear. Additionally, studies have focused on immune-related adverse events, timing of onset and immunosuppressive treatments. This review focuses on pivotal studies of the association between immune-related adverse events and outcomes in patients treated with immune checkpoint inhibitors.

Phase II trial of niraparib for BRCA-mutated biliary tract, pancreatic and other gastrointestinal cancers: NIR-B.

Due to the widespread use of cancer genetic testing in gastrointestinal cancer, the BRCA1/2 genetic mutation has been identified in biliary tract cancer as well as pancreatic cancer. Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor, and PARP inhibitors exert their cytotoxicity against cancer cells in the context of homologous recombination deficiency, such as BRCA mutations, via the mechanism of synthetic lethality. The aim of this phase II NIR-B trial is to evaluate the efficacy and safety of niraparib for patients with unresectable advanced or recurrent biliary tract cancer, pancreatic cancer or other gastrointestinal cancers with germline or somatic BRCA1/2 mutations revealed by genetic testing. The primary end point is an investigator-assessed objective response rate in each cohort.Clinical Trial Registration: jRCT2011200023 (ClinicalTrials.gov).

A clinical study to confirm the efficacy and safety of niraparib for people with advanced biliary tract, pancreatic and other abdominal cancers with the BRCA genetic mutation: the NIR-B trial.BRCA gene is involved in repairing DNA injury and plays an important role in cancer growth. Cells with a mutation in the BRCA gene cannot repair DNA using a method called homologous recombination repair. Niraparib is part of a class of drugs called 'PARP inhibitors' that inhibit enzymes called 'PARP' involved in repairing DNA injury, and has shown efficacy against cancers with BRCA gene mutations. BRCA gene mutations are infrequent but have been found in a variety of cancers. The NIR-B trial is a clinical trial to evaluate the efficacy and safety of niraparib for people with advanced biliary tract, pancreatic and other abdominal cancers with BRCA gene mutations.

Importance of 3ß-hydroxysteroid dehydrogenases and their clinical use in prostate cancer.

Androgen receptor signaling is crucial for the development of treatment resistance in prostate cancer. Among steroidogenic enzymes, 3ß-hydroxysteroid dehydrogenases (3ßHSDs) play critical roles in extragonadal androgen synthesis, especially 3ßHSD1. Increased expression of 3ßHSDs is observed in castration-resistant prostate cancer tumors compared with primary prostate tumors, indicating their involvement in castration resistance. Recent studies link 3ßHSD1 to resistance to androgen receptor signaling inhibitors. The regulation of 3ßHSD1 expression involves various factors, including transcription factors, microenvironmental influences, and posttranscriptional modifications. Additionally, the clinical significance of HSD3B1 genotypes, particularly the rs1047303 variant, has been extensively studied. The impact of HSD3B1 genotypes on treatment outcomes varies according to the therapy administered, suggesting the potential of HSD3B1 genotyping for personalized medicine. Targeting 3ßHSDs may be a promising strategy for prostate cancer management. Overall, understanding the roles of 3ßHSDs and their genetic variations may enable the development and optimization of novel treatments for prostate cancer.

Immediate effect of upright position on lumbar disc using multiposture MRI: Preliminary results.

Objectives: Gravity loading on lumbar intervertebral discs (IVDs) is affected by body position. Although the long-term effects of gravity on IVDs have been reported, the immediate effects of gravity on IVDs remain unclear. We considered that changes in IVD structure in the upright and supine positions provided new diagnostic information. Therefore, we compared the apparent diffusion coefficient (ADC), transverse relaxation time (T2), and morphology of the lumbar spine between the quickly changing upright and supine positions using an original magnetic resonance imaging (MRI) system that can obtain images in any position (multiposture MRI). Material and Methods: On a 0.4-T multiposture MRI, diffusion-weighted images of the lumbar spine in seven healthy volunteers were obtained using single-shot diffusion echo-planar imaging (b = 0 and 600 s/mm2) in quickly changing upright and supine positions. Moreover, spin-echo images with multiple echo times (echo time = 30, 60, 90, and 120 ms) were obtained in each position. We calculated the ADC and T2 of each IVD (L1 and S1) without any disc degeneration. In addition, the lumbar lordosis angle and length of the lumbar spine were measured to evaluate the morphology of the lumbar spine. Results: The T2 of the IVD between L4 and L5 in the upright position was significantly lower than that in the supine position (P < 0.05). No significant differences were observed in the ADC. The morphology of the lumbar spine did not differ significantly between the two positions. Conclusion: The T2 of the IVD between L4 and L5 was likely decreased by the effect of gravity due to the postural change from supine to upright.

Urinary tract symptoms that should be improved to enhance post-operative urinary quality of life in patients treated with low-dose-rate brachytherapy for prostate cancer: An importance-performance analysis.

Purpose: To evaluate international prostate symptom score and urinary quality of life in patients with prostate cancer who underwent low-dose-rate brachytherapy, and to identify lower urinary tract symptoms that must be improved to enhance post-operative urinary quality of life and factors associated with lower urinary tract symptoms. Material and methods: This study included 193 patients who underwent low-dose-rate brachytherapy alone (145 Gy). Importance-performance analysis was conducted to identify lower urinary tract symptoms that should be prioritized to improve urinary quality of life. Association between lower urinary tract symptom scores and each factor was investigated. Receiver operating characteristic curve analysis was used to evaluate dosimetric parameters related to lower urinary tract symptom score to predict an average score of ≥ 3. Cut-off values were determined. Results: One to nine months post-implantation was a period of significantly increased urinary quality of life scores compared with baseline (p < 0.05 each). The importance-performance analysis conducted for 1-9 months revealed that frequency, nocturia, and weak stream required improvement. Multivariate analysis showed that each lower urinary tract symptom score presented a significant association with its baseline value (p < 0.001 each, positive correlation). Frequency, incomplete emptying, urgency, and straining scores were significantly associated with prostate volume, whereas weak stream and intermittency scores were associated with dose covering 90% of the prostate and dose covering 90% of the urethra, respectively (p < 0.05 each, positive correlations). Cut-off values for these doses were 167.01 Gy and 136.84 Gy, respectively. Conclusions: This study highlights the importance of prioritizing specific lower urinary tract symptoms for improvement in post-operative urinary quality of life, and identifies the associated factors that can help in personalized treatment planning and goal-setting for better patient satisfaction.

Reactive lymphoid hyperplasia of the liver: A case report featuring characteristic nodular and perinodular enhancement.

A 53-year-old female with primary biliary cholangitis was referred for the evaluation of a hepatic nodule identified during routine imaging. Ultrasonography revealed a homogeneous, hypoechoic, 18 mm nodule in segment 3 of the liver. On dynamic CT and MRI, the nodule showed mild enhancement at the hepatic artery-dominant phase. On diffusion-weighted images, the nodule exhibited pronounced hyperintensity with accompanying wedge-shaped perinodular hyperintensity (comet and comet-tail appearance). The nodule showed a portal perfusion defect on CT during arterial portography, and mild enhancement on CT during hepatic arteriography (CTHA). A nodular and wedge-shaped perinodular enhancement (comet and comet-tail appearance) in the CTHA was also clearly observed. The nodule demonstrated abnormal FDG uptake on 18F-FDG-PET/CT. An excisional biopsy was performed for histopathological diagnosis, and the nodule was diagnosed as reactive lymphoid hyperplasia (RLH). Diagnosing hepatic RLH by imaging is challenging due to its imaging findings overlapping with those of various malignant tumors, especially the nodular type of lymphomas, making differentiation particularly difficult. However, radiologists should note the perinodular early enhancement and the perinodular hyperintensity on diffusion weighted images, which are thought to be key imaging findings of RLH, along with other characteristics such as a single, small, homogeneous nodule with mild early enhancement and marked restricted diffusion. We propose to name the nodular lesion with perinodular early enhancement/hyperintensity on diffusion weighted images as 'comet and comet-tail appearances'.

Progression pattern and post-progression survival following atezolizumab and bevacizumab treatment in advanced hepatocellular carcinoma.

BACKGROUND: Although the combination of atezolizumab and bevacizumab (ATZ + BEV) is a standard treatment for advanced hepatocellular carcinoma (HCC), strategies for addressing treatment failure and prognostic factors of post-progression survival (PPS) remain unestablished. METHODS: We conducted a multicentre retrospective study to evaluate PPS following ATZ + BEV treatment in patients with advanced HCC. We classified the patients into three groups: BCLC stage B and BCLC stage C without or with new extrahepatic lesions (BCLCp-C1 and BCLCp-C2, respectively) at the time of progression. RESULTS: Of the 204 patients who started ATZ + BEV treatment between October 2020 and September 2022, 110 showed disease progression, with 33, 55 and 22 showing the BCLCp-B, BCLCp-C1 and BCLCp-C2 stages of the disease, respectively. Specifically, patients with the BCLCp-B stage of the disease showed better overall survival than those with the BCLCp-C1 and BCLCp-C2 stages (hazard ratios: 1.93 [95% confidence interval, CI, 1.06-3.51] and 2.64 [95% CI, 1.32-5.30] for HCC stages BCLCp-C1 and BCLCp-C2, respectively). Via multivariable analysis, we identified the BCLCp-C1 and BCLCp-C2 stages, as well as performance status, Child-Pugh class and alpha-fetoprotein as poor prognostic factors for PPS. CONCLUSIONS: BCLCp-B1 stage was identified as a better prognostic factor for PPS following ATZ + BEV treatment compared with BCLCp-C1 and BCLCp-C2 stages. This may help in making decisions regarding subsequent treatment after ATZ + BEV.

Evaluation of pancreatic cancer specimens for comprehensive genomic profiling.

Inadequate specimen quality or quantity hinders comprehensive genomic profiling in identifying actionable mutations and guiding treatment strategies. We investigated the optimal conditions for pancreatic cancer specimen selection for comprehensive genomic profiling. We retrospectively analyzed 213 pancreatic cancer cases ordered for comprehensive genomic profiling and compared results from pancreatic biopsy, liver biopsy of pancreatic cancer metastases, pancreatectomy, liquid, and nonliver metastatic organ specimens. We examined preanalytical conditions, including cellularity (tumor cell count/size). The successfully tested cases were those that underwent comprehensive genomic profiling tests without any issues. The successfully tested case ratio was 72.8%. Pancreatic biopsy had the highest successfully tested case ratio (87%), with a high tumor cell percentage, despite the small number of cells (median, 3425). Pancreatic biopsy, liver biopsy of pancreatic cancer metastases, and non-liver metastatic organ had higher successfully tested case ratios than that for pancreatectomy. Liver biopsy of pancreatic cancer metastases and pancreatectomy cases with tumor size (mm2) × tumor ratio (%) > 150 and >3000, respectively, had high successfully tested case ratios. The success of comprehensive genomic profiling is significantly influenced by the tumor cell ratio, and pancreatic biopsy is a potentially suitable specimen for comprehensive genomic profiling.

Notch appearance as a novel radiological predictor of transient expansion and good outcome of expanding schwannoma after radiotherapy.

OBJECTIVES: Schwannoma expansion after radiotherapy has not been well-studied despite the clinical importance of distinguishing transient increase from permanent expansion. Thus, this study aimed to identify the underlying mechanism and novel radiological predictors of schwannoma expansion after radiotherapy. MATERIALS & METHODS: We retrospectively examined the therapeutic effects of radiotherapy on schwannomas and magnetic resonance images of 43 patients with vestibular schwannomas who underwent stereotactic radiotherapy or radiosurgery at our facility between June 1, 2012 and September 1, 2018. Based on the size change pattern, the treated tumors were classified into six groups, including transient-expansion and consistent-increase groups. The apparent diffusion coefficient (ADC) ratio and appearance of any notch were included as evaluation items based on our hypothesis that transient expansion is due to edema with increased extracellular free water. A log-rank test was performed to evaluate the relationship between the local control rate and radiological signs. RESULTS: The mean overall 5-year local control rate was 90%, and the median follow-up period was 62 (24-87) months. Approximately 28% of the tumors showed transient expansion; all ADC ratios synchronized with size change, and 75% showed a new notch appearance. Approximately 9% of tumors showed consistent increase, with no notch on the outline. The log-rank test revealed a difference in the local control rate with or without notch appearance in expanding irradiated schwannomas. All tumors with notch appearance showed a significant regression 5 years after radiation. CONCLUSIONS: New notch appearance on the outline could indicate favorable long-term outcomes of expanding schwannomas post-treatment. CLINICAL RELEVANCE STATEMENT: Notch appearance can help differentiate a transient schwannoma from a real tumor expansion, and it is a novel predictor of better outcomes of expanding schwannomas after radiotherapy.

Clinical Impact of Preoperative Prognostic Nutritional Index in Surgical Patients With Pancreatic Cancer Treated With Perioperative Adjuvant Chemotherapy.

BACKGROUND/AIM: The prognostic nutritional index (PNI) is used as a marker to evaluate the nutritional and immunological status of patients with various cancers. This study aimed to investigate whether preoperative PNI is a prognostic factor in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. PATIENTS AND METHODS: We retrospectively enrolled 232 pancreatic cancer patients who underwent surgical resection with perioperative adjuvant chemotherapy between January 2013 and December 2022. Overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards regression models. RESULTS: The optimal cutoff value for the preoperative PNI was 44.3 in the present study. PNI <44.3 was associated with older age (p<0.001) and affected the clinical course of postoperative adjuvant chemotherapy. The PNI <44.3 had an important influence on the decreased OS (25.1 vs. 39.0 months) and RFS (13.1 vs. 22.8 months). In univariate and multivariate analyses, the preoperative PNI was an independent prognostic factor for OS [hazard ratio (HR)=1.682, 95% confidence interval (CI)=1.059-2.673, p=0.028] and RFS (HR=1.559, 95% CI=1.037-2.344, p=0.033). CONCLUSION: Preoperative PNI is a prognostic factor for both OS and RFS in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. This study suggests that a low PNI may cause a lack of full-dose adjuvant chemotherapy, leading to recurrence and resulting in a poor prognosis for surgical pancreatic cancer patients treated with perioperative adjuvant chemotherapy.

Imaged periductal infiltration: Diagnostic and prognostic role in intrahepatic mass-forming cholangiocarcinoma.

Purpose: This study examines periductal infiltration in intrahepatic mass-forming cholangiocarcinoma (IMCC), focusing on its importance for differentiating hepatic tumors and its influence on post-surgical survival in IMCC patients. Methods: Eighty-three consecutive patients with IMCC (n = 43) and liver cancer whose preoperative images showed intrahepatic bile duct dilatation adjacent to the tumor for differential diagnosis from hepatocellular carcinoma (HCC) [n = 21], metastatic liver cancer (MLC) [n = 16] and combined hepatocellular-cholangiocarcinoma (cHCC-CC) [n = 3] were enrolled. CT and MRI findings of simple bile duct compression, imaged periductal infiltration, and imaged intrabiliary growth adjacent to the main tumor were reviewed. Clinicopathological and imaging features were compared in each group. The sensitivity, specificity, and odds ratio were calculated for each imaging finding of IMCC versus the other tumor groups. Overall survival was compared between cases of IMCC with and without imaged periductal infiltration. Results: Simple bile duct compression and imaged intrabiliary growth were more frequently observed in HCC than in the others (p < 0.0001 and 0.040, respectively). Imaged periductal infiltration was observed more often in histopathologically confirmed large-duct type IMCC than in the small-duct type IMCC (p = 0.034). Multivariable analysis demonstrated that only imaged periductal infiltration (odds ratio, 50.67) was independently correlated with IMCC. Patients with IMCC who had imaged periductal infiltration experienced a poorer prognosis than those without imaged periductal infiltration (p = 0.0034). Conclusion: Imaged periductal infiltration may serve as a significant marker for differentiating IMCC from other liver cancers. It may also have the potential to predict post-surgical outcomes in patients with IMCC.

Salvage robot-assisted radical prostatectomy after carbon ion radiotherapy to the prostate.

PURPOSE: This study presents the surgical and oncological outcomes of salvage robot-assisted radical prostatectomy (RARP) after carbon ion radiotherapy at a single institution. METHODS: Patients who underwent salvage RARP for local recurrence after carbon ion radiotherapy at Kyushu University Hospital between 2020 and 2023 were included. A single surgeon performed salvage RARP with extended pelvic lymph node dissection. Clinicopathological characteristics and perioperative and postoperative outcomes were prospectively collected and electronically recorded. RESULTS: Ten cases were included. The preoperative clinical T-stage was T2, except for one case with T3a. The median console time was 171 min (range, 135-226 min). No severe perioperative or postoperative complications were noted. The pathological T-stage was T2, T3a, and T3b in four, four, and two cases, respectively. Biochemical recurrence was observed in one patient at 31.2 months after surgery. For patients with more than 1 year of follow-up, urinary continence recovery with ≤1 pad was achieved in two cases within 1 year, whereas four cases did not recover urinary continence within 1 year. CONCLUSIONS: This case series demonstrated the feasibility of salvage RARP after carbon ion radiotherapy. Although the urinary continence recovery was modest, short-term disease control was favorable.

Liposomal irinotecan plus fluorouracil/leucovorin in older patients with advanced pancreatic cancer: a single-center retrospective study.

BACKGROUND: The global phase 3 NAPOLI -1 trial of patients with pancreatic ductal adenocarcinoma (PDAC) demonstrated an overall survival (OS) benefit from using liposomal irinotecan and 5-fluorouracil/leucovorin (nal-IRI + 5-FU/LV) after treatment with gemcitabine (GEM) compared to 5-FU/LV alone. However, the efficacy and safety of this regimen in older patients are not well studied. METHODS: We conducted a single-center retrospective study to compare the therapeutic efficacy of nal-IRI + 5-FU/LV between older and younger patients with cutoff ages of 70 and 75 years, respectively. We included patients with a prior history of one or more GEM-based regimens for locally advanced or metastatic PDAC and were treated with nal-IRI + 5-FU/LV. RESULTS: Of the 115 patients, 54 (47.0%) and 24 (20.9%) were aged ≥ 70 and ≥ 75 years, respectively. The median OS and progression-free survival (PFS) of the entire cohort were 8.5 and 3.6 months, respectively. No significant differences were observed in OS and PFS hazard ratios using age cutoffs of 70 (P = 0.90 and 0.99, respectively) and 75 (P = 0.90 and 0.76, respectively) years. Additionally, no significant differences were found in the incidence of treatment-related adverse events (trAEs) between patients aged ≥ 70 and < 70 years or those aged ≥ 75 and < 75 years. Other than hematological toxicity, no trAEs higher than Grade 4 were observed in either age group. CONCLUSION: The efficacy and safety of nal-IRI + 5-FU/LV for patients with PDAC are not significantly different for those aged ≥ 70 years compared to younger patients.