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.

The relationship between observation interval and prognosis in pancreatic cancer concomitant with intraductal papillary mucinous neoplasia.

BACKGROUND: Intraductal papillary mucinous neoplasia (IPMN) is a risk factor for pancreatic cancer (PC). PC concomitant with IPMN shows rapid progression similar to de novo PC, therefore, the appropriate observation interval (OI) is not yet clear. PATIENTS AND METHOD: This was a multicenter retrospective observational study, and patients with PC concomitant with IPMN were analyzed. OI was defined as the interval between the date of imaging at PC diagnosis and just before the diagnosis. Clinical factors of PC and prognosis were assessed according to OI. RESULTS: From January 2010 to December 2018, 73 patients from 11 institutions were enrolled. The images performed just before PC diagnosis were contrast-enhanced CT/magnetic resonance imaging/endoscopic ultrasonography in 44/27/2 patients, respectively. The median cyst size was 14.0 mm, and the median main pancreatic duct diameter was 3.0 mm. The median OI was 6.8 months. In OI 6 months or less (OI ≤ 6 M)/OI more than 6 months (OI > 6 M), the mean tumor size, the frequencies of metastatic PC, resectable PC and early-stage PC were 20.1/21.5 mm (P = 0.91), 12.1 %/32.5 % (P = 0.05), 72.7 %/52.5 % (P = 0.09) and 27.3 %/25.0 % (P = 1.00), respectively. The median overall survival was 35.5 months in OI ≤ 6 M and 16.2 months in OI > 6 M (P = 0.05). CONCLUSION: In OI 6 months or less, the rate of resectable PC was high, however, the rate of early PC was almost the same as that of OI more than 6 months. Approximately 10 % of cases found in the advanced stage with metastasis even if OI 6 months or less.

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.

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.

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.

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.

Comprehensive review of undifferentiated carcinoma of the pancreas: from epidemiology to treatment.

Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer displaying no definitive direction of differentiation. UC has been reported as a highly aggressive malignant neoplasm, with a median overall survival of <1 year, except for several surgical series. On the other hand, UC tissue sometimes contains non-neoplastic osteoclast-like giant cells (OGCs), and such cases have been reported to have relatively longer survival. Thus, the World Health Organization (WHO) classification histologically distinguishes UC with OGCs (UCOGCs) from UC, and UCs were subclassified into three subtypes: anaplastic UC, sarcomatoid UC and carcinosarcoma. However, still less is known about UC due to its rarity, and such situations lead to further difficulties in treatment for UC. To date, only surgical resection can offer curative treatment for patients with UC, and no clear evidence for chemotherapy exists for them. However, a retrospective cohort study and case reports showed that relatively promising results paclitaxel-containing regimens for treatment of patients with unresectable UC. Furthermore, high programmed cell death protein 1 expression has been reported in sarcomatoid UCs and UCOGCs, and promising responses to anti-programmed death-ligand 1 therapy have been described in case reports of UCOGCs. Recent advances in chemotherapeutic agents and molecular technologies are opening up the possibilities for expanded treatments.

Predictors of malignancy in main duct intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND AND AIMS: The International Consensus Guidelines updated in 2017 recommended surgery to all main duct intraductal papillary mucinous neoplasms (MD-IPMNs) with the main pancreatic duct (MPD) of 10 mm or more and those with mural nodules regardless of size. The aim of the present study was to identify predictors of malignancy in MD-IPMN among preoperative factors including MPD and mural nodule size. METHODS: Twenty-six benign MD-IPMNs (7 resected and 19 nonresected) and 32 malignant MD-IPMNs (31 resected and 1 nonresected) were included in the study. MRCP, CT, EUS, and cytology were performed using pancreatic juice collected by endoscopic retrograde pancrestography (ERP). Resected IPMNs were classified as benign or malignant by histologic examination and nonresected MD-IPMNs by imaging, cytology, and observation. Cutoff values of candidate parameters were determined by receiver operating characteristic curves. Univariate and multivariate analyses by regression model were performed. RESULTS: MPD and mural nodule size and cytology results differed significantly between benign and malignant groups. Cutoff values of MPD and mural nodule sizes were 15 mm and 10 mm with areas under the curve of .66 and .86, respectively. Mural nodules of 10 mm or more (odds ratio, 8.32; 95% confidence interval, 1.13-61.2; P = .038) and positive cytology (odds ratio, 42.5; 95% confidence interval, 4.10-439; P = .002) were shown to be independent predictors of malignancy by multivariate analysis. When MD-IPMNs with either predictor were diagnosed to be malignant, sensitivities, specificities, and overall accuracy for malignancy were 94%, 85%, and 90%, respectively. CONCLUSIONS: Mural nodules of 10 mm or more and positive cytology were independent predictors of malignancy in MD-IPMN.

Investigation of acidic free-glycans in urine and their alteration in cancer.

Alterations to glycans in cancer patients have been used to identify novel tumor biomarkers. Most of these studies have focused on protein glycosylation but less attention has been paid to free-glycans. Here, we analyzed acidic free-glycans in the urine of cancer patients to identify novel tumor marker candidates. Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls. The free-glycans were extracted from creatinine-adjusted urine and fluorescently labeled with 2-aminopyridine. Initially, we performed profiling of urinary free-glycans by high-performance liquid chromatography and mass spectrometry with enzymatic and chemical degradation. More than 100 glycans, including novel structures, were identified. The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients. To verify cancer-associated alterations, we compared the glycan levels between cancer patients and normal controls by selected reaction monitoring. Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or ß1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galß1-4(+/-Fucα1-3) Xylα1-3Glc glycans. Our results provide further insight into urinary free-glycans and suggest the potential utility of these compounds as tumor markers.

Endoscopic biliary stenting as the risk factor for cholangitis after endoscopic ultrasound in patients with biliary strictures.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS) and EUS-guided fine needle aspiration (FNA) are established as efficient and safe diagnostic modalities. However, the risk of cholangitis after EUS/EUS-FNA (post-EUS cholangitis) in patients who have biliary strictures has not been fully examined. METHODS: We retrospectively reviewed 136 consecutive inpatients with biliary strictures who received EUS/EUS-FNA at our hospital from April 2012 to September 2017 and evaluated complications that occurred by the next day after EUS/EUS-FNA. Patients with percutaneous biliary drainage, those in whom it was difficult to reach the duodenum, and those receiving concurrent endoscopic retrograde cholangiopancreatography were excluded. RESULTS: We included 121 patients (147 cases); 90 patients were malignant. Endoscopic biliary stenting (EBS) with plastic stents had already been performed in 86 cases. Post-EUS cholangitis was observed in 4.1% (6/147). No other EUS-related complications were observed. The incidence of cholangitis with EBS was significantly higher than that in the cases without EBS (7.0% [6/86] vs 0% [0/61], P = 0.042). Biliary enzyme elevation was also identified as a risk factor of cholangitis. CONCLUSION: Endoscopic biliary stenting was identified as a risk factor associated with post-EUS cholangitis in patients with biliary strictures. Endoscopists should pay attention to post-EUS cholangitis, especially in cases with EBS and biliary enzyme elevation.

Decreased CT-number in the pancreatic parenchyma is a reliable imaging biomarker of the presence of malignancies in patients with high-risk intraductal papillary mucinous neoplasm.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a premalignant cystic neoplasm of the pancreas and is frequently detected in imaging investigations. A proportion of the patients with IPMN develop malignancies including high-grade dysplasia and invasive carcinoma. To predict the presence of malignancies in IPMN, constant imaging follow-up is usually required. Pancreatic steatosis (PS) has been recently identified as a facilitating factor for pancreatic cancer, and can be predicted through computed tomography (CT). We hypothesized that the CT-number of the pancreatic parenchyma could be a new reliable imaging biomarker for IPMN patients. METHODS: Eighty-six patients undergoing pancreatectomy for IPMN were investigated. Using preoperative CT, the pancreatic index (PI) was calculated by dividing the CT-number of the pancreas by that of the spleen. RESULTS: Malignancies were pathologically detected in 63 cases (73.3%). Patients were divided into two cohorts according to the presence of malignancies and were compared for various factors including the PI scores. The comparison of the two cohorts detected significant differences in two parameters (CA19-9 and PI score), and the PI score was the most sensitive biomarker to predict the presence of malignancies in patients showing high-risk stigmata of IPMN. CONCLUSIONS: Pancreatic CT-number is an additional reliable imaging biomarker in distinguishing patients with IPMN having malignancies when investigating the patients showing high-risk stigmata.

Soluble UL16-binding protein 2 is associated with a poor prognosis in pancreatic cancer patients.

The immune system plays important roles in pancreatic cancer. MHC class I-chain-related proteins A and B (MICA/B) and UL16-binding proteins (ULBPs) are known natural killer group 2D (NKG2D) ligands. Soluble NKG2D ligands can inhibit the activation of Natural killer (NK) cells. In pancreatic cancer, soluble ULBPs are relatively unstudied in contrast to soluble MICA/B. We examined the significance of soluble ULBPs, especially ULBP2, in pancreatic cancer. Soluble ULBP2 but neither soluble ULBP1 nor soluble ULBP3, was etected in the supernatants of pancreatic cancer cells. Soluble ULBP2 derived from pancreatic cancer cells could reduce the cytotoxicity of NK cells. Multivariate analysis demonstrated that serum soluble ULBP2 was a significant independent factor associated with poor overall survival (OS) in all pancreatic cancer patients, specifically in stage IV patients. In conclusion, pancreatic cancer-derived soluble ULBP2 might affect the prognosis in pancreatic cancer.

Autophagy impairment in pancreatic acinar cells causes zymogen granule accumulation and pancreatitis.

Basal autophagy degrades many kinds of proteins and organelles to maintain quality and plays important roles in cellular homeostasis. However, the impact of basal autophagy on zymogen granules in pancreatic acinar cells is unknown. In the present study, we examined the influence of autophagy impairment in acinar cells on zymogen granules and homeostasis of the pancreas, using mice with pancreas-specific autophagy impairment (Pdx1-Cre+/-Atg7fl/fl mice). The number of zymogen granules in acinar cells from these mice did not differ from that in acinar cells from their wild-type littermates at 3 weeks of age. However, the number of zymogen granules in acinar cells drastically increased at 4 weeks of age in mice with pancreas-specific autophagy impairment. In addition to the increased number of zymogen granules, serum lipase was elevated, and the pancreas became oedematous at 4 weeks of age, suggesting pancreatitis. After 5 weeks of age, acinar cell death was accelerated, and several histological features of chronic pancreatitis were observed, including glandular atrophy and pseudotubular complexes with fibrotic changes. In conclusion, the impairment of pancreas-specific basal autophagy caused spontaneous zymogen granule accumulation in acinar cells and pancreatitis, which eventually led to chronic pancreatitis.

The safety and benefit of pancreatic juice cytology under ERCP in IPMN patients.

BACKGROUND: International consensus guidelines 2012 for intraductal papillary mucinous neoplasia (IPMN), defined two characteristics: high-risk stigmata (HRS) and worrisome features (WF). Patients with WF require detailed examination including cytology. However, routine endoscopic retrograde cholangiopancreatography (ERCP) for cytology is not recommended in the guidelines due to risk of post-ERCP pancreatitis (PEP). Our aim was to clarify what types of IPMN were susceptible for PEP and gain benefit of ERCP. PATIENTS/METHODS: We examined 138 consecutive IPMN patients who underwent ERCP in our hospital, retrospectively. Patients were classified into HRS, WF and the others (N) based on imaging findings before ERCP. We assessed pancreatic juice cytology, PEP frequency and rate of malignant IPMN at 12 months after ERCP. RESULTS: The rates of cytological malignancy were 0% (N), 4.8% (WF) and 19.5% (HRS). The PEP frequency was 14.5%, and these risk factors were branch duct (BD)-IPMN, body/tail cysts and brush cytology by multivariate logistic analysis. The rates of malignant IPMN were 0% (N), 16.4% (WF) and 48.8% (HRS). Furthermore, we examined patients with WF in detail. The PEP frequency/rate of malignancy were 3.6%/23.1% in patients with main pancreatic duct (MPD) dilatation (5-9 mm), and the sensitivity of cytology was 33.3%. On the other hand, the PEP frequency/rate of malignancy were 17.2%/0% in patients with BD-IPMN fulfilling only cyst size over 30 mm. CONCLUSIONS: Routine ERCP for IPMN, especially for BD-IPMN, is not recommended. ERCP may be beneficial for WF patients with MPD dilatation based on a balance between PEP risk and presence of malignancy.

Comparative outcomes of elderly and non-elderly patients receiving first-line palliative chemotherapy for advanced biliary tract cancer.

BACKGROUND AND AIM: Few studies have reported the efficacy and safety of palliative chemotherapy in elderly patients with advanced biliary tract cancer. We aimed to investigate the clinical outcomes of palliative chemotherapy for advanced biliary tract cancer in elderly patients. METHODS: We retrospectively evaluated 403 consecutive patients who received palliative chemotherapy between April 2006 and March 2009 for pathologically confirmed unresectable or recurrent biliary tract cancer. Clinical outcomes of the elderly group (≥ 75 years old; n = 94) were compared with those of the non-elderly group (< 75 years old; n = 309). RESULTS: Except for the extent of disease, patient baseline characteristics were well balanced between both groups. The median overall survival was 10.4 months in the elderly group and 11.5 months in the non-elderly group (hazard ratio, 1.14; 95% confidence interval, 0.89-1.45; P = 0.31). Although the frequency of adverse events between both groups was similar, interstitial pneumonitis was significantly more frequent in the elderly group than in the non-elderly group (4.3% vs 0%, P < 0.01). CONCLUSIONS: In advanced biliary tract cancer, overall survival of elderly patients receiving palliative chemotherapy is comparable with that of non-elderly patients. To our knowledge, this is one of the largest studies that have reported the clinical outcomes of elderly patients following palliative chemotherapy.

Correlation between main pancreatic duct diameter measurements: Special pancreatic ultrasonography versus magnetic resonance cholangiopancreatography.

Main pancreatic duct (MPD) dilatation is reported to be a risk factor for pancreatic cancer (PC). Although magnetic resonance cholangiopancreatography (MRCP) and ultrasonographic modalities are valuable for monitoring the pancreas, there is limited information on the efficacy of different imaging modalities in measuring MPD diameter. To improve pancreatic imaging, we developed a specialized ultrasound approach focusing on the pancreas (special pancreatic US). We aimed to examine the correlation between MPD diameter measurements using special pancreatic US versus MRCP. We retrospectively reviewed the clinical data of patients with MPD dilation (≥2.5 mm) via special pancreatic US used for screening at our institution between January 2020 and October 2022 and included patients who underwent magnetic resonance imaging 2 months before and after pancreatic US. The MPD diameter on MRCP was measured at the pancreatic locus, where the maximum MPD diameter was obtained on special pancreatic US. This study included 96 patients, with a median interval of 8.5 days between the date of special pancreatic US and the date of undergoing MRCP. MPD dilatation and/or pancreatic cysts were diagnosed in 86 patients, PC in 5 patients, and other diseases in 5 patients. The median MPD diameter, measured using special pancreatic US, was 3.4 mm (interquartile range: 2.9-4.9 mm), whereas it was 3.5 mm using MRCP (interquartile range: 2.8-4.5 mm). There were strong positive correlations between MPD diameter measured on special pancreatic US and that measured on MRCP (R = 0.925, P < .001). This study revealed strong positive correlations between the MPD diameter measurements using special pancreatic US and MRCP. MPD diameter measurements from each imaging method can be helpful during follow-up in individuals at a high risk of PC.

Dosimetric characteristics of self-expandable metallic and plastic stents for transpapillary biliary decompression in external beam radiotherapy.

There is little evidence regarding radiation dose perturbation caused by the self-expandable metallic stents (SEMSs) used for transpapillary biliary decompression. We aimed to compare SEMSs with plastic stents (PSs) and clarify their dosimetric characteristics. Fifteen SEMSs (10 braided and 5 lasercut type) and six PSs (diameter: 2.3-3.3 mm) were inserted into a water-equivalent solid phantom. In total, 13 SEMSs had radiopaque markers, whereas the other two did not. Using radiochromic films, the dose difference adjacent to the stents at locations proximal, distal, and arc delivery to the radiation source was evaluated based on comparison to measurement of the dose delivery in phantom without any stent in place. The median values of the dose difference for each stent were used to compare the SEMS and PS groups.Results: The dose difference (median (minimum/maximum)) was as follows: proximal, SEMSs + 2.1% (1.8 / 4.7) / PSs + 5.4% (4.1 / 6.3) (p < 0.001); distal, SEMSs -1.0% (-1.6 /-0.4) / PSs -8.9% (-11.7 / -7.4) (p < 0.001); arc delivery, SEMSs 1.2% (0.9 / 2.3) / PSs 2.2% (1.6 / 3.6) (p = 0.005). These results demonstrated that the dose differences of SEMSs were significantly smaller than those of PSs. On the other hand, the dose difference was large at surface of the radiopaque markers for SEMSs: proximal, 10.3% (7.2 / 20.9); distal, -8.4% (-16.3 / -4.2); arc delivery, 5.5% (4.2 / 9.2). SEMSs for biliary decompression can be safely used in patients undergoing radiotherapy, by focusing on the dose distribution around the stents and by paying attention to local changes in the dose distribution of radiopaque markers.

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.

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.