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

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

Endoscopic papillectomy could be rewarding to patients with early stage duodenal ampullary carcinoma?

BACKGROUND/PURPOSE: There is currently no consensus on the use of endoscopic papillectomy (EP) for early stage duodenal ampullary adenocarcinoma. This study aimed to evaluate the feasibility of EP for patients with early stage duodenal ampullary adenocarcinoma. METHODS: Patients who underwent EP for ampullary adenocarcinomas were investigated. Complete and clinical complete resection rates were evaluated. Clinical complete resection was defined as either complete resection or resection with positive or unknown margins but no cancer in the surgically resected specimen, or no recurrence on endoscopy after at least a 1-year follow-up. RESULTS: Adenocarcinoma developed in 30 patients (carcinoma in situ [Tis]: 21, mucosal tumors [T1a(M)]: 4, tumors in the sphincter of Oddi [T1a(OD)]: 5). The complete resection rate was 60.0% (18/30) (Tis: 66.7% [14/21], T1a[M]: 50.0% [2/4], and T1a[OD]: 40.0% [2/5]). The mean follow-up period was 46.8 months. The recurrence rate for all patients was 6.7% (2/30). The clinical complete resection rates of adenocarcinoma were 89.2% (25/28); rates for Tis, T1a(M), and T1a(OD) were 89.4% (17/19), 100% (4/4), and 80% (4/5), respectively. CONCLUSIONS: EP may potentially achieve clinical complete resection of early stage (Tis and T1a) duodenal ampullary adenocarcinomas.

IgG4-related pancreatobiliary diseases could be associated with onset of pancreatobiliary cancer: A multicenter cohort study.

BACKGROUND: The risk and prognosis of pancreatobiliary cancer and in patients with autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) remain unclear. Therefore, we retrospectively investigated the risk of pancreatobiliary cancer and prognosis in patients with AIP and IgG4-SC. METHODS: Patients with AIP and IgG4-SC at seven centers between 1998 and 2022 were investigated. The following data were evaluated: (1) the number of cancers diagnosed and standardized incidence ratio (SIR) for pancreatobiliary and other cancers during the observational period and (2) prognosis after diagnosis of AIP and IgG4-SC using standardized mortality ratio (SMR). RESULTS: This study included 201 patients with AIP and IgG4-SC. The mean follow-up period was 5.7 years. Seven cases of pancreatic cancer were diagnosed, and the SIR was 8.11 (95% confidence interval [CI]: 7.29-9.13). Three cases of bile duct cancer were diagnosed, and the SIR was 6.89 (95% CI: 6.20-7.75). The SMR after the diagnosis of AIP and IgG4-SC in cases that developed pancreatobiliary cancer were 4.03 (95% CI: 2.83-6.99). CONCLUSIONS: Patients with autoimmune pancreatitis and IgG4-SC were associated with a high risk of pancreatic and bile duct cancer. Patients with AIP and IgG4-SC have a worse prognosis when they develop pancreatobiliary cancer.

Braided-type stent versus laser-cut-type stent for patients with unresectable distal malignant biliary obstruction: a randomized controlled trial.

BACKGROUND AND AIMS: Fully covered self-expandable metallic stents (SEMSs) are laser-cut (L) or braided (B); however, it remains unclear which approach is more effective for distal malignant biliary obstruction (DMBO). This study compared the clinical outcomes of using L-type and B-type stents because we believe that recurrent biliary obstruction (RBO) is less likely to occur with L-type stents. METHODS: Patients diagnosed with unresectable DMBO were randomly assigned to groups L and B in a stratified block fashion, and outcomes were compared. The primary outcome was the rate of RBO within 1 year; secondary outcomes were adverse events, clinical success rate, time to RBO (TRBO), and overall survival. RESULTS: Of the 60 enrolled participants, 56 (group L, n = 27; group B, n = 29) were included. The rates of RBO within 1 year were 44.4% and 17.2% in groups L and B, respectively (odds ratio, 2.57; 95% confidence interval [CI], 1.045-6.353). Early adverse events, which improved with conservative treatment, included pancreatitis (n = 4) in group L and pancreatitis (n = 3) and cholecystitis (n = 1) in group B (P = .913). The median TRBO (220 days [95% CI, 56-272] vs 418 days [95% CI, 232-454]) was significantly longer in group B than in group L (log-rank test, P = .0118). The median overall survival (group L, 158 days; group B, 204 days) after stenting was not significantly different between groups (P = .8544). CONCLUSIONS: In the setting of DMBO, B-type stents are associated with less recurrent obstruction than L-type stents, although there was no difference in safety. (UMIN Clinical Trials Registry number: UMIN000027239.).

Maintaining early diagnosis of pancreatic adenocarcinoma in Japan: Local resilience against COVID-19.

BACKGROUND AND AIMS: This study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on pancreatic adenocarcinoma (PA) practice in our region and discussed the effects of our institution's regional collaborative system, the "Early Stage Pancreatic Cancer Diagnosis Project," which was originally unrelated to this study's purpose. METHODS: We retrospectively investigated 150 patients with PA at Yokohama Rosai Hospital by defining three time periods: before (C0), during the first year (C1), and during the second year (C2) of the COVID-19 pandemic. RESULTS: Among the three periods (C0, C1, and C2), there were significantly less patients with stage I PA (14.0%, 0%, and 7.4%, p = 0.032) in C1, and significantly more patients with stage III PA (10.0%, 28.3%, and 9.3%, p = 0.014) in C1. The pandemic significantly prolonged the median durations from disease onset to patients' first visits (28, 49, and 14 days, p = 0.012). In contrast, there was no significant difference in the median durations from referral to first visit to our institution (4, 4, and 6 days, p = 0.391). CONCLUSIONS: The pandemic advanced the stage of PA in our region. Although the pancreatic referral network remained functional during the pandemic, there were delays from disease onset to patients' first visit to healthcare providers, including clinics. While the pandemic caused temporary damage to PA practice, the routine regional collaboration provided by our institution's project allowed for early resilience. A notable limitation is that the impact of the pandemic on PA prognosis was not evaluated.

Low skeletal muscle mass predicts poor prognosis for patients with stage III cervical cancer on concurrent chemoradiotherapy.

OBJECTIVES: The aim of this study was to evaluate whether low skeletal muscle mass before initial treatment is an independent prognostic factor defining overall survival (OS) and progression-free survival (PFS) in patients diagnosed with stage III cervical cancer. METHODS: Body composition and clinicopathologic data were collected retrospectively. Information was extracted and analyzed from the medical records of 92 patients with stage III cervical cancer and undergoing concurrent chemoradiotherapy. Skeletal muscle mass in the L3 region was measured using cross-sectional computed tomography images and corrected for body surface area to calculate the skeletal muscle index (SMI). The primary outcome was OS, and the secondary outcome was PFS. Statistical analyses were performed using the Mann-Whitney U test. The Kaplan-Meier method was used to determine OS and PFS. Univariate and multivariate analyses were performed with Cox proportional hazard ratios. RESULTS: The optimal cutoff value for predicting 5-y survival was 35.6 cm2/m2, defined based on data derived from 24 patients with a low SMI and 68 patients without a low SMI. A low SMI was significantly associated with shorter OS (hazard ratio [HR], 2.470; 95% confidence interval [CI], 1.208-5.053; P = 0.013), with no significant difference in PFS (HR, 1.651; 95% CI, 0.876-3.110; P = 0.121). Multivariate analysis also identified a low SMI as an independent OS-defining prognostic factor (HR, 2.473; 95% CI, 1.151-5.314; P = 0.020). CONCLUSION: A low pretreatment SMI is an independent prognostic factor for OS in patients diagnosed with stage III cervical cancer and treated with concurrent chemoradiotherapy.

Diagnosing malignant distal bile duct obstruction using artificial intelligence based on clinical biomarkers.

Diagnosing distal bile duct obstruction remains challenging. This study aimed to examine the diagnostic ability of artificial intelligence (AI) based on clinical biomarkers in diagnosing malignant distal bile duct obstruction. A total of 206 patients with distal bile duct obstruction were included in this study. Clinical laboratory parameters were collected from the patients and evaluated using AI. All clinical parameters were input into the AI algorithm, and the AI value for malignant distal bile duct obstruction was calculated. The benign and malignant diagnostic capabilities of AI and other factors (alkaline phosphatase [ALP], intrahepatic bile duct [IHBD] diameters, and total bile duct [CBD] diameters) were compared. Benign and malignant bile duct obstruction were diagnosed in 142 and 64 patients, respectively. The median AI value of malignant distal bile duct obstruction was significantly greater than that of benign distal bile duct obstruction (0.991 vs. 0.002, p < 0.001). The area under the receiver operating characteristic curve of AI, ALP, IHBD diameter, and CBD diameter were 0.908, 0.795, 0.794, and 0.775, respectively. AI showed a sensitivity, specificity, and accuracy of 83.1%, 87.2%, and 85.9%. AI-based on clinical biomarkers could serve as an auxiliary for diagnosing malignant bile duct obstruction.

Reducing relapse through maintenance steroid treatment can decrease the cancer risk in patients with IgG4-sclerosing cholangitis: Based on a Japanese nationwide study.

OBJECTIVE: IgG4-related sclerosing cholangitis (IgG4-SC) is recognized as a benign steroid-responsive disease; however, little is known about the risk of development of cancer in patients with IgG4-SC and about how to counter this risk. DESIGN: We conducted a retrospective review of the data of 924 patients with IgG4-SC selected from a Japanese nationwide survey. The incidence, type of malignancy, and risk of malignancy in these patients were examined. Then, the standardized incidence ratio (SIR) of cancer in patients with IgG4-SC was calculated. RESULTS: Relapse was recognized in 19.7% (182/924) of patients, and cancer development was noted in 15% (139/924) of patients. Multivariate analysis identified only relapse as an independent risk factor for the development of cancer. In most of these patients with pancreato-biliary cancer, the cancer developed within 8 years after the diagnosis of IgG4-SC. The SIR for cancer after the diagnosis of IgG4-SC was 12.68 (95% confidence interval [CI] 6.89-8.79). The SIRs of cancers involving the biliary system and pancreas were 27.35 and 18.43, respectively. The cumulative survival rate was significantly better in the group that received maintenance steroid treatment (MST) than in the group that did not; thus, MST influenced the prognosis of these patients. CONCLUSION: Among the cancers, the risk of pancreatic and biliary cancers is the highest in these patients. Because of the elevated cancer risk, surveillance after the diagnosis and management to prevent relapse are important in patients with IgG4-SC to reduce the risk of development of cancer.

Steroid therapy has an acceptable role as the initial treatment in autoimmune pancreatitis patients with pancreatic cyst formation: Based on a Japanese nationwide study.

BACKGROUND: We attempted to determine the indications and limitations of steroid therapy as the first-line therapy in patients with autoimmune pancreatitis (AIP) with cyst formation (ACF). METHODS: This Japanese multicenter survey was conducted to examine the merits/demerits of steroid treatment as the initial therapy for ACF. RESULTS: Data of a total of 115 patients with ACF were analyzed. Complete remission was achieved in 86% (86/100) of patients who had received steroid treatment, but only 33.3% (5/15) of patients who had not received steroids. Relapse after the remission (n = 86) occurred in 7.6% (6/86) of patients who had received steroid therapy, but 40% (2/5) of patients who had not received steroid therapy. Multivariate analysis identified adoption of the wait and watch approach without steroid treatment (odds ratio = 0.126, P < .001) as a significant and independent negative predictor of remission of ACF. As for predictors of relapse, the presence of varix (odds ratio = 5.83, P = .036) was identified as an independent risk factor. CONCLUSION: Steroid therapy plays an important role as first-line therapy in AIP patients with pancreatic cyst formation, however, varix formation, besides the diameter of the cyst(s), is a risk factor for refractoriness to steroid therapy.

Effectiveness and Prognostic Factors of Everolimus in Patients with Pancreatic Neuroendocrine Neoplasms.

Objective The effectiveness of everolimus for the management of pancreatic neuroendocrine neoplasms (PNENs), including the G3/NEC types, remains unclear. We therefore investigated the effectiveness of the drug for the management of PNENs. Methods We analyzed the progression-free survival (PFS) and overall survival (OS) associated with everolimus and factors influencing the PFS and OS. Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be significantly longer than that associated with the G3/NEC types [hazard ratio (HR), 0.45; p=0.005]. A multivariate analysis showed that the significant factors influencing the PFS were age (<65 years old; HR, 0.44; p=0.002), grade (G1/G2; HR, 0.42; p=0.006), everolimus treatment line (≤2nd; HR, 0.55; p=0.031), and presence of treatment with metformin (yes; HR, 0.29; p=0.044). The median OS was 63.8 months. In the multivariate analysis, the significant factors influencing the OS were grade (G1/G2; HR, 0.21; p<0.001), volume of liver metastasis (≤25%; HR, 0.27; p<0.001), everolimus treatment line (≤2nd; HR, 0.27; p<0.001), and presence of primary tumor resection (yes; HR, 0.33; p=0.005). Conclusion The effectiveness of everolimus in the management of G3/NEC types and prognoses tended to be poorer than those associated with the G1/G2 types. Everolimus combined with metformin and early-line treatment with everolimus may be effective for managing advanced PNENs.

Clinical Outcomes of Everolimus Rechallenge in Patients with Pancreatic Neuroendocrine Neoplasms with No Other Treatment Options.

BACKGROUND: The clinical outcomes of everolimus rechallenge in patients with pancreatic neuroendocrine neoplasms (PNENs) are unknown. This study aimed to investigate the treatment outcomes and safety of everolimus rechallenge treatment with PNENs. METHODS: Clinical data of everolimus-treated patients with PNENs at two institutions were collected. Patients who underwent everolimus rechallenge were included in the study. We analyzed the progression-free survival (PFS) and treatment response associated with everolimus rechallenge and the adverse events. RESULTS: Between 2008 and 2020, 117 patients received initial treatment with everolimus, of which 14 patients received everolimus rechallenge. With regard to the grade of PNENs, there were 2 cases of G1, 11 cases of G2, and 1 case of G3. The median rechallenge PFS was 5.7 months. The objective response rate was 21.4%. the disease control rate was 71.4%. The only major grade 3 or 4 adverse event was neutropenia (n = 1, 7.1%). No other severe adverse event was observed. CONCLUSION: The outcomes and safety of everolimus rechallenge were verified, and it was deemed an acceptable treatment. Everolimus rechallenge may provide a new drug therapy for patients with advanced PNENs for whom no other drug treatment option is available.

Factors Contributing to Tumor Shrinkage after Peptide Receptor Radionuclide Therapy in Patients with Unresectable Neuroendocrine Tumors.

Peptide receptor activation therapy (PRRT) is a promising treatment option for metastatic neuroendocrine tumors (NETs). However, predicting tumor shrinkage before treatment is challenging. We analyzed the shrinkage rate of each metastatic tumor lesion to identify predictive factors related to shrinkage. Patients with metastatic NET who underwent PRRT were included in this retrospective study. For each patient, between one to five metastatic lesions were selected in descending order of size, and the change in the maximum tumor diameter after treatment was defined as the shrinkage rate per lesion (L-SR). We analyzed the relationship between pretreatment clinicopathological factors and L-SR. The median L-SR of all 75 lesions in 20 patients was 20% (95% CI: 4.8−26.1%). While previous treatment with cytotoxic agents (34.4%, p < 0.05) and primary tumor of the pancreas (27.8%, p < 0.05) were significantly favorable factors, a primary tumor of the rectum was significantly more resistant to shrinkage (−20.5%, p < 0.001). Therefore, lesion-based analysis of PRRT for NETs showed that pancreatic NET and previous treatment with cytotoxic agents were favorable factors for tumor shrinkage; however, rectal NET was a factor associated with resistance to shrinkage.

Franseen Needles May Be Promising for Improving the Sampling Adequacy of EUS-FNA for Subepithelial Lesions.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is useful in diagnosing subepithelial lesions (SELs), and adequate tissue sampling is necessary to differentiate between benign and malignant diseases to determine therapeutic strategies. This study aimed to evaluate sampling adequacy and diagnostic performance of EUS-FNA for SELs with Franseen needles. This retrospective study enrolled 130 patients who underwent EUS-FNA with a 22-gauge needle for SELs from January 2010 to March 2021. We compared sampling adequacy and predictive factors influencing the sampling adequacy of EUS-FNA for SELs between Franseen and conventional needles. The sampling adequacy rates were 95.0% (38/40) with Franseen needles and 76.7% (69/90) with conventional needles (p = 0.011). The mean number of punctures with Franseen needles (2.80) was significantly less than that with conventional needles (3.42) (p < 0.001). In the multivariate analysis, the use of Franseen needles (p = 0.029; odds ratio [OR], 5.37; 95% confidence interval [CI], 1.18−23.36) was an independent factor influencing the sampling adequacy. Compared to conventional needles, the Franseen needle could play a vital role in accurately diagnosing SELs by yielding better sampling adequacy and reducing the number of passes.

Computed diffusion-weighted magnetic resonance imaging with high b-values in the diagnosis of gallbladder lesions.

PURPOSE: The diagnosis of gallbladder lesions remains challenging. The efficacy of computed diffusion-weighted imaging (DWI) with high b-values and apparent diffusion coefficient (ADC) for the diagnosis of gallbladder cancer remains unknown. We aimed to investigate the usefulness of computed DWI with high b-values and the combination of computed DWI and ADC in differentiating malignant and benign gallbladder lesions. METHODS: Sixty patients (comprising 30 malignant and 30 benign lesions) who underwent magnetic resonance imaging for gallbladder lesions were included in this retrospective study. Qualitative evaluations were performed using conventional DWI with b1000, computed DWI with b1500, b1000 DWI/ADC, and computed b1500 DWI/ADC, and their diagnostic performances were compared. RESULTS: The sensitivity, specificity, and accuracy of computed b1500 DWI/ADC were 90% (27/30), 80% (24/30), and 85% (51/60), respectively. The accuracy of computed b1500 DWI/ADC was higher than that of conventional b1000 DWI (52%, 31/60, p < 0.001), computed b1500 DWI (72%, 43/60, p = 0.008), and b1000 DWI/ADC (78%, 47/60, p = 0.125). The specificity of computed b1500 DWI/ADC was also higher than that of conventional b1000 DWI (7%, 2/30, p < 0.001), computed b1500 DWI (47%, 14/30, p = 0.002), and b1000 DWI/ADC (67%, 20/30, p = 0.125). No significant difference was observed in the sensitivity between the groups. CONCLUSION: This study shows that computed DWI with high b-values combined with ADC can improve diagnostic performance when differentiating malignant and benign gallbladder lesions. Computed diffusion-weighted magnetic resonance imaging with high b-values in the diagnosis of gallbladder lesions. *Computed DWI with b1500 combined with ADC can improve diagnostic performance when differentiating gallbladder lesions compared with conventional methods (b1000 DWI).

Detection rate of endoscopic ultrasound and computed tomography in diagnosing pancreatic neuroendocrine neoplasms including small lesions: A multicenter study.

BACKGROUND/PURPOSE: The detection ability and role of different imaging modalities to detect pancreatic neuroendocrine neoplasms (PNENs) including small lesions is unclear. This study aimed to compare the ability of endoscopic ultrasound (EUS) and computed tomography (CT) to detect PNENs. METHODS: Data of patients who underwent EUS and contrast-enhanced CT and were diagnosed with PNENs were analyzed. The detection rates of pancreatic lesions with EUS and CT based on tumor size and influencing factors were investigated. RESULTS: For 256 PNEN lesions, the detection rate of EUS was better than that of CT (94.5% vs 86.3%; P < .001). EUS was significantly superior to CT for PNENs ≤5 mm (58.3% vs 16.7%; P = .006) and 5-10 mm (97.7% vs 79.5%; P = .008). There was no significant difference in the detection rate between EUS and CT for PNENs >10 mm (98.4% vs 96.4%; P = .375). Size (≤5 mm) and insulinoma were independent factors associated with poor EUS and CT detection rates. CONCLUSIONS: Endoscopic ultrasound exhibited better detection ability than CT, with an excellent detection rate for PNENs >5 mm, except for insulinomas. CT could detect PNENs >10 mm, which are amenable to treatment.

Split-dose low-volume polyethylene glycol is non-inferior but less preferred compared with same-day bowel preparation for afternoon colonoscopy.

Currently, the same-day polyethylene glycol-electrolyte lavage solution (PEG-ELS) regimen is particularly recommended for afternoon colonoscopy as an alternative to the split-dose regimen in western countries. However, in Japan, the split-dose regimen has never been used as a standard colonoscopy preparation regimen. The aim of this study was to compare the efficacy and tolerability of split-dose PEG containing ascorbic acid (ASC) with same-day single dose PEG-ASC in Japan.This was a single-blinded, non-inferiority, two-center, randomized, controlled study. In-hospital patients were randomized to the same-day regimen or the split regimen using a web-based registry system. The same-day group was instructed to take 5 mL of sodium picosulfate in the evening, and on the day of the colonoscopy, they took 1.5 L of PEG-ASC. The split group was instructed to take 1 L of PEG-ASC before the day of colonoscopy, followed by another 1 L of PEG-ASC on the day of colonoscopy. Bowel cleansing was evaluated by the Boston Bowel Preparation Scale.A total of 153 patients were randomized to either the same-day group (n=78, males 60.0%, mean age 62.7 years) or the split group (n=75, 61.3%, 61.9 years). The rates of successful bowel cleansing were 83.3% in the same-day group vs. 92.0% (83.4%-97.0%) in the split group, P=0.10). No serious adverse events occurred in the study population. However, more patients in the same-day group were willing to repeat the same preparation regimen (P<0.001). The split-dose regimen was not inferior to the same-day regimen with respect to the efficacy of bowel preparation, but the patients preferred the same-day regimen.

Severe anaphylaxis caused by intravenous anti-cancer drugs.

BACKGROUND: The incidence and risk factors of severe anaphylaxis by intravenous anti-cancer drugs are unclear, whereas those of milder reactions have been reported. STUDY DESIGN: Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non-epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). RESULTS: Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66 years), 88,200 person-day anti-cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person-based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%-0.67%) and the administration-based incidence was 0.031% (27/88,200, 95% CI 0.019%-0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin-induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%-13.1%). Carboplatin caused severe anaphylaxis after at least 9-min interval since the drip started. Thirteen out of 14 patients experienced carboplatin-induced severe anaphylaxis within a 75-day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5 min after the first drip of the day at a life-long incidence of 0.93% (9/968, 95% CI 0.27%-1.59%). CONCLUSION: We elucidated the high-risk settings of chemotherapy-induced severe anaphylaxis.

Prognostic Impact of Sarcopenia in Patients With Biliary Tract Cancer Undergoing Chemotherapy.

AIM: Sarcopenia affects the treatment of various cancer types but its impact on chemotherapy efficacy and prognosis in biliary tract cancer remains unclear. Thus, we evaluated whether sarcopenia independently affects the outcome of chemotherapy for biliary tract cancer. PATIENTS AND METHODS: Data of 50 patients who underwent chemotherapy for biliary tract cancer at two affiliated centres were retrospectively analysed. The association of clinical factors, including sarcopenia, with overall survival and time to treatment failure was analysed. RESULTS: Sarcopenia was an independent factor negatively influencing overall survival and time to treatment failure in univariate and multivariate analyses (median overall survival, sarcopenic vs. non-sarcopenic patients: 10.6 vs. 16.6 months; hazard ratio=2.19, p=0.018; time to treatment failure: 5.3 vs. 13.1 months, hazard ratio=2.50, p=0.019). CONCLUSION: Sarcopenia may affect the efficacy of chemotherapy and prognosis in biliary tract cancer. Thus, improving sarcopenia may improve the prognosis of patients with biliary tract cancer undergoing chemotherapy.