Registry study of immune-related adverse events using electronic patient-reported outcome in patients with cancer receiving immune checkpoint inhibitors: protocol for a multicentre cohort study.

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) is rapidly expanding in cancer treatment. ICIs have a unique safety profile, characterised by immune-related adverse events (irAEs). The safety profile of ICIs lacks patient experience and perspectives. This study primarily aims to obtain a database for descriptive research on the status of irAEs using the Patient-Reported Outcomes version of the Common Terminology Criteria (PRO-CTCAE) in patients with gastrointestinal cancer, lung cancer and malignant pleural mesothelioma treated with regimens containing ICIs. METHODS AND ANALYSIS: This is an ongoing, multicentre, observational study in Japan. Eligible patients must be at least 20 years old and have been diagnosed with lung cancer, malignant pleural mesothelioma or gastrointestinal cancer and plan to use ICIs. Participants will install the electronic PRO (ePRO) application and report adverse events via ePRO using PRO-CTCAE once weekly for up to 48 weeks. A registry will be established using background information obtained from medical records. The sample size is determined by 1 year projection without using statistical methods. Statistical analyses will include point estimates and 95% CIs for the incidence of each adverse event by cancer type and regimen at each time point. ETHICS AND DISSEMINATION: This research will be conducted per the Declaration of Helsinki, the Ethical Guidelines for Life Science and Medical Research Involving Human Subjects issued by the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labor and Welfare, and the revised Personal Information Protection Law. The study protocol was approved by the Ethics Committee (approval ID T2021-0180) of Tokyo Medical University Hospital on 15 October 2021. REGISTRATION DETAILS: The study began enrolling patients in December 2021. The target enrolment is 260; as of October 2022, 141 have been enrolled, and the enrolment is scheduled to end on 30 June 2023. TRIAL REGISTRATION NUMBER: UMIN000046418.

Questionnaire Survey of Possible Association of Allergic Diseases with Adverse Reactions to SARS-CoV-2 Vaccination.

To protect against COVID-19, SARS-CoV-2 vaccines have been widely used. Besides anaphylaxis, some less severe adverse effects may occur at higher frequencies. It remains unclear whether present or past histories of allergic diseases exert effects on local and systemic reactions. We conducted a questionnaire survey among workers in our hospital. We analyzed the adverse effects occurring after the first and second doses of the Pfizer-BioNTech vaccine in 955 subjects. The presence or absence of local injection reactions and systemic reactions (headache, fatigability, fever, muscle pain, and joint pain) was questioned. The intensities of these reactions were graded on a scale of 0-4 (except fever) or 0-2 (fever). The allergic diseases that we focused on were bronchial asthma, atopic dermatitis, food allergy, pollinosis, and hand eczema. For the systemic reactions, fatigability after the first dose tended to be more severe in the bronchial asthma than in the non-allergic group. Headache, joint pain, and fever tended to be more severe in the food allergy than in the non-allergic group after the second dose. For the local skin reactions, atopic dermatitis subjects tended to show rather less severe local skin reactions after the second dose. The results contribute to the guidelines for the care of individuals with different allergy histories, so that they may safely receive their vaccine.

Impact of synbiotics treatment on bacteremia induced during neoadjuvant chemotherapy for esophageal cancer: A randomised controlled trial.

BACKGROUND & AIMS: To elucidate the impact of synbiotics on bacterial translocation and subsequent bacteremia during neoadjuvant chemotherapy for esophageal cancer. METHODS: Patients requiring neoadjuvant chemotherapy for esophageal cancer were randomized to receive synbiotics (synbiotics group) or no synbiotics (control group) during chemotherapy. Blood and fecal samples were taken before and after every chemotherapy cycle, and 1 day before surgery. Mesenteric lymph nodes (MLNs) were harvested at laparotomy (MLN-1) and after resection of the tumor (MLN-2). Bacteria in each sample were detected. Fecal microbiota and organic acid concentrations were also determined. The primary endpoint was the detection of bacteria in the blood samples, as well as the incidence of side effects during chemotherapy. The secondary endpoint was the detection rate of bacteria in the MLN samples collected during surgery. RESULTS: The study recruited a total of 42 patients (22 in the control group, 20 in the synbiotics group). Bacteria were detected in 16 of 101 blood samples in the control group, whereas those were detected only 2 of 100 blood samples in the synbiotics group (p < 0.001) during neoadjuvant chemotherapy. Additionally, bacteria were detected in 12 of 34 MLN samples in the control group, whereas no bacteria were detected in 38 MLN samples in the synbiotics group (p < 0.001). Suppression of bacterial translocation was at least partly associated with an increased fecal acetic acid concentration as well as a lowered fecal pH by synbiotics. The incidence rate of grade 3 gastrointestinal toxicity during chemotherapy was lower in the synbiotics group compared to the control group (8/22 vs. 1/20, p = 0.022). CONCLUSIONS: Neoadjuvant chemotherapy for esophageal cancer may induce bacterial translocation and subsequent bacteremia, which can be prevented by synbiotics administration. TRIAL REGISTRATION: The University Hospital Medical Information Network (http://www.umin.ac.jp; registration number ID 000007651).

Surface contamination of the outer and blister packages of oral anticancer drugs: A multicenter study.

INTRODUCTION: All guidelines necessitate wearing personal protective equipment during dispensing of oral anticancer drugs. This study aims to measure the degree of contamination on the press-through-package strips of oral anticancer drugs in Japan. METHOD: Surface contamination of the external packaging of anticancer drugs was examined by performing wipe tests at four hospitals and two community pharmacies. The following commercially available drugs were examined: Xeloda®, TS-1®, and methotrexate tablets and SA-1® and Rheumatrex® capsules. RESULTS: The wipe tests' results revealed that the contamination levels of Xeloda® and TS-1® tablets and SA-1® capsules were within their detection limits. In some facilities, the contamination levels on the press-through-package strips of Rheumatrex® capsules were 3.27 × 10-1, which is close to its detection limit. However, across all facilities, the contamination level of methotrexate tablets was above its detection limit. CONCLUSION: The results of this study suggested that adherence to oral anticancer drugs may not occur during manufacture or transportation. However, it may be due to the presence of pollutants in the facilities. Prevention of pollution in facilities might eliminate the need to wear personal protective equipment during dispensing of oral anticancer drugs.

The Impact of the Location of Esophagogastrostomy on Acid and Duodenogastroesophageal Reflux After Transthoracic Esophagectomy with Gastric Tube Reconstruction and Intrathoracic Esophagogastrostomy.

BACKGROUND: The aim of this study was to evaluate the impact of the location of esophagogastrostomy on acid and duodenogastroesophageal reflux (DGER) in patients undergoing gastric tube reconstruction and intrathoracic esophagogastrostomy. METHODS: Thirty patients receiving transthoracic esophagectomy without cervical lymph node dissection and gastric tube reconstruction by intrathoracic anastomosis were enrolled. All patients underwent 24-h pH and bilirubin monitoring and gastrointestinal endoscopy one year after surgery. Patients were divided into three groups according to esophagogastrostomy location: group A (n = 9), above the top of the aortic arch; group B (n = 15), between the top and bottom of the aortic arch; and group C (n = 6), below the bottom of the aortic arch. The relations among the esophagogastrostomy location, 24-h pH and bilirubin monitoring results, endoscopic findings, and reflux symptoms were investigated. RESULTS: No acid reflux into the remnant esophagus was observed in group A, whereas it was observed in three of 15 patients (20%) in group B and in two of six patients (33%) in group C (P = 0.139). No DGER was found in group A, whereas DGER was observed in eight (53%) patients in group B and all patients in group C (P < 0.001). Reflux esophagitis was observed in one patient (11%) in group A, five patients (33%) in group B, and all patients in group C (P = 0.002). CONCLUSION: In gastric tube reconstruction via intrathoracic anastomosis, esophagogastrostomy should be performed above the top of the aortic arch to prevent postoperative DGER and reduce the incidence of reflux esophagitis.

Does Braun Anastomosis Have an Impact on the Incidence of Delayed Gastric Emptying and the Extent of Intragastric Bile Reflux Following Pancreatoduodenectomy? - A Randomized Controlled Study.

BACKGROUND/AIMS: This study investigated the impact of Braun anastomosis on the incidence of delayed gastric emptying (DGE) and on the intragastric bile reflux after pancreatoduodenectomy with Child reconstruction. METHODS: Sixty-eight patients who underwent subtotal stomach-preserving pancreatoduodenectomy were included. Patients were randomly assigned to a group with or without Braun anastomosis intraoperatively. Twenty-four-hour intragastric bilirubin monitoring was performed to investigate the extent of intragastric bile reflux after surgery. The incidence of DGE and other complications was also monitored. RESULTS: There were no differences between the non-Braun and Braun groups in terms of patient characteristics. The incidence rate of DGE was 29.4% (n = 10/34) in the non-Braun group and 20.6% (n = 7/34) in the Braun group (p = 0.401). Forty-six of the 68 patients consented to intragastric bilirubin monitoring. The fraction time of intragastric bilirubin reflux was comparable between the 2 groups. Although the fraction time of intragastric bilirubin reflux had no impact on the incidence of DGE, the incidence of pancreatic fistula was significantly higher in patients with DGE than those without DGE (47.1 vs. 21.6%, p = 0.043). CONCLUSION: The addition of Braun anastomosis after pancreatoduodenectomy did not effectively reduce the intragastric bile reflux and had minor impact in reducing the incidence of DGE.

[Information provided by pharmacists regarding the effective timing of the coadministration of first-generation serotonin receptor antagonists and dexamethasone for chemotherapy-induced nausea and vomiting in patients receiving Doxorubicin and cyclophosphamide chemotherapy for breast cancer - the second report].

In this report, we highly recommend the coadministration of first-generation serotonin receptor antagonists, dexamethasone, and aprepitant for chemotherapy-associated nausea and vomiting in patients with breast cancer receiving doxorubicin and cyclophosphamide (AC) chemotherapy. Aprepitant has an advantage of high efficacy rates for the treatment of nausea and vomiting; its disadvantages include the high cost and interactions with other drugs. Herein, we report the information provided by pharmacists regarding the effective timing of the coadministration of first-generation serotonin receptor antagonists and dexamethasone for nausea and vomiting in patients receiving AC chemotherapy for breast cancer. The primary end point was the proportion of patients who achieved a complete response (CR; no emesis or use of rescue therapy)in cycle 1 after receiving AC chemotherapy. A total of 46 patients were enrolled in this study between November 2010 and December 2011. The overall rate of CR (0-120 hours) was 85%. The rates of acute (0-24 hours) and delayed (24-120 hours)CR were 85% and 93%, respectively. These findings suggest that the information provided by pharmacists regarding the effective timing of the coadministration of first-generation serotonin receptor antagonists and dexamethasone is effective in patients who cannot be administered with aprepitant.

[A case of mediastinal lymph node gastric cancer recurrence during S-1 adjuvant therapy successfully treated with cisplatin + capecitabine as second-line chemotherapy].

S-1 adjuvant chemotherapy following radical surgery has been the standard therapy for the pStage II/III gastric cancer in Japan. However, there are few reports regarding treatment for gastric cancer recurrence during S-1 therapy. Here, we present a case of recurrent gastric cancer during S-1 adjuvant therapy that showed partial response to CDDP + capecitabine therapy. A 72-year-old man was diagnosed as having gastric cancer. We performed a distal gastrectomy+D2 dissection, with Roux-en Y reconstruction. The patient was treated with S-1 for adjuvant chemotherapy. Six months after operation, multiple mediastinal lymph node recurrence developed. CDDP + CPT-11 was applied for two courses as first-line treatment for the recurrence. However, the disease progressed with worsening mediastinal lymph node metastases (progressive disease). After two courses of CDDP + capecitabine as second-line chemotherapy, the recurrence site became smaller. After five courses, partial response (PR) had been achieved. Two years and five months after gastrectomy, capecitabine monotherapy was applied as third-line chemotherapy.

Single-incision laparoscopic cholecystectomy for porcelain gallbladder: a case report.

Single-incision laparoscopic cholecystectomy (SILC) has been performed in patients with gallbladder stones without inflammation. Porcelain gallbladder is a rare finding of chronic cholecystitis that is characterized by extensive calcification of the gallbladder wall. Herein we describe our experience with SILC for porcelain gallbladder with a successful outcome. A 67-old-year woman was diagnosed with porcelain gallbladder. We performed SILC using a SILS Port and a 5-mm forceps through the umbilical incision. Because a small amount of the omentum around the gallbladder was left to facilitate grasping the fundus, a view of both the cystic artery and the cystic duct was easily obtained. The operative time and the intraoperative blood loss were 66 min and less than 1 mL, respectively. The patient was discharged 3 days after surgery and was satisfied with the cosmetic results. Our procedure may represent an alternative to conventional laparoscopic cholecystectomy in patients with porcelain gallbladder.

High-vacuum vapor deposition and in situ monitoring of N-carboxy anhydride benzyl glutamate polymerization.

A high-vacuum physical vapor deposition (PVD) method was used to grow polypeptide chains from gold surfaces coupled with in situ monitoring using surface plasmon resonance spectroscopy (SPR). Polymerization of N-carboxy anhydride of benzyl-L-glutamate (BLG-NCA) was demonstrated, forming grafted polybenzyl-L-glutamate (PBLG) films. 2-Aminoethanethiol (AET) was used as the initiating site either deposited as a self-assembled monolayer (SAM), as a PVD film, or codeposited on the gold substrates. PBLG films up to 30 nm thick in which the formation of different secondary structures was monitored by in situ SPR and ex situ Fourier transform infrared spectroscopy (FT-IR) methods based on the parameters for deposition were prepared. Furthermore, surface topology and film morphology properties were determined on the basis of AFM measurements and were found to depend largely on the deposition process of the AET. Besides investigation of the AET surface density effects, the orientation of the PBLG chains was also characterized using ex situ FT-IR.

Preparation of plastic spherical microlenses by use of a fluoropolymer stencil and oil-bath heating.

A new method for fabricating plastic spherical microlenses was developed, which allowed self-alignment of lenses and self-organized formation of a spherical shape. First a low-surface-energy fluoropolymer thin film was deposited and patterned as a stencil. Then photosensitive phenol resin was patterned on it as the lens material. Finally the resin was annealed in an oil bath to form a sphere. The molten phenol resin spontaneously formed a sphere and positioned itself in the center of the fluoropolymer ring pattern as a result of the difference of surface free energy and the equivalently zero-gravity condition in the oil bath. When a light-emitting-diode printer head was loaded with spherical microlenses, its optical output increased by 1 order of magnitude.