Impact of the coronavirus disease 2019 pandemic on gastric and colorectal cancer surgeries: a multicenter epidemiologic study from the Kinki region of Japan.

The coronavirus disease 2019 pandemic affected cancer surgeries and advanced cancer diagnoses; however, the trends in patient characteristics in medical institutions during this time, and the surgical approaches used are unclear. We investigated the impact of the pandemic on gastric and colorectal cancer surgeries in the Kinki region of Japan. We grouped 1688 gastric and 3493 colorectal cancer surgeries into three periods: "pre-pandemic" (April 2019-March 2020), "pandemic 1" (April 2020-March 2021), and "pandemic 2" (April 2021-September 2021), to investigate changes in the number of surgeries, patient characteristics, surgical approaches, and cancer progression after surgery. Gastric and colorectal cancer surgeries decreased from the pre-pandemic levels, by 20% and 4%, respectively, in pandemic 1, and by 31% and 19%, respectively, in pandemic 2. This decrease had not recovered to pre-pandemic levels by September, 2021. Patient characteristics, surgical approaches, and cancer progression of gastric and colorectal surgeries did not change remarkably as a result of the coronavirus disease 2019 pandemic.

Clinicopathological features of appendiceal goblet cell adenocarcinoma in Japan: a multicenter retrospective study.

PURPOSE: In the 5th edition of the World Health Organization classification, appendiceal goblet cell adenocarcinoma (GCA) is categorized separately from neuroendocrine tumors and other appendiceal adenocarcinomas. We clarified the clinicopathological characteristics of Japanese appendiceal GCA. METHODS: We designed a retrospective multicenter cohort study and retrieved the data of patients with appendiceal neoplasms and histologically diagnosed appendiceal goblet cell carcinoid (GCC) treated from January 2000 to December 2017 in Japan. The available GCC slides were reviewed and diagnosed with a new grading system of GCA. RESULTS: A total of 922 patients from 43 institutions were enrolled; of these, 32 cases were patients with GCC (3.5%), and 20 cases were ultimately analyzed. The 5-year survival rate was 61.4% (95% confidence interval: 27.4-83.2), and the median survival time was 93.1 months. For peritoneal metastasis, regional lymph node metastasis was a significant factor (p = 0.04), and Grade 3 was a potential factor (p = 0.07). No peritoneal metastasis was observed in either T1/2 patients (n = 2) or Grade 1 patients (n = 4). We were unable to detect any significant factors associated with regional lymph node metastasis. CONCLUSION: For peritoneal metastasis, regional lymph node metastasis was a significant factor, and Grade 3 was a potential factor.

Clinicopathological Characteristics of Low-Grade Appendiceal Mucinous Neoplasm.

INTRODUCTION: Recently, "low-grade appendiceal mucinous neoplasms" (LAMNs) have been proposed as one subtype of appendiceal mucinous neoplasms, characterized by a villous or flat proliferation of mucinous epithelium with low-grade cytologic atypia. The aim of this study was to clarify the clinicopathological characteristics of LAMN. METHODS: In this multi-institutional cohort study, we retrospectively analyzed the clinicopathological characteristics in appendiceal neoplasms patients who underwent treatment from 2000 to 2017. RESULTS: In total, 922 patients were enrolled, with 279 (30.3%) cases of LAMN, and 93 (10.1%) cases of non-LAMN disease. In comparison with patients with non-LAMN disease, those with LAMN had significantly lower levels of CA19-9 (p = 0.045), a lower frequency of T4 tumors (p < 0.0001), a lower frequency of lymph node metastasis (p < 0.0001), and a lower frequency of distant metastasis (p < 0.0001). Survival analysis revealed that patients with LAMN had a significantly better prognosis than did those with non-LAMN disease (p < 0.001). Among the patients with distant metastasis, those with LAMN had a significantly better prognosis than did those with non-LAMN disease (p = 0.0020), but among the patients without distant metastasis, the difference between the 2 groups was not significant (p = 0.26). However, among patients who underwent complete resection, the difference in prognosis between the 2 groups was not significant (p = 0.10). CONCLUSIONS: A multicenter retrospective study revealed that the clinicopathological characteristics of LAMN was different from those of non-LAMN.

Open versus laparoscopic surgery for primary appendiceal tumors: a large multicenter retrospective propensity score-matched cohort study in Japan.

BACKGROUND: The feasibility of laparoscopic surgery for primary appendiceal tumors compared to that of open surgery has not been demonstrated to date because primary appendiceal tumors are rare. This study aimed to compare the long-term outcomes between laparoscopic and open surgeries for primary appendiceal tumors. METHODS: In this multicenter retrospective cohort study, the data of patients who had been histologically diagnosed with primary appendiceal tumors at 43 tertiary hospitals in Japan between 2000 and 2017 were analyzed. In total, 922 patients were assessed, and 679 cases were eligible for analysis. Using propensity scores, the baseline characteristics were matched for 114 open surgery cases and 114 laparoscopic surgery cases. The primary endpoints were recurrence-free survival (excluding patients with stage IV disease with distant metastasis) and overall survival. RESULTS: The rate of conversion from laparoscopic to open surgery was 1.5%. The 5-year recurrence-free survival rates were 80.4% (95% confidence interval: 71.0-89.7) and 78.2% (95% confidence interval: 69.0-87.3) in the laparoscopic and open surgery groups, respectively, with no significant difference (p = 0.57). No significant difference was observed in the 5-year overall survival rates between the laparoscopic [83.5% (95% confidence interval: 74.4-92.7)] and open surgery [72.7% (95% confidence interval: 62.3-83.0); p = 0.09] groups. In multivariate analysis, laparoscopic surgery was not identified as an independent prognostic factor for overall survival [hazard ratio: 0.49 (95% confidence interval: 0.23-1.06), p = 0.0707]. CONCLUSIONS: Laparoscopic surgery is comparable to open surgery and can be considered a treatment option for primary appendiceal tumors.

ATAD5 deficiency alters DNA damage metabolism and sensitizes cells to PARP inhibition.

Replication factor C (RFC), a heteropentamer of RFC1-5, loads PCNA onto DNA during replication and repair. Once DNA synthesis has ceased, PCNA must be unloaded. Recent findings assign the uloader role primarily to an RFC-like (RLC) complex, in which the largest RFC subunit, RFC1, has been replaced with ATAD5 (ELG1 in Saccharomyces cerevisiae). ATAD5-RLC appears to be indispensable, given that Atad5 knock-out leads to embryonic lethality. In order to learn how the retention of PCNA on DNA might interfere with normal DNA metabolism, we studied the response of ATAD5-depleted cells to several genotoxic agents. We show that ATAD5 deficiency leads to hypersensitivity to methyl methanesulphonate (MMS), camptothecin (CPT) and mitomycin C (MMC), agents that hinder the progression of replication forks. We further show that ATAD5-depleted cells are sensitive to poly(ADP)ribose polymerase (PARP) inhibitors and that the processing of spontaneous oxidative DNA damage contributes towards this sensitivity. We posit that PCNA molecules trapped on DNA interfere with the correct metabolism of arrested replication forks, phenotype reminiscent of defective homologous recombination (HR). As Atad5 heterozygous mice are cancer-prone and as ATAD5 mutations have been identified in breast and endometrial cancers, our finding may open a path towards the therapy of these tumours.

[A Case of Anaphylactic Shock after First Administration of Oxaliplatin].

A 48-year-old woman with advanced gastric cancer with peritoneal dissemination was treated with weekly paclitaxel from October 2015 and was then administered the CapeOX regimen. Although she had no adverse event during the 2-hour administration of the first oxaliplatin(L-OHP), sudden wheezing, subsequent decrease in blood pressure, and vomiting occurred after completing the administration. After intravenous injection of epinephrine(1mg)and drip infusion of methylprednisolone( 500mg), she received continuous administration of norepinephrine for 5 days. Hypersensitivity reaction to LOHP typically occurs after several cycles and within 30 minutes of starting the administration. However, we have to recognize that the hypersensitivity can also occur after the first cycle and at a later onset.

Mdx respiratory impairment following fibrosis of the diaphragm.

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease that causes respiratory or cardiac failure and results in death at about 20 years of age. An animal model of DMD, the mdx mouse, is commonly used to estimate dystrophic pathology. The pathological features of limb muscles are relatively mild, however the diaphragm is severely affected and exhibits a degenerative pattern similar to that observed in human DMD. Although, the muscle strength assay of the dystrophic diaphragm has been used to estimate mdx respiratory impairment, systemic functional assessments compared with histopathological analysis have not been demonstrated. Here, we report a sensitive procedure using whole-body plethysmography to monitor respiratory parameters detected during early respiratory insufficiency in the mdx mouse. The dystrophic changes in the diaphragm lead to respiratory dysfunctions. These methods may be useful to assess the therapeutic approaches for the mdx mouse.

Molecular mechanism of satratoxin-induced apoptosis in HL-60 cells: activation of caspase-8 and caspase-9 is involved in activation of caspase-3.

Satratoxins have been recognized as potential immunomodulatory agents in outbreaks of building-related illness. Here we report that satratoxin G-treated human leukemia HL-60 cells underwent apoptosis through the action of caspase-3 which was activated by both caspase-8 and caspase-9. Western blot analysis of caspase-3 in the satratoxin G-treated cells apparently indicated the appearance of a catalytically active fragment of 17 kDa. Increased caspase-3 activity was also detected by using a fluorogenic substrate, DEVD-AMC. Next, exposure to satratoxin G led to cleavage of PARP from its native 116 kDa form to a 85 kDa product. Moreover, DFF-45/ICAD were cleaved into a 12.5 kDa fragment via satratoxin G treatment. Enzymic assay on IETD-AMC revealed that caspase-8 is strongly activated by exposure to satratoxin G while T-2 toxin (T-2) could not activate caspase-8 at an early stage of apoptosis. Furthermore, satratoxin G caused a release of cytochrome c from mitochondria into the cytosol and increased the activity of caspase-9 against LEHD-AMC. These findings indicate that satratoxin G-induced apoptosis involves activation of caspase-3 and DFF-40/CAD through both activation of caspase-8 and cytosolic accumulation of cytochrome c along with activation of caspase-9.