Favorable Outcome of Repeated Salvage Surgeries for Rare Metastasis to the Ligamentum Teres Hepatis and the Upper Abdominal Wall in a Stage IV Gastric Cancer Patient

Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only four known cases. Herein, we report salvage surgery of successive metastases to the abdominal wall and LTH in a patient originally presenting with advanced gastric cancer with peritoneal metastasis, leading to long-term survival. A 72-year-old man with advanced gastric cancer underwent curative-intent distal gastrectomy with D2 lymph node dissection for gastric outlet obstruction. During this procedure, three small peritoneal metastases were detected in the lesser omentum, the small mesentery, and the mesocolon; however, intraoperative abdominal lavage cytology was negative. We added cytoreductive surgery for peritoneal metastasis. The pathological diagnosis of the gastric cancer was tubular adenocarcinoma with pT4aN1pM1(PER/P1b)CY0 stage IV (Japanese classification of gastric carcinoma/JCGC 15th), or T4N1M1b stage IV (UICC 7th). Post-operative adjuvant chemotherapy with S-1 (TS-1)+cisplatin (CDDP) was administered for 8 months followed by S-1 monotherapy for 4 months. At 28 months after the initial surgery, a follow-up computed tomography (CT) detected a small mass beneath the upper abdominal wall. The ass showed mild avidity on 18F-fluorodeoxyglucose positron-emission (FDG-PET) CT. Salvage resection was performed for diagnosis and treatment, and pathological findings were consistent with primary gastric cancer metastasis. At 49 months after the initial gastrectomy, a new lesion was detected in the LTH with a similar level of avidity on FDG-PET CT as the abdominal wall metastatic lesion. We performed a second salvage surgery for the LTH tumor, which also showed pathology of gastric cancer metastasis. There has been no recurrence up to 1 year after the LTH surgery. With multidisciplinary treatment the patient has survived almost 5 years after the initial gastrectomy. Curative-intent gastrectomy with cytoreductive surgery followed by adjuvant chemotherapy for advanced gastric cancer with localized peritoneal metastasis might have had a survival benefit in our patient. Successive salvage surgeries for oligometastatic lesions in the abdominal wall and the LTH also yielded favorable outcomes

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Tumor lysis syndrome after the effective chemotherapy in a patient with recurrence of colon cancer

A case of recurrence of colon cancer with marked tumor reduction after effective chemotherapy is reported. The patient was a 27-years-old female who was admitted to the 1st department of surgery because of a giant abdominal tumor. She had undergone surgery for cecal cancer 16 months before admission. Abdominal and pelvic CT-SCAN revealed a giant tumor (21×18cm) invading the rectum and uterus. Surgical cannulation was performed into bilateral internal iliac arteries, and anti-cancer drugs (5-FU : 5000mg, ADR : 40mg, CDDP : 200mg) were administered intraarterially. The occurrence of hyperkalemia and striking rises in LDH, CEA, CA19-9 after the chemotherapy strongly suggested the tumor lysis syndrome, which to our knowledge, has not been reported as a complication of the treatment of colon carcinoma

Possibility of Neoadjuvant Treatment for Radiologically Judged Resectable Pancreatic Cancer

Survival remains poor even after resection of pancreatic cancer and the postoperative recurrence rate is extremely high. Thus, neoadjuvant treatment may improve outcomes for resectable pancreatic cancer (RPC). This study evaluated the efficacy of neoadjuvant therapy for radiologically judged RPC. A prospectively maintained institutional database was reviewed to identify patients who underwent potentially curative resection of radiologically judged RPC. Patient characteristics and intermediate-term outcomes were compared between groups that received neoadjuvant treatment or upfront surgery (UFS). We identified 353 eligible patients, including 55 patients who received neoadjuvant chemoradiotherapy (CRT group), 53 patients who received neoadjuvant gemcitabine plus nab-paclitaxel (GnP group), and 245 patients who underwent UFS (UFS group). The cumulative rates of pancreatic cancer recurrence at 2 years after pancreatic surgery were 49.5% in the UFS, 48.1% in the CRT group, and 52.7% in the GnP group. The recurrence rate tended to be improved after neoadjuvant treatment, although the difference was not significant at this follow-up point. While the clinical TNM classifications were noticeably different from the final pathological findings, the clinical and pathological TNM classifications were more similar in the groups that underwent neoadjuvant treatment. Neoadjuvant treatment can help identify good surgical candidates and avoid unnecessary laparotomy. Our results also suggest that neoadjuvant therapy might help improve the preoperative diagnostic accuracy for patients with RPC

Endoscopic esophageal mucosal resection for esophageal mucosal carcinoma

From December 1992 to October 1994, 15 patients who had esophageal superficial mucosal lesions (18 lesions) underwent endoscopic esophageal mucosal resection (EEMR). Among them, 12 cases and 12 lesions were squamous cell carcinomas. Although perforation complicated this procedure in one patient and hemorrhage in another, these were improvde by conservative treatment. Marked subcutaneous emphysema occurred in the neck and face during EEMR without esophageal perforation in one patient. Therfore the procedure was stopped and the patient underwent radical operation 41 days later. Two of the 12 patients with carcinoma underwent radical operation 30 days after EEMR because pathological study revealed m3 and ly1 in one them and sm1, ly2 and v1 in the other. Radiotherapy was indicated for another patient who had m3, ly0 and v0. In the other patients, the cancerous lesions devaloped within m2, ly0 and v0 except in one who had minimal m3 invasion, and the therapy was completed with only EEMR. The mean period of observation after EEMR was 15.1 months (7-24). Follow-up did not reveal any recurrence of carcinoma in these 9 patients. EEMR seems to be a highly useful method for treatment of esophageal mucosal carcinoma