Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19.

Although the importance of virus-specific cytotoxic T lymphocytes (CTL) in virus clearance is evident in COVID-19, the characteristics of virus-specific CTLs related to disease severity have not been fully explored. Here we show that the phenotype of virus-specific CTLs against immunoprevalent epitopes in COVID-19 convalescents might differ according to the course of the disease. We establish a cellular screening method that uses artificial antigen presenting cells, expressing HLA-A*24:02, the costimulatory molecule 4-1BBL, SARS-CoV-2 structural proteins S, M, and N and non-structural proteins ORF3a and nsp6/ORF1a. The screen implicates SARS-CoV-2 M protein as a frequent target of IFNγ secreting CD8+ T cells, and identifies M198-206 as an immunoprevalent epitope in our cohort of HLA-A*24:02 positive convalescent COVID-19 patients recovering from mild, moderate and severe disease. Further exploration of M198-206-specific CD8+ T cells with single cell RNA sequencing reveals public TCRs in virus-specific CD8+ T cells, and shows an exhausted phenotype with less differentiated status in cells from the severe group compared to cells from the moderate group. In summary, this study describes a method to identify T cell epitopes, indicate that dysfunction of virus-specific CTLs might be an important determinant of clinical outcomes.

[A Case of Primary Jejunal Cancer Treated with Laparoscopic Jejunectomy with Appearance of Ileus].

An 83-year-old man visited our hospital for vomiting. Chest-abdominal computed tomography(CT)revealed that a tumor whose inside was imaged in the jejunum about 15 cm after leaving the Treitz ligament was pointed out, and dilation of the oral intestinal tract of the tumor was observed. Upper gastrointestinal endoscopy showed a type 3 circumferential tumor at the jejunum. He was diagnosed with obstructive ileus due to jejunal cancer. Laparoscopic-assisted partial jejunal resection was performed. Although the patient was followed up without chemotherapy, CT showed multiple lung and liver metastases and a mass lesion was found in the right entire chest, and a biopsy revealed skin metastasis 6 months after the operation. The patient is being followed up 10 months after surgery, there is no progression of liver, lung, and skin metastasis.

[A Case of Advanced Rectal Cancer with the Metastatic Abdominal Aortic Bifurcation Lymph Node Performed by Laparoscopic Surgery after Chemotherapy].

A 63-year-old underwent examination for constipation and was found to have an unresectable advanced rectal cancer. Metastatic abdominal aortic bifurcation lymph node and lung metastasis were suspected upon CT(cT3N3M1a[PUL1], cStage Ⅳa), and chemotherapy was administered(CapeOX plus Bmab). After 4 courses of chemotherapy, the size of the primary tumor and the lymph nodes decreased(PR). We performed laparoscopic rectum resection and abdominal aortic bifurcation lymph node. The pathological diagnosis indicated partial response(residual cancer cells)(Grade 1a). After 4 courses of chemotherapy(CapeOX), we performed pulmonary partial resection for metastatic lung cancer. This case suggests that laparoscopic resection of rectum after chemotherapy with CapeOX plus Bmab for locally advanced rectal cancer is a potential- ly effective procedure.

Phase II study of S-1-based sequential combination chemotherapy including oxaliplatin plus bevacizumab and irinotecan with or without cetuximab for metastatic colorectal cancer: the SOBIC trial.

BACKGROUND: Fluorouracil and leucovorin combined with oxaliplatin or irinotecan plus bevacizumab (Bmab) or cetuximab (Cmab) are now widely accepted treatment options as first-line or second-line chemotherapy for metastatic colorectal cancer (mCRC). Sequential chemotherapy with oral 5-FU backbone for mCRC without using central venous ports is beneficial for both patients and physicians. We designed the SOBIC trial to validate the effectiveness of the first- and second-line oral combination chemotherapy for mCRC. PATIENTS AND METHODS: From May 2010 through March 2013, 52 patients were enrolled from 47 institutions in the Hyogo Colorectal Cancer Surgery Group. First-line chemotherapy was S-1 + oxaliplatin (SOX) plus Bmab, and second-line chemotherapy after first-line failure was irinotecan + S-1 (IRIS) + Cmab, IRIS + Bmab, or IRIS based on the KRAS status. RESULTS: The 50 finally included patients received first-line chemotherapy. Second-line therapy was administered to 20 patients (40%): 12 patients received IRIS + Cmab and 8 patients received IRIS + Bmab. The median follow-up period was 48.6 months (range 35-67 months). The median second progression-free survival was 24.2 months (95% confidence interval [CI] 17.7-35.2). The response rate after first- and second-line chemotherapy was 46.7% and 15%, respectively. The median overall survival was 35.2 months (95% CI: 27.8 to not reached). The main grade 3-4 adverse events were sensory neuropathy (18%) and fatigue (10%). There were no treatment-related deaths. CONCLUSION: Sequential S-1-based combination regimens including oxaliplatin, irinotecan, Bmab, and Cmab were beneficial for patients with mCRC.

[Locally Advanced Breast Cancer Successfully Treated with Abemaciclib and Fulvestrant-A Case Report].

A 78-year-old woman visited our hospital for a tumor in her left breast with discharge. The 10 cm tumor had ulceration and foul smell. Scirrhous breast carcinoma was diagnosed based on core-needle biopsy findings. Chest and abdominal computed tomography( CT) revealed the tumor invading the pectoralis major muscle and a large number of swollen lymph nodes from the left axilla to the subclavian region, but no distant metastases. After 6 months of locally advanced breast cancer treatment with abemaciclib and fulvestrant, ulceration improved. CT revealed that the tumor and lymph nodes tended to shrink. Left mastectomy with axillary lymph node dissection and combined resection of pectoralis major muscle was performed. Postoperative pathological histology revealed ypT2, ypN0, ypM0, ypStage ⅡA. Subsequently, abemaciclib plus fulvestrant therapy was continued as an adjuvant therapy. The patient has survived without recurrence 6 months after the operation. We report a case of locally advanced breast cancer in which abemaciclib and fulvestrant were effective.

[Palliative Laparoscopic Operation for an Extremely Elderly Patient with Cecum Cancer].

Symptomatic colorectal cancer in extremely elderly patients is difficult to treat. A 97-year-old woman was initially suspected of having appendicitis because of worsening right lower abdominal pain with persistent fatigue. After antimicrobial therapy, advanced cecum cancer with lymph node involvement was found. Palliative laparoscopy-assisted ileocecal resection without radical lymph node dissection was performed to prevent further inflammation. The patient was transferred to another hospital for rehabilitation on postoperative day 24, when she regained walking function. This palliative procedure can be an effective treatment for elderly patients with symptomatic advanced colon cancer.

[A Case of Laparoscopic Surgery for Advanced Rectal Cancer with Lateral Lymph Node Metastasis Resected after Neoadjuvant Chemotherapy].

A 62-year-old man with diarrhea and metastases was found to harbor 2 rectal cancers. Both lateral lymph nodes were suspected based on CT and PET-CT(cT3N3M0, cStage Ⅲb). We planned to administer neoadjuvant chemotherapy(NAC) (CapeOX plus Bmab). After 4 courses of NAC, the sizes of both the primary tumor and lymph nodes decreased(partial response: PR). We performed laparoscopic abdominoperineal resection of the rectum(APR)with dissection of both lateral lymph nodes. The therapeutic effect was PR(few residual cancer cells)(Grade 2). After 4 courses of adjuvant chemotherapy (CapeOX), there have been no signs of recurrence for 8 months. This case suggests that laparoscopic APR after NAC with CapeOX plus Bmab for locally advanced rectal cancer is a potentially effective procedure.

[A Case of Ascending Colon Cancer with Intestinal Malformation Treated via Laparoscopic Surgery].

A 66-year-old man attended a health check-up after a positive fecal occult blood test. Colonoscopy revealed a 2 cm type 2 lesion near the ascending colon and the upper lip ofBauhin 's valve. Contrast-enhanced computed tomography ofthe abdominal region revealed aplasia ofthe ligament ofTreitz, with the duodenum running through the center. Three-dimensional vascular construction revealed intestinal malrotation, in which the superior mesenteric artery was present on the right side of the superior mesenteric vein. A diagnosis ofascending colon cancer(T2N0M0, cStage I )was made, and a laparoscopic ileocecal resection was performed. The ascending colon was not fixed to the abdominal wall, and the colon was widely depressed within the pelvis. Because no adhesion was noted, vascular processing was performed after converting to extracorporeal manipulation via a small incision in the umbilical region. The controlling vessel was the ileocolic artery, and D2 dissection was performed. The patient suffered no postoperative complications and was discharged on hospital day 13. Most reports ofintestinal malrotation concern pediatric patients, and reports ofadult cases are relatively rare. The intestinal malrotation was confirmed intraoperatively, and the procedure was performed safely. This suggests that if intestinal malrotation can be confirmed, laparoscopic surgery can be safely performed.

A case of gastric cancer with heterogeneous components of EB virus (+)/TP53 (+) and EB virus (-)/TP53 (-).

Epstein-Barr virus (EBV)-associated gastric adenocarcinoma is a histological subtype of gastric adenocarcinoma, in which all of the carcinoma cells are basically positive for EBV-encoded small RNA (EBER) by in situ hybridization. Although its typical histology has some overlap with gastric carcinoma with lymphoid stroma, absence of massive lymphoid infiltrate is sometimes observed either in whole or in part. EBV-associated adenocarcinoma is one of the four representative molecular pathological subtypes recently identified by comprehensive genomic analysis of gastric adenocarcinomas. According to the analysis, typical EBV-associated gastric adenocarcinoma constitutes an independent molecular pathological subgroup, which is mutually exclusive to TP53-mutated adenocarcinoma with chromosomal instability, another molecular pathological subtype in gastric adenocarcinomas. Here, we report a rare case of gastric cancer heterogeneously composed of EBER (+)/TP53 (+) and EBER (-)/TP53 (-) portions. The EBER (+)/TP53 (+) component with massive lymphoid infiltrate surrounded the EBER (-)/TP53 (-) component showing well to moderately differentiated tubular adenocarcinoma. Although collision of two independent gastric cancers could be the simplest and most possible explanation for this situation, we discussed another possibility. In the case of gastric collision tumors, concurrent development of EBER (+) gastric adenocarcinomas and EBER (-) gastric adenocarcinomas in a single stomach is a rare incident. Since presence of the EBER (+)/TP53 (+) tumor component is atypical in itself, we also discussed the mechanism of development of the clone.

[A case of metastatic gastric cancer originating from transverse colon cancer].

Metastatic gastric cancer is uncommon, and metastasis of colorectal cancer to the stomach is extremely rare. We report a case of metastatic gastric cancer that originated from transverse colon cancer. A 52-year-old woman underwent a left hemicolectomy and D3 lymph node dissection based on a diagnosis of transverse colon cancer. The pathology results were as follows: mucinous adenocarcinoma, type 2, 6 × 11 cm, ss, ly1 v1, pm (-), dm (-), n1 (+), P0, H0, M0, Stage IIIa. The patient received XELOX as postoperative adjuvant therapy for 6 months. One year and 3 months after the left hemicolectomy, gastroscopy revealed a submucosal tumor in the lower body of the stomach and an incipient cancer in the cardia of the stomach, and a colonoscopy revealed an incipient cancer in the transverse colon. An endoscopic ultrasonography fine needle aspiration biopsy of the submucosal tumor in the lower body of the stomach was performed. Histology showed that this tumor was a mucinous adenocarcinoma similar to the primary transverse colon cancer, which led to a diagnosis of metastatic gastric cancer originating from transverse colon cancer. Distant metastasis was not detected. Endoscopic submucosal dissection of the incipient gastric cancer was performed, as were distal gastrectomy and partial colectomy. Peritoneal dissemination and para-aortic lymph node recurrence were detected 7 months after the second surgery.

[A case of primary carcinoma associated with anal fistula].

A 47-year-old man with no history of anal fistula was admitted to our hospital with a complaint of perianal pain. Computed tomography (CT) imaging revealed perianal abscess. Incision and drainage were performed under spinal anesthesia. Ten months after drainage, magnetic resonance imaging revealed anal fistula on the left side of the anus. Subsequently, core-out and seton procedures were performed for ischiorectalis type III anal fistula. Pathological examination of the resected specimen of anal fistula revealed a moderately differentiated adenocarcinoma, leading to the diagnosis of carcinoma associated with anal fistula. No distant metastases or enlarged lymph nodes were observed on positron emission tomography (PET)/CT. We performed abdominoperineal resection with wide resection of ischiorectalis fat tissue. The pathology results were tub2, A, ly0, v0, n0, PM0, DM0, RM0, H0, P0, M0, Stage II. Negative pressure wound therapy was performed for perineum deficiency, after which rapid wound healing was observed. Left inguinal lymph node recurrence was detected 8 months after surgery, for which radiotherapy was administered. Distant metastasis was detected 11 months after surgery. The patient died 21 months after surgery.