Minimally invasive elective gastrectomy after preoperative chemotherapy in a patient with frailty who presented with locally far advanced-stage gastric cancer: a case report.

BACKGROUND: Herein, we report a case of gastric antrum cancer with multiple invasions to other organs that was completely cured with laparoscopic distal gastrectomy after preoperative chemotherapy in a patient with poor general condition. CASE PRESENTATION: An 80-year-old male patient was diagnosed with anemia during follow-up for cerebral lacunar infarction at another hospital. He was diagnosed with advanced-stage gastric antrum cancer and was referred to our hospital. On esophagogastroduodenoscopy, type 2 advanced-stage gastric cancer was detected at the greater curvature of the antrum, and the biopsy results revealed tubular adenocarcinoma. Contrast-enhanced computed tomography scan revealed multiple invasions to other organs, thick gastric wall with contrast effect, and superior mesenteric vein tumor thrombus. However, there was no evidence of distant metastasis on positron emission tomography/computed tomography scan. The clinical diagnosis was stage IVA gastric cancer. Pancreatoduodenectomy with portal vein resection could be important at this point. However, preoperative chemotherapy with S-1 and oxaliplatin was administered instead of performing extended surgery because the patient had poor general condition (performance status score of 3). The patient received three cycles of preoperative chemotherapy at the hospital along with rehabilitation and nutritional management with oral nutritional supplements. After treatment, the performance status score of the patient improved from 3 to 1. Furthermore, in terms of clinical therapeutic effect, the patient achieved partial response. Hence, laparoscopic distal gastrectomy with D2 lymph node dissection and partial transverse colectomy was performed. After surgery, the patient was admitted for oral intake on postoperative day 6 and was discharged on postoperative day 21. Based on the histopathological examination, gastric cancer had disappeared, and there were no evident malignant findings. Therefore, gastric cancer was classified as grade 3 according to the histological treatment efficacy criteria. The patient did not present with recurrence at 2 years after surgery. CONCLUSIONS: By actively administering preoperative chemotherapy, minimally invasive radical surgery with maximum preservation of the surrounding organs can be performed for locally far advanced-stage gastric cancer in older patients with poor general condition.

Safety and Efficacy of Neoadjuvant Chemotherapy for Advanced Gastric Cancer in Elderly Patients.

BACKGROUND/AIM: Elderly patients with pathological stage II/III gastric cancer struggle to complete adjuvant chemotherapy. Neoadjuvant chemotherapy (NAC) for treating locally advanced gastric cancer (LAGC) has drawn attention; however, its indication for elderly patients who are vulnerable to chemotherapy is unclear. This study aimed to investigate the feasibility and efficacy of NAC for elderly patients with gastric cancer. PATIENTS AND METHODS: In this study, patients aged ≥75 years who underwent curative gastrectomy for LAGC or adenocarcinoma of the esophagogastric junction between April 2013 and November 2021 were included. Vulnerable patients, with poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 2-3 were also included. The patients were classified into NAC+ (n=20) and NAC - (n=45) groups. The clinicopathological data of the patients were retrospectively investigated. RESULTS: The NAC+ group showed a higher R0 resection rate than the NAC- group (100% vs. 89.1%, p=0.3) and pathological downstaging was achieved in 12 (60%) cases, including five (25%) pathological complete responses. The incidence of adverse events during postoperative chemotherapy was 35%, and the rate of postoperative complications greater than Clavien-Dindo Grade II was comparable between the two groups (35% vs. 46.7%, p=0.43). The NAC+ group showed a higher three-year overall survival rate (75% vs. 36%, p=0.015). CONCLUSION: NAC was feasible and effective for elderly patients including vulnerable patients with LAGC or adenocarcinoma of the esophagogastric junction. It can be considered as treatment option, with a high down staging rate and better survival.

Deep Learning-based Image Cytometry Using a Bit-pattern Kernel-filtering Algorithm to Avoid Multi-counted Cell Determination.

BACKGROUND/AIM: In pathology, the digitization of tissue slide images and the development of image analysis by deep learning have dramatically increased the amount of information obtainable from tissue slides. This advancement is anticipated to not only aid in pathological diagnosis, but also to enhance patient management. Deep learning-based image cytometry (DL-IC) is a technique that plays a pivotal role in this process, enabling cell identification and counting with precision. Accurate cell determination is essential when using this technique. Herein, we aimed to evaluate the performance of our DL-IC in cell identification. MATERIALS AND METHODS: Cu-Cyto, a DL-IC with a bit-pattern kernel-filtering algorithm designed to help avoid multi-counted cell determination, was developed and evaluated for performance using tumor tissue slide images with immunohistochemical staining (IHC). RESULTS: The performances of three versions of Cu-Cyto were evaluated according to their learning stages. In the early stage of learning, the F1 score for immunostained CD8+ T cells (0.343) was higher than the scores for non-immunostained cells [adenocarcinoma cells (0.040) and lymphocytes (0.002)]. As training and validation progressed, the F1 scores for all cells improved. In the latest stage of learning, the F1 scores for adenocarcinoma cells, lymphocytes, and CD8+ T cells were 0.589, 0.889, and 0.911, respectively. CONCLUSION: Cu-Cyto demonstrated good performance in cell determination. IHC can boost learning efficiencies in the early stages of learning. Its performance is expected to improve even further with continuous learning, and the DL-IC can contribute to the implementation of precision oncology.

Safety of Laparoscopic Gastrectomy for Advanced Gastric Cancer With Greater than Serosal Invasion Depth.

BACKGROUND/AIM: There are several concerns about oncological contamination and technical difficulty in the laparoscopic approach for locally advanced gastric cancer. We aimed to determine the safety and usefulness of laparoscopic gastrectomy for patients with advanced gastric cancer with tumor depth greater than serosal invasion. PATIENTS AND METHODS: Sixty-two laparoscopic and 82 laparotomy gastric cancer cases surgically diagnosed as serosal or other organ invasions intraoperatively between 2011 and 2021 were included. The laparoscopic and open gastrectomy results were compared by propensity score matching using stage, preoperative chemotherapy, curative resection, surgical technique, and age as explanatory variables and laparoscopy and open resection as outcome variables. RESULTS: No difference in median operative time (341 vs. 386 minutes, p=0.24) was observed, but median blood loss (0 vs. 510 ml, p<0.001) and blood transfusion requirement (9.5 vs. 43%, p<0.001) were lower in the laparoscopic group. No difference was observed between the two groups regarding complications. Furthermore, 3-year overall survival was also similar (43 vs. 42%, p=0.74). CONCLUSION: The laparoscopic surgery results are comparable to those of open surgery in treating gastric cancer with T4a or greater depth. In addition, it is minimally invasive with less blood loss, making it a standard approach.

Assessment of risk factors for delayed gastric emptying after distal gastrectomy for gastric cancer.

The risk factors for delayed gastric emptying (DGE) following gastrectomy are unclear. This study aimed to investigate the risk factors for DGE and the severity of DGE. We retrospectively evaluated 412 patients who underwent gastrectomy for gastric cancer between 2011 and 2019. The cases were classified into the DGE (n = 27) and non-DGE (n = 385) groups; the DGE group was further classified into two subgroups based on nasogastric tube insertion as an indicator of severity. For determining the relationship between resected stomach volume and DGE, we calculated the area of each surgical specimen using the ImageJ software. Female sex (odds ratio [OR] 2.55; 95% confidence interval [CI] 1.09-5.93; P = 0.03), diabetes (OR 2.38; 95% CI 1.02-5.57; P = 0.03), and distal gastric tumors (OR 2.61; 95% CI 1.10-6.19; P = 0.02) were identified as independent risk factors by multivariate analysis. The duration of hospital stay was longer in the DGE group than in the non-DGE group (29 vs. 15 days, P < 0.01). Overall, 24 cases of DGE (89%) were found in more than 1 week following surgery. No correlation was observed between clinical features and the severity of DGE. The resected area in the DGE group was significantly larger than that in the non-DGE group (198.0 vs. 173.9 cm2, P = 0.03). In conclusion, DGE was frequently observed in females and in patients with diabetes and distal gastric tumors. Most of the DGE cases occurred after 7-14 days of surgery, patients who are discharged early should be informed to seek hospitalization if they have symptoms caused by DGE.

Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression.

Obesity, a known risk factor for various types of cancer, reduces the number and function of cytotoxic immune cells in the tumor immune microenvironment (TIME). However, the impact of obesity on CD4+ T cells remains unclear. Therefore, this study aimed to clarify the impact of obesity on CD4+ T cells in the TIME. A tumor-bearing obese mouse model was established by feeding with 45% high-fat diet (HFD), followed by inoculation with a colon cancer cell line MC38. Tumor growth was significantly accelerated compared to that in mice fed a control diet. Tumor CD4+ T cells showed a significant reduction in number and an increased expression of programmed death-1 (PD-1), and decreased CD107a expression and cytokine such as IFN-γ and TNF-α production, indicating dysfunction. We further established CD4+ T cell-depleted HFD-fed model mice, which showed reduced tumor infiltration, increased PD-1 expression in CD8+ T cells, and obesity-induced acceleration of tumor growth in a CD4+ T cell-dependent manner. These findings suggest that the reduced number and dysfunction of CD4+ T cells due to obesity led to a decreased anti-tumor response of both CD4+ and CD8+ T cells to ultimately accelerate the progression of colorectal cancer. Our findings may elucidate the pathogenesis for poor outcomes of colorectal cancer associated with obesity.

Vaccine Based on Dendritic Cells Electroporated with an Exogenous Ovalbumin Protein and Pulsed with Invariant Natural Killer T Cell Ligands Effectively Induces Antigen-Specific Antitumor Immunity.

(1) Background: Cancer vaccines are administered to induce cytotoxic CD8+ T cells (CTLs) specific for tumor antigens. Invariant natural killer T (iNKT) cells, the specific T cells activated by α-galactosylceramide (α-GalCer), play important roles in this process as they are involved in both innate and adaptive immunity. We developed a new cancer vaccine strategy in which dendritic cells (DCs) were loaded with an exogenous ovalbumin (OVA) protein by electroporation (EP) and pulsed with α-GalCer. (2) Methods: We generated bone marrow-derived DCs from C57BL/6 mice, loaded full-length ovalbumin proteins to the DCs by EP, and pulsed them with α-GalCer (OVA-EP-galDCs). The OVA-EP-galDCs were intravenously administered to C57BL/6 mice as a vaccine. We then investigated subsequent immune responses, such as the induction of iNKT cells, NK cells, intrinsic DCs, and OVA-specific CD8+ T cells, including tissue-resident memory T (TRM) cells. (3) Results: The OVA-EP-galDC vaccine efficiently rejected subcutaneous tumors in a manner primarily dependent on CD8+ T cells. In addition to the OVA-specific CD8+ T cells both in early and late phases, we observed the induction of antigen-specific TRM cells in the skin. (4) Conclusions: The OVA-EP-galDC vaccine efficiently induced antigen-specific antitumor immunity, which was sustained over time, as shown by the TRM cells.

[A Case Report of Pancreatic Neuroendocrine Tumor Resected with the Preoperative Diagnosis of Gastrointestinal Stromal Tumor of the Jejunum].

A 61-year-old man was examined for cervical pain and CT showed a 9 cm tumor to the third part of the duodenum and proximal jejunum. CT /MRI showed that the tumor was separated from the pancreas body. We scheduled a laparoscopic partial resection of the intestine with a suspected diagnosis of GIST of the intestine. The tumor was adhered to both the proximal jejunum and uncinate process of the pancreas. Therefore, we converted to an open surgery and resected part of the pancreas, duodenum, and proximal jejunum including the tumor. Histopathological examination showed the tumor capsule included the tissue of the pancreas and that the border between the intestine and the tumor was clear, suggesting that the origin of the tumor was the pancreas. We diagnosed the patient as having a grade 2 pancreatic neuroendocrine tumor based on the tumor growth pattern and immunohistochemistry findings. We examined the preoperative CT images retrospectively and found that the tumor had adhered to the uncinate process of the pancreas, which extends over the left side of the superior mesenteric artery. When GIST close to the proximal jejunum is suspected, the possibility of pancreatic neuroendocrine tumor should be considered.

[A Case of Epithelioid Sarcoma of the Sigmoid Mesocolon].

A 73-year-old man visited our hospital with the chief complaints of anorexia and weight loss. Computed tomography showed a 5 cm tumor(diameter)in the sigmoid mesocolon. We performed laparoscopic Hartmann operation; however, because of sacral invasion of tumor, curative surgery was difficult. Therefore, the tumor was excised together with the sigmoid colon. Histopathological examination of the tumor confirmed the diagnosis of epithelioid sarcoma. Postoperatively, the patient received heavy-particle radiotherapy at another facility as treatment for the residual tumor. The size of the residual tumor decreased 6 months after the surgery. Up until 1 year after surgery, the patient's condition has remained stable without any disease progression. Epithelioid sarcoma is a rare soft-tissue tumor and often leads to a poor prognosis. We present a case of epithelioid sarcoma occurring in the sigmoid mesocolon.