Duration of Postoperative Fever as a Simple and Useful Prognostic Indicator in Gastric Cancer Patients

[Background] Postoperative inflammation is associated with cancer progression in several cancers. However, the prognostic significance of postoperative fever remains unclear in gastric cancer patients. [Methods] We enrolled 442 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery. [Results] The mean duration of postoperative fever ≥ 37°C was 8.7 days (range: 0–186 days) and significantly longer in patients with advanced gastric cancer, venous invasion, and open or total gastrectomy vs. patients with early gastric cancer (P = 0.0072), no venous invasion (P = 0.025), laparoscopic gastrectomy (P = 0.027), and either proximal or distal partial gastrectomy (P = 0.0015). Five-year overall survival rates were 69.5% vs. 83.6% in the prolonged postoperative fever group (≥ 6 days of ≥ 37°C) vs. the nonprolonged group (< 6 days of ≥ 37°C), respectively (P = 0.0008). In patients without Clavien-Dindo classification postoperative infectious complications grade ≥ 2, 5-year overall survival was 69.7% vs. 84.0% in patients with prolonged postoperative fever vs. those without, respectively (P = 0.0067). Five-year disease-specific survival was 85.9% vs. 93.1% in patients with prolonged fever vs. those without, respectively (P = 0.041). Multivariate analysis indicated that postoperative fever was an independent prognostic indicator. [Conclusion] Postoperative fever ≥ 37°C duration may be useful in predicting prognosis in gastric cancer patients

A Comparison of Gastric Cancer Surgery Between Japan and China

Background: The differences in gastric cancer between East and West have been frequently discussed. However, there are few studies that have compared Japan and China in Asia. Methods: Patient characteristics, surgical procedures and pathologic information were compared among gastric cancer patients who underwent curative-intent gastrectomy at two large volume cancer centers in China and Japan. Results: The median age of Japanese patients is 70 years, seven years older than those in China, and more than 25% of Japanese patients were older than 75. In China, the tumor was thicker, and lymph node metastasis was frequently observed. Total gastrectomy was more common in China (35.6% vs 21.9%). Distal gastrectomy rate was 56.0 percent in Japan, compared to 42.2 percent in China. The proportion of patients undergoing proximal gastrectomy was almost equal in China and Japan. Further analysis of the characteristics of patients undergoing total gastrectomy revealed that in China, more advanced gastric cancer patients with larger tumors and more lymph node metastasis underwent total gastrectomy, while in Japan, more early stage gastric cancer patients underwent total gastrectomy. Conclusion: There are some differences in gastric cancer between Japan and China. China needs to learn from Japan by establishing some screening programs for the diagnosis and treatment of early gastric cancer

Comparisons of Postoperative Complications and Nutritional Status After Proximal Laparoscopic Gastrectomy with Esophagogastrostomy and Double-Tract Reconstruction

[Background] The purpose of this study was to compare postoperative complications and nutritional status between esophagogastrostomy and double-tract reconstruction in patients who underwent laparoscopic proximal gastrectomy, and assess the advantages of both surgical procedures. [Methods] Between 2010 and 2018, 47 cases underwent proximal gastrectomy with esophagogastrostomy (n = 23) or double-tract reconstruction (n = 24) at our institution for the treatment of clinical T1N0 adenocarcinoma located in the upper third of the stomach. Patient clinical characteristics, short-term outcomes, nutrition status, and skeletal muscle index were compared among the two groups. [Results] There was no significant difference between esophagogastrostomy and double-tract reconstruction in terms of operation time, blood loss, and length of postoperative hospital stay. Reflux symptoms and anastomotic stenosis were significantly higher in the esophagogastrostomy group compared with the double-tract reconstruction group (P < 0.001 and P = 0.004, respectively). There was no significant difference in anastomotic leakage, surgical site infection, and pancreatic fistula. For the nutritional status, the decrease rate of cholinesterase was significantly higher in the esophagogastrostomy group compared with the double-tract reconstruction group at 6 months (P = 0.008) There was no significant difference in the decrease rate of skeletal muscle mass index at 1 year after surgery. [Conclusion] Compared with esophagogastrostomy, double-tract reconstruction tends to have better short-term nutritional status and postoperative outcomes in terms of preventing the occurrence of gastroesophageal reflux and anastomosis stenosis. These findings suggest that double-tract reconstruction may be a useful method in laparoscopic proximal gastrectomy

Therapeutic Value of Lymph Node Dissection Along the Superior Mesenteric Vein and the Posterior Surface of the Pancreatic Head in Gastric Cancer Located in theLower Third of the Stomach

【Background】 Therapeutic value of lymph node dissection along the superior mesenteric vein (14v) and the posterior surface of the pancreatic head (13) remains unclear in gastric cancer patients. 【Methods】 We reviewed 355 patients with advanced gastric cancer in the lower third of the stomach who had undergone gastrectomy at our hospital. 【Results】 The frequency of lymph node (LN) metastasis was 10.2% and 7.4% in stations 13 and 14v, respectively. The frequency of station 13 metastasis was 26.8% for T3/T4 tumors with group 2 LNs metastasis and 1.4% for all other tumors. The frequency of station 14v metastasis was 22.2% for T3/T4 tumors with group 2 LNs metastasis and 1.8% for all other tumors. The therapeutic values for dissecting LN stations 13 and 14v were 1.9 and 0.9, respectively, similar to the therapeutic value for group 2 LN dissection. 【Conclusion】 Because metastasis to stations 13 and 14v occurs frequently in patients with T3/T4 gastric cancer located in the lower third of the stomach who also have metastasis to group 2 LNs, stations 13 and 14v should be dissected in these patients

Neuroendocrine Tumor Arising From Meckel’s Diverticulum Unexpectedly Diagnosed After Diverticulectomy and in Which Multiple Lymph Node Metastases Were Found After Reoperation: A Case Report

A 47-year-old man with progressive anemia possibly due to digestive tract bleeding was referred to our hospital. Contrast-enhanced computed tomography of the abdomen showed a 2-cm tumor lesion arising near the small intestine. Enteroscopy revealed a 3-cm submucosal tumor at the ileum. A gastrointestinal stromal tumor of the small intestine was suspected, and the patient underwent surgery. During the operation, a diverticulum approximately 60 cm orad to the terminal ileum and a tumor at the top of the diverticulum were observed. Considering the location, Meckel’s diverticulum was suspected. No lymphadenopathy was present in the mesentery. Laparoscopy-assisted resection of the diverticulum without lymph node dissection was performed. The histological diagnosis of the tumor was a well-differentiated neuroendocrine tumor. Given the possibility of lymph node metastasis, we performed a second operation to remove the small intestine and lymph nodes. Histologically, 7 of the 18 dissected lymph nodes were metastatic. he postoperative course was uneventful, and the patient survived without tumor recurrence for another 2 years 8 months. Neuroendocrine tumors of Meckel’s diverticulum are aggressive. Therefore, small intestinal resection along with lymph node dissection might be necessary as part of the surgical strategy

Postoperative Serum Albumin is a Potential Prognostic Factor for Older Patients with Gastric Cancer

【Background】 The incidence of gastric cancer (GC) among older adults is increasing. Therefore, determining postoperative age-associated prognostic factors is clinically important. This study retrospectively investigated the prognostic significance of serum albumin level in older GC patients. 【Methods】 We enrolled 135 patients aged ? 75 years, who underwent gastrectomies with histopathological diagnoses of gastric adenocarcinoma. 【Results】 Preoperative albumin (pre-Alb) levels in patients with advanced GC and stage III/IV GC were significantly lower than those in patients with early GC (P = 0.0032) and stage I/II GC (P = 0.006), respectively. Postoperative albumin (post-Alb) levels (measured 1 month after surgery) in male patients and in patients with advanced GC were significantly lower than those in female patients (P = 0.024) and those with early GC (P = 0.044), respectively. Post-Alb levels of patients who died of other diseases were significantly lower than those who were still living (P = 0.0004). Prognosis of patients with high post-Alb levels (? 4g/dL) was significantly better than that of patients with low post-Alb levels (< 4g/dL; P = 0.045); and in multivariate analysis, post-Alb level was an independent prognostic indicator. 【Conclusion】 Post-Alb level is a useful predictive factor for the prognosis of older GC patients. Postoperative nutritional support might help improve the prognosis of older GC patients

Platelet-to-Lymphocyte Ratio Multiplied by the Cytokeratin-19 Fragment Level as a Predictor of Pathological Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma

[Background] The standard treatment for resectable advanced esophageal squamous cell carcinoma in Japan is surgery followed by neoadjuvant chemotherapy, and it is important to predict the effect of neoadjuvant chemotherapy before treatment. Therefore, this study aims to extract conventional blood examination data, such as tumor markers and/or inflammatory/nutritional index levels, that can predict the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy. [Methods] We retrospectively analyzed the medical records of 66 patients with thoracic esophageal squamous cell carcinoma who received neoadjuvant chemotherapy, followed by curative esophagectomy at Tottori University Hospital between June 2009 and December 2019. [Results] We demonstrated that the product of the platelet-to-lymphocyte ratio (PLR) multiplied by the cytokeratin-19 fragment (CYFRA) level, which was termed “PLR-CYFRA,” is the most accurate indicator that predicts the pathological response to neoadjuvant chemotherapy, with the highest area under the curve [0.795 (95% confidence interval: 0.665–0.925), P < 0.001] in receiver operating characteristic analyses. Therefore, we divided patients into the PLR-CYFRALow (< 237.6, n = 21) and PLR-CYFRAHigh (≥ 237.6, n = 45) groups and found that the percentage of PLR-CYFRALow was significantly higher in patients with a better pathological response (P < 0.001). Furthermore, patients with good pathological response had significantly better prognoses in terms of disease-specific survival (P = 0.014), recurrence-free survival (P = 0.014), and overall survival (P = 0.032). In the multivariate analysis, PLR-CYFRA was an independent predictor of the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy (P = 0.002). [Conclusion] Pretreatment PLR-CYFRA might be a useful and simple tool that predicts the pathological effect of neoadjuvant chemotherapy in esophageal squamous cell carcinoma

Carcinosarcoma of Stomach Confined to the Mucosa

Carcinosarcoma is a malignant tumor composed of both epithelial and mesenchymal malignant tumor components. A 78-year-old man was transferred to our hospital because of hematemesis and tarry stool. An emergency gastrointestinal endoscopic examination revealed active bleeding from an ulcerative lesion on the posterior wall of the gastric body; endoscopic hemostasis was successfully performed. A gastrointestinal endoscopy performed two months later showed a polypoid lesion at the same place where the ulcer had been. The biopsy specimen was histologically diagnosed as well to moderately differentiated tubular adenocarcinoma. The patient underwent a laparoscopic distal gastrectomy with D2 lymph node dissection under a diagnosis of gastric adenocarcinoma. A 28 × 15 mm polypoid tumor was resected from the gastric body, and was found on microscopic examination to consist of both carcinoma and sarcoma components, showing atypical spindle cells, which were positive for α-smooth muscular actin, calponin, and h-caldesmon, but negative for CD34, CD117 (c-kit), desmin, and dog 1. These findings led to a diagnosis of gastric carcinosarcoma. The tumor was confined to the mucous membrane. Lymph node metastasis was found in one node and contained only the carcinoma component. The postoperative course was uneventful. The patient lived without recurrence for 2 years. Carcinosarcoma of the stomach is a rare tumor with high malignant potential and poor prognosis. Careful follow up is required for early detection of any recurrence

Anti-Tumor Effect against Human Cancer Xenografts by a Fully Human Monoclonal Antibody to a Variant 8-Epitope of CD44R1 Expressed on Cancer Stem Cells

BACKGROUND: CD44 is a major cellular receptor for hyaluronic acids. The stem structure of CD44 encoded by ten normal exons can be enlarged by ten variant exons (v1-v10) by alternative splicing. We have succeeded in preparing MV5 fully human IgM and its class-switched GV5 IgG monoclonal antibody (mAb) recognizing the extracellular domain of a CD44R1 isoform that contains the inserted region coded by variant (v8, v9 and v10) exons and is expressed on the surface of various human epithelial cancer cells. METHODS AND PRINCIPAL FINDINGS: We demonstrated the growth inhibition of human cancer xenografts by a GV5 IgG mAb reshaped from an MV5 IgM. The epitope recognized by MV5 and GV5 was identified to a v8-coding region by the analysis of mAb binding to various recombinant CD44 proteins by enzyme-linked immunosorbent assay. GV5 showed preferential reactivity against various malignant human cells versus normal human cells assessed by flow cytometry and immunohistological analysis. When ME180 human uterine cervix carcinoma cells were subcutaneously inoculated to athymic mice with GV5, significant inhibition of tumor formation was observed. Furthermore, intraperitoneal injections of GV5markedly inhibited the growth of visible established tumors from HSC-3 human larynx carcinoma cells that had been subcutaneously transplanted one week before the first treatment with GV5. From in vitro experiments, antibody-dependent cellular cytotoxicity and internalization of CD44R1 seemed to be possible mechanisms for in vivo anti-tumor activity by GV5. CONCLUSIONS: CD44R1 is an excellent molecular target for mAb therapy of cancer, possibly superior to molecules targeted by existing therapeutic mAb, such as Trastuzumab and Cetuximab recognizing human epidermal growth factor receptor family