Prognostic factors for gastric cancer patients aged ≥ 85 years.

BACKGROUND: As gastric cancer patients aged ≥ 85 years have a short life expectancy and often die from other diseases such as pneumonia, indications for surgery are controversial. In this study, we retrospectively analyzed the prognostic factors of elderly patients with gastric cancer who are candidates for curative gastrectomy. METHODS: Among 114 patients aged ≥ 85 years with gastric cancer at our hospital between 2010 and 2019, prognostic factors were examined using the Cox proportional hazards model in 76 patients excluding those with cStage IVB or endoscopic submucosal dissection. We also analyzed the factors of pneumonia death. RESULTS: cStage was I/IIA/IIB/III/IVA in 37/6/14/14/5 patients, respectively. Treatment included distal gastrectomy in 28 patients, total gastrectomy in 6, local resection in 9, others in 3, and no surgery in 30. In univariate analyses of overall survival, Eastern Cooperative Oncology Group Performance Status, physiological score of Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM), Onodera's prognostic nutritional index, cStage, and treatment were prognostic factors. In a multivariate analysis, POSSUM physiological score, cStage, treatment method {no surgery vs. distal gastrectomy: hazard ratio (HR) 5.78, 95% confidence interval (CI) 2.33-14.3}, (total gastrectomy vs. distal gastrectomy: HR 4.26, 95% CI 1.22-14.9) were independent prognostic factors. In univariate analyses of pneumonia-specific survival, treatment (total gastrectomy vs. distal gastrectomy: HR 6.98, 95% CI 1.18-41.3) was the only prognostic factor. CONCLUSIONS: The prognosis of distal gastrectomy was better than that of non-surgery even in patients aged ≥ 85 years. However, total gastrectomy was considered to be avoidable due to the high rate of postoperative pneumonia death.

High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer.

BACKGROUND: To improve the prognosis of patients with metastatic colorectal cancer (mCRC), investigating predictive biomarkers of their prognosis and chemotherapeutic responsiveness is necessary. This study aimed to analyze the clinical significance of serum proteinase-3 (PRTN3) as a predictor for prognosis and chemosensitivity, especially to bevacizumab therapy, in mCRC. METHODS: This single-center retrospective observational study enrolled 79 patients with mCRC in our hospital and 353 patients with colorectal cancer in the TCGA database. Preoperative serum PRTN3 levels were measured using an enzyme-linked immunosorbent assay. The clinicopathological characteristics and prognosis according to serum PRTN3 levels were then evaluated. PRTN3 expression in tumor and stromal cells was evaluated immunohistochemically. The impact of PRTN3 levels on angiogenesis and bevacizumab sensitivity was evaluated using the tube formation assay. RESULTS: Serum PRTN3 levels were an independent poor prognostic factor for progression-free survival (PFS) (hazard ratio, 2.082; 95% confidence interval, 1.118-3.647; P=0.010) in patients with mCRC. Similarly, prognostic analysis with TCGA data sets showed poorer overall survival in patients with PRTN3 expression than that in patients without PRTN3 expression, especially in patients with stage IV. Immunohistochemical analysis of resected specimens revealed that stromal neutrophils expressed PRTN3, and their expression level was significantly correlated with serum PRTN3 levels. Interestingly, the effectiveness of first-line chemotherapy was significantly poorer in the high serum PRTN3 level group. High serum PRTN3 was significantly associated with poor PFS (hazard ratio, 3.027; 95% confidence interval, 1.175-7.793; P=0.0161) in patients treated with bevacizumab, an anti-angiogenic inhibitor. The tube formation assay revealed that PRTN3 administration notably augmented angiogenesis while simultaneously attenuating the anti-angiogenic influence exerted by bevacizumab therapy. CONCLUSIONS: Serum PRTN3 levels could be a novel predictive biomarker of PFS of first-line chemotherapy, especially for bevacizumab therapy, in patients with mCRC.

Optimization of decellularization methods using human small intestinal submucosa for scaffold generation in regenerative medicine.

Porcine small intestinal submucosa, despite its successful use as a scaffold in regenerative medicine, has innate biomechanical heterogeneity. In this study, we hypothesized that human small intestinal submucosa could be a viable alternative bio-scaffold. For the first time, we characterize submucosal extraction from human small intestine and examine appropriate decellularization methods. In total, 16 human small intestinal submucosal samples were obtained and decellularized using three reported methods of porcine decellularization: Abraham, Badylak, and Luo. For each method, four specimens were decellularized. The remaining four specimens were designated as non-decellularized. We measured the amount of residual DNA and growth factors in decellularized human intestinal samples. Additionally, decellularized human small intestinal submucosa was co-cultured with mouse bone marrow-derived mesenchymal stem cells to examine mesenchymal stem cell survival and proliferation. The reference value for the amount of residual DNA deemed appropriate in decellularized tissue was established as 50 ng/mg of extracellular matrix dry weight or less. Abraham's method most successfully met this criterion. Measurement of residual growth factors revealed low levels observed in samples decellularized using the Abraham and Badylak methods. Co-culture of each small intestinal submucosal sample with mouse bone marrow-derived mesenchymal stem cells confirmed viable cell survival and proliferation in samples derived using protocols by Abraham and Badylak. Abraham's method most successfully met the criteria for efficient tissue decellularization and cell viability and proliferation. Thus, we consider this method most suitable for decellularization of human small intestinal submucosa.

IL-6 Levels Correlate with Prognosis and Immunosuppressive Stromal Cells in Patients with Colorectal Cancer.

BACKGROUND: The prognosis for patients with colorectal cancer (CRC) is determined by tumor characteristics as well as the host immune response. This study investigated the relationship between an immunosuppressive state and patient prognosis by evaluating the systemic and tumor microenvironment (TME) interleukin (IL)-6 levels. METHODS: Preoperative serum IL-6 levels were measured using an electrochemiluminescence assay. Expression of IL-6 in tumor and stromal cells was evaluated immunohistochemically in 209 patients with resected CRC. Single-cell analysis of tumor-infiltrating immune cells was performed using mass cytometry in 10 additional cases. RESULTS: Elevated serum IL-6 levels were associated with elevated stromal IL-6 levels and a poor prognosis for patients with CRC. High IL-6 expression in stromal cells was associated with low-density subsets of CD3+ and CD4+ T cells as well as FOXP3+ cells. Mass cytometry analysis showed that IL-6+ cells among tumor-infiltrating immune cells were composed primarily of myeloid cells and rarely of lymphoid cells. In the high-IL-6-expression group, the percentages of myeloid-derived suppressor cells (MDSCs) and CD4+FOXP3highCD45RA- effector regulatory T cells (eTreg) were significantly higher than in the low-IL-6-expression group. Furthermore, the proportion of IL-10+ cells in MDSCs and that of IL-10+ or CTLA-4+ cells in eTregs correlated with IL-6 levels. CONCLUSION: Elevated serum IL-6 levels were associated with stromal IL-6 levels in CRC. High IL-6 expression in tumor-infiltrating immune cells also was associated with accumulation of immunosuppressive cells in the TME.

The comparison of prognoses between total and distal gastrectomy for gastric cancer in elderly patients ≥ 80 years old.

PURPOSE: In Japan, the number of distal gastrectomy for patients ≥ 80 years old is increasing, whereas that of total gastrectomy is decreasing. Surgeons seem to avoid total gastrectomy for elderly patients. Total gastrectomy is reported to have a poorer prognosis than distal gastrectomy, and postoperative pneumonia may be involved in the cause. METHODS: The medical records of 39 and 108 patients ≥ 80 years old who underwent total and distal gastrectomy, respectively, at 2 affiliated institutions between 2010 and 2019 were retrospectively reviewed. Prognoses were compared between the two groups, focusing on death from pneumonia. RESULTS: The median overall survival time after total and distal gastrectomy was 21.3 and 74.1 months, respectively, with a significantly poorer prognosis after total gastrectomy than after distal gastrectomy (p < 0.01, hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.37-3.53). The gastric cancer-specific survival time was significantly worse after total gastrectomy than after distal gastrectomy (p < 0.01, HR 2.73, 95% CI 1.29-5.79). The pneumonia-specific survival time was also significantly worse after total gastrectomy than after distal gastrectomy (p = 0.01, HR 3.44, 95% CI 1.25-9.48). CONCLUSIONS: Patients who underwent total gastrectomy had a poorer prognosis than those who underwent distal gastrectomy, because many patients died of pneumonia early after total gastrectomy.

Impact of the hospital volume and setting on postoperative complications of surgery for gastroenterological cancers in a regional area of Western Japan.

PURPOSE: A research subgroup was established by the Japanese Society of Gastroenterological Surgery to improve the health care quality in the Chushikoku area of Western Japan. METHODS: The records of four surgical procedures were extracted from the Japanese National Clinical Database and analyzed retrospectively to establish the association between hospital characteristics, defined using a combination of hospital case-volume and patients' hospital travel distance, and the incidences of perioperative complications of ≥ Grade 3 of the Clavien-Dindo classification after gastroenterological surgery. RESULTS: This study analyzed 11,515 cases of distal gastrectomy for gastric cancer, 4,705 cases of total gastrectomy for gastric cancer, 4,996 cases of right hemicolectomy for colon cancer, and 5,243 cases of lower anterior resection for rectal cancer, with composite outcome incidences of 5.6%, 10.2%, 5.5%, and 10.7%, respectively. After adjusting for patient characteristics and surgical procedures, no association was identified between the hospital category and surgical outcomes. CONCLUSION: The findings of our study of the Chushikoku region did not provide positive support for the consolidation and centralization of hospitals, based solely on hospital case volume. Our grouping was unique in that we included patient travel distance in the analysis, but further investigations from other perspectives are needed.

[A Case of Stage â £c dMMR Transverse Colon Cancer with Complete Response to Combination Therapy with Immune Checkpoint Inhibitor in Stage â £B Lung Adenocarcinoma].

The patient is a 72-year-old man. He was diagnosed as a duplication of left upper lobe lung adenocarcinoma cStage ⅣB and transverse colon cancer cStage Ⅳc. Because he had symptoms of atelectasis and esophageal stricture due to the progression of lung cancer, we decided to precede immunochemotherapy(CBDCA plus PEM plus pembrolizumab)for lung cancer. After the start of treatment, both lung and colorectal cancer were shrinking, but after the 3 courses of treatment, he developed intestinal obstruction due to transverse colon cancer. Because generalized peritonitis due to perforation of the colon by endoscopic stenting for the obstruction and then emergency surgery was performed. The resected transverse colon lesion was diagnosed as pathologically complete response. Lung cancer was also diagnosed as clinically complete response. Since his ADL decreased postoperatively, he is under observation without reintroduction of immunochemotherapy. Fourteen months have passed since the last administration, and no progression has been observed in either lung nor colon cancers. Pembrolizumab is considered to be successful in the patient with dMMR colorectal cancer lacking MLH1 and PMS2.

[A Curatively Resected Case of Recto-Sigmoidal Cancer with Massive Bladder Invasion after Multimodal Therapy Including Chemotherapy].

A 68-year-old male patient was referred to our hospital because of unfit to treat his recto-sigmoidal cancer massively invaded to bladder at the former hospital. During drug administration to treat heart failure, we could perform a transverse colostomy and initiated mFOLFOX plus Pmab. During chemotherapy, he improved malnutrition. After 7 courses, CT scan showed a marked reduction in tumor diameter, which was PR. Since his nutritional and heart status were improved, he underwent a high anterior resection with partial bladder resection. Pathological findings showed that a few cancer cells were remained at bladder and bowel wall. He was diagnosed as Stage Ⅱc. His postoperative course was almost uneventful. No symptom of recurrence has been observed at 9 months after surgery without adjuvant chemotherapy.

[A Case of Liver Metastasis of Gastric Cancer Successfully Treated with SOX plus Nivolumab].

An 82-year-old, male. He visited his local doctor with a chief complaint of dyspnea on exertion. Anemia was noted, and upper gastrointestinal endoscopy was performed, which revealed an ulcerative lesion in the gastric antrum. A biopsy revealed Group 5, tub2, and HER2 negative, with PD-L1≥5%. cT3N1H1(M1 HEP), cStage ⅣB was diagnosed based on CT scan showing enlarged #8 lymph node and a single liver metastasis in the 2 cm range in S6 of the liver. The patient was deemed unresectable and was started on SOX plus nivolumab therapy. On day 11 after initiation, the patient had Grade 3 diarrhea by CTCAE v5.0, and S-1 was withdrawn for 3 days, but was administered for 2 courses. CT and MRI after chemotherapy showed shrinkage of both the primary tumor and liver metastases; R0 resection was deemed possible, and pyloric gastrectomy, D2 lymph node dissection, and partial hepatic S6 resection were performed. The histological evaluation of response to treatment was Grade 1b, and the patient was in ypStage ⅠA. The patient has been alive without recurrence for 6 months postoperatively while receiving S-1 monotherapy on an outpatient basis.

The prognostic significance of preoperative nutritional/inflammatory markers and clinicopathological features in resectable esophagectomy patients: possibility of nutritional intervention.

BACKGROUND: Preoperative inflammatory or nutritional biomarkers and clinicopathological features may be survival predictors in resectable esophageal squamous cell carcinoma. METHODS: We included 118 patients with resectable squamous esophageal carcinoma (stages I-IV), assessing preoperative CRP- and albumin-based modified Glasgow prognostic score, the modified controlling nutritional status score, C-reactive protein, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, pathologic stage, and tumor location(s), looking for correlation with overall survival and relapse-free survival. Using univariate and Cox analysis, we selected the most reliable prognostic factors. RESULTS: Five-year overall survival and recurrence-free survival were 54.9% and 48.5%, respectively. C-reactive protein values correlated negatively with hypoalbuminemia (P = 0.0036). On univariate analysis, tumor stage, invasion depth, location, nodal involvement, albumin, and modified Glasgow prognostic score were significant prognostic factors for overall and recurrence-free survival. Preoperative C-reactive protein was prognostic factor for overall survival, but not for relapse-free survival (P = 0.017, 0.063, respectively). The Cox proportional hazards model showed the modified Glasgow prognostic score to be an independent prognostic factor for relapse-free survival and overall survival after using the stepwise variable selection procedure. Cox analysis including clinicopathological factors and modified Glasgow prognostic scores showed that only tumor location(s) and pathologic stage were independent prognostic factors for overall survival and recurrence-free survival. CONCLUSION: Although the modified Glasgow prognostic score is not superior to pathologic stage and tumor location as a biomarker of preoperative nutrition/inflammation and clinicopathological factors, it remains an important prognostic marker in resectable esophageal cancers. Preoperative decreased inflammatory response and improved nutritional status may contribute to prognosis in patients with esophageal cancer.

CD4 and FOXP3 as predictive markers for the recurrence of T3/T4a stage II colorectal cancer: applying a novel discrete Bayes decision rule.

BACKGROUND: We recently reported the relapse-free survival (RFS) significance of the combination of CD4+ and forkhead box P3+ (FOXP3) T-cell densities identified by immunohistochemistry in patients with stage I, II, and III colorectal cancer (CRC) who underwent curative resections. This study was designed to determine the optimal combination of markers that predict recurrence in patients with T factors of T3/T4a stage II CRC by applying a novel Bayes decision rule. METHODS: Using 137 cancer tissue specimens from T3/T4a stage II patients, 12 clinicopathologic and immune factors were analysed as predictive candidates for recurrence. RESULTS: Our study showed that the combination of low CD4+ and low FOXP3+ T-cell densities resulted in extremely poor RFS. CONCLUSIONS: Adjuvant chemotherapy may be considered for patients with a combination of low CD4+ and low FOXP3+ T-cell densities. The discovery of this new prognostic indicator is important for the appropriate management of patients undergoing curative resection for T3/T4a stage II CRC.

Subjective factors affecting prognosis of 469 patients with esophageal squamous cell carcinoma: a retrospective cohort study of endoscopic screening.

BACKGROUND: To date, no in-depth studies have focused on the impact of various clinical characteristics of esophageal squamous cell carcinoma (ESCC), including its association with subjective symptoms, on patient prognosis. We aimed to investigate the clinical factors that affect the prognosis of patients with ESCC and to clarify how subjective symptoms are related to prognosis. METHODS: We retrospectively evaluated the clinical records of 503 consecutive patients with ESCC from April 2011 to December 2019. Six established prognostic factors for ESCC (body mass index, alcohol drinking, cigarette smoking, sex, clinical stage, and age) and subjective symptoms were used to subgroup patients and analyze survival differences. Next, the patients were divided into two groups: a symptomatic group and an asymptomatic group. In the symptomatic group, differences in the incidence of subjective symptoms according to tumor size, tumor location, macroscopic tumor type, and clinical stage were examined. Finally, subjective symptoms were divided into swallowing-related symptoms and other symptoms, and their prognosis was compared. RESULTS: Multivariate Cox regression analysis identified sex [hazard ratio (HR) 1.778; 95% CI 1.004-3.149; p = 0.049], TNM classification (HR 6.591; 95% CI 3.438-12.63; p < 0.001), and subjective symptoms (HR 1.986; 95% CI 1.037-3.803; p = 0.0386) as independent risk factors for overall survival. In the symptomatic group, the mean time from symptom onset to diagnosis was 2.4 ± 4.3 months. The incidence of subjective symptoms differed by clinical stage, and the prognosis of patients with swallowing-related symptoms was significantly worse than that of patients with other symptoms. CONCLUSION: The results of this study suggest that screening by upper gastrointestinal endoscopy, independent of subjective symptoms (especially swallowing-related symptoms), may play an important role in the early detection and improvement of prognosis of ESCC, although further validation in a large prospective study is needed.

Prognostic factors for elderly gastric cancer patients who underwent gastrectomy.

BACKGROUND: Patients with gastric cancer are aging in Japan. It is not clear which patients and which surgical procedures have survival benefits after gastrectomy. A multivariate analysis was performed. METHODS: The medical records of 166 patients aged ≥ 80 years who underwent gastrectomy without macroscopic residual tumors were retrospectively reviewed. Univariate and multivariate analyses using Cox proportional hazard models were performed to detect prognostic factors for overall survival. RESULTS: In univariate analyses, age (≥ 90 vs. ≥ 80, < 85), performance status (3 vs. 0), American Society of Anesthesiologists physical status (ASA-PS) (3, 4 vs. 1, 2), Onodera's prognostic nutritional index (< 40 vs. ≥ 45), the physiological score of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) (≥ 40 vs. ≥ 20, ≤ 29), surgical approach (laparoscopic vs. open), extent of gastrectomy (total, proximal vs. distal), extent of lymphadenectomy (D1 vs. ≥ D2), pathological stage (II-IV vs. I), and residual tumor (R1 vs. R0) were significantly correlated with worse overall survival. Multivariate analysis revealed that ASA-PS [3, 4 vs. 1, 2, hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.24-4.24], extent of gastrectomy (total vs. distal, HR 2.17, 95% CI 1.10-4.31) (proximal vs. distal, HR 4.05, 95% CI 1.45-11.3), extent of lymphadenectomy (D0 vs. ≥ D2, HR 12.4, 95% CI 1.58-97.7), and pathological stage were independent risk factors for mortality. CONCLUSIONS: ASA-PS was a useful predictor for postoperative mortality. Gastrectomy including cardia is best avoided.

Survival analyses of elderly gastric cancer patients with or without surgery.

PURPOSE: Deciding whether or not surgery should be performed for elderly patients is sometimes difficult. This study examined the prognosis of patients ≥ 80 years old with gastric cancer who underwent surgery or not. METHODS: The medical records of 111 patients who underwent surgery (surgery group) and 35 who received best supportive care (BSC group) were retrospectively reviewed, excluding those with clinical stage IVB disease, those with a performance status of 4, and those who underwent endoscopic submucosal dissection. The overall survival was compared between the two groups. RESULTS: The patients in the BSC group were significantly older and had worse performance status scores, worse physiological scores, and lower prognostic nutritional indexes than those in the surgery group. The patients in the surgery group showed a significantly better survival than those in the BSC group (median survival time, 38.9 vs. 11.4 months; p = 0.01) even after propensity score matching. In the subgroups of patients ≥ 90 years old and those with a performance status of 3, no marked difference in the survival between the 2 groups was observed. CONCLUSIONS: Surgery imbued a survival benefit to elderly gastric cancer patients, except for those ≥ 90 years old and those with a performance status of ≥ 3. The surgical indication of patients ≥ 90 years old and those with a performance status of ≥ 3 requires careful deliberation.

[Long-Term Survival following Multidisciplinary Therapy for Unresectable Pancreatic Body Cancer].

A 57-year-old man was diagnosed with a tumor in the pancreatic body at a nearby hospital and consulted our hospital. Examinations revealed that carbohydrate antigen 19-9(CA19-9)levels were 1,765.0 U/mL. We confirmed metastatic liver tumors in S4 and S8 of the liver by EOB-MRI. We diagnosed unresectable pancreatic cancer(T3N0M1, cStage Ⅳ)and administered 10 courses of gemcitabine(GEM)plus nab-paclitaxel(nab-PTX)therapy. The main lesion and the lesion in S4 subsequently disappeared, and the lesion in S8 degenerated into a cyst. CA19-9 levels were 113 U/mL. Surgery was determined as the best course of action after normalizing CA19-9 levels. Therefore, we further administered 6 courses of FOLFIRINOX therapy and 4 courses of GEM plus nab-PTX therapy, but CA19-9 was not normalized. We decided that it would be difficult to normalize CA19-9, and thus proceeded with surgery. During the operation, cystic degenerative lesions were found in S8 and peritoneal dissemination was found in the transverse mesentery. Because the ascites cytopathology was negative, it was judged that the peritoneal dissemination was localized. We performed distal pancreatectomy(D2)plus partial hepatectomy(S8)plus peritoneal dissemination resection. On day 52 after surgery, we resumed GEM plus nab-PTX. The patient has survived without any recurrence for 3 years after the initial surgery.

Novel adjuvant dendritic cell therapy with transfection of heat-shock protein 70 messenger RNA for patients with hepatocellular carcinoma: a phase I/II prospective randomized controlled clinical trial.

INTRODUCTION: A proteomic analysis of hepatocellular carcinoma (HCC) has revealed that Heat Shock Protein 70 (HSP70) is among the cancer antigen proteins of HCC. Moreover, we confirmed that HSP70 was highly expressed in HCC by immunohistochemical staining. Based on these results, we developed an HSP70 mRNA-transfected dendritic cell (DC) therapy for treating unresectable or recurrent HCC, and the phase I trial was completed successfully. Thus, we aimed to investigate the safety and efficacy of this therapy as a postoperative adjuvant treatment after curative resection for HCC to prevent recurrence by conducting a phase I/II randomized controlled clinical trial. METHODS: Patients (n = 45) with resectable HCC of stages II-IVa were registered and randomly assigned into two groups (DC group: 31 patients, control group: 14 patients) before surgery. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were safety and overall survival. The DC therapy was initially administered at approximately 1 week after surgery, and twice every 3-4 weeks thereafter. RESULTS: No adverse events specific to the immunotherapy were observed in the DC group. There was no difference in DFS between the DC and control groups (p = 0.666). However, in the subgroup with HSP70-expressing HCC, DFS of the DC group tended to be better (p = 0.090) and OS of the DC group was significantly longer (p = 0.003) than those of the control group. CONCLUSION: The HSP70 mRNA-transfected DC therapy was performed safely as an adjuvant therapy. The prognosis of HSP70-expressing HCC cases could be expected to improve with this therapy.

Prognostic factors for cytology-positive gastric cancer: a multicenter retrospective analysis.

BACKGROUND: The prognosis of patients with gastric cancer and positive peritoneal lavage cytology is poor, even after gastrectomy. Though the standard therapy for this population is radical gastrectomy followed by S-1 chemotherapy, treatments vary among institutions and eras. We conducted a multicenter retrospective study to investigate the prognostic factors for cytology-positive gastric cancer. METHODS: We reviewed the medical records obtained from 6 institutions, covering 2000-2019. There were 128 patients with positive cytology and no other distant metastases that underwent R1 gastrectomy. Univariate and multivariate analyses to identify prognostic factors for overall survival were conducted using Cox's proportional hazards models. RESULTS: The median overall survival time was 18.6 months. In univariate analyses, age (≥ 80 years vs. < 70 years), performance status (2, 3 vs. 0), prognostic nutritional index (< 35 vs. ≥ 40), the extent of lymphadenectomy (D1 vs. ≥ D2), macroscopic type (type 4 vs. non-type 4), and postoperative chemotherapy (none vs. S-1) were significantly correlated with worse survival. Multivariate analysis revealed that lymph node metastasis (pN3b vs. pN0, hazard ratio 4.46, 95% confidence interval 1.17-16.9, p = 0.03) and postoperative chemotherapy (none vs. S-1, hazard ratio 2.28, 95% confidence interval 1.16-4.45, p = 0.02) were independent risk factors for death. No postoperative chemotherapy regimen showed a survival benefit over S-1 monotherapy. CONCLUSIONS: Massive lymph node metastasis was an independent risk factor in cytology-positive gastric cancer. Postoperative chemotherapy was also an independent prognostic factor, though the most beneficial regimen was still uncertain.

Determining the protective characteristics and risk factors for the development of anastomotic leakage after low anterior resection for rectal cancer.

PURPOSE: Anastomotic leakage is one of the most serious postoperative complications associated with surgery for rectal cancer. The present study aimed to identify the protective characteristics and risk factors associated with anastomotic leakage after low anterior resection for rectal cancer. METHODS: This was a retrospective, single-center study conducted between January 2009 and December 2017 at our institution. In total, 136 rectal cancer patients who underwent low anterior resection were included in the study. We analyzed preoperative and intraoperative factors. In addition, the pelvic dimensions were measured using computed tomography in all cases. RESULTS: Among the 136 patients, anastomotic leakage occurred in 21 (15.4%), including 18 males and 3 females. The median body mass index was 21.1 kg/m2. The construction of a covering stoma was found to be a protective factor. In addition, the operation time (≥ 373 min), intraoperative blood loss (≥ 105 ml), and size of the pelvic inlet (≥ 113 mm) were identified as risk factors for anastomotic leakage. CONCLUSION: The construction of a covering stoma was a possible protective factor. However, a longer operation time, higher intraoperative blood loss, and larger pelvic inlet dimensions were possible risk factors for developing anastomotic leakage after low anterior resection in patients with rectal cancer.

[A Resected Case of Advanced Lower Rectal Cancer with Neoadjuvant Chemotherapy by FOLFOXIRI plus Cetuximab].

Although the current standard of care for patients with lower rectal cancer in Japan includes total mesorectal resection with lateral lymph node dissection, postoperative local and distant recurrence rates are high. Multidisciplinary treatment is important to improve the prognosis. A man in his 30s was diagnosed with lower rectal cancer due to bloody stool and referred to our department. He was diagnosed as cT3N3M0, cStage Ⅲc with right obturator lymph node metastasis. Four courses of neoadjuvant chemotherapy(NAC)with FOLFOXIRI plus cetuximab were performed. Because Grade 3 neutropenia was observed in the first cycle(CTCAE v5.0), pegfilgrastim was administered in the second and subsequent cycles, and NAC was completed without dose reduction. The patient underwent laparoscopy-assisted intersphincteric rectal resection and D3+rtLD2 dissection. Histopathological resection margins were negative, and the resection was R0. Lymph node metastasis was found only in No. 263d-rt, and the pathological diagnosis was ypT3N3M0, pStage Ⅲc. Histological evaluation of response to treatment was Grade 2. The postoperative course was good and the patient was discharged on postoperative day 15. The patient received 8 courses of adjuvant chemotherapy with mFOLFOX6 from the 7th postoperative week and is alive and recurrence-free 6 months after surgery.

[A Case of Pancreas Neuroendocrine Carcinoma Achieved Long-Term Survival by Carboplatin plus Etoposide Therapy].

A 70-year-old man with the history of diabetes mellitus complained of lower abdominal discomfort. Abdominal ultrasonography revealed a pancreatic mass. Contrast enhanced CT showed a 2.6 cm-enhanced tumor ventral to the pancreatic head. It was diagnosed with a pancreatic neuroendocrine carcinoma(PanNEC-G3)by EUS-FNA. The patient underwent pancreatoduodenectomy with the wedge resection of the portal vein and partial resection of the transverse colon. We administered 6 cycles of adjuvant therapy with CDDP plus CPT-11. With the presentation of lymph node metastases and the local recurrence in the anastomotic site of the transverse colon 15 months after surgery, the patient received carboplatin plus etoposide(CE)therapy. Although local recurrence completely responded to the CE therapy, bone metastases were detected 27 months after surgery. Metastatic lesion did not respond to systemic chemotherapy including gemcitabine plus nab-paclitaxel and nal-IRI plus 5-FU/LV, and the patient eventually died 37 months after the surgery. PanNECs represent for less than 1% of all pancreatic tumor. They are characterized by high malignant potential and short time survival with the reported OS of 8.5 to 21 months. This case served as an important reminder to consider multimodal treatment for PanNEC patients to obtain longer survival.