Multicenter phase II study of capecitabine plus oxaliplatin in older patients with advanced gastric cancer: the Tokyo Cooperative Oncology Group (TCOG) GI-1601 study.

BACKGROUND: Capecitabine plus oxaliplatin (CapeOX) is a standard treatment option for advanced gastric cancer (AGC). We conducted a prospective multicenter phase II study to evaluate the efficacy and safety of CapeOX as a first-line therapy for AGC in older patients. METHODS: Chemotherapy-naive patients aged ≥ 70 years with AGC were eligible. Initial treatment comprised capecitabine (2000 mg/m2 on days 1-14) and oxaliplatin (130 mg/m2 on day 1) every 3 weeks. After the initial feasibility assessment, the dose was reduced considering toxicity (capecitabine, 1500 mg/m2 on days 1-14; and oxaliplatin, 100 mg/m2 on day 1 every 3 weeks). The primary endpoint was overall survival (OS). RESULTS: In total, 108 patients were enrolled, of whom 104 were evaluated. Thirty-nine patients received the original-dose treatment, whereas 65 received the reduced-dose treatment. The median OS, progression-free survival (PFS), and time to treatment failure (TTF) were 12.9 (95% CI 11.6-14.8), 5.7 (95% CI 5.0-7.0), and 4.3 (95% CI 3.9-5.7) months, respectively, for all patients; 13.4 (95% CI 9.5-16.0), 5.8 (95% CI 4.1-7.8), and 5.3 (95% CI 3.5-7.2) months in the original-dose group; and 12.8 (95% CI 11.3-15.3), 5.7 (95% CI 4.4-7.0), and 4.1 (95% CI 3.7-5.7) months in the reduced-dose group. The most common grade 3/4 toxicities were neutropenia (17.9%), anemia (12.8%), and thrombocytopenia (12.8%) in the original-dose group and neutropenia (13.8%) and anorexia (12.3%) in the reduced-dose group. CONCLUSIONS: These findings demonstrate CapeOX's efficacy and safety in older AGC patients.

A descriptive comparison of postoperative outcomes between hybrid mediastino-thoracoscopic approach and conventional thoracoscopic esophagectomy for esophageal cancer.

BACKGROUND: The purpose of this study was to compare the results of the hybrid mediastino-thoracoscopic approach with that of the conventional thoracoscopic approach and to identify the advantages and disadvantages of the hybrid approach. METHODS: We retrospectively analyzed 172 patients who underwent thoracoscopic esophagectomy for esophageal cancer from July 2009 to June 2021, excluding salvage surgery. In the mediastinoscopic approach, the lymph nodes were dissected from a small incision in the left aspect of the neck to the aortic arch with supine double-lung ventilation. Thereafter, the middle-to-lower mediastinum and right superior mediastinum were dissected thoracoscopically in the prone position. The patients' demographics, surgical outcomes, postoperative complications, and postoperative recurrence patterns were compared between 51 patients in the hybrid approach and 121 patients in the conventional approach. RESULTS: The hybrid group had more elderly patients (71 years vs. 67 years; P = 0.010), more cardiovascular disease (33.3% vs. 16.7%; P = 0.021), lower rates of preoperative chemotherapy (49.0% vs. 69.4%; P = 0.015), and shorter right lung collapse time (196 min vs. 264 min; P < 0.001). Postoperative hoarseness was not different between the two groups (31.4% vs. 27.3%; P = 0.584), and there was a significant difference in the sternal-vertebral distance at the level of the sternal notch (41 mm in the hybrid group vs. 48 mm in the conventional group; P = 0.029). The sternal-vertebral distance of less than 45 mm was an independent risk factor for postoperative hoarseness in the logistic analysis (odds ratio 3.636, 95% confidence interval 1.054-12.546; P = 0.041). CONCLUSION: The hybrid mediastino-thoracoscopic approach could be safely adapted to elderly or cardiopulmonary diseased patients; however, short sternal-vertebral distance might be a risk factor of postoperative recurrent laryngeal nerve palsy.

Meta-analysis of three randomized trials of capecitabine plus cisplatin (XP) versus S-1 plus cisplatin (SP) as first-line treatment for advanced gastric cancer.

BACKGROUND: S-1 plus cisplatin (SP) and capecitabine plus cisplatin (XP) are standard first-line regimens for advanced gastric cancer (AGC) worldwide. We conducted a meta-analysis using individual participant data (IPD) to investigate which is more suitable. METHODS: IPD from three randomized trials were collected. In these trials, patients with AGC were randomly allocated to SP (S-1 80-120 mg for 21 days plus cisplatin 60 mg/m2 (q5w)) or XP (capecitabine 2000 mg/m2 for 14 days plus cisplatin 80 mg/m2 (q3w)). RESULTS: In 211 eligible patients, median overall survival (OS) for SP versus XP was 13.5 and 11.7 months (hazard ratio [HR], 0.787; p = 0.114), progression-free survival (PFS) was 6.2 and 5.1 months (HR, 0.767; P = 0.076), and TTF was 5.1 and 4.0 months (HR, 0.611; P = 0.001). The most common grade ≥ 3 adverse events with SP or XP were neutropenia (18% vs. 29%) and anorexia (16% vs.18%). Subgroup analysis demonstrated significant interaction between treatment effect and performance status > 1 (HR, 0.685; P = 0.036), measurable lesion (HR, 0.709; P = 0.049), primary upper third tumor (HR, 0.539; P = 0.040), and differentiated type (HR, 0.549; interaction, 0.236; P = 0.019). For the differentiated type, OS was significantly longer in the SP group (13.2 months) than in the XP group (11.1 months) (HR, 0.549; P = 0.019). For the undifferentiated type, OS was similar in the SP group (14.2 months) and in the XP group (12.4 months) (HR, 0.868; P = 0.476). CONCLUSIONS: SP and XP were both effective and well tolerated. SP might be suitable for the pathological differentiated subtype of AGC. CLINICAL TRIAL REGISTRATION: The HERBIS-2, HERBIS-4A, and XParTS II trials were registered with UMIN-CTR as UMIN000006105, UMIN000006755, and UMIN000006045, respectively.

A case of perioperative artificial pancreas therapy for a patient with esophageal cancer with type 1 diabetes.

A 72-year-old female with type 1 diabetes, a history of interstitial pneumonia, and diabetic ketoacidosis was admitted to our hospital with dysphagia. Endoscopy revealed a circumferential neoplastic lesion in the upper to middle esophagus, and a biopsy revealed squamous cell carcinoma. Computed tomography revealed invasion of the left main bronchus, and induction chemotherapy was initiated with a diagnosis of unresectable locally advanced esophageal cancer. After one course of induction chemotherapy, the tumor size reduced, bronchial invasion improved, and thoracoscopic esophagectomy was performed. During surgery and until 3 days after surgery, the patient's blood glucose level was controlled using an artificial pancreas, and the target blood glucose range was set at 140-180 mg/dL. On the fourth postoperative day, the patient was managed using a sliding scale. Mean blood glucose was 186.7 ± 70.0 mg/dL for 3 days before surgery, 190.5 ± 25.0 mg/dL during artificial pancreas therapy from the surgery to the next day, 169.8 ± 22.0 mg/dL during artificial pancreas therapy on the second to third postoperative days, and 174.5 ± 25.0 mg/dL during sliding scale therapy for 4-15 days after surgery. No hypoglycemia or ketoacidosis was noted.

Near-infrared fluorescence imaging with indocyanine green to assess the blood supply of the reconstructed gastric conduit to reduce anastomotic leakage after esophagectomy: a literature review.

The blood supply of the right gastroepiploic artery after esophagectomy with gastric tube reconstruction is essential for avoiding anastomotic leakage. Near-infrared fluorescence (NIRF) imaging with indocyanine green is widely used to assess the blood supply because it can visualize it in real-time during navigation surgery. However, there is no established protocol for this modality. One reason for this lack of protocol is that NIRF provides subjective information. This study aimed to evaluate NIRF quantification. We conducted a literature review of risk factors for anastomotic leakage after esophagectomy, NIRF procedures, NIRF quantification, and new methods to compensate for NIRF limitations. Major methods for the quantification of NIRF include measuring the blood flow speed, visualization time, and fluorescence intensity. The cutoff value for the blood flow speed is 2.07 cm/s, and that for the visualization time is 30-90 s. Although the time-intensity curve provided patterns of change in the blood flow, it did not show an association with anastomotic leakage. However, to compensate for the limitations of NIRF, new devices have been reported that can assess tissue oxygenation perfusion, organ hemoglobin concentration, and microcirculation.

[Long-Term Survival of an Adolescent and Young Adult Patient with Unresectable Advanced Gastric Cancer in Whom Multidisciplinary Treatment Was Effective].

We report the case of a long-term-surviving adolescent and young adult patient with unresectable advanced gastric cancer for whom multidisciplinary treatment was effective. A 29-year-old woman was referred to our hospital for further examination following a diagnosis of gastric cancer by a local physician. Esophagogastroduodenoscopy showed a deep ulcerated lesion in the lower third of the stomach, and analysis of biopsy specimens revealed an adenocarcinoma. Abdominal contrast- enhanced computed tomography showed gastric wall thickening in the lower third of the stomach. The patient underwent distal gastrectomy with lymph node dissection, including resection of localized peritoneal metastases, followed by Roux-en- Y reconstruction. The pathological diagnosis was serosa-invading poorly differentiated adenocarcinoma with 1 lymph node metastasis measuring 6.0×5.5 cm in the posterior wall of the lower third of the stomach and negative immunohistochemical staining for human epidermal growth factor receptor 2. The patient received postoperative chemotherapy with S-1 and oxaliplatin. She developed bilateral ovarian metastases measuring 13.0 cm and 7.8 cm after 17 months. The patient presented with severe lower abdominal pain and underwent an emergency bilateral ovarian metastasectomy, which revealed torsion of the right ovarian tumor, which had twisted twice on its pedicle, and a left ovarian mass. After the operation, 41 courses of ramucirumab with nab-paclitaxel were administered as a second-line treatment, and she received systemic drug treatment. Sixty months after the gastrectomy, the patient developed left hydronephrosis due to peritoneal metastases and was treated with nivolumab after ureteral stent replacement. No effective treatment was proposed in cancer multigene panel testing, and she died 66 months after the initial treatment because of disease progression. Comprehensive multidisciplinary treatment, including surgical and local therapy for peritoneal dissemination based on drug therapy for unresectable advanced gastric cancer, may result in long-term survival. Further research and accumulation of such cases would lead to the development of novel treatments.

Frequency and therapeutic strategy for patients with ovarian metastasis from gastric cancer.

PURPOSE: This study aimed to analyze the clinicopathological features and treatment outcomes of ovarian metastasis from gastric cancer. METHODS: This study included 155 female patients with unresectable advanced or recurrent gastric cancer at the Kochi Medical School between January 2007 and December 2021. A review of patients with ovarian metastasis was conducted, and their clinicopathological information and survival outcomes were compared with respect to ovarian metastasis. RESULTS: Fifteen patients were diagnosed with ovarian metastasis from gastric cancer with a median age of 54 years (range: 30-87 years) and an incidence of 9.7%. The median age of patients who developed ovarian metastasis was significantly lower those without ovarian metastasis (54 years vs. 71 years, P = 0.014). The median survival time (MST) for 15 patients with unresectable advanced gastric cancer who developed ovarian metastasis was 21.4 months (range: 0.2-41.4 months). The MST for 15 patients who underwent surgical resection and systemic drug treatment including chemotherapy to ovarian metastasis was significantly higher than those who received systemic drug treatment alone (28.1 months vs. 10.0 months; P = 0.021). CONCLUSION: Ovarian metastasis was found in 9.7% of female patients with unresectable advanced or recurrent gastric cancer and in younger patients than in those without ovarian metastasis. Multidisciplinary treatment, including surgical resection and systemic drug treatment for ovarian metastasis from gastric cancer, may benefit selected patients.

Neutrophil-to-lymphocyte ratio and C-reactive protein-to-albumin ratio as prognostic factors for unresectable advanced or recurrent gastric cancer.

PURPOSE: This study evaluated the prognostic value of C-reactive protein-to-albumin (CAR) and neutrophil-to-lymphocyte ratios (NLR) in conjunction with host-related factors in patients with unresectable advanced or recurrent gastric cancer. METHODS: A total of 411 patients with unresectable advanced gastric cancer were treated at Kochi Medical School between 2007 and 2019. Associations between clinicopathological parameters and systemic inflammatory and nutritional markers, including CAR and NLR, with overall survival were analyzed retrospectively. RESULTS: The optimal cut-off values of predicted median survival time were 0.096 (sensitivity, 74.9%; specificity, 42.5%) for CAR and 3.47 (sensitivity, 64.1%; specificity, 57.5%) for NLR, based on the results of receiver operating characteristic analysis. A weak significant positive correlation was identified between CAR and NLR (r = 0.388, P < 0.001). The median survival time was significantly higher in patients with intestinal-type than those with diffuse-type histology (18.3 months vs. 9.5 months; P = 0.001), CAR < 0.096 than those with CAR ≥ 0.096 (14.8 months vs. 9.9 months; P < 0.029), and those with NLR < 3.47 than NLR ≥ 3.47 (14.7 months vs. 8.8 months; P < 0.001). Multivariate survival analysis revealed that diffuse-type histology (hazard ratio (HR) 1.865; 95% confidence interval (CI) 1.397-2.490; P < 0.001)), 1 or more performance status (HR 11.510; 95% CI 7.941-16.683; P < 0.001), and NLR ≥ 3.47 (HR 1.341; 95% CI 1.174-1.769; P = 0.023) were significantly associated with independent predictors of worse prognosis. CONCLUSIONS: High CAR and NLR are associated with poor survival in patients with unresectable and recurrent gastric cancer.

Frequency and prognostic impact of cachexia during drug treatment for unresectable advanced gastric cancer patients.

PURPOSE: Patients with unresectable advanced metastatic gastric cancer have a poor prognosis. This study examined the incidence and prognostic impact of cachexia during systemic drug treatment in such patients. METHODS: We enrolled patients with unresectable advanced gastric cancer who were treated with chemotherapy at Kochi Medical School from 2007 to 2020. Cancer cachexia was defined as > 5% weight loss or > 2% weight loss with a body mass index of < 20 kg/m2 within the past 6 months. Associations between clinicopathological parameters, cancer cachexia, and the overall survival were analyzed. RESULTS: Cancer cachexia occurred in 55.2% of 134 enrolled patients 6 months after chemotherapy. The incidence of cancer cachexia in initial unresectable gastric cancer was significantly higher than that in patients with recurrent cancer after curative resection. The median overall survival was significantly lower in the patients with cancer cachexia than in those without cancer cachexia at 6 months after starting systemic chemotherapy (13.7 months vs. 21.6 months, P = 0.032). Cancer cachexia at 6 months of starting treatment and CRP > 0.14 were identified as significantly associated with poor outcomes in a multivariate analysis (hazard ratio [HR] 1.339, 95% confidence interval [CI] 1.160-2.085, P = 0.019; HR 1.885, 95% CI 1.124-3.161, P = 0.016); respectively). CONCLUSIONS: Cancer cachexia was frequently observed in unresectable advanced gastric cancer patients who received chemotherapy and was useful as a prognostic factor for the overall survival.

[Brain Metastasis Arising from Gastric Cancer during Long-Term Treatment Using Nivolumab].

Metastasis to the central nervous system from gastric cancer is exceedingly uncommon. We report a gastric cancer patient with cerebral metastasis during the period when durable response was obtained by systemic drug treatment using nivolumab. A 78-year-old male was referred to our hospital for further examination following diagnosis of gastric cancer by a local medical doctor. Esophagogastroduodenoscopy showed a slightly elevated lesion with central depressed area in the upper-third of the stomach, and analysis of biopsy specimens revealed an adenocarcinoma. The patient underwent laparoscopic total gastrectomy with lymph nodes dissection followed by Roux-en-Y reconstruction, resulting in submucosal invasive carcinoma and no lymph node metastasis. The patient developed solitary splenic metastasis measuring 4.2 cm after 28 months later, and the patient underwent a splenectomy, since there was no evidence of further metastatic lesions in any other organs. Subsequently, the patient was received S-1 plus oxaliplatin chemotherapy based on negative immunohistochemical staining of the resected specimens for human epidermal growth factor receptor 2. Four months after the splenectomy, the patient developed multiple liver metastases and was treated with ramucirumab plus paclitaxel. Because of disease progression, the patient was administered 3 mg/kg, iv, nivolumab every 2 weeks. After 4 courses of systemic treatment using nivolumab, abdominal computed tomography revealed marked shrinkage of the liver metastases. After 12 courses of nivolumab, the liver metastases had disappeared completely. The patient developed hypothyroidism, which could be controlled by thyroid hormone replacement treatment. The patient continues to receive nivolumab, and there is no evidence of disease recurrence in the 33 month period since starting nivolumab. However, he developed cerebral metastases after 69 months after surgery, complaining of articulation disorder. The patient underwent tumor resection by craniotomy followed by radiation therapy; however, he died 3 months after the operation. Although brain metastasis arising from gastric cancer is rare, future identification of risk factors and development of novel treatments are desired by further investigations and accumulation of these cases.

Enteral Vitamin B12 Supplementation Is Effective for Improving Anemia in Patients Who Underwent Total Gastrectomy.

BACKGROUND: This study aimed to investigate the efficacy of enteral supplementation of vitamin B12 for vitamin B12 deficiency in patients who underwent total gastrectomy for gastric cancer. METHODS: The study enrolled 133 patients who underwent total gastrectomy for gastric cancer at Kochi Medical School. Clinical data were obtained to investigate associations between vitamin B12 supplementation and vitamin B12 levels. Vitamin B12 deficiency was defined as serum vitamin B12 less than 200 pg/mL. Baseline characteristics and changes in hematological variables, including vitamin B12 levels, were examined. RESULTS: Vitamin B12 deficiency was present in 71.4% of the 133 patients. Vitamin B12 levels at 3, 6, and 12 months after enteral supplementation were 306 pg/mL, 294 pg/mL, and 367 pg/mL, respectively, which were all significantly higher than those before supplementation (p < 0.001 for all comparisons). The median red blood cell count at 3, 6, and 12 months after enteral supplementation were 380 × 104/mm3, 394 × 104/mm3, and 395 × 104/mm3, respectively, which were all significantly higher than those before supplementation (p = 0.020, p = 0.001, and p = 0.003, respectively). Vitamin B12 levels at 3, 6, and 12 months after supplementation were significantly higher in patients supplemented enterally than those supplemented parenterally (p < 0.001 for all comparisons). CONCLUSIONS: Vitamin B12 deficiency was found in 71.4% of postoperative patients who underwent total gastrectomy for gastric cancer, and enteral vitamin B12 supplements might be effective to improve anemia in these patients.

Clinical biomarkers in adjuvant chemotherapy for gastric cancer after D2 dissection by a pooled analysis of individual patient data from large randomized controlled trials.

BACKGROUND: Adjuvant therapy for gastric cancer is a standard among the world with no regimen selection criteria. Also, prognostic factors except for tumor staging have not been established. We aimed to identify prognostic and predictive markers for gastric cancer adjuvant therapy from large randomized controlled trials with standard lymph node dissection. METHODS: Three studies: ACTS-GC, CLASSIC, and SAMIT were found and selected for a pooled analysis, following PRISMA guideline. The integrity of individual participant data (IPD) was verified in the eligible 3527 patients registered, and fixed-effect model was used. The primary endpoint was relapse-free survival (RFS) and the secondary endpoint was overall survival (OS). RESULTS: Age was a significant prognostic factor in addition to tumor stages both in "surgery alone" and "adjuvant" groups. Adjuvant therapy was effective for every TN stage; however, it tended to be more effective in T1-2 than in T3-4. Also, it was more effective in low- or middle-BMI than in high-BMI group with Hazard ratio [HR]s: 0.58, 0.58, and 1.05, respectively. Capecitabine plus oxaliplatin (CAPOX) was more effective than S-1 for T1-2, N2-3, and differentiated type with HRs between 0.59 and 0.70, but with no difference among TNM stages. Combining histology to TN; the HRs in differentiated T1-2 N1-3 groups were between 0.29 and 0.45. For T3-4 N0-1 group, S-1 was likely to be effective, not significant. CONCLUSIONS: Age is a significant prognostic factor both in surgery alone and adjuvant group. CAPOX is more effective for differentiated T1-2 tumors with lymph node metastasis.

Evaluation of Perioperative Intestinal Motility Using a Newly Developed Real-Time Monitoring System During Surgery.

BACKGROUND: This study aimed to investigate perioperative intestinal motility using a novel bowel sound monitoring system in patients undergoing breast and neck surgery. MATERIALS AND METHODS: This study enrolled 52 patients who underwent surgery for breast cancer, thyroid tumor, and parathyroid tumor at Kochi Medical School from May 2019 to June 2020. Perioperative bowel sound counts (BSCs) were recorded using a newly developed real-time analysis system in the operating theater. Clinical information and BSC per minute (cpm) data during the preanesthetic, preoperative, operative, postoperative periods, and period in recovery room were obtained to compare between each period. The Mann-Whitney U and Pearson Chi-square tests were used in data analysis. RESULTS: The BSCs during the intraoperative period and postoperative period were significantly decreased compared to those during the preanesthetic period (0.07 cpm versus [vs.]. 1.4 cpm, P = 0.002 and 0.1 cpm vs. 1.4 cpm, P = 0.025, respectively). The preoperative BSC with a preanesthetic BSC < 1.4 was significantly lower than that with a preanesthetic BSC ≥ 1.4 (0.40 cpm vs. 1.78 cpm, P = 0.006). The preanesthetic, preoperative, and postoperative BSCs with an intraoperative BSC < 0.07 were significantly lower than those with an intraoperative BSC ≥ 0.07 (0.48 cpm vs. 2.83 cpm, P = 0.007; 0.40 cpm vs. 1.81 cpm, P = 0.008; and 0.07 cpm vs. 0.42 cpm, P = 0.006, respectively). CONCLUSION: The real-time bowel sound analysis system demonstrated an inhibitory effect associated with anesthetic and surgical stress on intestinal motility as the BSC sequentially.

Serum zinc deficiency in patients after gastrectomy for gastric cancer.

PURPOSE: Zinc is an essential dietary component for humans and the second most prevalent trace element; however, serum zinc levels after gastrectomy have not been fully elucidated. This study aimed to evaluate the correlation between clinicopathologic features and serum zinc levels in patients who underwent gastrectomy for gastric cancer. METHODS: The study enrolled 617 patients who underwent gastrectomy for gastric cancer at the Kochi Medical School. Clinical data were obtained to investigate associations between clinicopathological features, including nutritional indicators and serum zinc levels. Serum zinc deficiency was defined as serum zinc level < 80 µg/dL. RESULTS: The median zinc level of the 617 patients was 73 µg/dL (range, 31-144 µg/dL), and serum zinc deficiency was present in 68.6% of patients. Median age was significantly higher in the zinc low level group than in the normal group (69 vs. 66 years, P < 0.001). Albumin was significantly lower in the zinc low level group than in the normal group (3.9 vs. 4.2 g/dL, P < 0.001). C-reactive protein level was significantly higher in the zinc low level group than in the normal group (0.12 vs. 0.10 mg/dL, P = 0.014). The median serum zinc level was significantly lower in the patients who received chemotherapy after gastrectomy than in those who were not received chemotherapy (72 vs. 76 µg/dL, P < 0.001). Serum zinc levels showed a significant positive correlation with serum albumin (r = 0.505, P = 0.044). Multivariate analysis showed that serum albumin level was significantly associated with serum zinc level (ß = 0.489, P < 0.001). CONCLUSIONS: Serum zinc deficiency was found in 68.6% of postoperative patients who underwent gastrectomy for gastric cancer, which was highly correlated with serum albumin.

A phase II study of FOLFOXIRI plus bevacizumab as initial chemotherapy for patients with untreated metastatic colorectal cancer: TRICC1414 (BeTRI).

PURPOSE: FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. METHODS: Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). RESULTS: Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8-77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. CONCLUSIONS: FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.

The updated five-year overall survival and long-term oxaliplatin-related neurotoxicity assessment of the FACOS study.

PURPOSE: We previously reported the first evidence of oncological benefits from a Japanese phase II trial of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (the FACOS study). We herein report the long-term survival and persistent oxaliplatin-related peripheral sensory neuropathy (PSN) for patients enrolled in this trial. METHODS: Patients were scheduled to receive the mFOLFOX6 or CAPOX regimen in the adjuvant setting. The five-year overall survival (OS) rate and persistent PSN were evaluated. RESULTS: A total of 130 patients (mFOLFOX6, n = 73; CAPOX, n = 57) were eligible. The 5-year OS rate was 91.4%. No significant difference in the OS rate was observed between regimens (mFOLFOX6, 94.4%; CAPOX, 87.4%; P = 0.25). The incidence of PSN during adjuvant treatment was 55.4% in grade 1 (G1), 30.0% in G2, and 4.6% in G3. No patients showed G3 PSN at 12 months, but G1 or G2 residual PSN after 5 years was observed in 21.8% (G1, 20%; G2, 1.8%). CONCLUSIONS: Updated results from the FACOS study support the benefits of oxaliplatin-based adjuvant chemotherapy in terms of the long-term survival among Japanese patients with stage III colon cancer. However, long-term persistent PSN occurs in about 20% of survivors, counterbalancing the favorable OS.

[Curative Resection for Advanced Gastric Cancer with Lymph Node Metastasis along the Middle Colic Artery].

Mesenteric lymph node metastasis of gastric cancer is extremely rare. We report the case of a patient with advanced gastric cancer having lymph node metastasis in the transverse mesocolon who underwent gastrectomy with lymph node dissection followed by chemotherapy. A 74-year-old male complaining of tarry stool was referred to our hospital for further examination following a diagnosis of gastric cancer by a local medical doctor. Esophagogastroduodenoscopy revealed an irregular and ulcerated lesion in the lower third of the stomach, and analyses of biopsy specimens revealed adenocarcinoma. Abdominal computed tomography revealed abdominal wall thickening in the lower third of the stomach, with enlarged lymph nodes in the perigastric area and the left side area of the middle colic artery. With a clinical diagnosis of gastric cancer, the patient underwent distal gastrectomy with lymph node dissection followed by Billroth Ⅰ reconstruction. During surgery, the enlarged lymph node along with the middle colic artery in the transverse mesocolon was dissected. The gross appearance of the resected specimen shows a large and ulcerated tumor measuring 6.0×5.5 cm in the lesser curvature side of the lower third of the stomach. The pathological examination of the resected specimen showed solid-type poorly-differentiated adenocarcinoma with lymph nodes metastases, which was detected in the perigastric area and transverse mesocolon. The final diagnosis according to the Japanese classification of gastric carcinoma by the Japanese Gastric Cancer Association was L, Less-Post-Ant, Type 2, 6.0×5.5 cm, T3(SS), N2(5/19), M1(LYM), P0, H0, CY0, por1, Ly0, V1a, Stage Ⅳ, R0. Subsequently, the patient received S-1 plus oxaliplatin chemotherapy; however, he developed para-aortic lymph node metastases 18 months after surgery. Therefore, the patient was treated with ramucirumab plus nab-paclitaxel and was alive 20 months after the operation. Although mesocolonic lymph node metastasis of gastric cancer is rare, future identification of risk factors and the development of novel treatments should be achieved through further investigations and the accumulation of 3 cases.

Evaluation of Systemic Inflammatory Response and Nutritional Biomarkers as Predictive Factors in Patients with Recurrent Gastric Cancer.

BACKGROUND: The present study sought to evaluate host-related factors as predictors in patients receiving chemotherapy for recurrent advanced gastric cancer. METHODS: Sixty-three patients were enrolled in the study and received chemotherapy for recurrent gastric cancer at the Kochi Medical School from 2008 to 2015. Clinicopathological information and systemic inflammatory response data were obtained retrospectively to investigate associations between baseline cancer-related prognostic variables and survival outcomes. RESULTS: The median survival time was significantly higher for patients with a Glasgow prognostic score (GPS) of 0 compared to a GPS of 1 or 2 (18.2 vs. 7.1 months; p = 0.006), and for patients in the normal range for carbohydrate antigen-125 (CA125) compared to higher levels (17.9 vs. 4.1 months; p = 0.003). There was no significant influence on overall survival by age, gender, disease status, metastatic site, time to recurrence, carcinoembryonic antigen level, CA19-9 level, prognostic nutrition index, or neutrophil to lymphocyte ratio according to the results of the univariate log-rank tests. Multivariate survival analysis identified a GPS of 1 or 2 (hazard ratio, 3.520; 95% confidence interval, 1.343-9.227; p = 0.010) and a high CA125 level (hazard ratio, 3.135; 95% confidence interval, 1.276-7.697; p = 0.013) as significant independent predictors associated with a poorer prognosis in the studied group of cancer patients. CONCLUSIONS: A GPS of 1 or 2 and a high level of CA125 are independent predictors of a poorer prognosis in patients receiving chemotherapy for recurrent gastric cancer.

Near-infrared fluorescent solid material for visualizing indwelling devices implanted for medical use.

BACKGROUND: In clinical practice, various devices are implanted into the body for medical reasons. As X-ray fluoroscopy is necessary to visualize medical devices implanted into the body, the development of a less-invasive visualization method is highly desired. This study aimed to investigate the clinical applicability of our novel solid material that emits near-infrared fluorescence. METHODS: We developed a solid resin material that emits near-infrared fluorescence. This material incorporates a near-infrared fluorescent pigment, with quantum yield ≥ 20 times than that of indocyanine green. It can be sterilized for medical treatment. This resin material is designed to be molded into a catheter and inserted into the body with an endoscope clip. In this preclinical experiment using a swine model, the resin material was embedded into the body of the swine and visualized with a near-infrared fluorescence camera system. RESULTS: Endoscopic clips were placed in the mucosa of the stomach, esophagus, and large intestine, and the indwelling ureteral catheters were successfully visualized by near-infrared fluorescence laparoscopy. CONCLUSIONS: We confirmed the tissue permeability of the fluorescence emitted by our novel near-infrared fluorescent material and the possibility of its clinical application. This material may allow visualization of devices embedded in the body.

Novel endoscopic marking clip equipped with resin-conjugated fluorescent indocyanine green during laparoscopic surgery for gastrointestinal cancer.

PURPOSE: Intraoperative identification of the cancer location is often difficult to conduct during laparoscopic surgery, especially in early-stage cancers. This study aimed to investigate the feasibility and accuracy of a novel endoscopic clip resin-conjugated fluorescent indocyanine green during laparoscopic surgery for gastrointestinal cancer. METHODS: Preoperative placement of endoscopic marking clips equipped with resin-conjugated fluorescent indocyanine green was performed to determine the resection margin in eight patients with gastrointestinal cancer. During laparoscopic surgery, a dedicated laparoscopic system with a xenon light source was used to detect fluorescence. The evaluation determined whether the fluorescent from the clips was visualized during laparoscopic surgery. RESULTS: Fluorescent signal emitted from ICG in the resin of the clips was detected in six patients from the outer layer of the serosal surfaces of the gastrointestinal tract, and the clips aided in accurate resection line of the organ. There were no significant differences of age, gender, and BMI between the patients in whom we could and could not detect ICG fluorescence. CONCLUSIONS: The results demonstrated the usefulness of a novel clip-equipped fluorescent resin, which is a promising diagnostic tool to detect accurate tumor location during laparoscopic surgery.