Risk factors for intraoperative and delayed perforation related with gastric endoscopic submucosal dissection.

BACKGROUND AND AIM: Perforation is one of the most important complications of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Several studies have examined risk factors for intraoperative and delayed perforations, but most were retrospective analyses with small numbers of patients. METHODS: This study represents a secondary analysis of a Japanese multicenter prospective cohort study. We investigated the factors associated with each type of perforation using 9015 patients with 9975 EGCs undergoing ESD between July 2010 and June 2012. RESULTS: Intraoperative perforation occurred in 198 patients (2.2%) with 203 lesions (2.0%), necessitating emergency surgery for four lesions (0.04% [2.0%, 4/203]). Delayed perforation occurred in another 37 patients (0.4%) with 42 lesions (0.4%), requiring emergency surgery for 12 lesions (0.12% [28.6%, 12/42]). Factors showing significant independent correlations with intraoperative perforation were upper or middle third of the stomach; remnant stomach or gastric tube; procedure time ≥100 min; tumor size >35 mm; body mass index (BMI) < 18.5 kg/m2; and ≥72 years. Factors showing significant independent correlations with delayed perforation were procedure time ≥60 min; BMI < 18.5 kg/m2; ≥75 years; ulceration; and tumor size >20 mm. Intraoperative perforation occurred most frequently at the greater curvature in the upper third of the stomach (7.9%), whereas delayed perforation occurred most frequently at the greater curvature in the middle third (1.2%). CONCLUSION: This multicenter prospective cohort study clarified the risk and risk factors of intraoperative and delayed perforation related to ESD for EGCs, providing information to help endoscopists reduce perforation.

Potential for expanding indications and curability criteria of endoscopic resection for early gastric cancer in elderly patients: results from a Japanese multicenter prospective cohort study.

BACKGROUND AND AIMS: Evidence for endoscopic resection (ER) in elderly patients with early gastric cancer (EGC) is limited. We assessed its clinical outcomes, and explored new indications and curability criteria. METHODS: We analyzed data from a Japanese multicenter prospective cohort study. Patients aged ≥75 years with EGC treated with ER were included. We classified "eCuraC-2 (corresponding to noncurative ER, defined in the Japanese gastric cancer treatment guidelines)" into "elderly-high (EL-H)" (>10% estimated metastatic risk) and "elderly-low (EL-L)" (≤10%). RESULTS: In total, 3,371 patients with 3,821 EGCs were included; endoscopic submucosal dissection (ESD) was the prominent treatment choice. Among them, 3,586 lesions met the guidelines' ER indications and 235 did not. The proportions of en bloc and R0 resections and perforations were 98.9%, 94.4%, and 0.8%, respectively, in EGCs within the indications. In EGCs beyond the indications, they were 99.5%, 85.4%, and 5.9%, respectively, for lesions diagnosed as ≤3 cm, and 96.0%, 64.0%, and 18.0% for those >3 cm. Curative ER ("eCuraA/B") and EL-L were observed in 83.6% and 6.2% of lesions within the indications, respectively, and in 44.2% and 16.8% of lesions <3 cm beyond the indications, respectively. The 5-year cumulative gastric cancer death rates following eCuraA/B and EL-H were 0.3% (95% CI, 0.2-0.6) and 3.5% (2.0-5.7), respectively. Following EL-L, the rate was 0.9% (0.2-3.5) even without subsequent treatment. CONCLUSIONS: Usefulness of ESD for elderly EGC patients was confirmed by their clinical outcomes. Lesions ≤3 cm and EL-L emerged as new ER indication and curability criterion, respectively.

The efficacy and safety of multi-loop traction device for gastric endoscopic submucosal dissection: a single center prospective pilot study.

Although gastric endoscopic submucosal dissection (ESD) is widely used, the degree of difficulty varies greatly depending on the lesion. Since the multi-loop traction device (MLTD) has been suggested to shorten the procedure time in colorectal ESD, we examined the efficacy and safety of using the MLTD in gastric ESD. Thirty patients with gastric neoplasms were prospectively enrolled from February 2022 to December 2022, and the outcomes of ESD with the MLTD were evaluated. The primary outcomes were procedure time and dissection speed. The secondary outcomes were en bloc and R0 resection rates, MLTD attachment time, and complications of ESD with the MLTD. After excluding 1 patient, 29 patients (29 lesions) were treated by ESD with the MLTD. The median procedure time was 26 min (range, 9-210 min), and the median submucosal dissection speed was 39.9 mm2/min (12.4-102.7 mm2/min). The rate of en bloc resection was 100%, the median MLTD attachment time was 3 min (1-7 min), and none of the patients showed intraoperative or postoperative perforations. Thus, gastric ESD with the MLTD showed a favorable procedure time and dissection speed and an acceptable complication rate. Hence, the MLTD may be effective for gastric ESD.

Clinical characteristics and long-term prognosis of type 1 gastric neuroendocrine tumors in a large Japanese national cohort.

OBJECTIVES: Optimal management of type 1 gastric neuroendocrine tumors (T1-GNETs) remains unknown, with few reports on their long-term prognosis. This study investigated the clinical characteristics and long-term prognosis of T1-GNETs. METHODS: We reviewed the medical records of patients diagnosed with T1-GNET during 1991-2019 at 40 institutions in Japan. RESULTS: Among 172 patients, endoscopic resection (ER), endoscopic surveillance, and surgery were performed in 84, 61, and 27, respectively, including 27, 77, and 2 patients with pT1a-M, pT1b-SM, and pT2 tumors, respectively. The median tumor diameter was 5 (range 0.8-55) mm. Four (2.9%) patients had lymph node metastasis (LNM); none had liver metastasis. LNM rates were significantly higher in tumors with lymphovascular invasion (LVI) (15.8%; 3/19) than in those without (1.1%; 1/92) (P = 0.016). For tumors <10 mm, LVI and LNM rates were 18.4% (14/76) and 2.2% (2/90), respectively, which were not significantly different from those of tumors 10-20 mm (LVI 13.3%; 2/15, P = 0.211; and LNM 0%; 0/17, P = 1.0). However, these rates were significantly lower than those of tumors >20 mm (LVI 60%; 3/5, P = 0.021; and LNM 40%; 2/5, P = 0.039). No tumor recurrence or cause-specific death occurred during the median follow-up of 10.1 (1-25) years. The 10-year overall survival rate was 97%. CONCLUSIONS: Type 1 gastric neuroendocrine tumors showed indolent nature and favorable long-term prognoses. LVI could be useful in indicating the need for additional treatments. ER for risk prediction of LNM should be considered for tumors <10 mm and may be feasible for tumors 10-20 mm. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network (UMIN) under the identifier UMIN000029927.

Evaluation of Prognostic Factors for Unresectable or Recurrent Gastric Cancer Treated with Nivolumab.

PURPOSE: Nivolumab is useful for the treatment of unresectable/recurrent gastric cancer as third-line or later chemotherapy. However, the factors that predict the efficacy of nivolumab monotherapy remain unclear. METHODS: We retrospectively studied the predictive factors of response in 59 consecutive patients treated with nivolumab as third-line or later chemotherapy for unresectable/recurrent gastric cancer at our hospital from October 2017 to May 2020. RESULTS: The median follow-up was 5.9 months. The study included 45 men and 14 women (median age: 71 years). We observed that 7 patients had an Eastern Cooperative Oncology Group performance status of 0 and 52 patients had a performance status of 1-2. Forty-three patients were treated with third-line therapy, seven with fourth-line therapy, and three with fifth-line therapy. The response rate to nivolumab was 6.7% and disease control rate was 35.5%. There were 19 (32.2%) immune-related adverse events for all grades and 9 (15.2%) for grades 3 and 4. Progression-free survival was 1.90 months, and overall survival was 6.30 months. Patients with immune-related adverse events had significantly longer overall survival than those without immune-related adverse events. Multivariate analysis showed that the occurrence of immune-related adverse events and a ratio for neutrophil-to-lymphocyte ratio after 8 weeks of nivolumab treatment to the baseline neutrophil-to-lymphocyte ratio before treatment of ≤ 1.5 were independent prognostic factors for overall survival. CONCLUSIONS: Occurrence of immune-related adverse events and changes in neutrophil-to-lymphocyte ratio during nivolumab treatment may help predict the therapeutic efficacy of nivolumab monotherapy for unresectable or recurrent gastric cancer.

Long-term Survival After Endoscopic Resection For Gastric Cancer: Real-world Evidence From a Multicenter Prospective Cohort.

BACKGROUND & AIMS: We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study. METHODS: We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative, >2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C). RESULTS: Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS. CONCLUSION: ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).

Phase IIb study of pembrolizumab combined with S-1 + oxaliplatin or S-1 + cisplatin as first-line chemotherapy for gastric cancer.

The KEYNOTE-659 study evaluated the efficacy and safety of first-line pembrolizumab plus S-1 and oxaliplatin (SOX) (cohort 1) or S-1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open-label phase IIb study enrolled patients with advanced programmed death-ligand 1 (PD-L1)-positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)-negative G/GEJ adenocarcinoma. The primary end-point was the objective response rate (ORR). Other end-points were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow-up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment-related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD-L1-positive, HER2-negative G/GEJ adenocarcinoma.

Factors for unsuccessful endoscopic hemostasis in patients with severe peptic ulcer bleeding.

OBJECTIVES: Although the first approach for peptic ulcer bleeding is endoscopic hemostasis, quick determination of a hemostatic strategy is important in patients with vitals indicating shock. However, the unsuccessful factors for endoscopic treatment have yet to be sufficiently examined. We aimed to investigate the factors for unsuccessful endoscopic hemostasis in severe peptic ulcer bleeding. MATERIALS AND METHODS: Unsuccessful factors were retrospectively investigated in 150 eligible patients who underwent endoscopic hemostasis for shock-presenting peptic ulcer bleeding at our critical care center between April 2007 and March 2021. RESULTS: There were 123 and 27 cases of successful and unsuccessful endoscopic hemostasis, respectively. Causative diseases included gastric ulcer bleeding in 124 patients (82.7%) and duodenal ulcer bleeding in 26 patients (17.3%). Shock index (SI) (1.46 vs. 1.60) (p = .013), exposed blood vessel diameter (1.4 mm vs. 3.1 mm) (p < .001) identified on contrast-enhanced computed tomography (CE-CT), duodenal ulcer bleeding (p = .012), and Forrest classification Ia (p = .004) were extracted as independent factors for unsuccessful endoscopic hemostasis. In receiving operating curve analysis, when the cut-off value for the SI was set at 1.53, the sensitivity and specificity were 70.4% and 63.4%, respectively. When the cut-off value for the exposed blood vessel diameter was set at 1.9 mm, these were 88.9% and 83.7%, respectively. CONCLUSIONS: When these factors (SI ≥ 1.53, exposed blood vessel diameter ≥1.9 mm identified on CE-CT, duodenal ulcer bleeding, and Forrest Ia) are present in patients with severe peptic ulcer bleeding, non-endoscopic hemostasis, such as interventional radiology (IVR) and surgery, should be considered.

Preoperative chemotherapy could modify recurrence patterns through postoperative complications in patients with gastric cancer.

PURPOSE: Postoperative infectious complications have a negative impact on survival outcomes in patients with gastric cancer. It is recently reported that preoperative chemotherapy may eliminate this negative impact. This study aimed to confirm whether preoperative chemotherapy can eliminate the negative impact of postoperative infectious complications (IC) on survival outcomes and elucidate the association between postoperative infectious complications and recurrence patterns. METHODS: We retrospectively reviewed data of 86 patients who received preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by R0 gastrectomy at the Kitasato University between 2006 and 2016. Patients who developed grade II or higher infectious complications during hospitalization were grouped into the IC group, while others were grouped into the non-IC (NIC) group. Survival outcomes and recurrence patterns were analyzed between the two groups. RESULTS: Infectious complications with Clavien-Dindo classification of grade II or higher were found in 12 patients (14.0%, IC group). The median observational period was 61 months. Overall survival and progression-free survival were similar in the IC and NIC groups. Recurrence occurred in 39 patients. The proportions of peritoneal and lymph node recurrences were not significantly different between the two groups. However, the proportion of distant metastasis in the IC group was significantly higher than that in NIC group (3/4 [75%] vs. 9/35 [17%], p = 0.04). CONCLUSIONS: Pathological stage after neoadjuvant therapy plays a stronger role in recurrence than postoperative complications. Lymph node and peritoneal metastasis may be suppressed by preoperative chemotherapy.

Usefulness of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in elderly patients: a single-center retrospective cohort study.

BACKGROUND: The effectiveness of endoscopic treatment for superficial esophageal squamous cell carcinoma in the elderly is unclear. METHODS: We retrospectively studied efficacy and safety of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in 358 patients at our hospital from July 2005 to December 2018. Patients were divided into elderly (≥75 years) and young (≤74 years) groups. Efficacy was evaluated based on overall survival and disease-specific survival, whereas safety was investigated based on the frequency of endoscopic submucosal dissection-related adverse events. RESULTS: The median observation period was 50 months. The elderly group comprised 111 patients, and young group comprised 247 patients. In the elderly and young groups, 76 (68.5%) and 159 (64.4%) underwent curative resection (P = 0.450), 8 (7.2%) and 34 (13.8%) underwent non-curative resection plus additional treatment and 12 (10.8%) and 15 (6.0%) underwent follow-up, respectively. The frequency of additional treatment for non-curative resection was significantly lower in the elderly group (P = 0.023). The 3-year overall survival of the elderly and young groups was 85.6 and 94.1%, respectively (P = 0.003). The 3-year disease-specific survival of the elderly and young groups was 98.4 and 98.5% (P = 0.682), respectively. The frequency of endoscopic submucosal dissection-related adverse events did not differ significantly between the groups (P = 0.581). The Charlson Comorbidity Index ≥2 was an independent prognostic factor for survival in the elderly group (P = 0.010; hazard ratio, 5.570; 95% confidence interval, 1.519-20.421). CONCLUSIONS: Endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in elderly patients is as safe as that for young patients. The evaluation of Charlson Comorbidity Index was considered to help estimate the prognosis of elderly patients.

Predictive Significance of Promoter DNA Methylation of Cysteine Dioxygenase Type 1 (CDO1) in Metachronous Gastric Cancer.

PURPOSE: Promoter DNA methylation of various genes has been associated with metachronous gastric cancer (MGC). The cancer-specific methylation gene, cysteine dioxygenase type 1 (CDO1), has been implicated in the occurrence of residual gastric cancer. We evaluated whether DNA methylation of CDO1 could be a predictive biomarker of MGC using specimens of MGC developing on scars after endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: CDO1 methylation values (TaqMeth values) were compared between 33 patients with early gastric cancer (EGC) with no confirmed metachronous lesions at >3 years after ESD (non-MGC: nMGC group) and 11 patients with MGC developing on scars after ESD (MGCSE groups: EGC at the first ESD [MGCSE-1 group], EGC at the second ESD for treating MGC developing on scars after ESD [MGCSE-2 group]). Each EGC specimen was measured at five locations (at tumor [T] and the 4-point tumor-adjacent noncancerous mucosa [TAM]). RESULTS: In the nMGC group, the TaqMeth values for T were significantly higher than that for TAM (P=0.0006). In the MGCSE groups, TAM (MGCSE-1) exhibited significantly higher TaqMeth values than TAM (nMGC) (P<0.0001) and TAM (MGCSE-2) (P=0.0041), suggesting that TAM (MGCSE-1) exhibited CDO1 hypermethylation similar to T (P=0.3638). The area under the curve for discriminating the highest TaqMeth value of TAM (MGCSE-1) from that of TAM (nMGC) was 0.81, and using the cut-off value of 43.4, CDO1 hypermethylation effectively enriched the MGCSE groups (P<0.0001). CONCLUSIONS: CDO1 hypermethylation has been implicated in the occurrence of MGC, suggesting its potential as a promising MGC predictor.

Randomized study of prevention of gastrointestinal toxicities by nutritional support using an amino acid-rich elemental diet during chemotherapy in patients with esophageal cancer (KDOG 1101).

BACKGROUND: This randomized study was designed to evaluate the clinical effect of an elemental diet during chemotherapy in patients with esophageal cancer. METHODS: The inclusion criteria were as follows: (1) esophageal squamous cell carcinoma, (2) stage IB-IV, (3) schedule to receive docetaxel, cisplatin, and 5-fluorouracil (DCF chemotherapy), (4) 20-80 years old, (5) performance status of 0-2, (6) oral intake ability, and (7) written informed consent. Patients were divided into two groups: the elemental supplementary group and the non-supplementary group. Patients received ELENTAL® (160 g/day) orally 9 weeks after the start of chemotherapy. Primary endpoint was the incidence of grade 2 or higher gastrointestinal toxicity according to the Common Terminology Criteria for Adverse Events, version 4.0. Secondary endpoints were the incidence of all adverse events and the evaluation of nutritional status. RESULTS: Thirty-six patients in the elemental supplementary group and 35 patients in the non-supplementary group were included in the analysis. The incidence of grade 2 or higher gastrointestinal toxicity and all grade 3 or 4 adverse events did not differ significantly between the groups. In the elemental supplementary group, the body weight (p = 0.057), muscle mass (p = 0.056), and blood levels of transferrin (p = 0.009), total amino acids (p = 0.019), and essential amino acids (p = 0.006) tended to be maintained after chemotherapy. CONCLUSION: Nutritional support provided by an amino acid-rich elemental diet was ineffective for reducing the incidence of adverse events caused by DCF chemotherapy in patients with esophageal cancer.

Barrett's Esophageal Adenocarcinoma Involving a White Globe Appearance within the Long-Segment Barrett's Esophagus.

The diagnosis of Barrett's esophageal adenocarcinoma (BEA) in patients with Barrett's esophagus (BE) using endoscopy can be difficult and there are few specific endoscopic findings for BEA. However, white globe appearance (WGA) has been reported to be a specific endoscopic finding for early gastric cancer. We encountered a 51-year-old male patient with BEA exhibiting WGA. Esophagogastroduodenoscopy identified a red, depressed lesion of 10 mm within the long-segment BE (LSBE), while magnifying endoscopy with narrow-band imaging identified WGA. Endoscopic submucosal dissection (ESD) was performed based on our suspicion of BEA. Based on the ESD findings, we diagnosed adenocarcinoma accompanying LSBE histopathologically. WGA was identified, and intraglandular necrotic debris was discovered histologically at the same site. Therefore, WGA may be helpful in the diagnosis of BEA.

Usefulness of argon plasma coagulation for superficial esophageal squamous cell neoplasia in patients at high risk or with limited endoscopic resectability.

BACKGROUND/AIMS: Endoscopic resection is the standard treatment for superficial esophageal squamous-cell neoplasia (SESCN). However, we encounter patients in whom endoscopic resection is difficult to perform. We retrospectively studied the usefulness of argon plasma coagulation (APC) in patients with SESCN. MATERIALS AND METHODS: The study comprised 45 patients with SESCN (81 lesions) who underwent APC in our hospital from March 1999 through August 2016. Clinicopathological characteristics, treatment time, the presence or absence of metastasis and recurrence, adverse events, and outcomes were studied. RESULTS: The median follow-up was 40 months. The median age was 70 years. The tumor diameter was 10 mm or longer in 48 lesions and less than 10 mm in 33 lesions. The median treatment time was 22 minutes. The reasons for selecting APC were as follows: technical difficulty caused by the presence of metachronous multiple lesions in the radiation field after chemoradiotherapy or close proximity to the ulcer scar remaining after endoscopic treatment in 49 lesions (60.4%), and the presence of underlying diseases in 26 lesions (32.0%). Adverse events occurred in 2 patients (4.4%) who had hypoxemia due to over-sedation. Two lesions (2.5%) recurred locally but could be locally controlled by additional APC. No patient had metastasis or recurrence or died of esophageal neoplasia. The 3-year overall survival rate was 87.0%, and the 3-year recurrence-free survival rate was 97.2%. CONCLUSION: APC can be a useful treatment option for SESCN in patients with a limited life expectancy, poor performance status, or technical difficulty in resection of superficial neoplasms.

Neoadjuvant chemotherapy plus surgery for high-risk advanced gastric cancer: long-term results of KDOG1001 trial.

PURPOSE: The purpose of this study is to evaluate the long-term survival outcomes of KDOG1001 trial after a minimum follow-up of 3 years. METHODS: Patients with bulky N2 lymph nodes, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) received up to four 28-day cycles of DCS neoadjuvant chemotherapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 lymphadenectomy plus adjuvant S-1 therapy for 1 year. The final preplanned analysis of long-term outcomes including overall survival and relapse-free survival was conducted after minimum follow-up of 3 years. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN 000003642, and has been completed. RESULTS: From May 2010 through January 2017, 40 patients were enrolled. All included patients underwent neoadjuvant chemotherapy with DCS followed by gastrectomy with D2 lymphadenectomy, and 32 (80%) completed adjuvant S-1 therapy for 1 year. After a median follow-up for surviving patients of 68 months at the last follow-up in January 2020, 3-year overall survival rate was 77.5% (95% confidence interval 62.1-87.9%), while 3-year relapse-free survival rate was 62.5% (95% confidence interval 46.8-76.0%). CONCLUSION: Neoadjuvant chemotherapy with 4 cycles of DCS followed by D2 gastrectomy plus adjuvant S-1 was associated with relatively good long-term oncologic outcomes for patients with the high-risk gastric cancer.

Multiple gastrointestinal metastasis after endoscopic submucosal dissection for poorly differentiated gastric adenocarcinoma.

A 76-year-old man had a diagnosis of double primary cancers consisting of poorly differentiated esophageal squamous cell carcinoma (ESCC) invading the submucosa and poorly differentiated gastric adenocarcinoma (GAC) invading the submucosa. The clinical stage of both ESCC and GAC was T1N0M0 stage I. The tumor diameter of ESCC and GAC was 20 mm and 25 mm, respectively. We performed chemoradiotherapy for ESCC. Chemotherapy consisted of nedaplatin in an intravenous dose of 90 mg/m2 on day 1 and 5-fluorouracil in an intravenous dose of 800 mg/m2 on days 1-5, repeated every 4 weeks for two cycles. Radiotherapy consisted of 50.4 Gy in 28 fractions for ESCC. GAC was down-staged after chemoradiotherapy for ESCC and was treated by endoscopic submucosal dissection (ESD). The tumor was histopathologically confirmed to be down-staged to intramucosal cancer with a diameter of 18 mm and no evidence of lymphovascular invasion and ulceration. Multiple metastasis occurred in the stomach, the small intestine and the colorectum after ESD. ESD is not a curative treatment even if chemotherapy is effective for poorly differentiated GAC invading the submucosa. Multiple gastrointestinal metastasis may be a unique recurrence pattern after ESD for such a lesion.

A phase I study of docetaxel/oxaliplatin/S-1 (DOS) combination neoadjuvant chemotherapy for patients with locally advanced adenocarcinoma of the esophagogastric junction.

BACKGROUND: The optimal dose of each drug used in the docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy remains to be clarified for the Japanese population. The purpose of this study was to determine a recommended dose for a combination neoadjuvant DOS chemotherapy for Japanese patients with locally advanced adenocarcinoma of the esophagogastric junction (AEG). METHODS: Patients with cT3 or more advanced AEG without distant metastasis were eligible for this study. The planned dosages of docetaxel (mg/m2, day 1), oxaliplatin (mg/m2, day 1), and S-1 (mg/day, days 1-14) were: 50/100/80-120 at level 1, and 60/100/80-120 at level 2, respectively. The treatment cycle was repeated every 3 weeks, and patients were assessed for response to the treatment after 2 and 3 cycles. This study was registered in the UMIN Clinical Trial Registry (UMIN 000022210). RESULTS: We enrolled 12 patients with locally advanced AEG in this study. At dose level 1, one of the six patients experienced dose-limiting toxicity (DLT) of grade 3 diarrhea and grade 3 febrile neutropenia. Two of the next six patients also experienced DLT of need for more than 2-week delay of the start of the second cycle due to adverse events at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. CONCLUSION: Recommended doses of docetaxel (mg/m2), oxaliplatin (mg/m2), and S-1 (mg/day) were 60/100/80-120. This chemotherapy scheme showed good preliminary efficacy with acceptable toxicity warranting a further phase II trial to investigate the efficacy of this regimen.

A retrospective study of definitive chemoradiotherapy in patients with resectable small cell neuroendocrine carcinoma of the esophagus.

BACKGROUND: Standard treatment for resectable small cell neuroendocrine carcinoma of the esophagus (SCNEC-E) remains to be established. METHODS: We retrospectively studied 7 consecutive patients with resectable SCNEC-E who received definitive chemoradiotherapy (dCRT) to evaluate the safety and efficacy. Treatment consisted of two courses of chemotherapy with cisplatin (80 mg/m2 on day 1) and etoposide (100 mg/m2 on days 1-3) or carboplatin (AUC 5 on day 1) and etoposide (80 mg/m2 on days 1-3) given every 4 weeks during dCRT. The total radiation dose was 50.4 Gy (28 fractions). RESULTS: The clinical stage was IA in 1 patient, IB in 2 patients, IIA in 3 patients, and IIB in 1 patient. Definitive CRT was completed in all patients. The median overall treatment time of radiotherapy was 44 days. The chemotherapy regimen included in dCRT was cisplatin and etoposide in 3 patients and carboplatin and etoposide in 4 patients. Acute adverse events of grade 3 or 4 were neutropenia 100%, thrombocytopenia 43%, febrile neutropenia 43%, and nausea 14%. There were no late grade 3 or 4 adverse events. The median survival time was 32 months. The complete response rate was 100%. The recurrence rate was 43%. The median survival of the 4 patients without recurrence was 56 months. CONCLUSIONS: Definitive CRT with cisplatin and etoposide or carboplatin and etoposide is a feasible treatment for the resectable SCNEC-E, and long-term survival can be achieved in some patients.

Usefulness of narrow band imaging with magnifying endoscopy for the differential diagnosis of cancerous and noncancerous laryngeal lesions.

BACKGROUND: We evaluated the accuracy of endoscopic findings observed by narrow band imaging (NBI) combined with magnifying gastrointestinal endoscopy (GIE) for the differential diagnosis of cancerous and noncancerous laryngeal lesions. METHODS: A total of 166 vocal cord lesions for which good images were obtained on NBI with magnifying GIE were evaluated with respect to the following 6 variables: macroscopic type, tumor location, color, white coat, keratinization, and abnormal microvessels. RESULTS: Multivariate analysis showed that white coat (odds ratio [OR], 2.95, P = 0.05), keratosis (OR, 3.14, P = 0.02) and abnormal microvessels (OR, 31.1, P < 0.0001) were significantly related to laryngeal cancer. In the diagnosis of laryngeal cancer, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of abnormal microvessels were 84.4%, 88.6%, 91%, 80.5%, and 86.1%, respectively. CONCLUSION: The abnormal microvessels on NBI combined with magnifying GIE are useful for the differential diagnosis of laryngeal lesions.

Short-term outcomes of multicenter prospective cohort study of gastric endoscopic resection: 'Real-world evidence' in Japan.

OBJECTIVES: A Japanese multicenter prospective cohort study examining endoscopic resection (ER) for early gastric cancer (EGC) has been conducted using a Web registry developed to determine the short-term and long-term outcomes based on absolute and expanded indications. We hereby present the short-term outcomes of this study. METHODS: All consecutive patients with EGC or suspected EGC undergoing ER at 41 participating institutions between July 2010 and June 2012 were enrolled and prospectively registered into the Web registry. The baseline characteristics were entered before ER, and the short-term outcomes were collected at 6 months following ER. RESULTS: Nine thousand six hundred and sixteen patients with 10 821 lesions underwent ER (endoscopic submucosal dissection [ESD]: 99.4%). The median procedure time was 76 min, and R0 resections were achieved for 91.6% of the lesions. Postoperative bleeding and intraoperative perforation occurred in 4.4% and 2.3% of the patients, respectively. Significant independent factors correlated with a longer procedure time (120 min or longer) were as follows: tumor size >20 mm, upper-third location, middle-third location, local recurrent lesion, ulcer findings, gastric tube, male gender, and submucosa. Histopathologically, 10 031 lesions were identified as common-type gastric cancers. The median tumor size was 15 mm. Noncurative resections were diagnosed for 18.3% of the lesions. Additional surgery was performed for 48.6% (824 lesions) of the 1695 noncurative ER lesions with a possible risk of lymph node (LN) metastasis. Among them, 64 (7.8%) exhibited LN metastasis. CONCLUSIONS: This multicenter prospective study showed favorable short-term outcomes for gastric ESD.