Five-Year Survival Outcomes of Laparoscopy-Assisted vs Open Distal Gastrectomy for Advanced Gastric Cancer: The JLSSG0901 Randomized Clinical Trial.

Importance: Evidence of implementation of laparoscopic gastrectomy for locally advanced gastric cancer is currently insufficient, as the primary end point in previous prospective studies was evaluated at a median follow-up time of 3 years. More robust evidence is necessary to verify noninferiority of laparoscopic gastrectomy. Objective: To compare 5-year survival outcomes between laparoscopy-assisted distal gastrectomy (LADG) and open distal gastrectomy (ODG) with D2 lymph node dissection for locally advanced gastric cancer. Design, Setting, and Participants: This was a multicenter, open-label, noninferiority, prospective randomized clinical trial. Between November 26, 2009, and July 29, 2016, eligible patients with histologically proven gastric carcinoma from 37 institutes in Japan were enrolled. Two interim analyses and final analysis were performed in October 2014, May 2018, and November 2021, respectively. Interventions: Patients were randomly assigned (1:1) to either the ODG or LADG group. The procedures were performed exclusively by qualified surgeons. Main Outcomes and Measures: The primary end point was 5-year relapse-free survival, and the noninferiority margin for the hazard ratio (HR) was set at 1.31. The secondary end points were 5-year overall survival and safety. Results: A total of 502 patients were included in the full-analysis set: 254 (50.6%) in the ODG group and 248 (49.4%) in the LADG group. Patients in the ODG group had a median (IQR) age of 67 (33-80) years and included 168 males (66.1%). Patients in the LADG group had a median (IQR) age of 64 (34-80) years and included 169 males (68.1%). No significant differences were observed in severe postoperative complications between the 2 groups in the safety analysis (ODG, 4.7% [11 of 233] vs LADG, 3.5% [8 of 227]; P = .64). The median (IQR) follow-up for all patients after randomization was 67.9 (60.3-92.0) months. The 5-year relapse-free survival was 73.9% (95% CI, 68.7%-79.5%) and 75.7% (95% CI, 70.5%-81.2%) for the ODG and LADG groups, respectively, and the HR was 0.96 (90% CI, 0.72-1.26; noninferiority 1-sided P = .03). Further, no significant difference was observed in overall survival time between the 2 groups, and the HR was 0.83 (95% CI, 0.57-1.21; P = .34). The pattern of recurrence was similar between the 2 groups. Conclusions and Relevance: Results of this study show that on the basis of 5-year follow-up data, LADG with D2 lymph node dissection for locally advanced gastric cancer, when performed by qualified surgeons, was proved noninferior to ODG. This laparoscopic approach could become a standard treatment for locally advanced gastric cancer. Trial Registration: UMIN Clinical Trial Registry: UMIN000003420.

Frequency of lymph node metastasis according to tumor location in clinical T1 early gastric cancer: supplementary analysis of the Japan Clinical Oncology Group study (JCOG0912).

BACKGROUND: The frequency of lymph node metastases per lymph node site in early gastric cancer has not been well clarified from the data based on prospective studies. This exploratory analysis aimed to determine the frequency and location of lymph node metastases in clinical T1 gastric cancer using the data from JCOG0912 to investigate the validity of the extent of standard lymph node dissection defined in Japanese guidelines. METHODS: This analysis included 815 patients with clinical T1 gastric cancer. The proportion of pathological metastasis was identified for each lymph node site per tumor location (middle third and lower third) and four equal parts of the gastric circumference. The secondary aim was identification of the risk factor for lymph node metastasis. RESULTS: Eighty-nine patients (10.9%) had pathologically positive lymph node metastases. Although the overall frequency of metastases was low (0.3-5.4%), metastases were widely located in each lymph node sites when primary lesion was in the middle third of the stomach. No. 4sb and 9 showed no metastasis when primary lesion was in the lower third of the stomach. Lymph node dissection of metastatic nodes resulted in a 5-year survival in more than 50% of patients. A tumor greater than 3 cm and a T1b tumor were associated with lymph node metastasis. CONCLUSIONS: This supplementary analysis demonstrated that nodal metastasis from early gastric cancer is widely and disorderly not depending on the location. Thus, systematic lymph node dissection is necessary to cure the early gastric cancer.

Anti-Helicobacter pylori antibody status is associated with cancer mortality: A longitudinal analysis from the Japanese DAIKO prospective cohort study.

Paradoxically, patients with advanced stomach cancer who are Helicobacter pylori-positive (HP+) have a higher survival rate than those who are HP-. This finding suggests that HP infection has beneficial effects for cancer treatment. The present study examines whether HP+ individuals have a lower likelihood of death from cancer than those who are HP-. Prospective cohort data (n = 4,982 subjects enrolled in the DAIKO study between 2008-2010) were used to assess whether anti-HP antibody status was associated with cancer incidence. The median age in the primary registry was 53 years-old (range 35-69 years-old). Over the 8-year observation period there were 234 (4.7%) cancer cases in the cohort and 88 (1.8%) all-cause deaths. Urine anti-HP antibody data was available for all but one participant (n = 4,981; 99.98%). The number of HP+ and HP- individuals was 1,825 (37%) and 3,156 (63%), respectively. Anti-HP antibody distribution per birth year revealed that earlier birth year was associated with higher HP+ rates. With a birth year-matched cohort (n = 3,376), all-cancer incidence was significantly higher in HP+ individuals than those who were HP- (p = 0.00328), whereas there was no significant difference in the cancer death rate between HP+ and HP- individuals (p = 0.888). Cox regression analysis for prognostic factors revealed that the hazards ratio of HP+ was 1.59-fold (95%CI 1.17-2.26) higher than HP- in all-cancer incidence. Potential systemic effects of HP+ status may contribute to reduced likelihood of death for patients after an initial diagnosis of cancer.

Helicobacter pylori Modulated Host Immunity in Gastric Cancer Patients With S-1 Adjuvant Chemotherapy.

BACKGROUND: Paradoxically, Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systemic mechanisms modulated by HP are involved in this more favorable outcome. METHODS: A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1) and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse-free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors. RESULTS: Among 491 patients that were analyzed, 175 (36%) and 316 (64%) patients were HP+ and HP-, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 dose (Pinteraction = .049) and PD-L1 (P = .02). HP+ patients in the PD-L1- group had statistically higher 5-year OS and RFS than HP- patients (81% vs 68%; P = .0011; hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.303 to 0.751, and 76% vs 63%; P = .001; HR = 0.508, 95% CI = 0.335 to 0.771, respectively). The 5-year OS and RFS was also statistically higher for HP+ compared with HP- patients in the "PD-L1- and S-1-r educed" group (86% vs 46%; P = .001; HR = 0.205, 95% CI = 0.07 to 0.602, and 83% vs 34%; P = .001; HR = 0.190, 95% CI = 0.072 to 0.498, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival. CONCLUSION: This retrospective study suggests that an HP-modulated host immune system may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.

Choking injuries: Associated factors and error-producing conditions among acute hospital patients in Japan.

Choking can lead to mortality and residual impairments. This study aimed to determine the factors associated with choking among acute hospital patients and examine error-producing conditions to suggest choking-prevention policies. Among 36,364 cases reported by hospital staff at an acute university hospital from 2012 to 2018 were examined using a retrospective study, 35,440 were analysis as the number of cases analysed for the study. We used descriptive statistics to present patient characteristics and conducted univariable and multivariable logistic regression analyses to identify factors associated with choking. Additionally, we conducted content analysis (root cause analysis) to examine error-producing conditions and prevention policies. Sixty-eight cases were related to choking injuries; of these, 43 patients (63.2%) were male, and 38 (55.9%) were aged 65 years and older. Choking cases had a high percent of adverse outcomes involving residual impairment or death (n = 23, 33.8%). Mental illness (adjusted odds ratio [95% confidence interval]: 3.14 [1.39-7.08]), and hospitalisation in the general wards (adjusted odds ratio [95% confidence interval]: 3.13 [1.70-5.76]) were associated with an increased probability of choking. Error production was caused by food (n = 25, 36.8%) and medical devices or supplies (n = 13, 19.1%). Almost all contributory factors were associated with inadequate checking (n = 66, 97.1%) and misperception of risk (n = 65, 95.6%). Choking poses a highly significant burden on patients, and hospital administrators should minimise the risk of choking to prevent related injuries. Hospital administrators should provide training and education to their staff and develop adequate protocols and procedures to prevent choking.

Laparoscopic distal pancreatectomy for metastatic melanoma originating from the choroidal membrane: a case report.

BACKGROUND: Metastatic melanoma originating from the choroidal membrane is extremely rare. Here, we report a case of laparoscopic distal pancreatectomy for malignant melanoma that developed after heavy-particle therapy for malignant choroidal melanoma. CASE PRESENTATION: A 43-year-old Japanese woman underwent 70 Gy heavy-particle radiotherapy for a right choroidal malignant melanoma. Positron emission tomography-computed tomography examination was performed 4 years after treatment, when contrast accumulation was observed on the posterior wall of the stomach. Endoscopic ultrasonography and computed tomography showed a mass with contrast enhancement in contact with the stomach wall. Based on the imaging findings, a gastrointestinal stromal tumor of the posterior wall of the lower gastric corpus with extramural growth was suspected. Laparoscopic surgery was performed under general anesthesia. A black-pigmented tumor originating from the pancreas was discovered. Following an intraoperative diagnosis of metastasis of malignant melanoma, a laparoscopic distal pancreatectomy was performed. The pathological diagnosis was pancreatic metastasis of malignant melanoma. The patient was treated with adjuvant immune checkpoint inhibitors and chemotherapy after surgery, which led to long-term survival. CONCLUSIONS: Including this case, only eight case reports on pancreatic resection for metastatic ocular malignant melanoma have been reported. The ocular malignant melanoma with distant metastasis has a poor prognosis. Therefore, in our case, careful follow-up is required. A single pancreatic metastasis from a malignant melanoma of the choroid can be successfully managed by laparoscopic radical resection of the pancreas, and molecularly targeted adjuvant chemotherapy.

Comparison of effects of six main gastrectomy procedures on patients' quality of life assessed by Postgastrectomy Syndrome Assessment Scale-45.

BACKGROUND: The effects of various gastrectomy procedures on the patient's quality of life (QOL) are not well understood. Thus, this nationwide multi-institutional cross-sectional study using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45), a well-established questionnaire designed to clarify the severity and characteristics of the postgastrectomy syndrome, was conducted. AIM: To compare the effects of six main gastrectomy procedures on the postoperative QOL. METHODS: Eligible questionnaires retrieved from 2368 patients who underwent either of six gastrectomy procedures [total gastrectomy with Roux-en-Y reconstruction (TGRY; n = 393), proximal gastrectomy (PG; n = 193), distal gastrectomy with Roux-en-Y reconstruction (DGRY; n = 475), distal gastrectomy with Billroth-I reconstruction (DGBI; n = 909), pylorus-preserving gastrectomy (PPG; n = 313), and local resection of the stomach (LR; n = 85)] were analyzed. Among the 19 main outcome measures of PGSAS-45, the severity and characteristics of postgastrectomy syndrome were compared for the aforementioned six gastrectomy procedures using analysis of means. RESULTS: TGRY and PG significantly impaired the QOL of postoperative patients. Postoperative QOL was excellent in LR (cardia and pylorus were preserved with minimal resection). In procedures removing the distal stomach, diarrhea subscale (SS) and dumping SS were less frequent in PPG than in DGBI and DGRY. However, there was no difference in the postoperative QOL between DGBI and DGRY. The most noticeable adverse effects caused by gastrectomy were meal-related distress SS, dissatisfaction at the meal, and weight loss, with significant differences among the surgical procedures. CONCLUSION: Postoperative QOL greatly differed among six gastrectomy procedures. The severity and characteristics of postgastrectomy syndrome should be considered to select gastrectomy procedures, overcome surgical shortcomings, and enhance postoperative care.

Safety and activity of trifluridine/tipiracil and ramucirumab in previously treated advanced gastric cancer: an open-label, single-arm, phase 2 trial.

BACKGROUND: Findings of preclinical and clinical trials in colorectal cancer have shown promising antitumour effects of the co-formulation trifluridine/tipiracil and VEGF inhibition. We aimed to investigate the safety and activity of trifluridine/tipiracil and ramucirumab for previously treated advanced gastric cancer. METHODS: We did an open-label, single-arm, two-cohort, phase 2 study at eight centres in Japan. We enrolled patients with unresectable advanced gastric cancer or gastro-oesophageal junction adenocarcinoma. Cohort A included patients previously treated with one line of chemotherapy without ramucirumab and cohort B included patients previously treated with two to four lines of chemotherapy, including ramucirumab. Patients received trifluridine/tipiracil (35 mg/m2) orally twice daily on days 1-5 and days 8-12 of each 28-day treatment cycle, plus intravenous ramucirumab (8 mg/kg) on days 1 and 15. The primary endpoint was the disease control rate, assessed by investigators and defined as the proportion of patients with a confirmed best overall response, according to Response Evaluation Criteria in Solid Tumors version 1.1. This trial is registered on JapicCTI (JapicCTI-194596) and is ongoing but not recruiting. FINDINGS: Between April 8 and Oct 11, 2019, 64 patients were enrolled and included in the safety and activity analyses, 33 in cohort A and 31 in cohort B. In cohort A, the disease control rate was 85% (95% CI 68-95; 28 of 33 patients) and in cohort B it was 77% (59-90; 24 of 31 patients). Common treatment-related adverse events of grade 3 or worse were neutrophil count decreased (27 [82%] in cohort A and 23 [74%] in cohort B), white blood cell count decreased (eight [24%] and seven [23%]), and platelet count decreased (eight [24%] and four [13%]). Serious treatment-related adverse events were recorded in three patients in cohort A (fatigue and neutrophil count decreased; large intestine perforation; and febrile neutropenia, platelet count decreased, and anaemia). No patients in cohort B had a serious treatment-related adverse event, and no treatment-related deaths were reported in either cohort. INTERPRETATION: Trifluridine/tipiracil and ramucirumab showed an acceptable safety profile and clinical activity in patients with previously treated advanced gastric cancer regardless of previous ramucirumab exposure. FUNDING: Taiho Pharmaceutical and Eli Lilly.

Effect of early tumor response on the health-related quality of life among patients on second-line chemotherapy for advanced gastric cancer in the ABSOLUTE trial.

BACKGROUND: This study evaluated the association between early tumor response at 8 weeks, previously reported as a positive outcome prognosticator, and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients enrolled in the ABSOLUTE trial. METHODS: HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D) utility index score in patients with complete response (CR) + partial response (PR) and progressive disease (PD) at 8 weeks, and time-to-deterioration (TtD) of the EQ-5D score, with the preset minimally important difference (MID) of 0.05, was compared between these populations. Among the enrolled patients, 143 and 160 patients were assessable in weekly solvent-based paclitaxel (Sb-PTX) arm and weekly nanoparticle albumin-bound paclitaxel (nab-PTX) arm, respectively. RESULTS: Changes of the EQ-5D score from baseline to 8 weeks in the nab-PTX arm were 0.0009 and - 0.1229 in CR + PR and PD patients, respectively; the corresponding values for the Sb-PTX arm were - 0.0019 and - 0.1549. For both treatments, changes of the EQ-5D score from baseline at 8 weeks were significantly larger in patients with PD than in those with CR + PR. The median TtD was 3.9 and 2.2 months in patients with CR + PR and PD, respectively, for nab-PTX [hazard ratio (HR) = 0.595, 95% confidence interval (CI) 0.358-0.989]. For Sb-PTX, the corresponding values were 4.7 and 2.0 months (HR = 0.494, 95% CI 0.291-0.841). CONCLUSIONS: Early tumor shrinkage was associated with maintained HRQOL in AGC patients on the second-line chemotherapy with taxanes.

Efficacy of enhanced prehabilitation for patients with esophageal cancer undergoing esophagectomy.

BACKGROUND: Several studies have demonstrated that prehabilitation helps reduce the incidence of postoperative complications. In this study, we investigated the safety and efficacy of enhanced prehabilitation (EP) in the hospital for patients with esophageal cancer. METHODS: We retrospectively reviewed the data of 48 consecutive patients who underwent radical esophagectomy with gastric tube reconstruction between September 2015 and June 2019. EP program had been introduced in August 2017. In the EP group, patients received the EP program during hospitalization 7 days before surgery in addition to conventional perioperative rehabilitation. The EP program consisted of aerobic exercise and muscle strength training in the morning and afternoon. Operative outcomes were compared between patients who received EP (EP group; 23 patients) and patients who did not receive EP (control group; 25 patients). RESULTS: The preoperative (EP group vs. control group, 492.9 ± 79.7 vs. 418.9 ± 71.8 m, p < 0.001) and postoperative (EP group vs. control group, 431.5 ± 80 vs. 378 ± 68.7 m, p < 0.001) 6-min walk distance was significantly higher in the EP group than in the control group. The respiratory complications rate was significantly lower in the EP group (4.3%) than in the control group (36%) (p = 0.007). The incidence of atelectasis was particularly significantly lower in the EP group (0%) than in the control group (24%) (p = 0.012). CONCLUSIONS: EP was performed safely for patients before esophagectomy. EP improved the exercise tolerance of the patients before esophagectomy and might be useful in preventing respiratory complications.

Incident reports involving hospital administrative staff: analysis of data from the Japan Council for Quality Health care nationwide database.

BACKGROUND: Task shifting and task sharing in health care are rapidly becoming more common as the shortage of physicians increases. However, research has not yet examined the changing roles of hospital administrative staff. This study clarified: (1) the adverse incidents caused by hospital administrative staff, and the direct and indirect impact of these incidents on patient care; and (2) the incidents that directly involved hospital administrative staff. METHODS: This study used case report data from the Japan Council for Quality Health care collected from April 1, 2010 to March 31, 2019, including a total of 30,823 reports. In April 2020, only the 88 self-reported incidents by hospital administrative staff were downloaded, excluding incidents reported by those in medical and co-medical occupations. Data from three reports implicating pharmacists were rejected and the quantitative and textual data from the remaining 85 case reports were analyzed in terms of whether they impacted patient care directly or indirectly. RESULTS: Thirty-nine reports (45.9%) involved direct impact on patient care, while 46 (54.1%) involved indirect impact on patient care. Most incidents that directly impacted patient care involved administrative staff writing prescriptions on behalf of a doctor (n = 24, 61.5%); followed by errors related to system administration, information, and documentation (n = 7, 17.9%). Most reported errors that indirectly affected patient care were related to system administration, information, and documentation used by administrative staff (n = 22, 47.8%), or to reception (n = 9, 19.6%). Almost all errors occurred during weekdays. Most frequent incidents involved outpatients (n = 23, 27.1%), or occurred next to examination/operation rooms (n = 12, 14.1%). Further, a total of 14 cases (16.5%) involved patient misidentification. CONCLUSIONS: Incidents involving hospital administrative staff, the most common of which are medication errors from incorrect prescriptions, can lead to severe consequences for patients. Given that administrative staff now form a part of medical treatment teams, improvements in patient care may require further submission and review of incident reports involving administrative staff.

Primary esophageal malignant melanoma successfully treated with anti-PD-1 antibody for retroperitoneal recurrence after esophagectomy: A case report.

INTRODUCTION: Primary malignant melanoma of the esophagus (PMME) is a rare disease with a poor prognosis. Here, we report a case of retroperitoneal recurrence of PMME successfully treated with the anti-programmed cell death 1 antibody, nivolumab. PRESENTATION OF CASE: A 70-year-old male with dysphagia was referred to our hospital. Esophagogastroscopy showed an elevated tumor in the lower thoracic esophagus. A histopathological examination of the biopsy revealed poorly differentiated squamous cell carcinoma. The patient was diagnosed with clinical T3N1M0 stage III esophageal squamous cell carcinoma and was treated with neoadjuvant chemotherapy followed by radical esophagectomy. A postoperative histopathological examination revealed that atypical cells with a brown pigment were scattered in the tumor. Immunohistochemical staining demonstrated positive expression of human melanoma black 45, melan A, and S100. A pathological diagnosis of PMME was confirmed. Sixteen months after surgery, abdominal computed tomography revealed solitary retroperitoneal recurrence in the lateral portion of the ascending colon. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) showed hypermetabolic accumulation with a maximum standardized uptake value of 5.8. The patient was treated with nivolumab (240 mg) every two weeks. After eight courses of nivolumab, abnormal accumulation of the retroperitoneal mass disappeared on PET, and this therapeutic effect continued for 20 months. CONCLUSIONS: Nivolumab was effective for recurrence of PMME in our case. There are few reports of treatment with nivolumab for PMME. Further studies are necessary to establish the usefulness of nivolumab for PMME in the future.

Esophageal carcinosarcoma in which the sarcomatous element has sloughed off: A case report.

INTRODUCTION: Most esophageal carcinosarcoma (ECS) tumors present as a polypoid tumor that is continuous with the superficial lesion and suspended by a pedicle. Here, we report a case of ECS in which a polypoid lesion sloughed off before surgery. PRESENTATION OF CASE: A 76-year-old man with dysphagia was admitted to our hospital. Esophagogastroscopy revealed a 20-mm polypoid tumor continuous with a superficial lesion and attached to the lesion by a thin pedicle in the mid-thoracic esophagus. Histopathological examination of the endoscopic biopsy showed that the superficial lesion was a moderately differentiated squamous cell carcinoma and that the polypoid tumor contained a sarcomatous element. He was diagnosed with ECS and underwent radical esophagectomy with three-field lymph node dissection. In the resected specimen, no polypoid tumor was found, and only a superficial lesion was observed. The histopathological findings revealed only squamous cell carcinoma, and the pathological diagnosis was esophageal squamous cell carcinoma, pT1bN0M0, pathological stage I. The patient was discharged from the hospital 22 days after surgery and did not experience any complications. He is currently alive and remained cancer-free for three years since surgery was performed. DISCUSSION: Due to the distinctive configuration in which the polypoid lesion was connected to the superficial cancerous lesion by a very thin pedicle, researchers suggested that the polypoid tumor, which consisted of a sarcomatous element, was sloughed off before surgery. CONCLUSION: We encountered a rare case of ECS in which the sarcomatous element sloughed off prior to surgical resection.

Feasibility of totally laparoscopic pylorus-preserving gastrectomy with intracorporeal gastro-gastrostomy for early gastric cancer: a retrospective cohort study.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) has been accepted as a function-preserving surgery for the treatment of early gastric cancer in East Asian countries. Therefore, this study aimed to evaluate the feasibility and safety of totally laparoscopic PPG (TLPPG) with intracorporeal anastomosis. METHODS: A total of 43 patients with early gastric cancer underwent laparoscopy-assisted PPG (LAPPG) with extracorporeal anastomosis between May 2006 and November 2012. The operative outcomes of 22 patients who underwent TLPPG between November 2012 and February 2019 were evaluated, and data were compared with that of the LAPPG group. RESULTS: No significant difference in the operative time was observed between the two groups. Blood loss was lower in the TLPPG group (18.5 mL) than in the LAPPG group (30.7 mL, p = 0.008), and the length of abdominal incision was shorter in the TLPPG group (3.8 cm) than in the LAPPG group (4.7 cm, p < 0.001). No significant difference in the complication rate was observed between the two groups (13.6% in the TLPPG vs. 9.3% in the LAPPG group, p = 0.594). No anastomosis-related complications occurred in either group. No significant between-group difference was observed in the delayed gastric emptying (TLPPG, 9.1 vs. LAPPG, 7%, p = 0.762). The initiation of postoperative fluid (TLPPG, 1.0 day vs. LAPPG, 3.0 days, p < 0.001) and meal (TLPPG, 3.0 days vs. LAPPG, 4.0 days, p < 0.001) intake was earlier in the TLPPG group than in the LAPPG group. No significant between-group difference was observed in the postoperative hospital stay. CONCLUSIONS: The findings of this study suggest that TLPPG with intracorporeal reconstruction not only is as feasible and safe as LAPPG for the treatment of patients with early gastric cancer but also provides certain advantages such as reduced blood loss and wound size.

[A Thoracic Aortic Dissection Case during Treatment with Ramucirumab plus Nab-Paclitaxel].

Ramucirumab(RAM)plus nab-paclitaxel(nab-PTX)therapy is a regimen that is recommended for the second round of chemotherapy in recurrent, progressive gastric cancer. We report the first case of a thoracic aortic dissection developed during RAM plus nab-PTX therapy. A 59-year-old male who had undergone a proximal gastrectomy for esophagogastric junction cancer had a recurrence of cancer 6 years later(metastasis to the para-aortic lymph node and left adrenal gland, local recurrence, and multiple bone metastases). He was treated with RAM plus nab-PTX therapy for second-line chemotherapy. On day 9 of the third cycle, he experienced sudden, severe neck pain and visited the outpatient emergency department. Computed tomography detected a Stanford type-A thoracic aortic dissection. However, the patient suffered from a myocardial infarction before the operation, and died. This is the first report of an aortic dissection associated with RAM. Clinicians must be aware of this complication.

Super-late pulmonary recurrence after radical esophagectomy for esophageal squamous cell carcinoma.

INTRODUCTION: Pulmonary metastases from esophageal squamous cell carcinoma (ESCC) are often detected bilateral and multiple lesions and are often accompanied by metastases to other sites. The concept of oligometastasis has been developed, and limited distant metastases have been considered as indications for surgical resection for the purpose of extending overall survival. We herein present a long-surviving case of super-late pulmonary recurrence of ESCC, seven years after radical esophagectomy. PRESENTATION OF CASE: A 71-year-old woman who underwent radical subtotal esophagectomy with three-field lymph node dissection with a diagnosis of an advanced poorly differentiated ESCC with cT3N1M0 seven years ago visited our hospital. Chest X-ray and computed tomography at the 7-year follow-up revealed a solitary pulmonary tumor, 1.5 cm in diameter, at the right middle lobe without any extrapulmonary metastases; however, we could not diagnose whether primary lung cancer or pulmonary metastasis of ESCC was present. Therefore, we performed thoracoscopic partial resection of the right middle lobe. A histopathological examination including immunohistochemical staining revealed that the tumor was not derived from both alveolar epithelium and neuroendocrine cells and was diagnosed as pulmonary oligometastasis of ESCC. She has been followed for four years without re-recurrence. CONCLUSION: Pulmonary oligometastases of ESCC should be considered as surgical indications if the tumor is detected after a long disease-free interval without any extrapulmonary recurrences.

Survival outcomes after laparoscopy-assisted distal gastrectomy versus open distal gastrectomy with nodal dissection for clinical stage IA or IB gastric cancer (JCOG0912): a multicentre, non-inferiority, phase 3 randomised controlled trial.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) is increasingly being used as an alternative to open distal gastrectomy (ODG) for gastric cancer treatment. Retrospective studies have shown equivalent survival with the two procedures, but these studies are limited by selection bias because LADG is more technically difficult than ODG. We aimed to evaluate whether LADG was non-inferior to ODG in terms of long-term survival outcomes. METHODS: We did an open-label, multicentre, non-inferiority, phase 3 randomised controlled trial at 33 institutions in Japan. Patients aged 20-80 years with histologically confirmed gastric adenocarcinoma (T1N0, T1N1, or T2[MP]N0), clinical stage I, in the middle or lower third of the stomach, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with a body-mass index of less than 30 kg/m2, were randomly assigned (1:1) to receive ODG or LADG. Randomisation was done by telephone, fax, or with a web-based system in the Japan Clinical Oncology Group Data Center; a minimisation method with a random component was used to adjust for institution and clinical stage (IA or IB). Only study-accredited surgeons performed ODG and LADG. The primary endpoint was relapse-free survival and was analysed according to the intention-to-treat principle. The non-inferiority margin (LADG vs ODG) was set at a hazard ratio (HR) of 1·54. The trial was registered with the UMIN Clinical Trials Registry, UMIN000003319. FINDINGS: Between March 15, 2010, and Nov 29, 2013, 921 patients were enrolled and randomly assigned to receive ODG (n=459) or LADG (n=462). 912 (99%) participants had the assigned surgery. 5-year relapse-free survival was 94·0% (95% CI 91·4-95·9) in the ODG group and 95·1% (92·7-96·8) in the LADG group. LADG was non-inferior to ODG for relapse-free survival (HR 0·84 [90% CI 0·56-1·27]), p=0·0075). The most common grade 3 or 4 adverse event was bowel obstruction, occurring in 11 (2%) of 455 patients in the ODG group and five (1%) of 457 patients in the LADG group. There were no treatment-related deaths. INTERPRETATION: This trial supports the non-inferiority of LADG compared with ODG for clinical stage I gastric cancer relapse-free survival, suggesting that LADG should be considered a standard treatment option when performed by experienced surgeons. FUNDING: Japan National Cancer Center, Ministry of Health, Labour and Welfare of Japan, Japan Agency for Medical Research and Development.

Safety of thoracoscopic esophagectomy after induction chemotherapy for locally advanced unresectable esophageal squamous cell carcinoma.

INTRODUCTION: Recent studies have reported that induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) is an effective treatment for unresectable, locally advanced esophageal cancer. The aim of this study was to investigate the safety and feasibility of thoracoscopic esophagectomy (TE) after DCF for initially unresectable esophageal squamous cell carcinoma (ESCC). METHODS: Twenty-three patients with initially unresectable T4 thoracic ESCC underwent TE after induction DCF. RESULTS: The neighboring organs with tumors were the tracheobronchus in nine patients, thoracic aorta in 13, and pericardium and diaphragm in three each (concurrent overlapping invasion occurred in five patients). The mean total operation time was 556.3 ± 107.2 minutes, and the mean time of the thoracic procedure was 258.9 ± 83.9 minutes. The mean total blood loss was 166.2 ± 117.8 mL, and the loss during the thoracic procedure was 33.5 ± 24.6 mL. All patients achieved complete R0 resection under TE. No conversions to open thoracotomy were performed. The postoperative morbidity rate was 34.8%. The postoperative hospital stay was 24.3 (range, 13-38) days. Five patients had recurrence: four had distant metastasis (lung, two; liver, three; and one with overlap), and one had mediastinal lymph node recurrence. No local recurrence was noted at the site of the primary T4 tumor. CONCLUSIONS: TE was safely performed in 23 patients after DCF therapy for locally advanced unresectable ESCC. Induction DCF, followed by TE, could be an alternative treatment for unresectable T4 ESCC.

Recurrence risk evaluation in T1N1M0/T2N0M0/T3N0M0 gastric cancer with TP53 codon 72 polymorphisms.

BACKGROUND: Postoperative adjuvant chemotherapy is not indicated for T1N1M0/T2N0M0/T3N0M0 gastric cancer. However, approximately 10% to 30% of these patients experience recurrence and metastasis. METHODS: Among 658 patients with gastric cancer who received gastrectomy with curative intent, 130 T1N1M0/T2N0M0 and 73 T3N0M0 patients were enrolled. Overall survival (OS) and relapse-free survival (RFS) were analyzed based on TP53 codon 72 polymorphisms Arg/Arg, Arg/Pro, and Pro/Pro. The hazard ratio (HR) for each subgroup was compared by TP53 codon 72 polymorphisms. RESULTS: Of the 189 patients for whom polymorphism analysis results were available, the 5- and 10-year OS was 84.9% and 65.1%, respectively. The 5- and 10-year RFS was 81.8% and 65.4%, respectively. When the study cohort was divided into two groups according to polymorphism status (ie, "Arg/Arg and Arg/Pro" vs Pro/Pro), both the OS (HR, 2.799; 95% confidence interval [CI], 1.071-7.315; P = .036) and RFS (HR, 2.639; 95% CI, 1.025-6.794; P = .044) of the Pro/Pro group were significantly lower than those for the Arg/Arg and Arg/Pro groups across the entire observation period. CONCLUSIONS: The TP53 codon 72 Pro/Pro polymorphism may isolate a relatively high-risk patient group in T1N1M0/T2N0M0/T3N0M0 gastric cancer.