Short-term outcomes of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis (JCOG1704).

BACKGROUND: The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial. METHODS: Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), and S-1 (80-120 mg/body, days 1-14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria. RESULTS: Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred. CONCLUSIONS: Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM.

Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2.

In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.

English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology.

The Japan Society of Clinical Oncology Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) have been published in accordance with the Minds Manual for Guideline Development 2014 and 2017. A specialized team independent of the working group for the revision performed a systematic review. Since GIST is a rare type of tumor, clinical evidence is not sufficient to answer several clinical and background questions. Thus, in these guidelines, we considered that consensus among the experts who manage GIST, the balance between benefits and harms, patients' wishes, medical economic perspective, etc. are important considerations in addition to the evidence. Although guidelines for the treatment of GIST have also been published by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), there are some differences between the treatments proposed in those guidelines and the treatments in the present guidelines because of the differences in health insurance systems among countries.

Long-term outcomes of a phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumors of the stomach.

BACKGROUND: Neoadjuvant treatment is recommended for large GISTs due to their friability and risk of extensive operations; however, studies on the indications and long-term results of this approach are lacking. METHODS: Patients with large (≥ 10 cm) gastric GISTs were enrolled from multiple centers in Korea and Japan after a pathologic confirmation of c-KIT ( +) GISTs. Imatinib (400 mg/d) was given for 6-9 months preoperatively, and R0 resection was intended. Postoperative imatinib was given for at least 12 months and recommended for 3 years. RESULTS: A total of 56 patients were enrolled in this study, with 53 patients receiving imatinib treatment at least once and 48 patients undergoing R0 resection. The 5-year overall survival and progression-free survival rates were 94.3% and 61.6%, respectively. Even patients with stable disease by RECIST criteria responded well to preoperative imatinib treatment and could undergo R0 resection, with most being evaluated as partial response by CHOI criteria. The optimal reduction in tumor size was achieved with preoperative imatinib treatment for 24 weeks or more. No resumption of imatinib treatment was identified as an independent prognostic factor for recurrence after R0 resection. No additional size criteria for a higher risk of recurrence were identified in this cohort with a size of 10 cm or more. CONCLUSIONS: Neoadjuvant imatinib treatment is an effective treatment option for gastric GISTs 10 cm or larger. Postoperative imatinib treatment is recommended even after R0 resection to minimize recurrence.

Late complication after gastrectomy for clinical stage I cancer: supplementary analysis of JCOG0912.

BACKGROUND: Late complications following gastric cancer surgery, including postgastrectomy syndromes, are complex problems requiring a solution. Reported risk factors for developing late complications include surgery-related factors, such as the surgical approach and the extent of resection and reconstruction. However, this has not been assessed in a prospective study with a large sample size. Therefore, this study aimed to evaluate associations between surgery-related factors and the development of late complications. Data from the JCOG0912 trial were used. It compared laparoscopy-assisted distal gastrectomy (LADG) to open distal gastrectomy (ODG) in clinical stage I gastric cancer patients. METHODS: This study included 881/921 patients enrolled in the JCOG0912 trial. The incidence of late complications was compared between the ODG and the LADG arms. In addition, associations between surgery-related factors and the development of late complications were assessed by multivariable analyses using the proportional odds model to identify relevant risk factors. RESULTS: There was no difference in the type or number of patients with late complications between the LADG and the ODG arms. The multivariable analysis for each late complication revealed that the Billroth-I reconstruction (vs. R-en-Y or Billroth-II) had a lower risk of cholecystitis [odds ratio (OR) 0.187, 95% confidence interval (CI) 0.039-0.905, P = 0.037] or ileus (OR 0.116, 95%CI 0.033-0.406, P < 0.001), and pylorus-preserving gastrectomy (vs. R-en-Y or Billroth-II) had a higher risk of reflux esophagitis (OR 3.348, 95% CI 1.371-8.176, P = 0.008). The surgical approach was not a risk factor for any late complications. CONCLUSION: Differences in surgical approaches did not constitute a risk for developing late complications after gastrectomy. Billroth-I reconstruction reduced the risk of ileus and cholecystitis, but pylorus-preserving gastrectomy carried a risk for reflux esophagitis.

Five-year follow-up of a randomized clinical trial comparing bursectomy and omentectomy alone for resectable gastric cancer (JCOG1001).

BACKGROUND: Bursectomy, the total resection of the bursa omentalis, is a standard procedure in gastrectomy for resectable gastric cancer. A phase III trial (JCOG1001) comparing bursectomy and omentectomy alone was terminated early at the interim analysis. The final results of the updated analysis after a minimum follow-up of 5 years are reported here. METHODS: Patients with histologically proven adenocarcinoma of the stomach (cT3-T4a) were randomized (1 : 1) during surgery to bursectomy or omentectomy-alone groups and then underwent D2 gastrectomy. The primary endpoint was overall survival, analysed on an intention-to-treat basis. RESULTS: A total of 1204 patients (602 bursectomy and 602 omentectomy alone) were enrolled between June 2010 and March 2015. The bursectomy group had a significantly higher incidence of Clavien-Dindo grade III-IV intra-abdominal abscess than the omentectomy-alone group (5.5 versus 2.5 per cent respectively; P = 0.008). The updated 5-year overall survival rates were 74.9 (95 per cent c.i. 71.2 to 78.2) per cent in the bursectomy group and 76.5 (72.8 to 79.7) per cent in the omentectomy-alone group; the adjusted HR for death in the bursectomy group was 1.03 (95 per cent c.i. 0.83 to 1.27) (1-sided P = 0.598). Bursectomy did not decrease peritoneal recurrence (12.1 versus 12.3 per cent respectively; P = 1.000). In a multivariable analysis, old age (above 65 years), tumour located in the lower third or posterior wall of the stomach, macroscopic type 3/5, total gastrectomy, and cT4a were independent predictors of poor overall survival, but omentectomy alone was not. CONCLUSION: In D2 gastrectomy, bursectomy is not recommended as a standard procedure for cT3-T4a gastric cancer. Registration number: UMIN000003688 (https://www.umin.ac.jp/ctr/).

Long-term adjuvant therapy for high-risk gastrointestinal stromal tumors in the real world.

PURPOSE: Three years of adjuvant imatinib is the standard therapy for gastrointestinal stromal tumors (GISTs) with high-risk features. The prognostic effects of long-term adjuvant therapy are unknown. PATIENTS AND METHODS: The prospective registry study recruited 515 patients with high-risk GISTs between Dec. 2012 and Dec. 2015 were analyzed. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints include overall survival (OS) and safety. The study was designed to compare RFS after 3.5 years of 3-year adjuvant therapy (3.0 ± 0.5 years: 3-year group) with that of more than 3.5 years (median 5.2 years: longer group). RESULTS: Five-year RFS and 5-year OS were 68.2% (95% confidence interval [CI] 63.8-72.1) and 92.3% (95% CI 89.5-94.4), respectively. The recurrence rate during adjuvant was estimated to be 2.9/100 person-years (95% CI 2.0-4.1) and those after the end of adjuvant, which appeared similar irrespective of the adjuvant duration or reason to stop adjuvant, were estimated 12.0/100 person-years (95% CI 10.2-14.0). The 5-year RFS rates of 3-year and longer groups were 78.7% (95% CI 70.8-84.7) and 92.7% (95% CI 85.2-96.4), respectively. RFS after 3.5 years of the longer group was significantly better than that of the 3-year group (adjusted hazard ratio [HR] 0.56; 95% CI 0.39-0.78; P < 0.001). CONCLUSION: The recurrence risk of high-risk GISTs after adjuvant therapy is similar irrespective of the adjuvant duration and imatinib adjuvant may not cure but may delay recurrence. RFS after long-term adjuvant therapy appeared better than that after 3-year adjuvant.

Impact of preoperative tumor rupture timing on gastrointestinal stromal tumor prognosis: a retrospective multicentric cohort study.

BACKGROUND: A gastrointestinal stromal tumor rupture entails a high risk of recurrence even after curative surgery. However, the definition of rupture is unclear, and the question of whether patients with a minor rupture should be treated with adjuvant imatinib remains controversial. METHODS: The present, retrospective, multicentric study enrolled 57 patients with gastrointestinal stromal tumor with a minor/major tumor rupture, of whom 46 were finally found to be eligible for analysis. Tumor ruptures were subclassified by their degree, timing and cause. Multivariate analysis was performed to identify the risk factors of all types of recurrence as well as of peritoneal recurrence only. RESULTS: The study cohort included minor (n = 24), intraoperative (n = 19) and iatrogenic (n = 20) ruptures besides the typical types (major, preoperative and spontaneous). All intraoperative ruptures were iatrogenic. In total, 27 patients (58.7%) had a recurrence in the peritoneum (n = 17) and/or the liver (n = 13) during a median follow-up period of 5.8 years, but no recurrence was observed in patients with tumor rupture as a single, high-risk factor. Multivariate analysis found the timing of tumor rupture to be an independent risk factor of poor recurrence-free survival (hazard ratio: 2.37; 95% confidence interval: 1.02-5.49; P = 0.045). CONCLUSIONS: Preoperative tumor rupture in patients with a ruptured gastrointestinal stromal tumor was associated with poor recurrence-free survival. Our results suggested that a distinction should be made between preoperative and intraoperative tumor ruptures when considering the indications for adjuvant imatinib therapy for gastrointestinal stromal tumor patients with tumor rupture as a single, high-risk factor of recurrence.

Evaluation of Lymph Node Staging Systems as Independent Prognosticators in Remnant Gastric Cancer Patients with an Insufficient Number of Harvested Lymph Nodes.

BACKGROUND: The lymph node (LN) ratio (LNR) and the log odds of positive LNs (LODDS) have been proposed as sensitive prognosticators in patients with primary gastric cancer, especially in patients with an insufficient number of harvested LNs. We investigated the association of LNR and LODDS with survival in patients with remnant gastric cancer (RGC) and explored whether these staging methods are prognostic factors in patients with an insufficient number of harvested LNs. METHODS: The present study retrospectively examined 95 patients with RGC who received gastrectomy between January 2000 and December 2018. The patients were classified according to the adjusted X-tile cutoff for LNR and LODDS. The association between survival rates and clinicopathological features was investigated. The predictive accuracy of the LNR and LODDS was compared with that of the Union for International Cancer Control pathological N factor. RESULTS: Multivariate analysis revealed that the LNR and LODDS were independent risk factors for recurrence-free survival (RFS) [hazard ratio (HR) 2.623, p = 0.020; HR 3.404, p = 0.004, respectively] and overall survival (OS) (HR 3.694, p = 0.003; HR 2.895, p = 0.022, respectively) in patients with RGC. Moreover, even in patients with 15 or fewer harvested LNs, only the LNR was a significant independent risk factor for RFS (HR 21.890, p < 0.001) and OS (HR 6.597, p = 0.002). The receiver operating characteristic curves revealed that the prognostic accuracy of the three methods was comparable (p > 0.05). CONCLUSION: LNR has significant prognostic value for patients with RGC, including those with an insufficient number of harvested LNs.

Risk factors of post-operative pneumonia in elderly patients with gastric cancer: a retrospective cohort study.

BACKGROUND: Post-operative pneumonia is a major complication after general elective surgery in elderly patients and is often caused by aspiration associated with oesophageal reflux. The aim of this study was to identify the risk factors of post-operative pneumonia after gastrectomy in elderly patients with gastric cancer with two potential risk factors of ageing and oesophageal reflux. METHODS: We retrospectively examined the data of 251 patients ≥75 years old who underwent gastrectomy between January 2014 and December 2018 in our institution. The reconstruction methods were Billroth-I or Roux-Y after distal gastrectomy, jejunal interposition or double tract after proximal gastrectomy and Roux-Y after total gastrectomy. The severity of pneumonia was evaluated by the Clavien-Dindo classification. RESULTS: Post-operative pneumonia was identified in 15 patients (5.9%) and was significantly associated with an age ≥80 years old, poor performance status, history of smoking and cardia-non-preserving gastrectomy (total gastrectomy and proximal gastrectomy) in univariate analyses. Multivariate analyses showed that a poor performance status and cardia-non-preserving gastrectomy were independent risk factors for post-operative pneumonia. The patients who suffered post-operative pneumonia required a longer hospital stay than those without post-operative pneumonia (P = 0.002). CONCLUSION: We identified a poor performance status and cardia-non-preserving gastrectomy, which are likely to lead to oesophageal reflux, as risk factors for post-operative pneumonia in elderly patients with gastric cancer. These results warrant further prospective studies to evaluate their utility for reducing the rate of post-operative pneumonia in elderly patients through cardia-preserving gastrectomy or anti-reflux reconstruction.

Short-term results of a phase II study of preoperative docetaxel/cisplatin/S-1 therapy for locally advanced gastric cancer.

BACKGROUND: A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer. METHODS: Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%. RESULTS: Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3-4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively. CONCLUSIONS: Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial.

Association Between Lymph Node Ratio and Survival in Patients with Pathological Stage II/III Gastric Cancer.

BACKGROUND: Lymph node ratio (LNR), defined as the ratio of metastatic nodes to the total number of examined lymph nodes, has been proposed as a sensitive prognostic factor in patients with gastric cancer (GC). We investigate its association with survival in pathological stage (pStage) II/III GC and explore whether this is a prognostic factor in each Union for International Cancer Control pStage (7th edition). PATIENTS AND METHODS: We retrospectively examined 838 patients with pStage II/III GC who underwent curative gastrectomy between June 2000 and December 2018. Patients were classified into low-LNR (L-LNR), middle-LNR (M-LNR), and high-LNR (H-LNR) groups according to adjusted X-tile cutoff values of 0.1 and 0.25 for LNR, and their clinicopathological characteristics and survival rates were compared. RESULTS: The 5-year recurrence-free survival (RFS) and overall survival (OS) rates postsurgery showed significant differences among the groups (P < 0.001). Multivariate analysis demonstrated that LNR was a significant predictor of poor RFS [M-LNR: hazard ratio (HR) 3.128, 95% confidence interval (CI) 2.254-4.342, P < 0.001; H-LNR: HR 5.148, 95% CI 3.546-7.474, P < 0.001] and OS (M-LNR: HR 2.749, 95% CI 2.038-3.708, P < 0.001; H-LNR: HR 4.654, 95% CI 3.288-6.588, P < 0.001). On subset analysis stratified by pStage, significant differences were observed between the groups in terms of the RFS curves of pStage II and III GC (P < 0.001 and < 0.001, respectively) and OS curves of pStage II and III GC (P = 0.001 and < 0.001, respectively). CONCLUSIONS: High LNR is a predictor of worse prognosis in pStage II/III GC, including each substage.

[Clinical Efficacy of mFOLFOX6 for Advanced Gastric Cancer].

FOLFOX therapy has been used for gastric cancer in Japan since 2017. We retrospectively analyzed the efficacy of FOLFOX therapy compared to that of FP. Forty-seven cases were evaluated between January 2010 and December 2018. Eighteen patients received mFOLFOX6 therapy, and 29 patients received FP therapy. The median time to treatment failure was 206 days in the mFOLFOX6 group and 58 days in the FP group. The response rate was 50% in the mFOLFOX6 group and 17% in the FP group. Neutropenia(56%), thrombocytopenia(50%), and peripheral neuropathy(56%)were the common adverse events in the mFOLFOX6 group, and leukopenia(69%)and neutropenia(69%)were the common adverse effects in the FP group. Based on our results, we conclude that, unlike FP, FOLFOX is an effective therapy for of gastric cancer.

[Successful Surgical Resection of Expansive-Growth Acinar Cell Carcinoma-A Case Report].

Here, we report a case of successful surgical resection of expansive-growth acinar cell carcinoma. A 59-year-old man was referred to a local hospital with abdominal distention. CT revealed a large abdominal tumor. Subsequently, he was referred to our hospital. Physical examination showed a large tumor on his left upper abdomen without tenderness. CT revealed an enhanced 18 cm-sized expansive-growth tumor on the left flank, suggesting a primary pancreatic tumor. EUS-FNA yielded a diagnosis of adenocarcinoma. Imaging findings were not typical for pancreatic ductal carcinoma. We performed distal pancreatectomy with splenectomy, transverse colon resection, and proximal gastrectomy. Pathological findings revealed a tumor, measuring 19.5×16.5×15.5 cm, originating from the pancreatic body, positive for trypsin, chymotrypsin, and elastase, consistent with a diagnosis of acinar cell carcinoma, pT3, N0, M0. Four courses of adjuvant chemotherapy with S-1 were provided, and the patient is currently alive without recurrence for 10 months.

Survival Outcomes of Two Phase 2 Studies of Adjuvant Chemotherapy with S-1 Plus Oxaliplatin or Capecitabine Plus Oxaliplatin for Patients with Gastric Cancer After D2 Gastrectomy.

BACKGROUND: Two phase 2 trials of oxaliplatin-containing adjuvant therapy for patients with gastric cancer (GC) after D2 gastrectomy were conducted in Japan. The SOXaGC trial evaluated the tolerability and safety of adjuvant therapy with S-1 plus oxaliplatin (SOX), whereas the J-CLASSIC trial evaluated the feasibility of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX). Because both were studies that did not evaluate survival results as study end points, the authors evaluated the survival outcomes for the patients in the two trials. METHODS: All 62 and 100 patients in the full analysis set of the SOXaGC and J-CLASSIC trials, respectively, were included in the current study. Their information about survival outcome was collected. The primary end point was relapse-free survival (RFS), and the secondary end point was overall survival (OS). RESULTS: For the pathologic stage (pStage 2) patients treated with CAPOX, the 3-year RFS rate was 87.8% and the 3-year OS rate was 92.7%. For the pStage 3 patients treated with SOX and CAPOX, the 3-year RFS rates were respectively 70.9% and 67.8% (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.50-1.72), whereas the 3-year OS rates were respectively 75.7% and 79.3% (HR, 1.10; 95% CI, 0.54-2.26). Subgroup analysis showed significant interactions between the treatment (SOX vs. CAPOX) and both sex (male vs. female; P = 0.024) and histologic type (diffuse vs. other, P = 0.069). CONCLUSIONS: This exploratory analysis demonstrated that SOX and CAPOX are suggested to have similar efficacy for pStage 3 GC patients after D2 gastrectomy. Differences in the treatment effect according to sex and histologic type warrant further evaluation.

Equivalent feasibility and safety of perioperative care by ERAS in open and laparoscopy-assisted distal gastrectomy for gastric cancer: a single-institution ancillary study using the patient cohort enrolled in the JCOG0912 phase III trial.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) has an advantage of earlier recovery after surgery due to having lower invasiveness and wound pain than open distal gastrectomy (ODG). However, whether the same enhanced recovery after surgery (ERAS) program for LADG is equally feasible and safe for ODG remains unclear. METHODS: We retrospectively extracted the clinical data of the patients enrolled in JCOG0912 from the medical record system of our hospital and compared the treatment process and short-term surgical outcomes between LADG and ODG. Our ERAS program consisted of 13 elements (4 preoperative, 4 intraoperative, and 5 postoperative elements). The morbidity was defined as complications of grade 2 or more. RESULTS: One hundred and sixty-three patients were entered from our hospital and randomized to undergo ODG (82 patients) or LADG (81 patients). The patient's backgrounds, surgical outcomes, and pathological outcomes were similar between the ODG and LADG groups. The rate of completing the clinical pathway was 95.1% in both groups, and the rates of completing each ERAS element were similar. However, the additional use of acetaminophen was significantly more frequent in the ODG group than in the LADG group (18.3% vs. 6.2%, p = 0.03). The median hospital stay after surgery was 9 days in both groups. Morbidity, defined as Clavien-Dindo classification > grade 2, was observed in 6.1% of the ODG group and 11.1% of the LADG group. No mortality occurred in either group. CONCLUSION: This study showed that the regimen of perioperative care performed by the ERAS program for LADG was equally feasible and safe for ODG with additional pain control. Less pain observed in LADG was not so apparent advantage for completion and safety of ERAS care.

Long-term quality of life and nutrition status of the aboral pouch reconstruction after total gastrectomy for gastric cancer: a prospective multicenter observational study (CCOG1505).

BACKGROUND: Several efforts have been made to alleviate harms and symptoms after gastrectomy for gastric cancer. We previously conducted a randomized controlled trial (CCOG1101) to compare quality of life (QOL) and nutritional status between Roux-en-Y (RY) and aboral pouch (AP) reconstructions for up to 1 year after total gastrectomy. However, long-term outcomes after AP reconstruction remain unclear. METHODS: A prospective multicenter observational study was conducted to compare QOL, body composition, and nutritional indicators between the RY and AP reconstructions at 5 years after surgery among patients who were enrolled in the CCOG1101 trial. QOL was assessed by the PGSAS-37 questionnaires as well as the EORTC QLQ-C30 and STO22. RESULTS: Sixty patients (31 for RY and 29 for AP) were recruited for analysis. There were no significant differences in baseline and perioperative characteristics between the two groups. No significant differences were found in the EORTC QLQ-C30 global health status and functional scales. Regarding symptom scales in the QLQ-C30 and STO22, a more favorable score for the diarrhea scale was observed in the AP group. Diarrhea was also the only item in the PGSAS-37 questionnaires in which significant benefit of AP was observed. Body weight and lean body mass continued to decrease throughout the postoperative 5 years in both groups. None of the conventional nutritional indicators using the serum samples showed significant difference between the two groups. CONCLUSIONS: Long-term observation suggested little benefit of AP reconstruction after total gastrectomy other than in alleviating diarrhea.

Safety and Feasibility of Linear Stapling Device with Bioabsorbable Polyglycolic Acid Sheet for Duodenal Closure in Gastric Cancer Surgery: A Multi-institutional Phase II Study.

BACKGROUND: Duodenal stump fistula (DSF) after gastrectomy is of low frequency but a critical complication in gastric cancer surgery. Manual oversewing for reinforcement of the duodenal stump is not applicable when free longitudinal margin is short and has technical difficulties in laparoscopic surgery. This trial evaluated the safety and feasibility of using a linear stapler with bioabsorbable polyglycolic acid (PGA) sheet for duodenal stump closure and reinforcement in gastric cancer surgery. METHODS: This multi-institutional, prospective phase II trial included gastric cancer patients who were scheduled to undergo distal or total gastrectomy with R-Y reconstruction. In all cases, duodenum was transected using a linear stapler with PGA sheet. The primary endpoint was the incidence of postoperative DSF. Sample size was set at 100 patients considering an expected value of 3% and threshold value of 8% with one-sided testing at a 10% significance level. RESULTS: Between June 2014 and June 2015, a total of 100 patients were registered in this trial. Postoperative DSF was observed in two cases (2.0%, 90% CI 0.4-6.2%) which was developed on postoperative days 13 and 20. Intraoperative bleeding at the duodenal stump staple line was observed in one case but was easily controlled without additional suturing. Postoperative bleeding was not observed in any of the cases. CONCLUSION: This study suggested that the use of PGA sheet as a reinforcement material for closure of the duodenal stump during gastrectomy for gastric cancer is both safe and feasible. Trial registration number UMIN 000014398.

[A Large Gastric Gastrointestinal Stromal Tumor Successfully Treated with Neoadjuvant Imatinib Followed by Surgery-A Case Report].

Neoadjuvant imatinib may prevent tumor rupture and the need for extended surgery by reducing the tumor size by approximately 35%, especially for large gastric gastrointestinal stromal tumors(GISTs), as shown in a previous phase Ⅱ study (Kurokawa et al. BJC 2017); however, the use ofneoadjuvant imatinib is not prevalent in clinical practice. Herein, we report a large gastric GIST that was successfully treated with neoadjuvant imatinib. A 74-year-old woman complained ofabdominal pain, and abdominal computed tomography(CT)revealed a 14 cm oval tumor in the left upper abdominal cavity. Gastric biopsy revealed that the tumor was a GIST. The patient also had a small lung tumor that was diagnosed as a primary lung carcinoma in the right upper lobe. We performed neoadjuvant imatinib for 6 months as the primary treatment. After 7 months ofimatinib administration, CT revealed that the GIST decreased in size but the lung cancer was slightly enlarged. Therefore, we performed right upper lung lobectomy and continued imatinib therapy for an additional 3 months. After a total of9 months ofneoadjuvant imatinib treatment, we performed partial gastrectomy combined with splenectomy without tumor rupture. The patient is scheduled to continue imatinib therapy for a total of 3 years.

Clinicopathological Features and Prognosis of Primary GISTs with Tumor Rupture in the Real World.

BACKGROUND: Patients with ruptured gastrointestinal stromal tumor (GIST) are recommended for imatinib adjuvant therapy; however, their clinicopathological features and prognosis in the era of imatinib are unknown. PATIENTS AND METHODS: The study cohort included 665 patients with histologically proven primary GISTs who underwent R0 or R1 surgery between 2003 and 2007; the validation cohort included 182 patients between 2000 and 2014. The definitions of tumor rupture in the study included perforation at tumor site, tumor fracture, piecemeal resection including open biopsy, and macroscopic injuries to the pseudocapsule. RESULTS: Tumor rupture occurred in 21 (3.2%) of 665 and 5 (2.9%) of 182 patients in the study and validation cohort, respectively. Ruptured GISTs were more symptomatic, were larger in size, and had higher mitotic count than nonruptured GISTs but were not associated with tumor location or laparoscopic surgery. GISTs with intraoperative rupture had clinicopathological features and prognostic outcomes similar to those with preoperative rupture. Recurrence rates were higher and median recurrence-free survival (RFS) and overall survival (OS) were shorter with ruptured than nonruptured GIST. Tumor rupture was one of the independent prognostic factors for RFS, but not OS, according to multivariate analysis. CONCLUSIONS: Ruptured GISTs were symptomatic larger tumors with high mitotic activity, frequent relapse, and shorter RFS. Tumor rupture was an independent prognostic factor for RFS, but not for OS, in the era of imatinib.