D2 Resection Research Articles

Survival outcomes following laparoscopic versus open D3 dissection for stage II or III colon cancer (JCOG0404): a phase 3, randomised controlled trial

Although benefits of laparoscopic surgery compared with open surgery have been suggested, the long-term survival of patients undergoing laparoscopic surgery for colon cancer requiring Japanese D3 dissection remains unclear. We did a randomised controlled trial to establish non-inferiority of laparoscopic surgery to open surgery. We did an open-label, multi-institutional, randomised, two-arm phase 3 trial in 30 hospitals in Japan. Patients aged 20-75 years who had histologically proven colon cancer; tumours located in the caecum or ascending, sigmoid, or rectosigmoid colon; T3 or deeper lesions without involvement of other organs, node stages N0-2, and metastasis stage M0; and tumour size of 8 cm or smaller were included. Only accredited surgeons did surgery as an operator or instructor. Patients were randomly assigned (1:1) preoperatively to undergo D3 resection either by an open route or a laparoscopic route, via phone call or fax to the Japan Clinical Oncology Group (JCOG) Data Center. Randomisation used a minimisation method with a biased-coin assignment according to tumour location (caecum, ascending vs sigmoid, rectosigmoid) and institution. The primary endpoint was overall survival and was analysed by intention to treat. The non-inferiority margin for the hazard ratio (HR) was set at 1·366. This study is registered with UMIN Clinical Trials Registry, number C000000105, and ClinicalTrials.gov, number NCT00147134. Between Oct 1, 2004, and March 27, 2009, 1057 patients were randomly assigned to either open surgery (n=528) or laparoscopic surgery (n=529). 5-year overall survival was 90·4% (95% CI 87·5-92·6) for open surgery and 91·8% (89·1-93·8) for laparoscopic surgery. Laparoscopic D3 surgery was not non-inferior to open surgery for overall survival (HR 1·06, 90% CI 0·79-1·41; pnon-inferiority=0·073). 65 (13%) patients in the open surgery group and 53 (10%) patients in the laparoscopic surgery group had grade 2-4 adverse events. Grade 2-4 adverse events included diarrhoea (15 [3%] in the open surgery group vs 14 [3%] in the laparoscopic surgery group), paralytic ileus (six [1%] vs nine [2%]), and small intestine bowel obstruction (16 [3%] vs 11 [2%]). Two treatment-related deaths occurred in the open surgery group: one patient died 7 days after surgery (probably due to myocardial infarction), and one patient died from febrile neutropenia, pneumonia, diarrhoea, and gastrointestinal haemorrhage during postoperative chemotherapy. Laparoscopic D3 surgery was not non-inferior to open D3 surgery in terms of overall survival for patients with stage II or III colon cancer. However, because overall survival in both groups was similar and better than expected, laparoscopic D3 surgery could be an acceptable treatment option for patients with stage II or III colon cancer. National Cancer Center Research and Development Fund, Grant-in-Aid for Cancer Research, and Health and Labour Sciences Research Grant for Clinical Cancer Research from the Ministry of Health, Labour and Welfare of Japan.

ISY-9-6 - Current status and future perspective of perioperative chemotherapy for localized gastric cancer

Establishment of perioperative chemotherapy is imperative to improve the surgical outcome of localized gastric cancer. There are the large disparities between Japan/Korea and Western countries in perioperative treatment of localized gastric cancer. The main reason for this difference is due to different prognosis of the patients. The better prognosis is considered due to early diagnosis based on the national screening program. Because of the status, development of adjuvant treatment after curative resection was the focus in Japan. In perioperative strategies, 5 years survival of western population is 20-40%, and that of Japan and Korea is around 70%. The standard treatment is also different. In Japan and Korea, D2 resection followed by adjuvant chemotherapy is the standard. At the same time postoperative chemo-radiotherapy is standard in US, and perioperative chemotherapy is standard in EU. In Japan, our standard strategy is D2 resection followed by oral S-1 for 1 year. Capecitabine plus oxaliplatin (cape-Ox) showed 6 months survival after D2 resection in the CLASSIC trial in Korea, Taiwan, and China. A phase 2 study in Japan on the same regimen is also available. Use of cape-Ox in the practice is under discussion based on the data. On the other hand, high intensity of post-operative chemotherapy is considered not feasible based results from perioperative chemotherapy trials in western countries. Considering the current status, we will discuss the future strategies of perioperative treatment of Japanese gastric cancer patients.

Application of en-bloc mesogastric excision in the treatment of advanced gastric cancer

To evaluate the value of en-bloc mesogastric excision (EME) in the treatment of advanced gastric cancer. A retrospective analysis on clinical data of 98 gastric cancer patients who underwent total gastrectomy in China-Japan Union Hospital of Jilin University from January 2013 to December 2015 was carried out, including EME group of 48 cases (according to the mesangial space) and D2 radical group of 50 cases(D2 lymphadenectomy according to the vascular markers). Operations were performed by the same single surgeon team. Surgical indexes and recent efficacy indexes were compared between two groups. General informations pertaining to two groups were comparable (P>0.05). All the operations were performed successfully. Compared with D2 radical group, EME group had a shorter operative time [(155.3±13.6) vs. (171.2±14.9) minutes, P=0.012] and less intraoperative blood loss [(95.1±19.5) vs.(122.6±28.0) milliliters, P=0.011]. There were no significant differences in the number of harvested lymph node (30.8±3.9 vs. 31.5±4.7, P=0.675), time to postoperative bowel function return [(3.2±1.2) vs.(3.9±1.4) days, P=0.179], postoperative hospital stay [(10.9±2.7) vs.(11.3±3.2) days, P=0.788], and the incidence of postoperative complication [8.3% vs. 10.0%, P=0.775]. During the follow-up of 1 year, all the patients had no long-term complications, no tumor recurrence or death. For advanced gastric cancer, EME result in the same clinical efficacy compared with standard D2 resection. At the same time, EME can shorten the operative time and reduce the intraoperative blood loss, which is a new technology and worthy promoting.

Surgical modalities and prognosis in elderly patients with gastric cancer

Objective To evaluate the surgical modalities and prognosis in elderly patients with gastric cancer. Methods Sixty three gastric cancer patients aged ≥75 years underwent radical surgery, with D0+ D1 resection in 32 cases and D2 resection in 31 cases, in Beijing Hospital from January 2005 to December 2009. Results More lymph nodes were dissected in D2 group than those in D0+ D1 group (27.42±12.75 vs. 14.59±12.11, t=-4.095, P 0.05] and perioperative death rate [3.23%(1/31) vs.6.25%(2/32), χ2=0.324, P>0.05]between two groups. The 5-year survival rate was higher in D2 group than that in D0+ D1 group (47.3% vs. 21.4%, χ2=6.346, P 0.05). Univariate analysis showed that PS<20 was associated with the prognosis of patients (χ2=5.492, P<0.05). Cox proportional hazards model showed that lymph node metastasis(OR=4.103, 95%CI: 1.790-9.405, P<0.05) and D2 radical gastrectomy(OR=0.313, 95%CI: 0.158-0.620, P<0.05) were the independent factors associated with the prognosis of patients aged ≥75 years with gastric cancer (all P<0.05). Conclusion Standardized D2 lymph node dissection is beneficial for gastric cancer patients aged ≥75 years. PS<20, lymph node metastasis and D2 radical gastrectomy are associated with the prognosis of patients. Key words: Stomach neoplasms; Gastrectomy; Aged

Open compared with laparoscopic complete mesocolic excision with central lymphadenectomy for colon cancer: a systematic review and meta‐analysis

Several studies report improved survival in colon cancer with use of extended lymphadenectomy techniques (ELTs), such as D3 lymphadenectomy or complete mesocolic excision. The noninferiority of laparoscopic versus open techniques has already been established in D2 resections. The aim of this study was to compare the safety and efficacy of open and laparoscopic approaches for ELTs in colon cancer. Major databases, including PubMed, Scopus and the Cochrane library, were searched using defined inclusion and exclusion criteria, and relevant data were extracted. The Cochrane and Newcastle-Ottawa tools were used for critical appraisal and quality assessment. Meta-analysis with various subgroup analyses were undertaken, and clinical and statistical heterogeneity, along with publication bias, were also assessed. One randomized and seven case-control trials were included. All studies were found to be of low methodological quality with some external validity issues. There was no difference in short-term mortality [OR=2.16 (95% CI: 0.73-6.41); P=0.16], anastomotic leakage, ileus or deep-sited infection/abscess. There was a trend for longer operative time [weighted mean difference (WMD)=-30.88 (95% CI: -62.38 to 0.61); P=0.05] and shorter length of hospital stay [WMD=2.29 (95% CI: -0.39 to 4.98); P=0.09] with the laparoscopic approach. Laparoscopic right hemicolectomy had a lower wound-infection rate [OR=2.87 (95% CI: 1.38-5.98); P=0.005] compared with the relevant open group. No statistically significant difference was found in overall survival [hazard ratio (HR)=0.85 (95% CI: 0.69-1.06); P=0.15], disease-free survival, local recurrence and distant metastases. Based on the current evidence, the laparoscopic technique appears to be at least as safe as the open technique when used in performing ELTs for colonic cancer, with similar morbidity and oncological outcomes.

Development and external validation of a prognostic nomogram for gastric cancer using the national cancer registry.

A nomogram based on both western and eastern populations to estimate the Disease Specific Survival (DSS) of resectable gastric cancer (RGC) has not been established. In current study, we retrospectively analyzed 4,379 RGC patients who underwent curative resection from the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed between 1998 and 2009 were assigned as training set (n= 2,770), and the rest were selected as SEER validation set (n= 1,609). An external validation was performed by a set of independent 1,358 RGC patients after D2 resection from Sun Yat–sen University Cancer Center (SYSUCC) in China. The nomogram was constructed based on the training set. The multivariate analysis identified that patient's age at diagnosis, race, tumor location, grade, depth of invasion, metastatic lymph node stage (mLNS) and total number of examined lymph node (TLN) were associated with patient's DSS. The discrimination of this nomogram was superior to that of the 7th edition of AJCC staging system in SEER validation set and SYSUCC validation set (0.73 versus 0.70, p=0.005; 0.76 versus 0.72, p=0.005; respectively). Calibration plots of the nomogram showed that the probability of DSS corresponded to actual observation closely. In conclusion, our nomogram resulted in more–reliable prognostic prediction for RGC patients in general population.

A Phase II Trial of Postoperative Radiation Therapy of Gastric Cancer Patients Basing on a New Method of Lymph Node Target Volume Delineation: The Study Protocol, Toxicity and Efficacy

Purpose/Objective(s): To prospectively investigate the safety and efficacy of neoadjuvant radiation therapy with concurrent weekly oxaliplatin plus TS-1 (nSOXRT) or TS-1 alone (nSRT) followed by D2 resection for locally advanced gastric cancer. Materials/Methods: The patients with stage IIB-IIIC gastric cancer who received chemoradiation therapy (CRT) and surgery in Peking University Cancer Hospital from March 2009 to October 2014 were enrolled. They were treated with neoadjuvant intensity-modulated radiation therapy (IMRT), given to 45 Gy to clinical targeting volume (CTV) and a concomitant boost to 50Gy to gross targeting volume (GTV) in 25 fractions, 5 fractions per week. Concurrent chemotherapy regimens included oral TS-1 (60 mg/m/day in twice daily) plus oxaliplatin 40 mg/m intravenously weekly or TS-1 alone (120mg/day in twice daily). Surgery was performed within 6-8 weeks after the last irradiation. Results: Thirty-five patients were studied according to the inclusive criteria. The median age was 61 years (range 33-73), and all were male. Clinical staging were as follows: 3 cT3, 32 cT4; 1 cN1, 24 cN2, 10 cN3. Twenty-five and ten patients received nSOXRT and nSRT, respectively. All patients completed radiation therapy. Five patients cannot tolerate concurrent chemotherapy due to toxicity, with a completion rate of 85.7%. There was no grade 4 toxicity. The incidence of grade 3 toxicity was 11.4%, including: thrombocytopenia (5.7%), neutropenia (2.9%) and radiation esophagitis (2.9%). The overall response rate (CR+PR) was 62.9%(22/35). None of these patients withdrew from surgery due to toxicity; two patients did not undergo resection due to distant metastases and five due to peritoneal metastases observed in time of laparoscopic approach. Twenty-eight patients (80%) underwent radical D2 resection. Pathological complete response occurred in 8.6% (3/35) of patients. The T and N downstaging rate were 92.9% (27/28) and 89.2% (25/28), respectively. Surgery-related complications consisted of anastomotic leakage in 2 (7.1%), infection in 3 (10.7%) and hemorrhage in 2 (7.1%) patients. The perioperative mortality was nil. The median survival time was 29.6 months (95% confidence interval, 19.7-39.5 months). The 1year and 2-year overall survival (OS) rates were 89.2% and 56.8% respectively. Conclusion: The present schedule of multimodality treatment for locally advantage gastric cancer showed an acceptable toxicity, promising efficacy and safety for D2 resection. Author Disclosure: Y. Li: None. Z. Li: None. X. Li: None. J. Ji: None. Y. Cai: None.

Quality control of lymph node dissection in the Dutch Gastric Cancer Trial.

Current guidelines indicate that D2 resection is the standard of care for patients with locally advanced gastric cancer. To assess the impact of quality assurance of lymph node removal, non-compliance and contamination in the D1 and D2 study arms of the Dutch Gastric Cancer Trial were investigated with respect to recurrence and survival. The location and numbers of lymph nodes detected at pathological investigation in the Dutch Gastric Cancer Trial were compared according to the guidelines of the Japanese Research Society for the study of Gastric Cancer. Non-compliance was defined as inadequate removal of lymph node stations. Contamination was defined as lymph nodes removed outside the intended level of resection. The dissection groups D1 and D2 were divided into non-compliance, compliance and contamination categories. Long-term overall survival was calculated for minor (2 or fewer lymph nodes) and major (more than 2 lymph nodes) non-compliance and contamination in the D1 and D2 group, using Kaplan-Meier plots. Some 1078 patients were included, of whom 711 with potentially curative surgical resections were evaluated. Overall non-compliance was 80·5 per cent in the D1 and 81·6 per cent in the D2 group. Major non-compliance occurred in 15·3 per cent of the D1 and 26·0 per cent of the D2 group. Major contamination hardly occurred. Overall 15-year survival rates in the randomized groups were 21·2 per cent (D1) and 29·0 per cent (D2) (P = 0·351). After exclusion of patients with major non-compliance and/or major contamination, survival rates were 23·2 per cent (319 patients) and 32·6 per cent (245) respectively (P = 0·261). Where there was major non-compliance, survival rates in the D1 (58 patients) and D2 (86) groups were 10 and 17 per cent respectively (P = 0·302). Survival in the D2 compliant + contaminated group (139 patients) was significantly better than that in the D1 group without contamination (282): 35·7 versus 19·9 per cent (P = 0·041). In the D2 group, there was a significant difference in survival between contaminated (95 patients) and non-contaminated (236) groups: 39 versus 25·1 per cent (P = 0·041). Non-compliance in the D2 dissection group may have obscured a significant difference in survival between the randomized groups. A D2 dissection with contamination was associated with the best survival, suggesting that extended D2 lymph node dissections improve survival.

Effects of adjuvant radiotherapy on completely resected gastric cancer: A radiation oncologist’s view of the ARTIST randomized phase III trial

PurposeWe investigated which subgroups might benefit from adjuvant radiotherapy (RT) and suggested optimal RT targets by analyzing the results of the Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) trial. MethodsWe conducted randomized controlled trial in 458 gastric cancer patients. Patients were randomly assigned to XP (6 cycles of capecitabine and) or XPRT (2 cycles of XP+RT 45Gy/25 fraction with capecitabine+2 cycles of XP) groups after D2 resection. Minimum follow-up was 5years. ResultsDuring follow-up, 77 patients (33.8%) in the XP arm and 60 (26.1%) in the XPRT arm experienced recurrence. Among these patients, locoregional recurrence (LRR) developed in 44 (9.6%; 29 in XP, 15 in XPRT; P=0.03). The local recurrence rate (4.8%) did not vary between arms. Regional recurrence was the most important difference between the two groups (23 in the XP arm, 5 in the XPRT arm, P<0.001). LRR-free survival (LRRFS) was significantly different between study arms (P=0.03), especially in patients with LN metastasis (P=0.009). ConclusionsAdjuvant RT after D2 resection in gastric cancer reduced LRR, especially in group 3 LNs, and improved LRRFS. Patients with LN metastasis benefited more from the adjuvant RT treatment than the other subgroups.

Mortality and Morbidity and Disease Free Survival after D1 and D2 Gastrectomy for Stomach Adenocarcinomas.

A number of randomized trials addressing alternative operative and multimodality approaches to gastric cancer have characterized early postoperative morbidity and mortality rates. The aim of this study was to compare mortality and morbidity and disease free survival after D1 and D2 gastrectomy for adenocarcinomas of the stomach From June 2006 to January 2012, patients were selected according to information of the cancer administrator center of Ahvaz Jundishapur Medical University. The inclusion criteria were age between 20-85 years and histologically proven adenocarcinoma of the stomach without evidence of distant metastasis. Patients were excluded if they had previous or coexisting cancer or disability disease. In this research, D1 was compared to D2 gastrectomy. 131 patients were randomised, 49 allocated to D1 and 82 to D2 gastrectomy. The two groups were comparable for age, sex, site of tumors, and type of resection performed. The overall post-operative morbidity rate was 17.5%. Complications developed in 14.2% of patients after D1 and in 19.5% of patients after D2 gastrectomy (p=0.07). Postoperative mortality rate was 0.8% (one death); it was 2% after D1 and 0% after D2 gastrectomy. In this research disease free-survival after 3 years was 71.2 % with 63.2% after D1 and 76.8% after D2 gasterctomy. This study indicates that D2 gastrectomy with pancreas preservation is not followed by significantly higher morbidity and mortality than D1 resection. Based on the results of present study, D2 resection should be recommended as the standard surgical approach for resectable gastric cancer.

A new approach to delineating lymph node target volumes for post-operative radiotherapy in gastric cancer: A phase II trial

PurposeIn the context of gastric cancer, lymph node target volume delineation for post-operative radiotherapy is currently built on the traditional system of dividing the stomach and 2-D treatment methods. Here, we have proposed a new delineation approach with irradiation indications for lymph node stations. Its safety and efficacy were evaluated in a phase II clinical trial. Materials and methodsFifty-four gastric cancer patients with D2 lymph node dissection received 2 cycles of FOLFOX4. They subsequently received concurrent chemoradiotherapy (45Gy at 1.8Gy per fraction, 5 fractions per week for 5weeks) with a 5-fluorouracil/leucovorin regimen, followed by 4 additional FOLFOX4 cycles. The target volume included the remnant stomach, anastomosis site, tumor bed, and regional lymph nodes selected through our new approach by taking gastric arteries as references. ResultsThe most common grade 3–4 adverse event was neutropenia (14.8%). Neutropenia, anemia, and nausea were common grade 1–2 toxicities. No treatment-related deaths occurred during treatment. The 3-year overall, disease-free, and locoregional recurrence-free survival rates were 81.6%, 70.2%, and 91.1%, respectively. Eight patients developed peritoneal or distant metastases. ConclusionsUsing our new approach and irradiation indications, delineation of the target volume of post-operative lymph node stations was feasible and well tolerated after D2 resection in patients with gastric cancer.

PTU-145 Prophylactic total gastrectomy for hereditory gastric cancer syndrome

<h3>Introduction</h3> 1–3% of gastric cancers arise from hereditary predisposition syndromes. E-cadherin gene (CDH1) mutations are the best characterised of these and confer a life-time risk of approximately 80% for patients developing diffuse gastric cancer. Currently, the only definitive treatment available is prophylactic total gastrectomy (PTG). We present our experience of open PTG, focusing on the early outcomes. <h3>Method</h3> Twenty four consecutive patients with CDH 1 mutation underwent PTG from 2005 to 2014 (median age 33, range 22–51). All patients had at least one gastroscopy with biopsies taken according to the Cambridge Protocol and were assessed by a multi-disciplinary team within a high-volume Cancer Centre. All patients had an open posterior vagal sparing total gastrectomy with stapled oesophagojejunal anastomosis and Roux-en-Y reconstruction by a single surgeon. Twenty three patients had a D0.5 -1 lymphadenectomy; one patient with suspected invasive tumour had a D2 resection. Nasogastric tubes and abdominal drains were not used. Patients were mobilised on the first postoperative day with epidural analgesia. Oral fluids were restarted on postop day 3 and diet on day 5. <h3>Results</h3> There were two postoperative complications (8%) but no deaths; One patient had a jejuno-jejuno anastomotic leak 10 days after surgery requiring revisional surgery but made a full recovery. Another patient had bleeding which was managed conservatively with transfusion. Two patients developed anastomotic strictures and were successfully treated with endoscopic balloon dilatation. Median follow-up to date is 5 years (range: 3 months to 9 years). Histology showed scattered microscopic foci of intramucosal signet ring carcinoma (pT1a) in 23/24 patients (96%); the median number of foci was 7 (range: 1–182). No invasive tumours were found, all nodes were negative for tumour and all longitudinal margins were clear. The median lymph node yield was 5.5 (range: 1–26) and median hospital stay was 8 days (range: 6–10). <h3>Conclusion</h3> Open PTG can be performed with acceptable mortality and morbidity. Our challenge for the future is to offer minimally invasive PTG without increasing the risks. <h3>Disclosure of interest</h3> None Declared.

A randomized phase III study of neoadjuvant chemotherapy with docetaxel(D), oxaliplatin(O), and S-1(S) (DOS) followed by surgery and adjuvant S-1 vs. surgery and adjuvant S-1 for resectable advanced gastric cancer (PRODIGY).

TPS4136 Background: Although adjuvant chemotherapy with S-1 is now considered a standard after D2 resection in stage II or III locally advanced gastric cancer (LAGC) in Asia, many patients still ex...

Intravenous Fluorouracil versus Oral Capecitabine: Postoperative Chemoradiation for Gastric Cancer

Purpose: Aim of this prospective, phase III trial was to compare the efficacy and toxicity of intravenous fluorouracil and oral capecitabine when given concurrently with radiation in adjuvant sitting for adenocarcinoma of the stomach after gastrectomy with D2 resection. Patients and Method: The study included 60 patients having histologically proven adenocarcinoma of the stomach or gastroesophageal junction; stage T2-4 N0-3 M0 after gastrectomy with D2 lymph node dissection. Eligible patients were randomly assigned to receive adjuvant radiotherapy concurrently with intravenous fluorouracil [arm A] or oral capecitabine [arm B]. Results: Ten patients cannot complete their whole treatment course because of either progressive [4 patients; 2 arm A and 2 arm B] or G 3 toxicity [1 patient] or refuse to complete their treatment [5 patients; 3 arm A and 2 arm B]. Patients received fluorouracil have significant increase grade 3 or 4 hematological [neutropenia] and gastrointestinal (diarrhoea, anorexia, and vomiting). During a median follow-up period of 24 months, the 2-year disease free and overall survivals in this study were 60% and 63.3%, for groups A and B respectively, while overall survival were 63.3% and 70% for groups A and B respectively without significant differences. Conclusion: Oral capecitabine concurrently with radiation therapy has comparable efficacy and favourable toxicity profile when compared to infusion fluorouracil as postoperative adjuvant therapy for gastric adenocarcinoma.

Quality control by photo documentation for evaluation of laparoscopic and open colectomy with D3 resection for stage II/III colorectal cancer: Japan Clinical Oncology Group Study JCOG 0404.

The quality of surgery with D3 resection in randomized controlled clinical trial [Japan Clinical Oncology Group study (JCOG0404)] was assessed by evaluation of the photo documentation of both open and laparoscopic surgeries. A multi-institutional randomized-controlled trial (JCOG0404) was conducted to evaluate open and laparoscopic D3 resection (complete mesocolic excision + ligation and dissection at the root of the main vessels) for Stage II/III colon cancer (UMIN-CTR number C000000105). A total of 1057 (open, 528; laparoscopic, 529) eligible patients were enrolled. For quality control, it was ensured that the surgeries were performed by accredited surgeons, and a central committee reviewed each surgery on the basis of the submitted photographs of the resected field, specimen and skin incision. For right-sided tumors, the rate of D3 resection was 98.5% (131/133) in the open arm and 100% (136/136) in the laparoscopic arm, and for left-sided tumors, they were 97.9% (322/329) and 98.2% (320/326), respectively. Sufficient length of the resected longitudinal margin was ensured in all cases. The skin incisions made in all the cases were <8 cm as defined in the protocol in laparoscopic arm. Completion of high quality surgery with D3 resection was confirmed in JCOG0404 by central peer review of photographs of the surgical procedures in addition to operator regulations. This study suggests that the central review of the photo documentation is one of the important tools to assure a quality control of surgical technique in the Phase III randomized-controlled study.

Quality control by photograph for evaluation of open (OP) and laparoscopic (LAP) colectomy with D3 resection for stage II/III colorectal cancer: Japan Clinical Oncology Group study JCOG 0404.

e14501 Background: The phase lll JCOG0404 (UMIN-00105) showed the favorable short term outcome in LAP arms (less blood loss, decreased pain, a shorter hospital stay, and fewer wound-related complications). In JCOG0404 (between Oct 2004 and March 2009, n=1057), for quality control, photographs of resection fields and, resected specimens, and the skin incision were taken in all patients. Methods: These photographs were sent to Study Coordinator and evaluated by the study-specific committee. Patients with distant metastasis and/or severe invasion were excluded in this study. The quality of resection was judged by the following criteria: Under inadequate to undergo lymphadenectomy; D3, where the main vessel was dissected and ligated at its root. In the subset analysis, were divided into Adequate D3 and Beyond Beyond D3 was defined as extended lymphadenectomy beyond D3. The association between a quality of resection with a number of harvested lymph nodes and intraoperative compli...

Adjuvant or neoadjuvant therapy for operable esophagogastric cancer?

Esophagogastric cancer encompasses proximal squamous cell carcinoma of the esophagus, distal esophageal/junctional adenocarcinoma of the esophagus and gastric adenocarcinoma. These diseases have different etiologies, geographic incidences and biologies. This review mainly focuses on the treatment of operable esophagogastric adenocarcinoma. In Asia, adjuvant chemotherapy is commonly used for patients with gastric cancer following the landmark ACTS-GC trial. In contrast, perioperative chemotherapy is a standard of care in many Western countries based on the results of the MAGIC trial. Neoadjuvant chemotherapy is better tolerated than adjuvant therapy, and therefore dose intensity is likely to be maintained in a greater proportion of patients. In addition, neoadjuvant treatment can lead to tumor downstaging, increasing the likelihood of achieving a complete surgical resection. This may be particularly important in Western populations, as these patients often present with more advanced tumors than Asian patients. Adjuvant chemoradiotherapy is a standard treatment option in the USA for adenocarcinoma of the stomach or gastroesophageal junction as a result of the INT-0116 trial, but the benefit of this approach after a D2 resection has not been confirmed. Neoadjuvant chemoradiotherapy may reduce the risk of local recurrence and may be particularly beneficial for patients with squamous cell carcinoma as these tumors are more radiosensitive. However, patients with esophagogastric adenocarcinoma are more likely to relapse with distant disease, and therefore a systemic disease approach with chemotherapy is likely to be more beneficial than a purely localized treatment strategy for these patients.

GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study

BackgroundIn Europe, gastric cancer remains diagnosed at advanced stage (serosal and/or lymph node involvement). Despite curative management combining perioperative systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection, 5-year survival rates of T3 and/or N + patients remain under 30%. More than 50% of recurrences are peritoneal and/or locoregional. The use of adjuvant hyperthermic intraperitoneal chemotherapy that eliminates free cancer cells that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal carcinomatosis recurrences, was extensively evaluated by several randomized trials conducted in Asia. Two meta-analysis reported that adjuvant hyperthermic intraperitoneal chemotherapy significantly reduces the peritoneal recurrences and significantly improves the overall survival. As it was previously done for the evaluation of the extension of lymph node dissection, it seems very important to validate on European or caucasian patients the results observed in trials performed in Asia.Methods/designGASTRICHIP is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of hyperthermic intraperitoneal chemotherapy with oxaliplatin on patients with gastric cancer involving the serosa and/or lymph node involvement and/or with positive cytology at peritoneal washing, treated with perioperative systemic chemotherapy and D1-D2 curative gastrectomy. Peroperatively, at the end of curative surgery, patients will be randomized after preoperatively written consent has been given for participation. Primary endpoint will be overall survival from the date of surgery to the date of death or to the end of follow-up (5 years). Secondary endpoint will be 3- and 5-year recurrence-free survival, site of recurrence, morbidity, and quality of life. An ancillary study will compare the incidence of positive peritoneal cytology pre- and post-gastrectomy in two arms of the study, and assess its impact on 5-year survival. The number of patients to be randomized was calculated to be 306.Trial registrationEudraCT number: 2012-005748-12, ClinicalTrials.gov identifier: NCT01882933.

Comprehensive standardization of complete mesocolic surgery is now possible

Dear Sir,We read with great interest the article of Storli et al. [1].The article compares two distinct surgical techniques forthe treatment of stage I–II colon cancer and very elegantlydemonstrates significant improvements in 3-year overallsurvival, and disease-free survival in patients who under-went a complete mesocolic excision (CME) with a high(apical) vascular tie (D3) when compared with conven-tional (standard, i.e., D2 resection) approach (n = 105).Although CME appears promising, the authors unfortu-nately did not describe the technique in any detail, nor didthey acknowledge the importance of adhering to funda-mental mesocolic surgical tissue planes while performingan oncologic colonic mobilization. Furthermore, the studyonly utilized lymph node yield as a surrogate measure ofradical resection and failed to provide any histologicaldescriptions of the surgical specimens.Despite the strong evidence supporting CME such asthat provided by Storli et al. [1], CME is still surrounded bycontroversy and has not as yet become the gold standard(unlike total mesorectal excision for rectal cancer). This islargely due to misconceptions related to mesocolic anat-omy, indoctrinated in mainstream literature, and whichhave hampered a clear understanding of planes utilized incolonic mobilization. Clinical papers such as that publishedby Storli et al. [1] justify a formal appraisal of the meso-colic anatomy which in turn can provide a level playingfield for surgeons to accurately conceptualize the meso-colon and associated surgical tissue planes and thereforerationalize the importance of performing a safe andeffective CME.Our group has recently provided novel insights into themesocolic anatomy. Interestingly, our gross anatomicfindings of the mesocolon are contrary to those described bySir Frederick Treves in 1889 (which are part of mainstreamliterature), and in fact mostly echo the mesocolic descrip-tions provided by Carl Toldt 10 years prior to Treves, in1879 [2]. We have noted that the mesocolon is continuousfrom the ileocaecal to rectosigmoid level; a mesentericconfluence occurs at the ileocaecal and rectosigmoid junc-tion as well as at the hepatic and splenic flexures; eachflexure (and ileocaecal junction) is a complex of peritonealand omental attachments to the colon centered on a mes-enteric confluence; the proximal rectum originates at theconfluence of the mesorectum and mesosigmoid; and themesocolic plane of Toldt’s fascia separates the entireapposed mesocolon from the true retroperitoneal compart-ment [3]. Histologically, the mesocolon is separated bydistinct mesothelial and connective tissue layers that sepa-rate it from the underlying retroperitoneum [4]. Further-more, we have systematically determined and quantified thedistribution of lymphatic vessels within the mesentericorgan and underlying Toldt’s fascia and shown a richlymphatic network within all levels of the mesenteric con-nective tissue lattice [2].The exciting clinical findings provided by Storli et al.[1] reinforce the argument for performing a safe andeffective CME that adheres to a crystallized comprehen-sion of mesocolic anatomy. The findings of Storli, when

Laparoscopic-Assisted Versus Open Distal Gastrectomy with D2 Lymph Node Resection for Advanced Gastric Cancer: Effect of Learning Curve on Short-Term Outcomes. A Meta-analysis

Laparoscopic-assisted distal gastrectomy (LADG) with D2 resection is gradually being performed for treating advanced gastric cancer. This meta-analysis aims to compare the clinical outcomes between LADG and open distal gastrectomy (ODG) when considering the impact of the learning curve. The PubMed, Embase, and ISI databases and the Cochrane Library were electronically searched. Randomized controlled trails and retrospective comparative studies published between 1994 and 2013 were collected. We divided the included studies into two subgroups according to whether the authors had experience of at least or fewer than 40 cases of LADG with D2 resection and then compared the operative time, intraoperative bleeding, the amount of resected lymph nodes, short-term recovery parameters, and complications between LADG and ODG groups. Ten comparative studies including 1100 patients were selected. Meta-analysis showed that when LADG was compared with ODG, surgeons with experience of at least 40 cases could achieve more resected lymph nodes (P=.002), reduced time to flatus (P<.0001), shortened time to liquid diet (P<.00001), and lower complication rates (P=.02). However, the above advantages of LADG faded in the subgroup of surgeons with experience of fewer than 40 cases. Our meta-analysis suggested that the learning curve has significant effects on most of the important surgical and short-term recovery outcome parameters. Accomplishment of 40 cases of LADG with D2 lymphadenectomy is required to achieve optimum proficiency.