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Background: Carcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal imaging dose of SGM-101 for intraoperative fluorescence imaging of primary and recurrent CRC., Methods: Patients were included and received a single dose of SGM-101 at least 24 h before surgery. Patients who received routine anticancer therapy (i.e., radiotherapy or chemotherapy) also were eligible. A dedicated near-infrared imaging system was used for real-time fluorescence imaging during surgery. Safety assessments were performed and SGM-101 efficacy was evaluated per dose level to determine the most optimal imaging dose., Results: Thirty-seven patients with CRC were included in the analysis. Fluorescence was visible in all primary and recurrent tumors. In seven patients, no fluorescence was seen; all were confirmed as pathological complete responses after neoadjuvant therapy. Two tumors showed false-positive fluorescence. In the 37 patients, a total of 97 lesions were excised. The highest mean intraoperative tumor-to-background ratio (TBR) of 1.9 (p = 0.019) was seen in the 10-mg dose. This dose showed a sensitivity of 96%, specificity of 63%, and negative predictive value of 94%. Nine patients (24%) had a surgical plan alteration based on fluorescence, with additional malignant lesions detected in six patients., Conclusions: The optimal imaging dose was established at 10 mg 4 days before surgery. The results accentuate the potential of SGM-101 and designated a promising base for the multinational phase III study, which enrolled the first patients in June 2019.

Iatrogenic injury of the ureters is a feared complication of abdominal surgery. Zwitterionic near-infrared fluorophores are molecules with geometrically-balanced, electrically-neutral surface charge, which leads to renal-exclusive clearance and ultralow non-specific background binding. Such molecules could solve the ureter mapping problem by providing real-time anatomic and functional imaging, even through intact peritoneum. Here we present the first-in-human experience of this chemical class, as well as the efficacy study in patients undergoing laparoscopic abdominopelvic surgery. The zwitterionic near-infrared fluorophore ZW800-1 is safe, has pharmacokinetic properties consistent with an ideal blood pool agent, and rapid elimination into urine after a single low-dose intravenous injection. Visualization of structure and function of the ureters starts within minutes after ZW800-1 injection and lasts several hours. Zwitterionic near-infrared fluorophores add value during laparoscopic abdominopelvic surgeries and could potentially decrease iatrogenic urethral injury. Moreover, ZW800-1 is engineered for one-step covalent conjugatability, creating possibilities for developing novel targeted ligands.

Background: Implementation of mass colorectal cancer screening, using faecal occult blood test or colonoscopy, is recommended by the European Union in order to increase cancer-specific survival by diagnosing disease in an earlier stage. Post-colonoscopy complications have been addressed by previous systematic reviews, but morbidity of colorectal cancer screening on multiple levels has never been evaluated before., Aim: To evaluate potential harm as a result of mass colorectal cancer screening in terms of complications after colonoscopy, morbidity and mortality following surgery, psychological distress and inappropriate use of the screening test., Methods: A systematic review of all literature on morbidity and mortality attributed to colorectal cancer screening, using faecal occult blood test or colonoscopy, from each databases' inception to August 2016 was performed. A meta-analysis was conducted to examine the pooled incidence of major complications of colonoscopy (major bleedings and perforations)., Results: Sixty studies were included. Five out of seven included prospective studies on psychological morbidity reported an association between participation in a colorectal screening program and psychological distress. Serious morbidity from colonoscopy in asymptomatic patients included major bleedings (0.8/1000 procedures, 95% CI 0.18-1.63) and perforations (0.07/1000 procedures, 95% CI 0.006-0.17)., Conclusions: Participation in a colorectal cancer screening program is associated with psychological distress and can cause serious adverse events. Nevertheless, the short duration of psychological impact as well as the low colonoscopy complication rate seems reassuring. Because of limited literature on harms other than perforation and bleeding, future research on this topic is greatly needed to contribute to future screening recommendations., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background & Aims: Patients with perianal fistulizing Crohn's disease have a poor prognosis because these lesions do not heal well. We evaluated the effects of local administration of bone marrow-derived mesenchymal stromal cells (MSCs) to these patients from healthy donors in a double-blind, placebo-controlled study., Methods: Twenty-one patients with refractory perianal fistulizing Crohn's disease were randomly assigned to groups given injections of 1 × 10(7) (n = 5, group 1), 3 × 10(7) (n = 5, group 2), or 9 × 10(7) (n = 5, group 3) MSCs, or placebo (solution with no cells, n = 6), into the wall of curettaged fistula, around the trimmed and closed internal opening. The primary outcome, fistula healing, was determined by physical examination 6, 12, and 24 weeks later; healing was defined as absence of discharge and <2 cm of fluid collection-the latter determined by magnetic resonance imaging at week 12. All procedures were performed at Leiden University Medical Center, The Netherlands, from June 2012 through July 2014., Results: No adverse events were associated with local injection of any dose of MSCs. Healing at week 6 was observed in 3 patients in group 1 (60.0%), 4 patients in group 2 (80.0%), and 1 patient in group 3 (20.0%), vs 1 patient in the placebo group (16.7%) (P = .08 for group 2 vs placebo). At week 12, healing was observed in 2 patients in group 1 (40.0%), 4 patients in group 2 (80.0%), and 1 patient in group 3 (20.0%), vs 2 patients in the placebo group (33.3%); these effects were maintained until week 24 and even increased to 4 (80.0%) in group 1. At week six, 4 of 9 individual fistulas had healed in group 1 (44.4%), 6 of 7 had healed in group 2 (85.7%), and 2 of 7 had healed in group 3 (28.6%) vs 2 of 9 (22.2%) in the placebo group (P = .04 for group 2 vs placebo). At week twelve, 3 of 9 individual fistulas had healed in group 1 (33.3%), 6 of 7 had healed in group 2 (85.7%), 2 of 7 had healed in group 3 (28.6%), and 3 of 9 had healed in the placebo group (33.3%). These effects were stable through week 24 and even increased to 6 of 9 (66.7%) in group 1 (P = .06 group 2 vs placebo, weeks 12 and 24)., Conclusions: Local administration of allogeneic MSCs was not associated with severe adverse events in patients with perianal fistulizing Crohn's disease. Injection of 3 × 10(7) MSCs appeared to promote healing of perianal fistulas. ClinicalTrials.gov ID NCT01144962., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Fistulas are a frequent manifestation of Crohn's disease (CD) and can result in considerable morbidity. Approximately 35% of all patients with CD will experience one fistula episode during their disease course of which 54% is perianal. The major symptoms of patients with perianal fistulas are constant anal pain, the formation of painful swellings around the anus and continuous discharge of pus and/or blood from the external fistula opening. The exact aetiology of perianal fistulas in CD patients remains unclear, but it is thought that a penetrating ulcer in the rectal mucosa caused by active CD forms an abnormal passage between the epithelial lining of the rectum and the perianal skin. Genetic, microbiological and immunological factors seem to play important roles in this process. Although the incidence of perianal fistulas in patients with CD is quite high, an effective treatment is not yet discovered. In this review all available medical and surgical therapies are discussed and new treatment options and research targets will be highlighted., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aims: Optimal staging in rectal cancer is indispensable for the decision on further treatment and estimation of prognosis. This study assesses the prognostic capacity of the metastatic lymph node ratio (LNR) in addition to the new TNM classification., Methods: LNR was determined, in stage III patients from the Dutch TME-trial. Six year median follow up data from the trial database were used to analyse the relation of LNR to overall survival (OS) and local recurrence (LR). The relation of LNR to lymph node yield was assessed and appropriate cut off values of LNR for clinical use were determined., Results: 605 patients were analyzed. 278 underwent pre-operative radiotherapy. 82 patients developed a local recurrence and 289 distant metastases. LNR was an independent risk factor for OS, hazard ratio (HR) 2.10 (95% CI 1.35-3.27) (in addition to age >= 65 years, involved circumferential resection margin (CRM) and new TNM stage) and LR, HR 2.25 (95% CI 1.02-4.56) (in addition to pre-operative radiotherapy and involved CRM). LNR is predictive of OS and LR from a lymph node yield of more than one and more than five respectively. A LNR value of 0.60 offers the best cut off to identify high risk patients (5-years OS was 61 vs. 32%, HR 2.45 (95% CI 1.96-3.08) and 5-years LR rate 12.6 versus 16.3%, HR 1.65 (95% CI 1.03-2.64))., Conclusions: LNR is an independent risk factor for OS and LR in addition to the 7th edition of the TNM classification. It can aid in predicting prognosis and identifying patients that should be considered for adjuvant treatment., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Purpose: The Intergroup 0116 trial has demonstrated that postoperative chemoradiotherapy (CRT) improves survival in gastric cancer. We retrospectively compared survival and recurrence patterns in two phase I/II studies evaluating more intensified postoperative CRT with those from the Dutch Gastric Cancer Group Trial (DGCT) that randomly assigned patients between D1 and D2 lymphadenectomy., Patients and Methods: Survival and recurrence patterns of 91 patients with adenocarcinoma of the stomach who had received surgery followed by radiotherapy combined with fluorouracil and leucovorin (n = 5), capecitabine (n = 39), or capecitabine and cisplatin (n = 47) were analyzed and compared with survival and recurrence patterns of 694 patients from the DGCT (D1, n = 369; D2, n = 325). For both groups, the Maruyama Index of Unresected Disease (MI) was calculated and correlated with survival and recurrence patterns., Results: With a median follow-up of 19 months in the CRT group, local recurrence rate after 2 years was significantly higher in the surgery only (DGCT) group (17% v 5%; P = .0015). Separate analysis of CRT patients who underwent a D1 dissection (n = 39) versus DGCT-D1 (n = 369) showed fewer local recurrences after chemoradiotherapy (2% v 8%; P = .001), whereas comparison of CRT-D2 (n = 25) versus DGCT-D2 (n = 325) demonstrated no significant difference. CRT significantly improved survival after a microscopically irradical (R1) resection. The MI was found to be a strong independent predictor of survival., Conclusion: After D1 surgery, the addition of postoperative CRT had a major impact on local recurrence in resectable gastric cancer.

In recent years there have been significant improvements in rectal cancer treatment. New surgical techniques as well as effective neoadjuvant treatment regimens have contributed to these improvements. Key is to spread these advances towards every rectal cancer patient and to ensure that not only patients who are treated within the framework of clinical trials may benefit from these advancements. Throughout Europe there have been interesting quality programmes that have proved to facilitate the spread of up to date knowledge and skills among medical professionals resulting in improved treatment outcome. Despite these laudable efforts there is still a wide variation in treatment outcome between countries, regions and institutions, which calls for a European audit on cancer treatment outcome.

Objective: To investigate the efficacy of preoperative short-term radiotherapy in patients with mobile rectal cancer undergoing total mesorectal excision (TME) surgery., Summary Background Data: Local recurrence is a major problem in rectal cancer treatment. Preoperative short-term radiotherapy has shown to improve local control and survival in combination with conventional surgery. The TME trial investigated the value of this regimen in combination with total mesorectal excision. Long-term results are reported after a median follow-up of 6 years., Methods: One thousand eight hundred and sixty-one patients with resectable rectal cancer were randomized between TME preceded by 5 x 5 Gy or TME alone. No chemotherapy was allowed. There was no age limit. Surgery, radiotherapy, and pathologic examination were standardized. Primary endpoint was local control., Results: Median follow-up of surviving patients was 6.1 year. Five-year local recurrence risk of patients undergoing a macroscopically complete local resection was 5.6% in case of preoperative radiotherapy compared with 10.9% in patients undergoing TME alone (P < 0.001). Overall survival at 5 years was 64.2% and 63.5%, respectively (P = 0.902). Subgroup analyses showed significant effect of radiotherapy in reducing local recurrence risk for patients with nodal involvement, for patients with lesions between 5 and 10 cm from the anal verge, and for patients with uninvolved circumferential resection margins., Conclusions: With increasing follow-up, there is a persisting overall effect of preoperative short-term radiotherapy on local control in patients with clinically resectable rectal cancer. However, there is no effect on overall survival. Since survival is mainly determined by distant metastases, efforts should be directed towards preventing systemic disease.

Background: Low anterior resection (LAR) may result in faecal incontinence. This study aimed to identify risk factors for long-term faecal incontinence after total mesorectal excision (TME) with or without preoperative radiotherapy (PRT)., Methods: Between 1996 and 1999, patients with operable rectal cancer were randomized to TME with or without PRT. Eligible patients who underwent LAR were studied retrospectively at 2 years (399 patients) and 5 years (339) after TME., Results: At 5 years after surgery faecal incontinence was reported by 61.5 per cent of patients who had PRT and 38.8 per cent of those who did not (P < 0.001). Excessive blood loss and height of the tumour were associated with long-term faecal incontinence, but only in patients treated with PRT., Conclusion: Faecal incontinence is likely to occur after PRT and TME, especially when the perineum is irradiated., (Copyright (c) 2007 British Journal of Surgery Society Ltd.)

Background: In many patients with rectal cancer, defunctioning stomas are created to limit the consequences of anastomotic leakage. Although intended to be temporary, a substantial proportion of these stomas might never be reversed for various reasons. We aimed to describe stoma policy by use of data from the total mesorectal excision (TME) trial in patients with rectal cancer and to identify factors that limit stoma reversal., Methods: 924 Dutch patients with rectal cancer who underwent a low anterior resection were selected from the TME trial, a prospective, randomised multicentre trial studying the effects of short-term preoperative radiotherapy in 1861 patients who underwent TME. Creation of stomas and time to stoma reversal were analysed retrospectively by use of multivariate analysis., Findings: In 523 of 924 (57%) patients, a primary stoma (defined as a stoma created at the time of TME) was constructed after a low anterior resection. Geographical differences in the number of primary stomas constructed were reported throughout the Netherlands. 19% of stomas that were created were never reversed. Postoperative complications and secondary constructed stomas (defined as a stoma created during a second or subsequent procedure after TME) were associated with a high likelihood of a permanent stoma. However, perioperative complications were not a limiting factor for stoma closure., Interpretation: Postoperative complications are an important limiting factor for stoma reversal because, after occurrence of these complications, patients and surgeons might be reluctant to reverse the stoma, so a substantial proportion of these stomas are never closed. Future guidelines for stoma creation and closure should consider these factors.

Based on more than 11 years of follow-up, autopsy-based analysis of recurrence in the Dutch D1-D2 Trial permits meaningful assessment of patterns of failure with respect to the Maruyama Index (MI). We previously reported that a low Maruyama Index was an independent predictor of both overall and disease-specific survival. Autopsy results are available for 441 deaths on study. Distant-only failure (15% vs 13%) was no different between the MI categories, but isolated "regional" failure (8% for MI < 5 group vs 21%) and "regional + distant" failure (19% for MI < 5 group vs 36%) occurred less frequently in the MI < 5 group (P < 0.001). We conclude that "low Maruyama Index" surgery enhances regional control and survival but does not alter the occurrence of isolated distant metastases unassociated with regional failure. Our results speak to the substantial survival value of local-regional control in this disease.

Aims: Presently, in Europe the treatment of node-negative colorectal cancer (CRC) patients consists of surgical resection of the primary tumour without adjuvant systemic therapy. However, up to 30% of these patients will develop disease recurrence. These high-risk patients are possibly identified by occult tumour cell (OTC) assessment in lymph nodes. In this paper, studies on the clinical relevance of OTC in lymph nodes are reviewed., Methods: A literature search was conducted in the National Library of Medicine by using the keywords colonic, rectal, colorectal, neoplasm, adenocarcinoma, cancer, lymph node, polymerase chain reaction, mRNA, immunohistochemistry, micrometastases and isolated tumour cells. Additional articles were identified by cross-referencing from papers retrieved in the initial search., Results: The upstaging percentages through OTC assessment and the prognostic relevance of OTC in lymph nodes vary among studies, which is related to differences in techniques used to detect OTC., Conclusions: We conclude that OTC examination techniques should be standardized to illuminate whether OTC in lymph nodes can reliably identify high-risk node-negative patients.

A quantitative estimate of residual nodal disease after gastric cancer surgery, the Maruyama index of unresected disease (MI), proved to be a strong independent predictor of survival in a large U.S. adjuvant chemoradiation study in which surgical undertreatment was frequent. Data from the Dutch D1-D2 Lymphadenectomy Trial permit an opportunity to assess the prognostic value of this variable in a cohort with lower-stage disease treated with minimum D-1 lymphadenectomy and no adjuvant chemoradiation. Blinded to survival, and excluding those cases with missing information, the MI was calculated for 648 of the original 711 patients treated with curative intent. Survival was assessed by log-rank and multivariate Cox regression analysis. All patients have been followed for a minimum of 11 years. Overall Dutch trial findings were not affected by the absence of 63 cases with incomplete data. As expected, the median MI was 26, much lower than in the previous U.S. study. In contrast to the D level, MI < 5 proved to be a strong predictor of survival by both univariate and multivariate analysis. The MI was an independent predictor of both overall survival [P = 0.016; hazard ratio (HR) = 1.45; 95% confidence interval (CI) 1.07-1.95] and relapse risk (P = 0.010; HR = 1.72; 95% CI 1.14-2.60). A strong dose-response reaction with respect to the MI and survival was also observed. We conclude that in this trial low-MI surgery is associated with enhanced survival, whereas outside of certain subgroups routine D2 lymphadenectomy is not. This observation suggests that surgeons might have more of an impact on patient survival by achieving a low-MI operation than a particular D level. A compelling dose-response effect reveals that the MI is a quantitative yardstick for assessing the adequacy of lymphadenectomy in gastric cancer.

Aims: Sentinel node mapping (SNM) has been introduced in colorectal cancer (CRC) to improve staging by facilitating occult tumour cell (OTC) assessment in lymph nodes that are most likely to be tumour-positive. In this paper, studies on the feasibility and reliability of SNM in CRC are reviewed., Methods: A literature search was conducted in the National Library of Medicine by using the keywords colonic, rectal, colorectal, neoplasm, adenocarcinoma, cancer and sentinel. Additional articles were identified by cross-referencing from papers retrieved in the initial search., Results: There is a large variation in identification rates and false-negative rates mainly due to the learning curve effect, differences in SNM technique and tumour stage., Conclusions: We conclude that SNM in CRC is technically feasible. Standardization of SNM procedures is mandatory to resolve the debate on the reliability of sentinel node status for predicting the tumour status of all lymph nodes. Only then can adjuvant treatment of patients upstaged by OTC detection in sentinel nodes be justified.

Purpose: Preoperative short-term radiotherapy improves local control in patients treated with total mesorectal excision (TME). This study was performed to assess the presence and magnitude of long-term side effects of preoperative 5 x 5 Gy radiotherapy and TME. Also, hospital treatment was recorded for diseases possibly related to late side effects of rectal cancer treatment., Patients and Methods: Long-term morbidity was assessed in patients from the prospective randomized TME trial, which investigated the efficacy of 5 x 5 Gy before TME surgery for mobile rectal cancer. Dutch patients without recurrent disease were sent a questionnaire., Results: Results were obtained from 597 patients, with a median follow-up of 5.1 years. Stoma function, urinary function, and hospital treatment rates did not differ significantly between the treatment arms. However, irradiated patients, compared with nonirradiated patients, reported increased rates of fecal incontinence (62% v 38%, respectively; P < .001), pad wearing as a result of incontinence (56% v 33%, respectively; P < .001), anal blood loss (11% v 3%, respectively; P = .004), and mucus loss (27% v 15%, respectively; P = .005). Satisfaction with bowel function was significantly lower and the impact of bowel dysfunction on daily activities was greater in irradiated patients compared with patients who underwent TME alone., Conclusion: Although preoperative short-term radiotherapy for rectal cancer results in increased local control, there is more long-term bowel dysfunction in irradiated patients than in patients who undergo TME alone. Rectal cancer patients should be informed on late morbidity of both radiotherapy and TME. Future strategies should be aimed at selecting patients for radiotherapy who are at high risk for local failure.

Surgery is the key to cure for patients with rectal cancer. Surgical techniques are evolving with conventional blunt dissection being increasingly abandoned for the sake of total mesorectal excision (TME), leading to favourable clinical and functional outcome. Surgical quality assurance programmes, involving training of general surgeons to adopt the TME technique, have proven to be feasible and result in improved outcome compared to historical controls. In this overview, developments in rectal cancer treatment are highlighted, the relation of surgeon and/or hospital volume with treatment outcome is discussed, and future directions in optimising rectal cancer treatment are considered.

Background: A statistical model for predicting disease-specific survival in patients with gastric carcinoma, based on a single U.S. institution experience, was tested for validity in a sample of patients treated at different institutions., Methods: The authors analysed 459 patients from the Dutch Gastric Cancer trial that compared limited (D1) with extended (D2) lymph node dissection. The discrimination ability of the nomogram with respect to 5 and 9-year disease-specific survival probabilities was superior to that of the American Joint Committee on Cancer (AJCC) staging system., Results: There was considerable heterogeneity of risk within many of the AJCC stages. Calibration plots suggested that predicted probabilities from the nomogram corresponded closely to actual disease-specific survival. The gastric carcinoma nomogram performed well when applied to patients treated in a large number of institutions., Conclusions: The nomogram provided predictions that discriminated better than the AJCC staging system, regardless of the extent of lymph node dissection. Patient counseling and adjuvant therapy decision-making should benefit from use of the nomogram., (Copyright (c) 2005 American Cancer Society.)

Background: Anastomotic leakage is a major complication of rectal cancer surgery. The aim of this study was to investigate risk factors associated with symptomatic anastomotic leakage after total mesorectal excision (TME)., Methods: Between 1996 and 1999, patients with operable rectal cancer were randomized to receive short-term radiotherapy followed by TME or to undergo TME alone. Eligible Dutch patients who underwent an anterior resection (924 patients) were studied retrospectively., Results: Symptomatic anastomotic leakage occurred in 107 patients (11.6 per cent). Pelvic drainage and the use of a defunctioning stoma were significantly associated with a lower anastomotic failure rate. A significant correlation between the absence of a stoma and anastomotic dehiscence was observed in both men and women, for both distal and proximal rectal tumours. In patients with anastomotic failure, the presence of pelvic drains and a covering stoma were both related to a lower requirement for surgical reintervention., Conclusion: Placement of one or more pelvic drains after TME may limit the consequences of anastomotic failure. The clinical decision to construct a defunctioning stoma is supported by this study.

Multimodality and quality controlled treatment result in improved treatment outcome in patients with solid tumours. Quality assurance focuses on identifying and reducing variations in treatment strategy. Treatment outcome is subsequently improved through the introduction of programs that reduce treatment variations to an acceptable level and implement standardised treatment. In chemotherapy and radiotherapy, such programmes have been introduced successfully. In surgery however, there has been little attention for quality assurance so far. Surgery is the mainstay in the treatment of patients with gastric and rectal cancer. In gastric cancer, the extent of surgery is continuously being debated. In Japan, extended lymph node dissection is favoured whereas in the West this type of surgery is not routinely performed with two large European trials concluding that there is no survival benefit from regional lymph node clearance. Post-operative chemoradiation is part of the standard treatment in the United States, although its role in combination with adequate surgery has not been established yet. These global differences in treatment policy clearly relate to the extent and quality of surgical treatment. As for gastric cancer, surgical treatment of rectal cancer patients determines patient's prognosis to a large extent. With the introduction of total mesorectal excision, local control and survival have improved substantially. Most rectal cancer patients receive adjuvant treatment, either pre- or post-operatively. The efficacy of many adjuvant treatment regimens has been investigated in combination with conventional suboptimal surgery. Traditional indications of adjuvant treatment might have to be re-examined, considering the substantial changes in surgical practise. Quality assurance programs enable the introduction of standardised and quality controlled surgery. Promising adjuvant regimens should be investigated in combination with optimal surgery.

Lymph node dissection plays an important role in staging and treatment of solid cancers. Sentinel node biopsy (SNB) has been introduced to minimize the extent of surgery and to enable assessment of minimal residual disease (MRD) without compromising accurate staging or survival. This review addresses the variation in technical aspects and outcome of SNB and MRD assessment in patients with breast and gastrointestinal cancer. Quality control leading to standardization of SNB and pathological examination will enable reliable comparison of studies, which is necessary for consensus of diagnostic and therapeutic strategies.

Gastric cancer continues to be a major public health problem and is the second most common cause of cancer-related deaths in the world. These statistics led the American Society of Clinical Oncology (ASCO) International Affairs Committee to choose gastric cancer as the topic for the International Symposium held at the 2003 ASCO Annual Meeting. Dr Yoshiaki Ito will discuss the role of RUNX3 in the genesis and progression of human gastric cancer. Dr Pelayo Correa will present a compelling argument on the use of Helicobacter pylori therapy and antioxidants in selected high-risk population as chemoprevention strategies for gastric cancer. The controversy regarding the role of extended lymph node dissection for gastric cancer will be discussed by Dr Cornelis J.H. Van De Velde and Dr Mitsuru Sasako. Dr Van De Velde will present the European surgical approach to gastric cancer, and Dr Sasako will review the Japanese experience. The issues of whether certain patients benefit from more aggressive surgical dissection and the potential risks compared with benefits will also be discussed. Dr John Macdonald will discuss the role of adjuvant chemotherapy and adjuvant chemoradiotherapy in resected gastric cancer, as well as the role of chemotherapy in metastatic gastric cancer.

One of the major problems in the treatment of rectal cancer has been the inability to achieve local control. Traditional surgery, now outmoded, involves blunt digital dissection and was associated with a high incidence of local recurrence. In an attempt to improve local control and survival, many adjuvant treatment modalities have been investigated. In the context of conventional nonstandardized surgical procedures, pre-operative radiotherapy has been shown to improve local control and overall survival. In recent years treatment outcome has been extensively improved by the introduction of the TME technique first described by Heald. This has resulted in such low recurrence rates and improved survival that the question had to be answered whether pre-operative short-term radiotherapy is still beneficial in TME treated patients. The question was answered in the TME trial set up by the Dutch ColoRectal Cancer Group that randomised between standardized and quality-controlled TME surgery alone and TME surgery preceded by short-term pre-operative radiotherapy. This paper reviews the developments in the treatment of resectable rectal cancer, highlights the results from the Dutch TME trial, and considers future directions in improving outcome.