Gastric cancer is the second most common cause of cancer death worldwide.¹ Two major histopathological variants of this cancer have been described: an intestinal type and a diffuse type.² A decline in the overall incidence of gastric cancer can be attributed primarily to a decrease of the intestinal variant of gastric cancer with the diffuse type remaining stable or possibly even increasing.³

Background: Juvenile polyposis (JP) is an autosomal dominant syndrome predisposing to colorectal and gastric cancer. We have identified mutations in two genes causing JP, MADH4 and bone morphogenetic protein receptor 1A (BMPR1A): both are involved in bone morphogenetic protein (BMP) mediated signalling and are members of the TGF-β superfamily. This study determined the prevalence of mutations in MADH4 and BMPR1A, as well as three other BMP/activin pathway candidate genes in a large number of JP patients. Methods: DNA was extracted from the blood of JP patients and used for PCR amplification of each exon of these five genes, using primers flanking each intron–exon boundary. Mutations were determined by comparison to wild type sequences using sequence analysis software. A total of 77 JP cases were sequenced for mutations in the MADH4, BMPR1A, BMPR1B, BMPR2, and/or ACVR1 (activin A receptor) genes. The latter three genes were analysed when MADH4 and BMPR1A sequencing found no mutations. Results: Germline MADH4 mutations were found in 14 cases (18.2%) and BMPR1A mutations in 16 cases (20.8%). No mutations were found in BMPR1B, BMPR2, or ACVR1 in 32 MADH4 and BMPR1A mutation negative cases. Discussion: In the largest series of JP patients reported to date, the prevalence of germline MADH4 and BMPR1A mutations is approximately 20% for each gene. Since mutations were not found in more than half the JP patients, either additional genes predisposing to JP remain to be discovered, or alternate means of inactivation of the two known genes are responsible for these JP cases.

Purpose: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy (“Watch-and-Wait”). Experimental Design: Biopsies from two independent cohorts (n1 = 131, n2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait. Results: ISB positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06–0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the “Watch-and-Wait” cohort (n = 73), no relapse was observed in patients with ISB high (23.3%). Conclusions: ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.

Our goal was to analyze the results of resection of colorectal cancer and liver metastases in one procedure. Between June 1982 and July 1998, 522 patients underwent liver resection for colorectal metastases. Liver resection was performed simultaneously with colorectal resection in 71 cases, representing the population in this study. Morbidity, mortality, overall survival, and disease-free survival times were analyzed. Median followup time was 29 months (range 6 to 162 months). Prognostic factors and their influence on outcomes were analyzed. The median hospital stay was 8 days (range 5 to 23 days). Morbidity was 21% and included nine pleural effusions, seven wound abscesses, four instances of hepatic failure, three systemic infections, three intraabdominal abscesses, and one colonic anastomosis leakage. Operative mortality was 0%. Recurrence rate was 57.7% (41 or 71), and progression of disease was detected in 33.8%. Overall and disease-free survivals at 1, 3, and 5 years were 88%, 45%, and 38% and 67%, 17%, and 9%, respectively. Prognostic factors with notable influence on patient outcomes were nodal stage as per TNM classification, number of liver metastases, diameter (smaller or larger than 5 cm), liver resection specimen weight (lighter or heavier than 90 g), and liver resection margin (smaller or larger than 1 cm). Simultaneous resection of colorectal cancer and liver metastases can be performed with low morbidity and mortality rates, avoiding a second surgical procedure.

This study was designed to assess the prognostic value of the lymph node ratio in patients with colon cancer treated by colorectal specialists. Three hundred and sixty-two Stage III consecutive cases were analyzed based on quartiles: lymph node ratio 1 (>0 and 0.12 and or=0.25). Disease-free survival rates were: lymph node ratio 1, 75.5%; lymph node ratio 2, 74.2%; lymph node ratio 3, 73.2%; and lymph node ratio 4, 40.1%. Similar differences were observed for cancer-specific and overall survival rates. Cases with lymph node ratio >or=0.25 had higher hazard ratios than cases with lymph node ratio or=0.25 was higher than that of cases with up to three positive nodes and lymph node ratios or=0.25 was an independent prognostic factor in Stage III colon adenocarcinoma regardless of the number positive nodes. It modified outcomes predicted by the current staging system.