Elderly patients with colorectal cancer have different clincopathological characteristics from younger patients. Colorectal cancers tend to localize in the proximal colon, from cecum to the splenic flexure in the elderly patients. Changes in the stools, rectal bleeding or black stool, abdominal pain, fatigue, weight loss and anemia are the common symptoms. Analysis showed that age is one of independent risk factors for lower completion rates of colonoscopy. Therefore, the choice of diagnosis methods in elderly patients should be careful. Achieving a clear diagnosis and avoiding complications should be considered at the same time. Most colorectal cancers in elderly are highly and moderately differentiated adenocarcinomas and locally advanced, and have less lymphatic and blood metastasis. The proportion of poorly differentiated adenocarcinoma increases with the increase of age, which should be concerned. Multiple colorectal cancers and colorectal cancer with extra-colorectal malignancy are not rare in the elderly patients. The common extra-colorectal tumors consist of gastric cancer, lung cancer, biliary carcinoma, pancreas cancer and malignancy from blood system. Molecular events, such as mutations of KARS, BRAF, TP53 and deficiency of DNA mismatch repair, are more frequent in elderly colorectal cancer patients. Many factors have impact on treatment decision in elderly patients with colorectal cancer, including age, comorbidities, physiological functions of organs and willingness of patients and their relatives. Although surgery is still the main treatment, the proportion of radical surgery is lower and emergency surgery is higher as compared to younger patients. With the development of minimally invasive surgical techniques and advances in anesthesia and perioperative management, laparoscopic surgery has become widespread in elderly patients with colorectal cancer. In addition, more attention should be paid to adjuvant therapy. Comprehensive individualized treatment plan should be taken to improve outcomes.
Adenocarcinoma ; pathology ; Aged ; Colonoscopy ; Colorectal Neoplasms ; diagnosis ; genetics ; pathology ; surgery ; Humans ; Laparoscopy ; Mutation ; Risk Factors

BACKGROUND/AIMS: Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. METHODS: Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. RESULTS: In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). CONCLUSIONS: The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma.
Adenoma/*genetics/surgery ; Aged ; Colonoscopy ; Colorectal Neoplasms/*genetics/surgery ; Endoscopy, Digestive System ; Female ; Humans ; Male ; *Microsatellite Instability ; Middle Aged ; Neoplasms, Multiple Primary/*genetics/surgery ; Predictive Value of Tests ; Stomach Neoplasms/*genetics/surgery

Differentiation-based histologic grading of colorectal carcinoma (CRC) is widely used, but its clinical impact is limited by insufficient prognostic value, interobserver disagreement, and the difficulty of its application to CRC with specific histologic types such as mucinous and medullary carcinoma. A recently proposed novel grading system based on quantifying poorly differentiated clusters (PDCs) claims to have the advantages of reproducibility and improved prognostic value, and might apply to heterogeneous CRC. We aimed to validate the clinicopathologic significance of the PDCs-based grading system and to determine the relationship between this grading system and microsatellite instability (MSI). Two hundred and one patients who had undergone radical surgery were reviewed. Based on the number of PDCs, 85, 58, and 58 tumors were classified as grade (G) 1 (42.3%), G2 (28.9%), and G3 (28.9%), respectively. PDCs-based grade was significantly associated with T, N, and M stages; lymphovascular invasion; conventional histologic grade; and frequent tumor budding (all P <0.001). In multivariate analysis, PDCs-based grade was found to be an independent prognostic factor for disease-free survival (P = 0.022; hazard ratio, 3.709 [G2], 7.461 [G3]). G3 CRC significantly correlated with high MSI (MSI-H) compared to G1 and G2 (P = 0.002; odds ratio, 5.750). In conclusion, this novel grading would provide valuable prognostic information to a greater number of patients and would require continued verification. PDCs-based grading is feasible for CRCs with heterogeneous morphology, and we propose that the association between G3 and MSI-H be further evaluated in different histological subtypes of CRC.
Colorectal Neoplasms/*genetics/*pathology/surgery ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis/pathology ; Male ; *Microsatellite Instability ; Middle Aged ; Neoplasm Grading/*methods ; Tumor Burden/*physiology

INTRODUCTIONThe Singapore Polyposis Registry (SPR) was established in 1989 in Singapore General Hospital (SGH). The aims were to provide a central registry service to facilitate identification, surveillance and management of families and individuals at high risk of colorectal cancer.

MATERIALS AND METHODSThis is a review of published literature in the department.

RESULTSThe registry currently has 253 families with several genetic conditions-93 familial adenomatous polyposis (FAP) families, 138 Amsterdam-criteria positive presumed Lynch syndrome (LS) families, 12 families with Peutz Jeghers syndrome, 2 families with Cowden's syndrome, and 8 families with hereditary mixed polyposis syndrome (HMPS). There are also 169 families with a strong family history of colorectal cancer but no abnormal genes yet identified. In FAP, a diagnostic tool developed has allowed a 94% local APC germline detection rate in FAP families. Knowledge obtained studying the phenotype of FAP patients has allowed better choice of surgery between ileal pouch anal anastomosis (IPAA) against an ileal-rectal anastomosis (IRA). In LS, our review has noted a highly heterogenous mutational spectrum and novel variants made up 46.7% (28/60) of all variants identified in this cohort. This may suggest that our Southeast Asian ethnic groups have distinct mutational variants from Western populations. Pathogenic mutations were only confined to MLH1 and MSH2, and identified in 28.8% of families.

CONCLUSIONThe impact of predictive gene testing for hereditary cancer risk in clinical practice has allowed evolution of care. Risk-reducing surgery and aggressive surveillance allows reduction in morbidity and mortality of patients. The SPR will continue to grow and improve outcomes in hereditary colorectal cancer patients and families.

Adaptor Proteins, Signal Transducing ; genetics ; Colorectal Neoplasms ; diagnosis ; ethnology ; genetics ; surgery ; Disease Management ; Female ; Genetic Testing ; methods ; Humans ; Male ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; genetics ; Mutation ; Neoplastic Syndromes, Hereditary ; classification ; diagnosis ; ethnology ; genetics ; surgery ; Nuclear Proteins ; genetics ; Registries ; statistics & numerical data ; Singapore ; epidemiology

Hyperplastic or serrated polyps were once believed to have little to no clinical significance. A subset of these polyps are now considered to be precursors to colorectal cancers (CRC) in the serrated pathway that may account for at least 15% of all tumors. The serrated pathway is distinct from the two other CRC pathways and involves an epigenetic hypermethylation mechanism of CpG islands within promoter regions of tumor suppressor genes. This process results in the formation of CpG island methylator phenotype tumors. Serrated polyps are divided into hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The SSA/P and the TSA have the potential for dysplasia and subsequent malignant transformation. The SSA/Ps are more common and are more likely to be flat than TSAs. Their flat morphology may make them difficult to detect and thus explain the variation in detection rates among endoscopists. Challenges for endoscopists also include the difficulty in pathological interpretation as well surveillance of these lesions. Furthermore, serrated polyps may be inadequately resected by endoscopists. Thus, it is not surprising that the serrated pathway has been linked with interval cancers. This review will provide the physician or clinician with the knowledge to manage patients with serrated polyps.
Adaptor Proteins, Signal Transducing/genetics/metabolism ; Adenomatous Polyps/genetics/metabolism/*surgery ; Colonoscopy ; Colorectal Neoplasms/genetics/metabolism/*surgery ; DNA Methylation ; Humans ; Intestinal Polyposis/genetics/metabolism/*surgery ; Intestinal Polyps/genetics/metabolism/*surgery ; Nuclear Proteins/genetics/metabolism ; Proto-Oncogene Proteins/genetics/metabolism ; Proto-Oncogene Proteins B-raf/genetics/metabolism ; ras Proteins/genetics/metabolism

OBJECTIVETo evaluate the correlation of clinical effect and prognosis between patients with metastatic colorectal cancer (mCRC) and different K-ras status.

METHODSThe clinical characteristics, chemotherapeutic regimens and survival of 153 mCRC patients with different K-ras status were analyzed retrospectively.

RESULTSThe median overall survival (OS) in patients without K-ras mutation were 31.7 months, significantly longer than 21.3 months in the patients with K-ras mutation (P = 0.037). The median progression-free survival (PFS) and OS in patients who received chemotherapy followed by anti-EGFR antibody treatment were 11.5 and 39.3 months, respectively, significantly longer as compared with the PFS and OS in those received chemotherapy in combination with anti-EGFR antibody concomitantly (5.7, P = 0.02, and 28.7 months, P = 0.034, respectively).

CONCLUSIONSK-ras status is a prognostic biomarker for mCRC patients treated with anti-EGFR antibody. The combination settings of anti-EGFR in combination with chemotherapy may improve survival of mCRC patients with wild-type K-ras status.

Aged ; Antibodies, Monoclonal ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Camptothecin ; analogs & derivatives ; therapeutic use ; Colorectal Neoplasms ; genetics ; pathology ; surgery ; therapy ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Genes, ras ; Humans ; Liver Neoplasms ; secondary ; therapy ; Lung Neoplasms ; secondary ; therapy ; Male ; Middle Aged ; Mutation ; Organoplatinum Compounds ; therapeutic use ; Receptor, Epidermal Growth Factor ; immunology ; Retrospective Studies ; Survival Rate

Adenomatous Polyposis Coli ; diagnosis ; drug therapy ; genetics ; surgery ; Antineoplastic Agents ; therapeutic use ; Colectomy ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; drug therapy ; genetics ; surgery ; DNA Mismatch Repair ; Humans ; Ileostomy ; Peutz-Jeghers Syndrome ; diagnosis ; drug therapy ; genetics ; surgery

OBJECTIVETo investigate the relationship between KRAS gene mutations and clinicopathological parameters in patients with colorectal carcinoma (CRC).

METHODSPCR-based direct sequencing was used to detect the mutations of KRAS gene and to correlate between clinicopathological characteristics and the presence of various KRAS mutations in 244 cases of CRC.

RESULTSKRAS mutations were identified in 92 cases (37.7%) of CRC. Five types of mutation were detected at codon 12, including G12D (40 cases, 16.4%), G12V (16 cases, 6.6%), G12A (7 cases, 2.9%), G12S (5 cases, 2.0%) and G12C (4 cases, 1.6%). Two types of mutation were detected at codon 13, including G13D (17 cases, 7.0%) and G13C (2 cases, 0.8%). One type of mutation was detected in codon 61, i.e. Q61K (1 case, 0.4%). KRAS mutation rate was higher in females (45.6%, 36/79) than in males (32.1%, 53/165; P < 0.05), but not related to another clinicopathological characteristics.

CONCLUSIONSFemale CRC patients have a higher KRAS mutation rate than the male patients. KRAS mutation has no significant correlation with patient's age, tumor site, tumor gross appearance, degree of differentiation, depth of invasion, TNM stages, lymphatic invasion, abdominal or distant metastases and prognosis in this study.

Adult ; Aged ; Aged, 80 and over ; Codon ; Colorectal Neoplasms ; genetics ; pathology ; surgery ; Female ; Genotype ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Polymerase Chain Reaction ; methods ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Sequence Analysis, DNA ; Sex Factors ; Survival Rate ; Young Adult ; ras Proteins ; genetics

Adaptor Proteins, Signal Transducing ; metabolism ; Adenocarcinoma, Clear Cell ; genetics ; metabolism ; pathology ; surgery ; Adenosine Triphosphatases ; metabolism ; Age Factors ; Carcinoma, Endometrioid ; genetics ; metabolism ; pathology ; surgery ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; metabolism ; pathology ; surgery ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; surgery ; DNA Mismatch Repair ; DNA Repair Enzymes ; metabolism ; DNA-Binding Proteins ; metabolism ; Endometrial Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Female ; Humans ; Mismatch Repair Endonuclease PMS2 ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; metabolism ; Neoplasms, Multiple Primary ; genetics ; metabolism ; pathology ; surgery ; Nuclear Proteins ; metabolism

Recent advances in chemotherapy lead to improved survival outcomes in patients with colorectal cancer. The 5-fluorouracil (5-FU) is still one of the important chemotherapeutic agents since 1950s, but the introduction of newer cytotoxic agents, irinotecan and oxaliplatin, or targeted agents, bevacizumab and cetuximab, have changed treatment strategies for these patients. A deliberate choice should be made for adjuvant chemotherapy, because it has became complicated more than ever before. Oxaliplatin plus 5-FU seemed to be superior in terms of disease-free and overall survival than 5-FU alone after curative surgery for colon cancers. However not all of these patients seemed to receive benefit from this intensive adjuvant treatment, and some limitations are present according to the postoperative stage, tumor biology and clinical characteristics. For metastatic disease, there is no doubt that more complicated strategies are present because we have more abundant chemotherapeutic agents available for metastatic setting compared to adjuvant setting. Recently, targeted agents, such as bevacizumab or cetuximab, also took an important place in the treatment of metastatic colorectal cancer, and many efforts are also made to find the biomarkers for predicting treatment responses to these targeted agents. In this review, we intended to sort up the standard strategies of chemotherapy for patients with colorectal cancer according to the latest pivotal publications.
Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; Chemotherapy, Adjuvant ; Colorectal Neoplasms/*drug therapy/surgery ; Drug Therapy, Combination ; Fluorouracil/therapeutic use ; Humans ; Organoplatinum Compounds/therapeutic use ; ras Proteins/genetics/metabolism