Osteoporosis Is Associated with an Increased Risk of Colorectal Neoplasms Regardless of Sex: Nationwide Population-Based Cohort Study.

Vitamin D may have anticancer effects against colorectal cancer (CRC). Bone mineral density (BMD) reflects the long-term vitamin D status. This study investigated the association between osteoporosis and colorectal neoplasms (CRN). The data were obtained from the National Health Insurance Service sample cohort, which included 60,386 osteoporosis patients and 8224 controls who underwent BMD in 2002-2019. The logistic regression models included age, sex, income level, and comorbidity. Sensitivity tests were performed using the data from the National Health Screening Program. In total, 7706 (11.2%) patients were diagnosed with CRN, and the proportion was significantly higher in osteoporosis patients than in controls (11.7% vs. 8.1%). In the multivariate analysis, osteoporosis was associated with an increased risk of CRN (odds ratio (OR) = 1.91, 95% confidence interval = 1.75-2.09, p < 0.0001), which was significant for both colorectal adenomas and CRC (OR = 1.88 and 1.83, respectively). A subgroup analysis by sex revealed a significant association between osteoporosis and CRN in both women and men (OR = 2.06 and 1.66, respectively). The sensitivity tests revealed results similar to those of the original dataset. In conclusion, osteoporosis is significantly associated with CRN risk in both sexes. In high-risk patients with low BMD, appropriate screening for CRN and vitamin D supplementation are required, regardless of sex.

Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still beneficial in patients diagnosed with colorectal peritoneal metastasis who underwent palliative chemotherapy?

BACKGROUND: With a 5-year overall survival of less than 5%, colorectal peritoneal metastasis (CPM) patients are often managed with palliative chemotherapy (CTx). In the past few decades, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced as a possible curative treatment for highly selective CPM patients. We share our experience of CRS and HIPEC given the unique characteristics of the medical system and the benefit of CRS and HIPEC in palliative setting. METHODS: From April 2017 to October 2021, CPM patients who underwent CRS and HIPEC were analyzed. Patients were allocated into perioperative and palliative CTx arm based on the duration between initial diagnosis of CPM to undergoing CRS and HIPEC of 6 months. Data including perioperative parameters, postoperative outcomes, and survival were analyzed with a median follow-up of 28.5 months. RESULTS: Twenty-six CPM patients underwent CRS and HIPEC. Mean time from diagnosis of CPM to CRS and HIPEC was 5.5 months with 14 patients in the perioperative arm and 12 patients in the palliative arm. Perioperative group showed a longer RFS of 13.5 months compared to 8 months in the palliative group. Median overall survival of palliative group was 41.50 months, and 18 patients among all groups are alive at the time of this report. CONCLUSION: CRS and HIPEC could be a treatment option for a carefully selected CPM patients performed by experienced surgeons. Overall survival of 41.50 months in palliative group compared to 16.8 months from conventional systemic CTx supports CRS and HIPEC even in palliative patients.

External validation of prognostic scores and comparison of predictive accuracy for patients with colorectal cancer with peritoneal metastases considered for cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: Prognostic scores are developed to facilitate the selection of patients with colorectal cancer peritoneal metastases (CRPM) for treatment with cytoreductive surgery (CRS) ± intraperitoneal chemotherapy (IPC). Three prominent prognostic scores are the Peritoneal Surface Disease Severity Score (PSDSS), the Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), and the modified COloREctal-Pc (mCOREP). We externally validate these scores and compare their predictive accuracy. METHODS: Data from consecutive CRPM patients who underwent CRS/IPC from 1996 to 2018 was used to externally validate COMPASS, PSDSS, and mCOREP. Analysis evaluated the efficacy of each score in predicting (1) open-close laparotomy-those found at laparotomy to not be eligible for curative intent CRS/IPC, (2) surgical futility-those who underwent open-close laparotomy, palliative debulking surgery, or had an overall survival of less than 12 months, and (3) overall and recurrence-free survival (OS, RFS). RESULTS: Prognostic scores were calculated for the 174-patient external validation cohort. COMPASS was most accurate in predicting open-close laparotomy, futile surgery, and survival (OS and RFS). Area under the curve (AUC) for open-close prediction was 0.78 (95% confidence interval, CI: 0.68-0.87), representing useful discrimination. However, AUC for futility prediction was 0.62 (95% CI: 0.52-0.71), and C-statistic for OS was 0.65 indicating only possibly helpful discrimination. C-statistic for RFS was 0.59 indicating poor discrimination. CONCLUSION: While COMPASS showed the best statistical behavior, accuracy for several clinically relevant outcomes remains low, and thus applicability to clinical practice limited.

Predictors of Small Bowel Obstruction Post-Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal malignancies carries considerable morbidity; however, the significance of postoperative small bowel obstruction (SBO) is not well defined. We aim to identify predictors for post-CRS/HIPEC SBO and their oncologic associations. METHODS: A retrospective review was conducted of all CRS/HIPEC cases performed at a surgical oncology center (2013-2018). Patient demographics, tumor characteristics, perioperative factors, and province-wide hospital readmissions were analyzed. Descriptive statistics were used for baseline characteristics, multivariate logistic regression for predictors of SBO at 1 year, and Kaplan-Meier method with log-rank test for survival analysis. RESULTS: A total of n = 97 CRS/HIPEC procedures were performed for diagnoses of low-grade appendiceal mucinous neoplasm (44%), high-grade appendiceal adenocarcinoma (8%), colorectal adenocarcinoma (34%), and mesothelioma (9%). The median peritoneal carcinomatosis index (PCI) score was 16. Cumulative incidence of post-CRS/HIPEC SBO readmission was 24% at 1 year and 38% at 2 and 3 years. Of 29 patients readmitted with SBO, 14 (48%) had more than one readmission for SBO, and nine surgeries were performed for obstruction. Multivariate regression identified significant independent predictors of SBO within 1-year post-CRS/HIPEC as high-grade appendiceal or colorectal primaries (odds ratio [OR] 4.58, p = 0.02) and PCI ≥ 20 (OR 3.27, p = 0.05). Overall survival (OS) was worse in patients readmitted with SBO within 1 year compared to those without (3-year OS 58% vs. 75%, p = 0.017). CONCLUSION: SBO is the most common readmission diagnosis post-CRS/HIPEC and is associated with worse survival. High-grade appendiceal and colorectal primary tumors and PCI ≥ 20 are predictors for SBO.

Chronotherapy of Early Colon Cancer: Advantage of Morning Dose Schedules.

Colon adenomas with proliferating mutant cells may progress to invasive carcinomas. Proliferation of cells in human colorectal tissue is circadian, greater in the interval 4 to 12 hours after midnight than 16 to 24 hours after midnight. We have tested the hypothesis that chemotherapy administered during the time of greater cell proliferation will be more effective than chemotherapy administered during the time of lesser proliferation. An agent-based computer model of cell proliferation in colon crypts was calibrated with measurements of cell numbers in human biopsy specimens. It was used to simulate cytotoxic chemotherapy of an early stage of colon cancer, adenomas with about 20% of mutant cells. Chemotherapy doses were scheduled at different 4-hour intervals during the 24-hour day, and repeated at weekly intervals. Chemotherapy administered at 4 to 8 hours after midnight cured mutant cells in 100% of 50 trials with an average time to cure of 7.82 days (s.e.m. = 0.99). In contrast, chemotherapy administered at 20 to 24 hours after midnight cured only 18% of 50 trials, with the average time to cure of 23.51 days (s.e.m. = 2.42). These simulation results suggest that clinical chemotherapy of early colon cancer may be more effective when given in the morning than later in the day.

Evaluation of the efficacy of probiotic VSL#3 and synbiotic VSL#3 and yacon-based product in reducing oxidative stress and intestinal permeability in mice induced to colorectal carcinogenesis.

The objective of the present study was to evaluate the effect of probiotic VSL#3 isolated or associated with a yacon-based product (synbiotic) on oxidative stress modulation and intestinal permeability in an experimental model of colorectal carcinogenesis. Forty-five C57BL/6J mice were divided into three groups: control (standard diet AIN-93 M); probiotic (standard diet AIN-93 M and multispecies probiotic VSL#3, 2.25 × 109 CFU), and synbiotic (standard diet AIN-93 M with yacon-based product, 6% fructooligosaccharides and inulin, and probiotic VSL#3, 2.25 × 109 CFU). The experimental diets were provided for 13 weeks. The probiotic and the yacon-based product showed antioxidant activity, with the percentage of DPPH radical scavenging equal to 69.7 ± 0.4% and 74.3 ± 0.1%, respectively. These findings contributed to reduce hepatic oxidative stress: the control group showed higher concentration of malondialdehyde (1.8-fold, p = 0.007 and 1.5-fold, p = 0.035) and carbonylated protein (2-fold, p = 0.008 and 5.6-fold, p = 0.000) compared to the probiotic and synbiotic groups, respectively. Catalase enzyme activity increased 1.43-fold (p = 0.014) in synbiotic group. The crypt depth increased 1.2-fold and 1.4-fold with the use of probiotic and synbiotic, respectively, compared to the control diet (p = 0.000). These findings corroborate the reduction in intestinal permeability in the probiotic and synbiotic groups, as measured by the percentage of urinary lactulose excretion (CON: 0.93 ± 0.62% × PRO: 0.44 ± 0.05%, p = 0.048; and CON: 0.93 ± 0.62% × SYN: 0.41 ± 0.12%, p = 0.043). In conclusion, the probiotic and synbiotic showed antioxidant activity, which contributed to the reduction of oxidative stress markers. In addition, they protected the mucosa from damage caused by chemical carcinogen and reduced intestinal permeability. PRACTICAL APPLICATION: The relationship between intestinal health and the occurrence of various organic disorders has been demonstrated in many studies. The use of probiotics and prebiotics is currently one of the main targets for modulation of intestinal health. We demonstrated that the use of a commercial mix of probiotic bacteria (VSL#3) isolated or associated with a yacon-based prebiotic, rich in fructooligosaccharides and inulin, is able to reduce the oxidative stress and intestinal permeability in a colorectal carcinogenesis model. These compounds have great potential to be used as a food supplement, or as ingredients in the development of food products.

Predictive value of KRAS mutation and excision repair cross-complementing 1 (ERCC1) protein overexpression in patients with colorectal cancer administered FOLFOX regimen.

BACKGROUND: Recent studies have reported that KRAS mutational status is correlated with ERCC1 expression level. The purpose of this study was to determine the clinical significance of the KRAS mutation and ERCC1 overexpression status as predictive factors for resistance against oxaliplatin-based treatment. METHODS: We retrospectively analyzed clinicopathologic features, KRAS mutation status, and ERCC1 overexpression status in 386 patients with colorectal cancer (CRC) who underwent curative-intent surgery. Of these patients, 84 were administered the FOLFOX regimen as a first-line or adjuvant treatment. Disease-free survival and overall survival in groups separated by KRAS and ERCC1 statuses were analyzed. RESULTS: Wild-type KRAS and ERCC1 overexpression were observed in 25.5% of all patients. Among the 84 patients who were treated with the FOLFOX regimen, 73 patients were evaluated for KRAS and ERCC1 status. There were no significant differences in disease-free survival or overall survival in groups separated by KRAS mutation and ERCC1 expression status. Subgroup analysis of patients with wild-type KRAS showed that overall survival in the ERCC1 overexpression group was lower than that of patients in the ERCC1 underexpression group (p = 0.029); however, no significant difference was found in the mutant KRAS patient group (p = 0.671). CONCLUSIONS: Our results suggest that CRC with wild-type KRAS and ERCC1 overexpression might be associated with oxaliplatin resistance. When considering oxaliplatin-based chemotherapy, the status of both KRAS mutation and ERCC1 overexpression should be evaluated.

Aerial Parts of Peucedanum chenur Have Anti-Cancer Properties through the Induction of Apoptosis and Inhibition of Invasion in Human Colorectal Cancer Cells.

Background: The Peucedanum species have many pharmacological effects due to the presence of coumarins, flavonoids, phenolic compounds, and essential fatty acids in these species. In this study, for the first time, the anticancer activity of Peucedanum chenur methanolic extract via the induction of apoptosis and inhibition of invasion in HCT-116 human colon cancer cells was investigated. Methods: P. chenur methanolic extract effect on HCT-116 cells viability and antioxidant activity were evaluated using MTT assay, 1,1-Diphenyl-2-picrylhydrazyl, and iron chelating tests, respectively. Changes in mRNA expression level in a panel of relevant genes were assessed by the quantitative real-time PCR. Also, apoptosis was assessed by cell cycle analysis and Annexin V/PI (propidium iodide) method, and the effect on cell migration was tested using scratch test. Results: P. chenur methanolic extract increased significantly the expression of BAX while decreased the expression of BCL-2, AKT1, FAK, RhoA, and matrix metalloproteinase (MMP) genes compared to the control group. BAX/BCL-2 ratio and apoptosis elevated, whereas cell migration reduced significantly. Besides, our extract showed an appropriate antioxidant activity. Conclusion: P. chenur may be introduced as a new chemopreventive agent in medicine due to its notable power in terms of induction of apoptosis and inhibition of invasion.

[The status analysis of diagnosis and treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China: a report of 1 003 cases in 16 domestic medical centers].

Objective: To analyze the status of domestic surgical treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China. Methods: Clinicopathological data of patients who underwent surgery from October 2003 to October 2018 in 16 domestic medical centers was retrospectively analyzed. Excel database was created which covered 77 fields of 7 parts: baseline information of patients, laboratory tests, imaging tests, chemoradiotherapy information, intra-operative findings, postoperative pathology and follow-up data. The Wilcoxon rank-sum test was used for comparison of the measurement data between groups. The χ(2) test was used for comparison of the categorical data between groups. The survival curve was calculated by the Kaplan-Meier method. Results: Of the 1 003 patients, there were 575 male and 428 female patients with the age of (58.5±14.1) years (range: 18 to 92 years). In a total of 920 patients, the carcinoma of sigmoid colon was performed in 292 cases (31.8%) with the highest ratio. The proportion of patients with liver metastasis and lung metastasis were 27.9% (219/784) and 8.3% (64/769). Preoperative detection of carcino-embryonic antigen level was the most common method in China (87.74%, 880/1 003), and the positive rate was 64.5% (568/880). The correct rate of preoperative imaging tests was 40.7% (280/688). The ratio of peritoneal carcinomatosis index (PCI) scores between 0 and 10 was the highest (59.6%, 170/285). Two hundred and sixty-two (27.0%) patients were performed by totally laparoscopic operation in 971 patients. The resection of primary tumor was performed in 588 of the 817 patients (72.0%). In a total of 457 cases, 253 (55.4%) patients were performed cytoreduction which group scored completeness of cytoreduction (CCR) 0. The postoperative hyperthermic intraperitoneal chemotherapy was implemented in 70 of the 334 cases (21.0%). Among 1 003 cases, 562 cases (56.03%) had complete follow-up data and the median overall survival was 15 months. The primary tumor resection and the CCR scores were affected by the PCI scores. The patients underwent primary tumor resection (187/205 vs. 26/80, χ(2)=105.085, P=0.000) and the patients were performed cytoreduction which scored CCR 0 or CCR 1 (162/204 vs. 8/78, Z=-10.465, P=0.000) had significant difference between the groups of PCI<20 and ≥20. There was a close correlation between the surgical method and the CCR scores (Z=-3.246,P=0.001).When the maximum degree of tumor reduction was planned, most surgeons would choose laparotomy. The overall survival time was longer in patients with primary tumor resection (P=0.000). The median survival time was 18.6 months in the group of primary tumor resection. Conclusions: It is difficult to diagnose the synchronous peritoneal carcinomatosis from colorectal cancer before the operation. Primary tumor resection has an obvious effect to prolong the survival time. It is necessary to standardize the treatment of peritoneal metastasis.

Expression of Selenoprotein Genes and Association with Selenium Status in Colorectal Adenoma and Colorectal Cancer.

Dietary selenium (Se) intake is essential for synthesizing selenoproteins that are important in countering oxidative and inflammatory processes linked to colorectal carcinogenesis. However, there is limited knowledge on the selenoprotein expression in colorectal adenoma (CRA) and colorectal cancer (CRC) patients, or the interaction with Se status levels. We studied the expression of seventeen Se pathway genes (including fifteen of the twenty-five human selenoproteins) in RNA extracted from disease-normal colorectal tissue pairs, in the discovery phase of sixty-two CRA/CRC patients from Ireland and a validation cohort of a hundred and five CRC patients from the Czech Republic. Differences in transcript levels between the disease and paired control mucosa were assessed by the Mann-Whitney U-test. GPX2 and TXNRD3 showed a higher expression and GPX3, SELENOP, SELENOS, and SEPHS2 exhibited a lower expression in the disease tissue from adenomas and both cancer groups (p-values from 0.023 to <0.001). In the Czech cohort, up-regulation of GPX1, SELENOH, and SOD2 and down-regulation of SELENBP1, SELENON, and SELENOK (p-values 0.036 to <0.001) was also observed. We further examined the correlation of gene expression with serum Se status (assessed by Se and selenoprotein P, SELENOP) in the Irish patients. While there were no significant correlations with both Se status markers, SELENOF, SELENOK, and TXNRD1 tumor tissue expression positively correlated with Se, while TXNRD2 and TXNRD3 negatively correlated with SELENOP. In an analysis restricted to the larger Czech CRC patient cohort, Cox regression showed no major association of transcript levels with patient survival, except for an association of higher SELENOF gene expression with both a lower disease-free and overall survival. Several selenoproteins were differentially expressed in the disease tissue compared to the normal tissue of both CRA and CRC patients. Altered selenoprotein expression may serve as a marker of functional Se status and colorectal adenoma to cancer progression.

The Relationship Between Health-Related Quality of Life and Survival in Metastatic Colorectal Cancer Patients Treated With Korean Medicine.

OBJECTIVES: This study aimed to identify the relationship between health-related quality of life (HRQoL) measured by the Functional Assessment Cancer Therapy-General (FACT-G) and survival in metastatic colorectal cancer (mCRC) patients. METHODS: The clinical characteristics and FACT-G scores were retrospectively reviewed in mCRC patients who visited the Cancer Center of Korean Medicine. The overall survival (OS) was calculated and compared using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were performed based on clinical characteristics and FACT-G scores. To identify significant differences in answer frequency, χ2 tests and Fisher's exact tests were used. RESULTS: A total of 58 patients were reviewed. The proportion of patients who had an Eastern Cooperative Oncology Group-Performance Status ≥ 2 was 43.1%, multiple distant metastatic sites was 77.6%, liver metastases was 43.1%, been previously treated was 89.7%, and received more than the second-line chemotherapy was 75.5%. The mean total FACT-G score was 65.3 (median 65.6). The median OS was 7 months. There was no significant difference in OS between the 2 groups divided by the median values of FACT-G total and subscores. In univariate analyses, functional well-being (FWB) score had a significant impact on survival. In multivariate analyses, presence of liver metastasis, FACT-G total score, and FWB score were significant prognostic predictors of survival. No statistically different answer frequency was observed for any question regarding FWB. CONCLUSIONS: This study found that FACT-G total and FWB scores were potential prognostic factors for predicting OS in relapsed or refractory mCRC patients treated with Korean Medicine.

CEA to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with colorectal cancer peritoneal carcinomatosis undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Serum tumor markers are prognostic in patients with colorectal cancer peritoneal carcinomatosis (CRPC) undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). Assessment of the ratio of tumor marker to volume, as depicted by peritoneal carcinomatosis index (PCI), and how this may affect overall (OS) and recurrence free survival (RFS) has not been reported. METHODS: Survival effect of this ratio was analyzed in patients with CRPC managed from 1996 to 2016 with CRS and IPC. RESULTS: Of 260 patients included, those with low CEA/PCI ratio (<2.3) had longer median OS (56 vs 24 months, P = 0.001) and RFS (13 vs 9 months, P = 0.02). The prognostic impact of CEA/PCI ratio was most pronounced in patients with PCI ≤ 10 (OS of 72 vs 30 months, P < 0.001; RFS of 21 vs 10 months, P = 0.002). In multivariable analysis, elevated CEA/PCI ratio was independently associated with poorer OS (adjusted HR 1.85, 95%CI 1.11-3.10, P = 0.02) and RFS (adjusted HR 1.58, 95%CI 1.04-2.41, P = 0.03). CONCLUSION: CEA/PCI ratio is an independent prognostic factor for OS and RFS in CRPC. This novel approach allows both tumor activity and volume to be accounted for in one index, thus potentially providing a more accurate indication of tumor biological behavior.

Pien Tze Huang induces apoptosis and inhibits proliferation of 5-fluorouracil-resistant colorectal carcinoma cells via increasing miR-22 expression.

The well-known traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used to treat various malignancies, including colorectal cancer (CRC). It was recently reported that PZH possesses the ability to overcome multidrug resistance in CRC cells. In the present study, a 5-fluorouracil (5-FU) resistant human CRC cell line (HCT-8/5-FU) was used to further evaluate the effect of PZH on chemotherapy (chemo)-resistance and investigate the mechanisms through which this occurs. The results identified that PZH significantly reduced the viability and cell density of HCT-8/5-FU cells in a dose- and time-dependent manner (P<0.05). PZH inhibited cell survival, reduced the proportion of cells in S-phase, and suppressed the expression of pro-proliferative proteins cyclin D1 and cyclin-dependent kinase 4. In addition, PZH treatment induced nuclear condensation and fragmentation, activated caspase-9 and -3 and increased the pro-apoptotic Bcl-2-associated X protein/B-cell lymphoma 2 protein ratio. Furthermore, PZH treatment upregulated the expression of microRNA-22 (miR-22) and downregulated the expression of c-Myc (a target gene of miR-22). In conclusion, the findings from the present study suggest that PZH can overcome chemo-resistance in cancer cells, likely through increasing miR-22 expression, and by reversing the imbalance between levels of proliferation and apoptosis.

Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance).

BACKGROUND: Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. PATIENTS AND METHODS: We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards. RESULTS: Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status. CONCLUSION: Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT00003835.

New era of colorectal cancer screening.

Colorectal cancer (CRC) is the 2(nd) most common cancer in women and 3(rd) most common cancer in men worldwide. Most CRCs develop from adenomatous polyps arising from glandular epithelium. Tumor growth is initiated by mutation of the tumor suppressor gene APC and involves other genetic mutations in a stepwise process over years. Both hereditary and environmental factors contribute to the development of CRC. Screening has been proven to reduce the incidence of CRC. Screening has also contributed to the decrease in CRC mortality in the United States. However, CRC incidence and/or mortality remain on the rise in some parts of the world (Eastern Europe, Asia, and South America), likely due to factors including westernized diet, lifestyle, and lack of healthcare infrastructure. Multiple screening options are available, ranging from direct radiologic or endoscopic visualization tests that primarily detect premalignant or malignant lesions such as flexible sigmoidoscopy, optical colonoscopy, colon capsule endoscopy, computed tomographic colonography, and double contrast barium enema - to stool based tests which primarily detect cancers, including fecal DNA, fecal immunochemical test, and fecal occult blood test. The availability of some of these tests is limited to areas with high economic resources. This article will discuss CRC epidemiology, pathogenesis, risk factors, and screening modalities with a particular focus on new technologies.

Comparable survival outcome of metastatic colorectal cancer in Indigenous and non-Indigenous patients: Retrospective analysis of the South Australian metastatic colorectal cancer registry.

OBJECTIVE: This study aims to investigate disparities in demographics, disease characteristics, treatment and overall survival between South Australian (SA) Indigenous and non-Indigenous patients with metastatic colorectal cancer (mCRC). DESIGN: This employs a retrospective population study using the SA mCRC registry. SETTING: The SA mCRC registry identifies mCRC patients from hospital encounters, histopathology reports, medical oncology letters, clinician notification, attendances at multidisciplinary meetings and death audits by the SA Cancer Registry. PARTICIPANTS: A total of 2865 adult mCRC patients including 14 Indigenous patients were identified through the SA mCRC registry between February 2006 and August 2013. Patients were linked to the SA Cancer Registry to obtain Indigenous status. MAIN OUTCOME MEASURES: Demographic, disease and treatment characteristics were compared using Chi-squared test and t-test; while overall survival defined as time to any cause of death was analysed using Cox regression. RESULTS: No difference was observed for clinical characteristics, except for a higher proportion of Indigenous patients receiving chemotherapy (85.7% versus 58.5%; P = 0.04). The rate of liver surgery was similar across the two groups (21.0% versus 15.1%; P = 0.40). The median overall survivals were equivalent (11.9 months versus 15.1 months; hazard ratio = 1.00; 95% confidence interval for hazard ratio, 0.54-1.86). CONCLUSIONS: Clinical characteristics and survival outcomes were similar between Indigenous and non-Indigenous patients captured on the SA mCRC registry, and outcome of those who have an access to comprehensive cancer care appeared independent of Indigenous status and in line with large clinical trials. Underestimation of Indigenous cases due to their lower utilisation of cancer service could not be excluded and ultimately the accurate reporting of these patients is crucial.

Perineal colostomy: an alternative to avoid permanent abdominal colostomy: operative technique, results and reflection / Colostomia perineal: uma alternativa para evitar a colostomia abdominal definitiva: técnica operatória, resultados e reflexão

BACKGROUND: The most common injury to indicate definitive stoma is rectal cancer. Despite advances in surgical treatment, the abdominoperineal resection is still the most effective operation in radical treatment of malignancies of the distal rectum invading the sphincter and anal canal. Even with all the effort that surgeons have to preserve anal sphincters, abdominoperineal amputation is still indicated, and a definitive abdominal colostomy is necessary. This surgery requires patients to live with a definitive abdominal colostomy, which is a condition that modify body image, is not without morbidity and has great impact on the quality of life. AIM: To evaluate the technique of abdominoperineal amputation with perineal colostomy with irrigation as an alternative to permanent abdominal colostomy. METHOD: Retrospective analysis of medical records of 55 patients underwent abdominoperineal resection of the rectum with perineal colostomy in the period 1989-2010. RESULTS: The mean age was 58 years, 40 % men and 60 % women. In 94.5% of patients the indication for surgery was for cancer of the rectum. In some patients were made three valves, other two valves and in the remaining no valve at all. Complications were: mucosal prolapse, necrosis of the lowered segment and stenosis. CONCLUSION: The abdominoperineal amputation with perineal colostomy is a good therapeutic option in the armamentarium of the surgical treatment of rectal cancer. .

RACIONAL: O câncer de reto é o agravo mais frequente para a indicação do estoma abdominal definitivo. Apesar dos avanços no tratamento cirúrgico, a amputação abdominoperineal ainda é a operação indicada mais efetiva nesta indicação com invasão de esfíncter e de canal anal, o que impõe aos pacientes colostomia abdominal definitiva, condição que altera a imagem corporal e grande repercussão na qualidade de vida. OBJETIVO: Avaliar a técnica de amputação abdominoperineal mais colostomia perineal com irrigação como alternativa à colostomia abdominal definitiva. MÉTODO: Análise retrospectiva de prontuário médico de cinquenta e cinco pacientes submetidos à amputação abdominoperineal do reto mais colostomia perineal no período de 1989 a 2010. RESULTADOS: A média de idade foi de 58 anos sendo 40% em homens e 60% em mulheres. Em 94,5% dos pacientes a indicação cirúrgica foi por câncer de reto. Em alguns foram confeccionadas três válvulas, em outros duas e nos demais não foi confeccionada nenhuma válvula. As complicações foram: prolapso mucoso, necrose do segmento abaixado e estenose. CONCLUSÃO: A técnica de amputação abdominoperineal mais colostomia perineal é boa opção terapêutica no arsenal do tratamento cirúrgico do câncer de reto. .

Clinical significance of primary tumor resection in colorectal cancer patients with synchronous unresectable metastasis.

BACKGROUND: The aim of this study was to compare the outcomes in colorectal cancer (CRC) patients with synchronous unresectable metastases who received either primary tumor resection (PTR) or chemotherapy as the first treatment and to investigate the clinical course of asymptomatic patients who received chemotherapy as the first treatment. METHODS: We retrospectively analyzed 324 CRC patients with synchronous unresectable metastases. Overall survival (OS) was analyzed for the two groups (upfront PTR group [n = 72] vs. upfront chemotherapy group [n = 252]). Surgical morbidity and mortality were recorded. In the asymptomatic patients who received upfront chemotherapy, the incidences of primary tumor-related complications were analyzed. RESULTS: In patients who underwent PTR as the first treatment, the median OS period was superior to those who received upfront chemotherapy (17.2 vs. 13.6 months, P = 0.002). In the PTR group, surgical morbidity and mortality were 11.6% and 1.9%, respectively. Of the 252 asymptomatic patients, the incidence of primary tumor-related complications was 35%. Emergent surgery was ultimately done in 14% of the 252 patients. CONCLUSION: CRC patients with synchronous unresectable metastases who underwent PTR followed by chemotherapy had significantly longer survival times compared to patients who received chemotherapy as the first treatment.

Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil and Low Dose Leucovorin in Patients with Advanced Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to evaluate the efficacy and tolerability of the oxaliplatin, 5-fluorouracil (5-FU) and low dose leucovorin (LV) combination in patients with advanced colorectal cancer. MATERIALS AND METHODS: Patients with unresectable or recurrent colorectal carcinomas were prospectively accrued. Up to one prior chemotherapy regimen was allowed. Patients received oxaliplatin, 85 mg/m2, administered as a 2-hour infusion on day 1, followed by LV, 20 mg/m2, as a bolus and 5-FU, 1, 500 mg/m2, via continuous infusion for 24 hours on days 1 and 2. Treatment was repeated every 2 weeks until disease progression or adverse effects prohibited further therapy. RESULTS: Between August 1999 and May 2004, 31 patients were enrolled in this study. Of the patients enrolled, 24 and 31 were evaluable for tumor response and survival analysis, respectively. The patients' characteristics included a median age of 59, with 6 (19%) having had prior chemotherapy. No patient achieved a complete response, but nine (38%) attained a partial response. Seven (29%) patients maintained a stable disease and 8 (33%) experienced increasing disease. The median duration of the response was 6 months. After a median follow-up of 9.6 months, the median time to progression was 3.8 months, with a median survival of 10.7 months. The hematological toxicities were mild to moderate, with no treatment-related mortality or infection. The major non-hematological toxicity was gastrointestinal toxicity. CONCLUSIONS: The combination chemotherapy of oxaliplatin, low dose LV and continuous infusion of 5-FU is safe and has a cost-benefit, but is a moderately effective regimen in advanced colorectal cancer. A randomized trial comparing low and high dosages of leucovorin in the FOLFOX regimen is warranted.

The efficacy of a modified chronomodulated infusion of oxaliplatin, 5-fluorouracil and leucovorin in advanced colorectal cancer (preliminary data).

PURPOSE: To determine the efficacy and tolerability of a modified chronomodulated infusion of oxaliplatin, 5-fluorouracil (5-FU) and leucovorin in the treatment of advanced colorectal cancer. MATERIALS AND METHODS: Sixteen patients with relapsed or metastatic colorectal cancer were treated with an intravenous infusion of oxaliplatin 25 mg/m(2), 5-FU 700 mg/m(2) and leucovorin 20 mg/m(2) on days 1 to 5. The infusion of oxaliplatin was chronomodulated with a peak delivery rate at 16:00 p.m., with 5-FU infused constantly overnight. Each course was repeated every 21 days. RESULTS: The response rate was 38.5% (95% confidence interval [CI], 13.9% to 68.4%) in the 13 measurable patients, including 1 complete response (7.7%) and 4 partial responses (30.8%). Five patients (38.5%) had a stable disease and 3 (23.0%) a progressive disease. Three patients without a measurable lesion had improved status. The median time to progression and overall survival were 29 weeks and 85 weeks, respectively. Grade 3 thrombocytopenia occurred in 2.5% (2 cycles) and grade 3 vomiting in 12.5% (2 patients). Anorexia, stomatitis, diarrhea, pruritus, alopecia and peripheral neuropathy were mild and tolerable. CONCLUSION: The modified chronomodulated infusion of oxaliplatin, 5-FU and leucovorin is effective and tolerable, but the number of patients was too small. Further study will be needed to confirm the efficacy of this regimen with a larger population of patients.