Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico.

BACKGROUND: The incidence of sporadic colorectal cancer (CRC) among individuals <50 years (early-onset CRC) has been increasing in the United States (U.S.) and Puerto Rico. CRC is currently the leading cause of cancer death among Hispanic men and women living in Puerto Rico (PRH). The objective of this study was to characterize the molecular markers and clinicopathologic features of colorectal tumors from PRH to better understand the molecular pathways leading to CRC in this Hispanic subpopulation. METHODS: Microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutation status were analyzed. Sociodemographic and clinicopathological characteristics were evaluated using Chi-squared and Fisher's exact tests. RESULTS: Of the 718 tumors analyzed, 34.2% (n = 245) were early-onset CRC, and 51.7% were males. Among the tumors with molecular data available (n = 192), 3.2% had MSI, 9.7% had BRAF, and 31.9% had KRAS mutations. The most common KRAS mutations observed were G12D (26.6%) and G13D (20.0%); G12C was present in 4.4% of tumors. A higher percentage of Amerindian admixture was significantly associated with early-onset CRC. CONCLUSIONS: The differences observed in the prevalence of the molecular markers among PRH tumors compared to other racial/ethnic groups suggest a distinct molecular carcinogenic pathway among Hispanics. Additional studies are warranted.

Implementation of Universal Colorectal Cancer Screening for Lynch Syndrome in Hispanics Living in Puerto Rico.

OBJECTIVE: Colorectal cancer is the leading cause of cancer death in Puerto Rico and third among Hispanics in the USA. Up to 2-4% of colorectal cancer cases are a result of Lynch syndrome (LS), a hereditary cancer syndrome caused by a germline mutation in at least one of the DNA mismatch repair genes. The objective of this study was to determine the prevalence of LS in colorectal tumors during the first 15-months after the implementation of universal tumor-based screening for LS in Puerto Rico. METHODS: A total of 317 colorectal tumors were evaluated in a large private pathology laboratory from September 2014 to December 2015. Clinical characteristics were obtained from the pathology reports. Unadjusted and adjusted logistic regression models were used to estimate the magnitude of association (odds ratio [OR] with 95% confidence intervals [CI]) between absent MMR protein expression and patient characteristics. RESULTS: Most cases (93.4%) were analyzed by immunohistochemistry; 11.8% (35 of 296) had deficient mismatch repair protein expression. While 29 of the 317 cases were subjected to PCR-based microsatellite instability analysis of which 10.3% (3 of 317) had microsatellite instability. In total, 11.0% of the tumors were reported MMR deficient. These tumors were more likely from females and more likely localized in the proximal colon compared to those with proficient MMR expression. CONCLUSIONS: Our data is consistent with the results from other studies including US Hispanics, where approximately 10% of Hispanic individuals with colorectal cancer have microsatellite instability. Our results support universal tumor-based screening for LS among Hispanics in accordance with National Comprehensive Cancer Network guidelines.

Association of genetic ancestry with colorectal tumor location in Puerto Rican Latinos.

BACKGROUND: Colorectal cancer (CRC) is the first cause of cancer deaths among Puerto Ricans. The incidence and mortality of CRC in Puerto Rico continue to be on the rise. The burden of CRC in Puerto Rico is higher than among US Hispanics and is second only to African Americans, thus supporting the importance of studying this CRC health disparity. The genetic background of the Puerto Rican population is a mix of European, African, and Amerindian races, which may account, in part, for the differences observed in the CRC mortality rates among Puerto Ricans. The objective of the study was to assess the role of genetic ancestry in CRC risk and its association with clinicopathological features of CRC tumors in Puerto Ricans. RESULTS: We used a validated panel of 105 ancestry informative markers (AIMs) to estimate genetic ancestry in 406 Puerto Rican CRC cases and 425 Puerto Rican controls. We examined the association of genetic ancestry with CRC risk and tumor clinicopathological characteristics. CONCLUSIONS: The mean ancestry proportions in the study population were 61% European, 21% African, and 18% Amerindian. No association was observed between genetic ancestry and risk of CRC. However, African ancestry was associated with an increased risk of developing rectal tumors (OR = 1.55, 95% CI 1.04-2.31). Additional studies are needed to fully elucidate the role of African ancestry in CRC carcinogenesis.

A systematic review of prognosis and therapy of anal malignant melanoma: a plea for more precise reporting of location and thickness.

Anal malignant melanoma (AMM) is a rare tumor with poor prognosis. We performed a systematic review of reports on wide local excision (WLE) and abdominoperineal resection (APR) for treatment of AMM in an attempt to define a precise set of reporting measures for outcomes of treatment of AMM. A systematic review of the literature was performed. Demographic data, surgical treatment, pathology, and survival rates were recorded. We compared WLE versus APR in terms of the overall survival time, the disease-free survival, and overall survival at 60 months. Twenty-one reports met the inclusion criteria. Notably, of these, 10 did not specify thickness of the primary melanoma. Interestingly, groin lymph node status was described in 19 of 21 reports, whereas location was specified in only 12 papers and thickness (depth in mm) in only 11. The median survival times of patients undergoing WLE (n = 324) and those undergoing APR (n = 369) are comparable (20 and 21 months, respectively). The mean median survival at 60 months was 15 per cent for WLE and 14 per cent for APR. The mean disease-free survival at 60 months was found to be 10 per cent for WLE and 6 per cent for APR. Patient selection for such a rare neoplasm yields very similar outcomes for both conservative and radical treatments. There is a wide variation in the reporting of both clinical and treatment outcomes. More uniformity of reporting of pathologic features and node status is essential before rational assessment of results can be done.

The difficulty with localization of rectal cancer after neoadjuvant chemoradiation therapy.

Neoadjuvant chemoradiation therapy (NCRT) has become the standard treatment for locally advanced rectal cancer. Subsequent downstaging can make identification of the primary tumor challenging. Complete pathologic response rates of 8 per cent to 27 per cent are seen with current NCRT regimen. Two patients were referred to our institution after NCRT and subsequent low anterior resection in whom no residual cancer was found in the resected specimen but who manifested cancer in the distal rectum in the early postoperative period. Resection of a locally advanced rectal cancer after NCRT associated with significant tumor shrinkage is facilitated by the surgeon's evaluation with proctoscopy and tumor tattooing before the initiation of NCRT. After NCRT, preoperative proctoscopy, distal rectal evaluation after a sphincter sparing procedure in the operating room, and thorough specimen evaluation help to insure that the surgeon has removed the rectal cancer with an appropriate margin. These cases emphasize how important it is for the surgeon to be involved in the staging phase of managing the patient with rectal cancer.

Rectosigmoid intussusception through the anus mimicking rectal prolapse.

Intussusception of the colon usually occurs in infants and children. Although rectal prolapse is not uncommon, presentation of more proximal segments of large bowel through the anus is extremely rare. We report two cases of rectosigmoid intussusception in which sigmoid colon intussusception was diagnosed as rectal prolapse preoperatively.

Long-segment, supercharged, pedicled jejunal flap for total esophageal reconstruction.

OBJECTIVE: Many patients with cancer have limited esophageal reconstruction options when the stomach is unavailable as a replacement conduit or when long-segment discontinuity exists. Jejunum has been used as an alternative conduit, both as a pedicled or free flap interposition; however, reports of this are usually limited to short-segment repairs. Microvascular augmentation of a pedicled jejunal flap allows creation of a longer conduit, making it possible to replace the entire esophagus with jejunum. Few reports describe this technique in patients with cancer. We report our initial experience with "supercharged" pedicled jejunum as an alternative conduit for total esophageal reconstruction. METHODS: Review of a prospectively collected departmental database was performed to identify those patients who underwent total esophageal reconstruction with supercharged pedicled jejunum. Data regarding their perioperative course and postoperative function were gathered from the prospectively collected clinical data, review of hospital records, and patient interviews. RESULTS: Total esophageal reconstruction with supercharged pedicled jejunum was attempted in 26 patients (age range, 37-74 years) between March 2000 and April 2004. Twenty-four of 26 patients were ultimately discharged with an intact supercharged pedicled jejunum flap, for an overall success rate of 92.3%. One patient experienced intraoperative flap loss caused by technical difficulties harvesting the flap and never had the flap interposed. One other flap loss occurred in the early postoperative period in a patient who had multisystem organ failure after a prolonged reconstruction. Cervical anastomotic leaks occurred in 19.2% (5/26) of the patients. Two midconduit leaks occurred that were suspicious for iatrogenic perforation from nasogastric tube placement; one required reoperation. One additional early reoperation was performed for cecal ischemia. There were no mortalities. Functional results were available in 95.4% (21/22) of the patients receiving supercharged pedicled jejunum who survived at least 6 months after reconstruction. At the time of follow-up, 95% (20/21) of the patients were tolerating regular diet, and 76.2% (16/21) did not require any supplemental alimentation. Ninety-five percent (20/21) of the patients were free from reflux symptoms, and 80.9% (17/21) had no dumping symptoms. Only 1 patient required dilation of a midconduit stricture. One patient required late reoperation for conduit redundancy. CONCLUSIONS: Supercharged pedicled jejunum is a suitable alternative conduit for total esophageal replacement in patients with cancer with otherwise limited reconstructive options. Functional outcomes are excellent, despite the severity of disease and technical challenges in this patient population.