Guilherme Cutait de Castro Cotti

Conservative therapies for hemorrhagic radiation proctitis: a review

Chronic radiation proctitis represents a challenging condition seen with increased frequency due to the common use of radiation for treatment of pelvic cancer. Hemorrhagic radiation proctitis represents the most feared complication of chronic radiation proctitis. There is no consensus for the management of this condition despite the great number of clinical approaches and techniques that have been employed. Rectal resection represents an available option although associated with high morbidity and risk of permanent colostomy. The effectiveness of nonoperative approaches remains far from desirable, and hemorrhagic recurrence represents a major drawback that leads to a need for consecutive therapeutic sessions and combination of techniques. We conducted a critical review of published reports regarding conservative management of hemorrhagic chronic radiation proctitis. Although prospective randomized trials about hemorrhagic radiation proctitis are still lacking, there is enough evidence to conclude that topical formalin therapy and an endoscopic approach delivering an argon plasma coagulation represent available options associated with elevated effectiveness for interruption of rectal bleeding in patients with chronic radiation proctitis.

Initial experience with stapled hemorrhoidopexy for treatment of hemorrhoids

BACKGROUND Introduction of stapled hemorrhoidopexy by Longo in 1998 represented a radical change in the treatment of hemorrhoids. By avoiding multiple excisions and suture lines in the perianal region, stapled hemorrhoidopexy is intended to offer less postoperative pain than with conventional techniques. OBJECTIVE To report and analyze the intra and postoperative results gained during initial experience with stapled hemorrhoidopexy. METHODS One hundred and fifty five patients (67 males) with average age of 39.5 years (21-67 years) underwent stapled hemorrhoidopexy between June 2000 and December 2003 with symptomatic third-degree (n = 74) and fourth-degree (n = 81) hemorrhoids. Mean follow-up period was 20 months (14-60 months). RESULTS Preoperative symptoms were prolapse (96.7%) and anal bleeding (96.1%). Overall mean operative time was 23 minutes (16-48 minutes). We observed one case of stapler failure and one case of failure to introduce the stapler occurred in a patient with previous anal surgery. Additional sutures for hemostasis were required in 103 patients (66.5%). Resection of skin tags was performed in 45 cases (29%). Postoperatively scheduled analgesia with oral dipyrone and celecoxib was enough for pain control in 131 patients (84.5%). Rescue analgesia was necessary in 24 cases (15.5%). Five patients needed opiates for pain control. Hospital discharge took place on the first postoperative day in 140 patients (90.3%). First defecation without pain was reported by 118 patients (76.1%). Postoperative complications were anal bleeding (10.3%), severe pain (3.2%), urinary retention (3.9%), fever without any signs of perianal infection (1.9%), incontinence for flatus (1.9%), hemorrhoidal thrombosis (1.3%). Two patients presented symptoms of recurrent hemorrhoidal disease and were successfully treated by conventional hemorrhoidectomy. They were no cases of anal stenosis, permanent incontinence, chronic pain or deaths in this series. CONCLUSIONS Hemorrhoidopexy can be considered a feasible and safe alternative technique to conventional hemorroidectomy for select patients.

Sclerosing mesenteritis as an unusual cause of fever of unknown origin: a case report and review

Fever of unknown origin (FUO), defined as a temperature higher than 38.3°C on several occasions and lasting longer than three weeks that is associated with a diagnosis that remains uncertain after one week of investigation (1), is a frequent condition in the infectious diseases specialty clinic. The condition is often associated with extensive diagnostic procedures and, not rarely, frustration for both the patient and the physician. An evidence-based approach has been used to group the causes of FUO (2) into four general categories: infectious, rheumatic/inflammatory, neoplastic, and miscellaneous disorders (3). Infectious diseases such as endocarditis, intra-abdominal abscesses, and tuberculosis, as well as inflammatory conditions such as temporal arteritis, adults Still disease, and late-onset rheumatoid arthritis, are commonly identified causes of FUO (3). However, unexpected and rare causes are sometimes diagnosed, as reported below in a case of sclerosing mesenteritis.

Hereditary nonpolyposis colorectal cancer identification and surveillance of high-risk families

Hereditary nonpolyposis colorectal cancer is an autosomal dominant condition caused by highly penetrant gene mutations. It is characterized by increased susceptibility for a specific group of cancer, mainly colorectal cancer. The syndrome originates from the inheritance of mutations in DNA mismatch repair genes. The most commonly affected genes in hereditary nonpolyposis colorectal cancer are hMLH1 and hMSH2. Their deficient expression renders the cell susceptible to the accumulation of many molecular defects, a condition which can be evaluated by the instability in sections of base repeats in the genoma known as microsatellite instability. The molecular detection of hereditary nonpolyposis colorectal cancer is possible in most of the highly suspicious cases. Genetic tests for hereditary nonpolyposis colorectal cancer also allow characterization of the individual that bears the mutation within a family. The high cost and restricted availability of these tests hamper their use for every person presenting colorectal cancer. Due to this fact, some clinical criteria have been developed by a hereditary nonpolyposis colorectal cancer international organization to select families with a high probability of carrying the mutation. Once families at risk are identified, they are encouraged to join a screening program that aims at early detection of hereditary nonpolyposis colorectal cancer-related cancers, increasing the possibility of its prevention and early detection.

Downstaging of a rectal gastrointestinal stromal tumor by neoadjuvant imatinib therapy allowing for a conservative surgical approach

Gastrointestinal stromal tumor (GIST) is a recently recognized pathology that originates from the interstitial cells of Cajal1 and is the most common mesenchymal neoplasm of the gastrointestinal tract. Although surgery is the only treatment available, it is only possible in approximately half of the cases2. This malignancy is characterized by a high risk of metastatic relapse, specifically in the liver and peritoneum. Imatinib mesylate, a tyrosine kinase inhibitor that inhibits c-kit signal transduction, is often used as a treatment for metastatic GIST. Neoadjuvant therapy is defined as a treatment administered prior to the main (usually surgical) treatment for a particular neoplasm. It is used not only to eliminate circulating tumor cells but also to reduce the size of the tumor, thereby facilitating surgery and perhaps increasing the chance of organ preservation. Since imatinib results in significant tumor shrinkage in at least 50% of treated patients,3,4 its use as a neoadjuvant treatment is logical.

Understanding the factors associated with reduction in the number of lymph nodes in rectal cancer patients treated by neoadjuvant treatment

IntroductionRectal cancer patients frequently present with locally advanced disease for which the standard of care includes neoadjuvant chemoradiotherapy followed by total mesorectal excision. Positive lymph nodes are one of the most powerful risk factors for recurrence and survival in colorectal cancer. In the absence of specific rectal guidelines, the literature recommends to the pathologist to optimize the number of rectal lymph nodes (LN) retrieved. We made a literature review in order to identify factors that could potentially affect the number of LN retrieved in specimens of patients with rectal cancer treated by chemoradiotherapy (CRT) followed by total mesorectal excision (TME).ResultsAge did not have a significant effect on LN yield. The effect of sex on LN number is not consistent in the literature. Most of the papers did not find a relationship between lower LN obtained and gender. Laparoscopy for primary rectal cancer is associated with a greater number of LN as well as short-term benefits. Tumors in the upper rectum are associated with a higher number of LN than those in the mid and lower rectum. The type of surgery had no effect on lymph node yield either. Tumors with complete or almost complete pathologic regression were exactly the ones with lower number of lymph nodes detected. Approximately one-third of patients with neoadjuvant treatment had less than 12 LN yield.ConclusionThe tumor regression grade is the most important factor for the decrease in the number of lymph nodes.

Pathologic complete response implies a fewer number of lymph nodes in specimen of rectal cancer patients treated by neoadjuvant therapy and total mesorectal excision

Studies have suggested that the use of neoadjuvant chemoradiation results in a lower lymph nodes yield in rectal cancer patients. OBJECTIVE To evaluate factors associated with less than 12 lymph nodes harvested on patients with rectal cancer treated with preoperative chemoradiotherapy followed by total mesorectal excision. PATIENTS This was a cohort/retrospective single cancer center study. Low and mid locally advanced rectal cancer or T2N0 under risk of sphincter resection underwent chemoradiotherapy followed by total mesorectal excision with curative intent. Chemotherapy consisted of 5-FU and leucovorin IV. Total dose of pelvic radiation was 5040 Gys. All patients were staged and restaged by digital rectal examination, proctoscopy, colonoscopy, CT of abdomen and chest, and MRI of the pelvis. Patients were stratified in two groups: ≥12 and < 12 L N retrieved. The possible factors affecting number of LN were analyzed. RESULTS 95 patients met the inclusion criteria. Mean LN harvest was 23.2 (3-67). 81 patients (85%) had ≥12 L N. Gender, age, tumor size, tumor stage, tumor location, length of specimen, presence of LN involvement, type of surgery, and surgical access showed no association with number of LN retrieved. Only pathological complete response showed a statistically significant association with <12 L N on univariate (p = 0.004) and multivariate analyses (p = 0.002). LIMITATIONS Data were collected retrospectively. The number of patients disparity between the two groups. CONCLUSIONS Complete pathologic response is associated with <12 L N harvested. Thus, the number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection in patients with pathologic complete response.

One-level step section histological analysis is insufficient to confirm complete pathological response after neoadjuvant chemoradiation for rectal cancer (vol 21, pg 745, 2017)

Unfortunately, one of the author name was wrongly published in the original publication. The complete correct name should read as follows “Beatriz Camargo Azevedo”. The original article was updated.

Prognostic factors affecting outcomes in multivisceral en bloc resection for colorectal cancer

OBJECTIVES: This study sought to determine the clinical and pathological factors associated with perioperative morbidity, mortality and oncological outcomes after multivisceral en bloc resection in patients with colorectal cancer. METHODS: Between January 2009 and February 2014, 105 patients with primary colorectal cancer selected for multivisceral resection were identified from a prospective database. Clinical and pathological factors, perioperative morbidity and mortality and outcomes were obtained from medical records. Estimated local recurrence and overall survival were compared using the log-rank method, and Cox regression analysis was used to determine the independence of the studied parameters. ClinicalTrials.gov: NCT02859155. RESULTS: The median age of the patients was 60 (range 23-86) years, 66.7% were female, 80% of tumors were located in the rectum, 11.4% had stage-IV disease, and 54.3% received neoadjuvant chemoradiotherapy. The organs most frequently resected were ovaries and annexes (37%). Additionally, 30.5% of patients received abdominoperineal resection. Invasion of other organs was confirmed histologically in 53.5% of patients, and R0 resection was obtained in 72% of patients. The overall morbidity rate of patients in this study was 37.1%. Ureter resection and intraoperative blood transfusion were independently associated with an increased number of complications. The 30-day postoperative mortality rate was 1.9%. After 27 (range 5-57) months of follow-up, the mortality and local recurrence rates were 23% and 15%, respectively. Positive margins were associated with a higher recurrence rate. Positive margins, lymph node involvement, stage III/IV disease, and stage IV disease alone were associated with lower overall survival rates. On multivariate analysis, the only factor associated with reduced survival was lymph node involvement. CONCLUSIONS: Multivisceral en bloc resection for primary colorectal cancer can be performed with acceptable rates of morbidity and mortality and may lead to favorable oncological outcomes.

Abstract 4845: VEGF-A and Cox-2 gene polymorphisms and susceptibility to colorectal cancer in Brazilian population.

Background: Brazilian population displays very high levels of genomic diversity due to the multi-ethnicity, which have important clinical/genomic implications. The vascular endothelial growth factor-A (VEGF-A) and Cyclooxygenase-2 (Cox-2) polymorphisms have been implicated in colorectal cancer (CRC) risk, however, the results on the association between polymorphisms and cancer risk are conflicting. VEGF and Cox-2 polymorphisms might modify the levels of mRNA and protein expression and may have a considerable influence on disease phenotype. Aim: We carried out a case-control study to evaluate whether polymorphisms of VEGF-A and Cox-2 genes modulate the risk of developing CRC. We also aimed to investigate possible interactions between these genetic variations and environmental factors in CRC. Methods: We evaluated VEGF-A and Cox-2 genotypes obtained from a series of 230 CRC patients and 194 controls from the Hospital-based Brazilian population. DNA was isolated from leukocyte using extraction and purification kit PureLink, followed by amplification by polymerase chain reaction (PCR). Real-time analysis was used for genotyping of polymorphisms of VEGF-A and Cox-2, through the TaqMan ® SNP Genotyping Assay. There was no difference between the cases and controls regarding gender, age, ethnicity, and no individual or familial history of cancer was found in control cases. Results: We determined frequencies of four VEGF-A biallelic polymorphisms (-2578C>A, -460T>C, -634G>C, +936C>T), with twelve genotypes; and three Cox-2 polymorphisms (-1195A>G, -765G>C, 8437T>C,) with nine genotypes. The genotypes frequencies were similar in both case and control groups, and there was, therefore, no association between these genotypes and CRC risk. A high frequency of the wild genotype Cox-2 -765GG and 8437TT and polymorphic genotype Cox-2 -1195GG and VEGF-A -634CC was found in an Asiatic (mostly Japanese) population. Moreover, VEGF-A -2578C>A, and -460T>C were associated to familial history of cancer in the cases series. Tobacco consumption was marginally associated to Cox-2 -1195A>G genotype. Conclusion: VEGF-A and Cox-2 gene polymorphisms are not associated with an increased risk of CRC in a Brazilian population. We could demonstrate the genotype differences among ethnicity, and the association of these polymorphisms with some risk-factors for CRC. Citation Format: Michele T. P. Tomitao, Marcia S. Kubrusly, Guilherme C. Cotti, Evelise P. Zaidan, Adriana V. Safatle-Ribeiro, Suely K. N. Marie, Ivan Cecconello, Sergio C. Nahas, Ulysses Ribeiro. VEGF-A and Cox-2 gene polymorphisms and susceptibility to colorectal cancer in Brazilian population. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4845. doi:10.1158/1538-7445.AM2013-4845