Risk factors for advanced duodenal and ampullary adenomatosis in familial adenomatous polyposis: a prospective, single-center study.

BACKGROUND AND STUDY AIMS: To determine the clinical features associated with advanced duodenal and ampullary adenomas in familial adenomatous polyposis. Secondarily, we describe the prevalence and clinical significance of jejunal polyposis. PATIENTS AND METHODS: This is a single center, prospective study of 62 patients with familial adenomatous polyposis. Duodenal polyposis was classified according to Spigelman and ampullary adenomas were identified. Patients with Spigelman III and IV duodenal polyposis underwent balloon assisted enteroscopy. Predefined groups according to Spigelman and presence or not of ampullary adenomas were related to the clinical variables: gender, age, family history of familial adenomatous polyposis, type of colorectal surgery, and type of colorectal polyposis. RESULTS: Advanced duodenal polyposis was present in 13 patients (21 %; 9 male) at a mean age of 37.61 ±â€Š13.9 years. There was a statistically significant association between family history of the disease and groups according to Spigelman ( P  = 0.03). Seven unrelated patients (6 male) presented ampullary adenomas at a mean age of 36.14 ±â€Š14.2 years. The association between ampullary adenomas and extraintestinal manifestations was statistically significant in multivariate analysis ( P  = 0.009). Five endoscopic types of non-ampullary adenoma were identified, showing that lesions larger than 10 mm or with a central depression presented foci of high grade dysplasia. Among 28 patients in 12 different families, a similar Spigelman score was identified; 10/12 patients (83.3 %) who underwent enteroscopy presented small tubular adenomas with low grade dysplasia in the proximal jejunum. CONCLUSIONS: Advanced duodenal polyposis phenotype may be predictable from disease severity in a first-degree relative. Ampullary adenomas were independently associated with the presence of extraintestinal manifestations.

Early mobilization programme improves functional capacity after major abdominal cancer surgery: a randomized controlled trial.

Background: Major abdominal oncology surgery is associated with substantial postoperative loss of functional capacity, and exercise may be an effective intervention to improve outcomes. The aim of this study was to assess efficacy, feasibility and safety of a supervised postoperative exercise programme. Methods: We performed a single-blind, parallel-arm, randomized trial in patients who underwent major abdominal oncology surgery in a tertiary university hospital. Patients were randomized to an early mobilization postoperative programme based on supervised aerobic exercise, resistance and flexibility training or to standard rehabilitation care. The primary outcome was inability to walk without human assistance at postoperative day 5 or hospital discharge. Results: A total of 108 patients were enrolled, 54 into the early mobilization programme group and 54 into the standard rehabilitation care group. The incidence of the primary outcome was nine (16.7%) and 21 (38.9%), respectively (P=0.01), with an absolute risk reduction of 22.2% [95% confidence interval (CI) 5.9-38.6] and a number needed to treat of 5 (95% CI 3-17). All patients in the intervention group were able to follow at least partially the exercise programme, although the performance among them was rather heterogeneous. There were no differences between groups regarding clinical outcomes or complications related to the exercises. Conclusions: An early postoperative mobilization programme based on supervised exercises seems to be safe and feasible and improves functional capacity in patients undergoing major elective abdominal oncology surgery. However, its impact on clinical outcomes is still unclear. Clinical trial registration: NCT01693172.

Erratum to: One-level step section histological analysis is insufficient to confirm complete pathological response after neoadjuvant chemoradiation for rectal cancer.

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.

One-level step section histological analysis is insufficient to confirm complete pathological response after neoadjuvant chemoradiation for rectal cancer.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) for rectal cancer may lead to cure. As we currently lack reliable methods to clinically confirm the absence of disease, some patients undergo radical resection and have pathological complete response (pCR) still undergo surgery. Furthermore, it is uncertain if conventional one-level histopathological analysis is accurate enough to determine complete response. Confirming pCR is essential to determine the prognosis and to consider the patient's inclusion in trials of adjuvant therapy. The aim of this study was to determine whether the current 1-level approach is sufficient to confirm pCR. METHODS: Four hundred and thirty-five patients with rectal cancer who received nCRT followed by radical resection were analyzed. All cases identified as pCR by 1-level step section histological evaluation were reassessed with 3-level step sections and immunohistochemical analysis to verify the presence of residual disease. RESULTS: Out of 435 patients, 75 (17.2%) were staged as ypT0. Of these, 6 had lymph node involvement and 1 had distant metastasis, leaving 68 (15.6%) who had pCR. After the additional step sections, residual tumor was detected in 12 (17.6%) of these 68. The final pCR rate was 12.9%. Distant recurrence was detected in 7.1% of real-pCR patients compared to 16.7% in the false-pCR group (p = 0.291). Sensitivity of clinical assessment for detecting pCR was 35.7%, and the accuracy of 1-section histological evaluation to identify pCR was 82.4%. CONCLUSIONS: Histopathological analysis with 1-level step section is insufficient to determine complete tumor eradication. The 3-level sections methodology revealed residual tumor cells in patients initially classified as ypT0. Further studies with larger sample size are required to verify the clinical relevance of these residual tumor cells. Caution should continue to be applied to watch and wait strategies following nCRT.

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

INTRODUCTION: Rectal 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). RESULTS: Age 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. CONCLUSION: The tumor regression grade is the most important factor for the decrease in the number of lymph nodes.

Gastric secretory and hormonal patterns in end-stage chagasic achalasia.

Achalasia surgical treatment alters the esophagogastric junction anatomy (cardiomyotomy plus fundoplication or esophagectomy and gastric pull-up), thus favoring a certain degree of gastroesophageal reflux. Gastric secretory and hormonal functioning is not completely known in chagasic patients. The aim of this study was to evaluate the gastric secretory and hormonal response in patients with end-stage chagasic achalasia compared with normal subjects. Gastric secretion and hormonal response were assessed by estimation of gastric acid secretion (GAS) in basal condition and after pentagastrin stimulation, basal serum gastrin, and serum pepsinogen (SP) in basal condition and after betazole hydrochloride (Histalog; Eli Lilly and Company, Indianapolis, IN, USA) stimulation in 27 patients with chagasic achalasia. The results were then compared with those of 24 normal subjects. In the chagasic group, the mean basal and stimulated GAS were significantly lower than in the control group (basal: 1.277 vs. 3.13, P = 0.002; stimulated: 15.9 vs. 35.8, P = 0.0001). Chagasic patients' SG levels showed a significantly higher basal value than the control group (83.3 vs. 36.8, P = 0.0001). There was a significant increase of SP after stimulation compared with the basal levels in both chagasic and control groups. Although the chagasic patients' SP values were higher than the controls, this difference was not statistically significant, either in basal and stimulated conditions (basal: 122.0 vs. 108.9, stimulated 120 min: 177.1 vs. 158.9). In patients with chronic Chagas' disease (ChD), although autonomic denervation does not suppress the strength of the gastric mucosal cells' secretory response to stimulation, it reduces GAS (parietal cell) without, however, affecting SP production (chief cells). On the other hand, the gastrin-producing cells have continuously been stimulated by low GAS.

Evaluation of molecular markers in hepatic metastasis of colorectal adenocarcinoma.

BACKGROUND/AIMS: There were 49 patients studied, coming from The Liver Unit at the "Hospital das Clinicas da Faculdade de Medicina da USP (N=41) and from "Prof. Dr. Angelita Habr-Gama and Joaquim Gama-Rodrigues Surgery Institute", SP (N=8); all of which had hepatic metastasis of colorectal adenocarcinoma, with no evidence of concurrent metastasis in any other organs and were submitted to surgical treatment, during the period of 1992 to 2002, with the aim of analyzing the immunoexpression of the p53, ki-67, p16 and molecular markers in order to relate the disease-free period with the prognosis. METHODOLOGY: The patient's clinical data were analyzed retrospectively for verification of information such as age, gender, size of the hepatic metastasis and/or the largest lesion, number of satellite nodules resected and compromised, margin of resection free from neoplasia. RESULTS: The immunoexpression of the p53 was associated with the shortest period of life free from disease (p = 0.04). The proliferation marker ki-67 was not associated with the reduction of the disease-free interval and survival; the immunoexpression of the proliferation marker p16 was not associated with the reduction of disease-free period and survival, however, it was associated with hepatic metastasis synchronism. In patients who received postoperative systemic chemotherapy with 5-FU and leucovorin, the immunoexpression on the hepatic metastasis was not associated with a longer disease-free interval. CONCLUSIONS: Molcular markers may be useful to evaluate hepatic metastasis of colorectal Adenocarcinoma.

Interleukin-2-activated natural killer cells may have a direct role in the control of Leishmania (Leishmania) amazonensis promastigote and macrophage infection.

To study the role of Natural Killer (NK) cells in Leishmania infection, peritoneal macrophages from BALB/c mice were infected with Leishmania (Leishmania) amazonensis promastigotes and incubated with interleukin-2 (IL-2)-activated NK (A-NK) cells at different ratios of A-NK cells to infected macrophages (5:1, 1:1, 0.2:1). The A-NK cells were added either together with the parasites (0-h group) or 24 h later (24-h group). Morphological studies of the cultures revealed predominance of parasitic debris within macrophages that were in close contact with A-NK cells and the decrease in parasite recovery was directly proportional to the A-NK cell concentration used. Interferon-gamma (IFN-gamma) and IL-12 were detected in the supernatant at levels proportional to the A-NK cell concentration used. No significant difference was observed between the groups with respect to NO levels in the culture supernatant. When A-NK cells were added directly to the L. (L.) amazonensis promastigote cultures, the parasite recovery decreased proportional to the number of A-NK cells added. In vivo studies demonstrated smaller lesion sizes in animals inoculated with both parasites and A-NK cells compared with parasites alone. Histopathology of the skin lesions from animals receiving A-NK cells together with the parasites showed moderate parasitism and a nodular inflammatory infiltrate formed by mononuclear cells and a few vacuolized macrophages. In contrast, animals inoculated only with the parasites showed a highly parasitized dermis with infiltration of intensely vacuolized macrophages. These results demonstrate the role of A-NK cells in parasite lysis and in resistance of macrophages to L. (L.) amazonensis in the early phase of infection.

Cell-mediated immune response in megacolon from patients with chronic Chagas' disease.

PURPOSE: The mechanisms that control chronic infection in vivo and the immunologic mechanisms involved in the pathogenesis of chagasic megacolon are not completely characterized. Although autoimmunity may play a role in the pathogenesis of Chagas' disease, recent studies, both in mice and in humans, suggest a positive association of tissue parasitism, inflammation, and severity of lesions. The aim of this study was to evaluate the role of inflammatory cells and the subclasses of lymphocytes involved in neuropathic lesions in the colon of patients who underwent resection for advanced megacolon. METHODS: Specimens from 23 patients were selected based on histopathologic analysis. Paraffin-embedded tissue blocks were sectioned and evaluated by immunohistochemistry for cluster of differentiation 3, cluster of differentiation 8, cluster of differentiation 20, and natural killer cell antibodies by an avidin-biotin peroxidase method. RESULTS: Almost all myenteric plexuses were damaged, characterized by degenerative changes, necrosis of ganglion cells, and inflammatory response. Mild lymphocytic infiltration around degenerated and normal ganglion cells was observed in all cases. Collagen fibers and mononuclear cells surrounded some ganglion cells. Most of the inflammatory cells were lymphocytes, identified as cluster of differentiation 3-positive cells. Cluster of differentiation 8-positive lymphocytes were associated with degenerated ganglion cells. Natural killer cell antibodies were detected in a lower proportion of cells and were distributed between muscle layers or in proximity to the myenteric plexus. All these findings were also observed in the submucosal plexus. Cluster of differentiation 20-positive lymphocytes were not present in muscle layers or in the vicinity of either plexus. CONCLUSION: Pathogenesis of the megacolon is based on a continuous process of ganglion cell damage with participation of T lymphocytes expressing cluster of differentiation 8 and natural killer cell membrane antigens. B lymphocytes do not take part in the chronic inflammatory reaction.

Prognostic significance of intraperitoneal free cancer cells obtained by laparoscopic peritoneal lavage in patients with gastric cancer.

Laparoscopy is a safe and useful method for examining the local extent and regional spread of disease in patients with gastric cancer. Peritoneal dissemination remains a frequent type of recurrence after surgical treatment. The aim of this study was to determine the prognostic value of intraperitoneal free cancer cells (IFCCs) detected by laparoscopic peritoneal lavage. Forty-nine patients with advanced gastric cancer underwent laparoscopy with cytologic examination for staging. Peritoneal lavage was performed when ascites was not present. Aspirated fluid from the peritoneal cavity was centrifuged and subjected to cytologic examination using Giemsa and Papanicolaou staining methods. Patients were surgically treated and followed for a minimum of 5 years. IFCCs were detected in 41% of the patients. In eight cases (16.3%) laparoscopy revealed carcinomatosis and/or multiple liver metastases, so laparotomy was not performed. Patterns of recurrence after curative resection included the following: peritoneal (n = 3), local (n = 4), liver (n = 1), and other (n = 1). All patients who tested positive for IFCCs had peritoneal recurrence. The absence of IFCCs was associated with improved overall survival (21 months for a 95% confidence interval of 7.4 to 34.6 vs. 4 months for a 95% confidence interval of 2.4 to 5.6). Overall survival adjusted for type of resection also demonstrated a favorable outcome for patients who were negative for IFCCs. The following conclusions were drawn: (1) laparoscopic peritoneal lavage cytology may be useful in identifying patients at high risk for peritoneal relapses and may alter treatment, and (2) lFCCs provide additional prognostic information in patients with gastric cancer.

Low rectal cancer: impact of radiation and chemotherapy on surgical treatment.

INTRODUCTION: The aim of this study was to evaluate the impact of combined radiotherapy and chemotherapy (leucovorin and 5-fluorouracil) on the treatment of potentially resectable low rectal cancer using the following end points: 1) toxicity of this combined modality regimen; 2) clinical and pathologic response rate and local control; 3) down-staging of the tumor and its influence on the number of sphincter-saving operations; 4) disease-free interval, patterns of relapse, and overall survival. METHODS: From 1991 to 1996, 118 patients with potentially resectable cases of histologically proven adenocarcinoma and no distant metastases were enrolled into this protocol. All patients were evaluated by clinical and proctologic examination, abdominal computed tomography, transrectal ultrasound, and chest radiography. Therapy consisted of 5,040 cGy (6 weeks) and concurrent leucovorin (20/mg/m2/day) with bolus doses of 5-fluorouracil administered intravenously at 425 mg/m2/day for three consecutive days on the first and last three days of radiation therapy. After two months, all patients underwent repeat evaluation and biopsy of any suspected residual lesions or scar tissue. RESULTS: Median follow-up was 36 months. Toxicity of chemotherapy regimen was minimum. Thirty-six patients (30.5 percent) were classified as being complete responders. In six of these patients, complete response was confirmed by the absence of tumor in the surgical specimens (3 abdominoperineal resections and 3 proctosigmoidectomies with coloanal anastomosis). In the remaining 30 patients, confirmation of a complete response was made by the absence of symptoms, negative findings on physical examination, and biopsy, transrectal ultrasound, and pelvic computed tomographic test results during follow-up. Eighty-two patients (69.4 percent) were considered incomplete responders. Residual lesions had already been identified during the first examination in 74 patients. In the other eight patients, residual tumor was only identified after 3 to 14 months. All patients underwent surgical treatment, except one patient who refused surgery. Eighty-seven patients underwent 90 surgical procedures: local excision, 9; coloanal anastomosis, 36; abdominoperineal resection, 4; Hartmann's procedure, 1. Isolated local recurrences occurred in five patients (4.3 percent) and combined local and distant failure in eight patients (6.7 percent). Ninety patients are alive and disease-free at a median follow-up of 36 months. CONCLUSIONS: Combined up-front chemoradiotherapy was associated with tolerable and acceptable side effects. A significant number of patients had complete disappearance of their tumors (30.5 percent) within a median follow-up of 36 months. This regimen spared 26.2 percent of patients from surgical treatment and allowed sphincter-saving management in 38.1 percent of patients who may have required abdominoperineal resection. Preliminary results of this trial suggests a reduction in the number of local recurrences and reinforces the concept that infiltrative low rectal cancer may be initially treated by chemoradiotherapy.

Value of peritoneal lavage cytology during laparoscopic staging of patients with gastric carcinoma.

Forty-nine consecutive patients with advanced gastric carcinoma underwent preoperative staging by laparoscopy between June 1991 and June 1992. Peritoneal lavage with cytologic examination was performed when ascites was not present. In eight cases (16.3%), laparoscopy revealed carcinomatosis and/or multiple hepatic metastases, so laparotomy was not performed. Intraperitoneal free cancer cells (IFCCs) were detected in 41% of patients (65% in patients with ascites and 28% by peritoneal lavage). In the absence of macroscopic peritoneal dissemination, IFCCs were encountered in 29% of patients. IFCCs were present only when invasion of the gastric serosa was >3 cm2 or when adjacent organs and structures were already invaded. Mucinous adenocarcinoma, Borrmann class IV tumors, and Stage IV patients had higher incidence of IFCCs. Cytologic results were similar at laparoscopy and laparotomy (p > 0.05). Therefore, cytologic evaluation of peritoneal lavage added sensitivity to laparoscopy in assessing patients with advanced gastric carcinoma and may alter their therapeutic approach.