Metastatic malignant melanoma presenting as an appendiceal mucocele.

Melanoma metastatic to the appendix is extremely rare. Here we describe a case of a 31-year-old female from Bolivia with a remote history of metastatic malignant melanoma first diagnosed as a cutaneous malignant melanoma ten years prior to this presentation. The patient was being followed for a mucocele which on resection was found to be metastatic melanoma. "Mucocele" is a generic diagnosis that warrants further characterization and treatment.

Gq-linked NK(2) receptors mediate neurally induced contraction of human sigmoid circular smooth muscle.

BACKGROUND & AIMS: Because tachykinins have been identified as neurotransmitters in the guinea pig colon and human ileum, we examined a possible role of tachykinin receptors and neurokinin (NK) A in neurally induced contraction of human sigmoid colon circular muscle. METHODS: Muscle strips were stimulated electrically for 10 seconds. Single cells were isolated by enzymatic digestion and permeabilized by saponin. [(35)S]GTPgammaS binding was assayed with or without NKA for 5 minutes. Intracellular Ca(2+) was measured using Fura 2. RESULTS: In the presence of 100 micromol/L L-NNA, 100 micromol/L atropine did not affect electrical field stimulation (EFS)-induced contraction. A peptide NK(2)-receptor antagonist (NK-2ra) but not an NK(1) antagonist FK888 (1 micromol/L) eliminated EFS-induced contraction. NKA-induced contraction in muscle strips and single cells was virtually abolished by NK-2ra, but not by FK888. In permeabilized cells, contraction was blocked by Gq-protein antibodies, but not by other G-protein antibodies, suggesting that NKA activates Gq, which was confirmed by a [(35)S]GTPgammaS binding assay. NKA-induced contraction and increase in cytosolic Ca(2+) were abolished by depletion of intracellular Ca(2+) stores. CONCLUSIONS: Tachykinins may be the main excitatory neurotransmitters in human sigmoid circular muscle. NKA activates Gq-linked NK(2) receptors, which cause Ca(2+) release, followed by contraction.

Colostomy closure: impact of preoperative risk factors on morbidity.

The objective of this study was to stratify patients for colostomy closure into risk categories according to preoperative variables. This was a retrospective case series. Median follow-up was 82 months. A tertiary care academic medical center was the setting for this study. A study sample of 155 consecutive patients who underwent colostomy closure at a single institution between 1985 and 1995 were included in this study. The following preoperative variables were analyzed: indication for colostomy fashioning; age; gender; American Society of Anesthesiology (ASA) class; presence of cardiac, renal, or pulmonary dysfunctions; presence of diabetes mellitus; and immunosuppression. The occurrence of adverse outcome, as evidenced by postoperative morbidity and mortality, was used as the main outcome measure. Complications occurred in 49 patients (31.6%), including a 1.3 per cent mortality. There was a trend of increasing morbidity with increasing ASA class. The single factor that showed a statistically significant increase in morbidity was the presence of diabetes (P = 0.036). Predicted probabilities of complications for patients with ASA III with renal disease was 31 per cent, increased to 47.9 per cent if cardiac disease was also present and to 77 per cent with the addition of diabetes. The presence of diabetes carries an independent risk factor for adverse outcome in colostomy closure. This study provides information about stratification of postoperative risk based on commonly available preoperative variables. In the majority of cases, colostomy closure seems to carry a very acceptable complication rate. In selected patients with multiple preoperative risk factors, the morbidity becomes significantly higher.

Gastrointestinal malignancies in patients with celiac sprue.

BACKGROUND: Celiac sprue is a malabsorption disease, which carries an increased risk of gastrointestinal malignancy, often underestimated. The purpose of this study was to examine the management of patients with gastrointestinal neoplasms complicating celiac disease. PATIENTS AND METHODS: The pathology database at our institution was searched from 1986 to present; and the literature from 1966 to 1997 was reviewed to identify reports of celiac sprue complicated by malignancy. A total of 82 cases were available for analysis. RESULTS: Two thirds of patients had carried the diagnosis of celiac sprue for a mean of approximately 10 years. The remaining one third were diagnosed with celiac disease and gastrointestinal malignancy simultaneously. Jejunal T-cell lymphoma was the most common malignancy. There was also an increased frequency of small intestinal adenocarcinoma and squamous cell carcinoma of the esophagus. Prognosis was generally poor, related to the histologic type and stage of the disease. CONCLUSIONS: Gastrointestinal malignant neoplasms, especially small bowel lymphomas, can occur in patients with celiac sprue. Patients with known celiac disease who present with exacerbation of symptoms should be promptly investigated for occult gastrointestinal malignancies, and considered for early surgical exploration.

Mutated p53 gene is an independent adverse predictor of survival in colon carcinoma.

OBJECTIVE: To evaluate the impact of p53 gene mutations on long-term survival in patients with intermediate stage carcinoma of the colon. DESIGN: Retrospective cohort study; median follow-up of 87 months. SETTING: Tertiary care academic medical center. PATIENTS: Mutational analysis was conducted in a single institution in 141 consecutive patients with resected stage II (n = 71) and stage III (n = 70) colon carcinoma. Archival pathology specimens were analyzed for point mutations of exons from the p53 gene by means of amplification and direct sequencing by polymerase chain reaction. MAIN OUTCOME MEASURES: The impact of p53 mutations and of adverse histopathologic features (i.e., poor differentiation, lymphovascular invasion, or mucin production) on patient survival. RESULTS: Median overall survival was 64 months (95 months for patients with stage II and 34 months for patients with stage III colon carcinoma; P = .001). Presence of a p53 mutation was the single most important risk factor associated with poorer survival in both patients with stage II (P = .02) and stage III colon carcinoma (P = .006) throughout the follow-up period. A p53 mutation increased the risk of death by 2.82 times in patients with stage II and by 2.39 times in patients with stage III colon carcinoma. There was an additive effect on the cumulative risk of death between p53 mutations and adverse histopathologic variables. CONCLUSIONS: The presence of p53 mutations carries an independent adverse prognostic value in colon cancer. These findings imply that the applicability of mutational analysis in clinical practice is likely to affect therapeutic choices in the future.

Topographic genotyping of colorectal carcinoma: from a molecular carcinogenesis model to clinical relevance.

BACKGROUND: In recent years, as a result of refinement in molecular biology techniques, significant progress has been made in the understanding of colorectal carcinogenesis. Particular attention has been drawn to identification of genetic mutation that may predispose to colorectal carcinoma (familial syndromes) and may affect tumor behavior and prognosis (sporadic cases). CONCLUSIONS: Our method of topographic genotyping of human colonic carcinomas has shown a correlation between K-ras-2 and p53 mutations and stage at diagnosis as well as long-term survival. Data from other investigators in this field confirm the importance of genetic analysis of human colorectal tumors. These findings are likely to impact management by allowing a more individualized therapeutic approach.

Effects of lambda-carrageenan induced experimental enterocolitis on splenocyte function and nitric oxide production.

A lambda-carrageenan induced rat model of inflammatory bowel disease (IBD) allowed evaluation of progressive histopathological changes over time and comparison with human disease. In addition, this model was used to test the hypothesis that the immunosuppression observed in IBD may be mediated in part by augmented production of nitric oxide by splenic lymphocytes. Male Sprague-Dawley rats were fed standard rat chow and a drinking solution of 2% lambda-carrageenan without prior sensitization to the compound. At 2, 4, 6, and 8 weeks, small and large intestines were removed for histological examination, and splenocytes were assayed for response to various mitogens and for nitrite production. Intestinal lesions gradually developed in lambda-carrageenan fed rats and were found to be morphologically similar to those observed in human ulcerative colitis. The proliferative response of splenocytes to known mitogens was significantly diminished in carrageenan fed rats, when compared with pair-fed controls, but was fully restored when cultured in the presence of NG-monomethyl-L-arginine, a specific inhibitor of nitric oxide synthase. Preliminary data suggest that overproduction of nitric oxide may provide a molecular mechanism for the immunosuppression observed during chronic inflammatory bowel disease. Further characterization of a reproducible rat model of IBD will allow further investigation into the pathogenesis of the human disease.

Selective preservation of the anal transition zone in ileoanal pouch procedures.

PURPOSE: A prospective trial was conducted to evaluate use of certain preoperative criteria in the choice of operative technique for ileal pouch-anal anastomosis (IPAA). Handsewn vs. stapled anastomotic techniques were compared as was preservation vs. excision of the anal transition zone (ATZ). METHODS: Over an 18-month period, 40 consecutive patients underwent restorative proctocolectomy with IPAA for ulcerative colitis (31 cases) or familial adenomatous polyposis (9 cases). In 28 patients, ATZ was completely excised, by either a transanal mucosectomy with handsewn anastomosis (Group I, 13 cases) or by double-stapled technique (Group II, 15 cases). The ATZ was preserved and the anastomosis was double-stapled in colitis patients with suboptimum sphincter function and/or greater than 50 years of age in the absence of dysplasia or severe distal proctitis (Group III, 12 cases). RESULTS: Groups I and II patients were homogeneous in their preoperative variables and had equivalent functional outcome. Group III patients were older (P = 0.0001), with weaker preoperative anal sphincter resting tone (P = 0.024). Compared with Groups I and II, patients in Group III had significantly greater 24-hour stool frequency (P = 0.0056), daytime stool frequency (P = 0.0125), and incidence of daytime fecal seepage (P = 0.007). There was no significant difference in other outcome variables in Group III patients. There was no difference in morbidity in the three groups. CONCLUSIONS: Transanal mucosectomy with handsewn anastomosis provided early functional results equivalent to low anal transection with double-stapled IPAA in younger patients with excellent preoperative sphincter function. A double-stapled technique with preservation of the ATZ may be reserved for older patients, with poorer anal sphincter function, at minimum dysplasia/cancer risk, to optimize continence figures.

Peritoneal silicosis.

A 73-year-old man with a clinical diagnosis of pulmonary silicosis (long-standing exposure to silica, pulmonary infiltrates, and flu-like symptoms) presented to the emergency room with fever, acute biliary colic, and cholelithiasis. The patient had a 2-year status postchemotherapy with complete remission of hepatic and splenic malignant lymphoma. At laparotomy we found studding of the undersurface of the diaphragm with multiple small dark nodules. Owing to the patient's history of previously treated abdominal malignant lymphoma, the lesions were grossly interpreted as abdominal lymphomatosis. The microscopic appearance of the lesions suggested silicotic nodules, which were confirmed by digital scanning electron microscopy and roentgenographic microanalysis performed on formalin-fixed, paraffin-embedded tissue. This is an unusual extrapulmonary pattern of peritoneal seeding in silicosis.

Prognostic value of TP53 and K-ras-2 mutational analysis in stage III carcinoma of the colon.

BACKGROUND: Genetic mutations involving oncogenes and tumor-suppressor genes occur in carcinogenesis, and may affect biologic behavior of neoplasms. In this study, we analyzed the prognostic value of mutational analysis in colon carcinoma. PATIENTS AND METHODS: Archival pathology specimens from 70 consecutive patients, resected for stage III colon carcinoma, were analyzed for point mutations by amplification and direct sequencing of exons from the K-ras-2 and the TP53 genes (topographic genotyping). Mutations were compared with adverse histopathologic features (poor differentiation, vascular and lymphatic invasion, mucin production) as prognostic markers. RESULTS: Five-year survival was 75% in patients with nonmutated lesions, significantly lower (21%) with TP53 mutations (P = 0.01), and intermediate with K-ras-2 only (45%) or both K-ras-2 and TP53 mutations (36%). A TP53 mutation carried the highest relative risk of death (2.39; 95% confidence interval, 1.29 to 4.42; P = 0.006). There was an additive effect on the risk of death between TP53 mutations and adverse histopathologic features. CONCLUSIONS: The information derived from mutational analysis is creating new prognostic variables that may play a role in the choice of therapy for colorectal carcinoma.

Malignant potential in intestinal juvenile polyposis syndromes.

BACKGROUND: Unlike familial polyposis coli, where the premalignant nature of adenomatous polyps is well established, the cancer risk in juvenile polyposis has generally been considered not increased. METHODS: This study reviews all cases of juvenile polyposis reported in the English language to date to assess the occurrence and prognosis of carcinoma in the gastrointestinal tract. RESULTS: A total of 218 patients met the inclusion criteria. Mean age at diagnosis was 18.5 years (range: 9 months to 67 years). No gender preference was identified. The most common presenting symptom was chronic anemia, followed by acute gastrointestinal bleeding, rectal prolapse of polyp, protein-losing enteropathy, and intussusception. A family history of juvenile polyposis could be established in approximately 50% of patients, and associated congenital malformations were detected in 15%. Ninety-nine patients underwent 138 gastrointestinal operations: 121 colorectal, 12 gastric, and 5 small intestinal procedures. The development of a gastrointestinal carcinoma was reported in 36 cases (17%). Mean age at diagnosis of carcinoma was 35.5 years (range: 4-60 years). Most malignancies were located in the distal colon and rectum, with only one case of gastric and one case of duodenal carcinoma. Tumor stage at diagnosis was usually advanced, with poor survival figures. CONCLUSIONS: This study shows that juvenile polyposis syndromes carry a more significant risk of carcinoma than generally appreciated. Therefore, more intense endoscopic surveillance may be warranted, and definitive surgical options should often be considered in these syndromes.

Malignant transformation of benign mesenteric cyst.

We describe the clinical and pathological features of a case of mesenteric cyst which was incompletely excised, recurred over several years, and eventually underwent malignant transformation. A review of the literature shows how mesenteric cysts are still poorly understood clinical entities, often difficult to classify even after histopathological evaluation. This is the first reported case of transformation of a benign mesenteric cyst into adenocarcinoma. Complete excision of all mesenteric cysts should be carried out, to prevent recurrence and possible malignant transformation.

Factors affecting prognosis and management of carcinoma of the colon and rectum in patients more than eighty years of age.

BACKGROUND: The safety and efficacy of operations for gastrointestinal diseases in very elderly patients has been a matter of debate in recent years. STUDY DESIGN: One hundred seventy-seven instances of carcinoma of the colon and rectum in patients more than 80 years of age who wee surgically treated between 1961 and 1987 were reviewed. They were compared with 623 similar instances in patients younger than 80 years of age who were treated during the same time period. RESULTS: Octogenarians and nonagenarians significantly more often displayed obstruction or perforation, elevated preoperative carcinoembryonic antigen, right-sided lesions, and solitary hepatic metastases, when present. Patients more than 80 years of age received adjuvant chemotherapy or radiotherapy less often. Carcinoma recurrence in very elderly patients implied a very poor prognosis, with only a 4 percent salvage rate. The actuarial five year survival rate was 32 percent for the older patients and 48 percent in the younger group (p < 0.05). There was no significant difference in operative mortality between the two groups. CONCLUSIONS: In general, age alone should not alter treatment strategy in patients with carcinoma of the colon and rectum.

Surgery for radiation injury to the large intestine. Variables influencing outcome.

PURPOSE: Surgery for colorectal radiation injury is technically difficult and often followed by complications. This study evaluates factors affecting outcome. METHODS: A retrospective 30-year review was carried out. Preoperative characteristics and operative variables were correlated with morbidity, mortality, and success in providing symptomatic relief. RESULTS: A total of 60 cases and 75 colon and rectal lesions were analyzed. After surgery, the morbidity rate was 65 percent, and the mortality was 6.7 percent. A successful outcome in providing symptomatic relief was achieved in 71.7 percent of cases. When comparing success after operations for the different lesions (stricture, 78.1 percent; hemorrhage, 64.3 percent; perforation, 100 percent; and fistula, 54.5 percent), the presence of a fistula was associated with symptomatic relief significantly less often than the remainder (P = 0.03). The type of operation had no effect on success rate: 72 percent for diversion, 66.7 percent for resection, and 83.3 percent for bypass. Morbidity and mortality rates were not significantly influenced by site of lesions, type of lesions, or choice of surgical operation. A permanent stoma was necessary in 70 percent of patients. CONCLUSIONS: The morbidity for surgical treatment of large bowel radiation injury is substantial, and largely unrelated to the type and location of the radiation lesion, as well as the type of operation. Success rates are reasonably high, but worst after fistula repair. The selection of therapy (medical, endoscopic, surgical) for radiation-induced colorectal lesions must take into account numerous factors and be highly individualized.

K-ras-2 topographic genotyping of pancreatic adenocarcinoma.

OBJECTIVE: To determine the frequency distribution of K-ras-2 point mutation genotypes in pancreatic adenocarcinoma and to evaluate the effectiveness of K-ras-2 genotyping as a means to predict localized disease and potential long-term survival. DESIGN: Topographic genotyping from archival formalin-fixed, paraffin-embedded large- and biopsy-sized tissue specimens as well as cytologic fluid using polymerase chain reaction products and direct sequencing together with clinicopathologic and statistical analysis. SETTING: Tertiary care medical center with molecular diagnostics pathology laboratory. PATIENTS: Patients treated between 1988 and 1993 at Rhode Island Hospital, Providence, yielding 55 primary and 56 metastatic specimens of pancreatic adenocarcinoma. RESULTS: Each primary pancreatic adenocarcinoma was found to contain one of eight specific genotypes that was maintained in all metastatic deposits of that individual tumor. Primary adenocarcinomas confined to the pancreatic bed at diagnosis were predominantly of a normal genotype (56% [14/25]). Pancreatic adenocarcinomas progressing to distant hematogenous metastasis were almost exclusively mutated (88% [7/8]; P < .005). Patients undergoing pancreatic resection (Whipple's operation) and having a normal K-ras-2-genotype (58% [11/19]) had a significantly longer survival (21.3 months) than similar patients with mutated tumors (8.2 months). CONCLUSIONS: The findings support the feasibility of K-ras-2 topographic genotyping to identify potentially indolent disease and suggest a potentially useful role in the preoperative evaluation of pancreatic adenocarcinoma.