Management of Cushing's syndrome secondary to adrenal adenoma during pregnancy.

This report discusses our experience with two patients who had unilateral adrenalectomy during pregnancy as treatment for Cushing's syndrome secondary to an adrenal adenoma. Previously only five patients with this clinical problem who underwent unilateral adrenalectomy during pregnancy had been reported. We have reviewed the world literature on Cushing's syndrome in pregnancy secondary to an adrenal adenoma. A total of 19 patients who had unilateral adrenalectomy for this problem after the completion of pregnancy were identified. The review of world literature and the two patients who are the subject of this report were the basis of our analysis of fetal death, neonatal complications, and maternal complications in seven pregnancies during which unilateral adrenalectomy was performed (group 1) compared to the 19 pregnancies that were associated with unilateral adrenalectomy at the completion of pregnancy (group 2). Of the seven pregnancies in group 1, one fetal death and no neonatal complications occurred, but fetal death and neonatal complications occurred in 12 of the 19 pregnancies in group 2. Four of the seven mothers in group 1 had complications; 16 of the 19 mothers in group 2 had complications. This study suggests that adrenalectomy during pregnancy should be considered as a therapeutic option in the management of Cushing's syndrome secondary to an adrenal cortical adenoma.

Extraorbital sebaceous carcinoma.

Although sebaceous carcinoma constitutes 1% to 5.5% of all malignant neoplasms of the eyelid, less than 100 cases arising in extraorbital sites have been reported. We treated two cases of extraorbital sebaceous carcinoma arising in anatomic regions never previously reported, to our knowledge. These tumors occur generally in older patients and affect both sexes equally. No clinical features are characteristic of the tumor, but larger skin lesions should be approached with suspicion. Appropriate histopathologic identification is particularly important in the differential diagnosis. Radical surgery is the only effective treatment for this rare tumor, which can recur locally or produce lymph node and even distant metastases.

Surgical repair of esophageal perforation due to pneumatic dilatation for achalasia. Is myotomy really necessary?

Esophageal perforation is a rare complication of pneumatic dilatation for achalasia. The few clinical series reported in the literature recommend, under most circumstances, esophageal repair combined with esophagocardiomyotomy. However, the superiority of this technique over repair alone has never been proven. We reviewed our experience, since 1979, with six operative cases of esophageal perforation from pneumatic dilatation for achalasia. After débridement, the esophagus was repaired and, if possible, buttressed with a gastric fundal patch. There was only one late postoperative death due to sepsis and one upper gastrointestinal bleeding complication in our series. Follow-up (1 to 12 years) revealed no dysphagia in any of the five surviving patients and mild gastroesophageal reflux in two. From a review of the literature we found no reports of similarly treated patients experiencing recurrent symptoms of achalasia. In these acutely ill patients, our operative strategy is more feasible than repair and esophagocardiomyotomy and equally effective.

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.

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.

Mammographic localization and biopsy of nonpalpable breast lesions. A 5-year study.

A malignancy rate of 24% was achieved as a result of needle localizations and biopsies of 548 nonpalpable mammographically detected breast lesions in 507 consecutive patients during a 5-year period. Malignancy was present in 74 (23.8%) of 311 irregular soft-tissue densities, in 40 (19.6%) of 204 cases with clustered microcalcifications, and in 33 cases (54.5%) when both features were present. Same-day admission and discharge were achieved in 491 patients and local anesthesia supplemented with intravenous sedation was used in 73 (74%) of the 98 patients (in 1989) by the end of the study period. Nonpalpable cancers were categorized pathologically as stage 0 in 25 patients (20.8%), stage I in 67 patients (55.8%), stage IIA in 24 patients (20.0%), and stage IIB in four patients (3.3%). The malignancy rate rose sharply from the fourth to the fifth decade.

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.

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.

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.

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.

Decompression after gastric surgery. Gastrostomy versus nasogastric tube.

The efficacy and associated morbidity and mortality of gastrostomy (G) versus nasogastric (NG) tube decompression after gastric surgery were analyzed in a review of 100 patients. Age, sex, and risk factors were homogeneously distributed between the two groups, while perforated ulcers and emergency operations were more common in the G group. A gastrostomy did not completely eliminate the need for NG tube decompression in the G group. Postoperative morbidity was similar in the two groups, with the exception of an increased incidence of atelectasis in the elective NG group and increased mortality in the emergency G group. There was also a significant increase in length and cost of hospitalization in the emergency G group compared with emergency NG patients. Gastrostomy does not appear to offer any significant advantage over nasogastric decompression after gastric surgery and should be limited to special cases.

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.

Necrotizing fasciitis as a complication of chickenpox.

Necrotizing fasciitis is a rapid, potentially fatal soft tissue infection. Chickenpox is a common childhood illness not usually associated with severe complications. We present the case of an 8-year-old girl with necrotizing fasciitis of the upper back arising from superinfection of varicella skin lesions. Necrotizing fasciitis may have devastating sequelae, including septic shock, which mandate vigorous fluid resuscitation, appropriate antimicrobial therapy, and early aggressive surgical debridement.

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.

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.

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.