Prophylactic total gastrectomy (PTG) for hereditary diffuse gastric cancer (HDGC): the Newfoundland experience with 23 patients.

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) results from truncating mutations of the CDH1 (E-cadherin) gene. It is an autosomal dominant cancer susceptibility syndrome with a lifetime risk of diffuse gastric cancer (DGC) of 60-80%, with a mean age of onset of 37 years. There exists no adequate screening test for DGC. Early intramucosal diffuse/signet-ring cell carcinomas have been found in prophylactic total gastrectomy (PTG) specimens following normal preoperative endoscopy. Total gastrectomy has been advocated on a prophylactic basis. The aim of this study was to report our experience with PTG in 23 patients from the Canadian province of Newfoundland and Labrador. This is the largest series worldwide. METHODS: A retrospective study of consecutive patients undergoing PTG for HDGC was performed. All patients were confirmed to have a truncating mutation of the CDH1 gene. RESULTS: Twenty-three patients underwent PTG between February 2006 and November 2008. Major complications were found in 4/23 patients (17%), with no mortality. Two of 23 patients (9%) had positive mucosal biopsies on preoperative EGD. Twenty-two of 23 patients (96%) had evidence of diffuse/signet-ring carcinoma on final standardized pathological evaluation. Therefore, 21/23 (91%) were not picked up by preoperative EGD screening. CONCLUSIONS: PTG can be performed in patients with HDGC with a low rate of serious complications. Methods of reconstruction incorporating a pouch reservoir and preservation of the postgastric branches of the vagus nerves need to be explored. More refined penetrance estimates, effective screening protocols, and long-term psychological and functional outcomes following PTG require organized multicenter collaborative efforts.

Mucinous cystadenoma of the appendix in a patient with systemic lupus erythematosus.

A 38-year-old female with systemic lupus erythematosus presented with abdominal pain, diarrhea and iron-deficient anemia. Computed tomogram showed a 2 x 4 cm inhomogeneous lesion of the right adnexa. An unusual mass was identified extending from the appendiceal orifice at colonoscopy, and an 8 cm tubular appendix, apparently prolapsed into the cecum, was identified at celiotomy. An appendectomy with cecectomy was performed. On cut section, mucin was extruded from the lumen of the appendix. A mucinous neoplasm of the appendix with mucinous dissection to the serosal surface was reported at the time of frozen section. No gross ovarian pathology or peritoneal implants were noted. Cystadenoma with associated mucocele formation was verified by permanent histology. Mucocele of the vermiform appendix is a rare condition associated with neoplastic transformation in approximately 75% of all cases. Benign mucinous cystadenoma of the appendix should be differentiated from cystadenocarcinoma by frozen section at the time of celiotomy to ensure appropriate treatment. While systemic lupus erythematosus can lead to cutaneous mucinosis, an association with mucinous cystadenoma of the appendix has not been previously reported. Surveillance for metachronous colonic neoplasms is warranted in patients diagnosed with a mucinous neoplasm of the appendix.

Hamartomatous polyposis syndromes: molecular genetics, neoplastic risk, and surveillance recommendations.

UNLABELLED: Hamartomatous polyposis syndromes are characterized by an overgrowth of cells or tissues native to the area in which they normally occur. Juvenile polyposis syndrome (JPS) results from germ-line mutations in the SMAD-4 gene (18q21.1) that encodes for an enzyme involved in transforming growth factor beta(TGF-beta) signal transduction. The increased neoplastic risk may result from SMAD-4 mutations in the stromal component, which stimulate epithelial dysplasia and progression to invasive malignancy. Peutz-Jeghers syndrome (PJS) is associated with germ-line mutations in the LKB1 gene (19p13.3) that encodes a multifunctional serine-threonine kinase. These mutations occur in the epithelial component, suggesting a direct tumor suppressor effect. Patients are at an increased risk of intestinal and extraintestinal malignancies, including breast, pancreatic, ovarian, testicular, and cervical cancer. Cowden's disease is associated with germ-line mutations in the PTEN gene (10q22-23) and an increased risk of breast and thyroid malignancies. Ruvalcaba-Myhre-Smith syndrome is less common; controversy suggests that it may represent a variant of Cowden's disease. CONCLUSIONS: Genetic alterations underlying hamartomatous polyposis syndromes are diverse. Carcinogenesis may result from either germ-line mutations in the stroma (JPS) or as a direct result of functional deletion of tumor suppressor genes (PJS). Diagnosis depends on clinical presentation and patterns of inheritance within families. Suggested surveillance guidelines for the proband and first-degree relatives are outlined.

Clinical presentation and treatment of non-Hodgkin's lymphoma of the thyroid gland.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) of the thyroid is a rare malignancy. The traditional approach to curative treatment of localized (stages I and II) NHL of the thyroid gland is surgical resection. The recent success of multimodality chemoradiotherapy suggests that surgery should be reserved for providing a tissue diagnosis or relief from acute airway obstruction. It is questionable whether this has made an impact on treatment approaches. METHODS: Retrospective chart review was conducted for all cases of localized NHL of the thyroid gland treated at Roswell Park Cancer Institute between January 1970 and January 1999. RESULTS: Ten patients (8 women, 2 men) with a mean age of 56.8 years were identified. Nine patients (90%) presented with a neck mass; seven patients (70%) had a history of Hashimoto's disease. Nine patients (90%) had extensive investigations to rule out extrathyroidal disease. All patients were treated with either a total thyroidectomy (eight patients) or a thyroid lobectomy (two patients). Nine (90%) were initially treated outside of Roswell Park Cancer Institute and referred secondarily for consideration of further therapy. Adjuvant therapy consisting of cyclophosphamide-based chemoradiotherapy was administered to nine patients. Overall survival was 80% at a mean follow-up of 8.6 years with a disease-specific survival rate of 100%. CONCLUSIONS: A review of the literature suggests that fine needle aspiration (FNA) with flow cytometry and immunohistochemistry can be used to accurately diagnose NHL of the thyroid gland. Open biopsy should be reserved for cases where this technique is not available or where the diagnosis can not be confirmed by FNA alone. Extrathyroidal NHL should be ruled out by chest x-ray, CT scan of the abdomen, and bone marrow biopsy. Further review suggests that the most efficacious therapy is systemic chemotherapy in combination with radiation for local control. Debulking surgery should be used only to provide relief from acute airway obstruction.

Disseminated peritoneal adenomucinosis: a critical review.

BACKGROUND: The term pseudomyxoma peritonei has been used in reference to any condition, benign or malignant, in which the peritoneal cavity becomes filled with a gelatinous substance. The term is nonspecific and does not denote therapeutic or prognostic significance. Controversy centers around which patients benefit from and should be treated by aggressive surgical debulking. METHODS: A review of the current literature pertaining to the classification, treatment, and prognosis of patients with pseudomyxoma peritonei was undertaken. RESULTS: Disseminated peritoneal adenomucinosis refers to a subset of patients with pseudomyxoma peritonei who derive the greatest long-term benefit from multimodality therapy including aggressive surgical debulking. These patients have a benign form of the disease in which the peritoneal implants are derived from the extrusion of epithelial cells from an adenoma of the appendix. The pathophysiology of mucin deposition is defined by the redistribution phenomenon. The adenomatous cells are distributed according to the fluid flow and gravitational forces within the peritoneal cavity. The small bowel is relatively spared until late in the disease (visceral sparing), and therefore aggressive surgical debulking should be attempted at the first laparotomy by an experienced surgeon. Preoperative computed tomographic imaging can establish the diagnosis and aid in defining which groups of patients are resectable for cure. CONCLUSIONS: Attempts at curative treatment should include aggressive debulking and intraperitoneal chemotherapy. Those patients with a high-grade malignant process should be treated symptomatically, because aggressive therapy is associated with high morbidity rates and no long-term improvement in survival.