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Biomedical subjects

M S Talamonti

Publications and source records attributed to M S Talamonti.

At least 19 recordsLinked to original sources

Indications and results of liver resection and hepatic chemoembolization for metastatic gastrointestinal neuroendocrine tumors.

BACKGROUND: We reviewed 36 patients with liver metastases from islet cell tumors of the pancreas (n = 18) and carcinoid tumors (n = 18) who were treated with surgical resection (n = 16) or hepatic chemoembolization (n = 20). METHODS: All resections were complete and included 4 lobectomies, 6 segmental resections, and 6 wedge resections. There were no operative deaths. RESULTS: Median survival has not yet been reached, and the actuarial 5-year survival rate is 70%. Prognostic variables associated with improved disease-free survival included prior resection of the primary tumor and 4 or fewer metastases resected (P <.05). With an average of 3 chemoembolization procedures per patient, 17 of 20 patients (90%) demonstrated either a significant radiographic response (n = 5), stabilization of tumor mass (n = 2), or improvement of clinical symptoms (n = 10). Factors related to a sustained response (more then 1 year) included surgical resection of the primary tumor, 4 or more chemoembolization procedures, and liver metastases of 5 cm or smaller. Median survival after treatment was 32 months (range, 7-63 months), and the actuarial 5-year survival rate was 40%. CONCLUSIONS: Surgical resection of metastatic neuroendocrine tumors provides the best chance for extended survival. Chemoembolization effectively improves clinical symptoms and, in selected patients, may provide sustained tumor control.

Adenoma, Islet Cell↗

Organization and expression of the human zo-2 gene (tjp-2) in normal and neoplastic tissues.

One of the tight junction components, zonula occludens protein 2 (ZO-2), is expressed as two isoforms, ZO-2A and ZO-2C, in normal epithelia. In pancreatic adenocarcinoma of the ductal type ZO-2A is absent, but none of the common mechanisms of gene inactivation is responsible for lack of ZO-2A expression. In the current study, we report the complete organization of the human zo-2 gene (tjp-2), its alternative splicing, and its expression in normal and neoplastic tissues of several organ sites. In addition to pancreatic adenocarcinoma, ZO-2 was found to be de-regulated in breast adenocarcinoma, but not in colon or prostate adenocarcinoma. The latter are considered to be of acinar rather than ductal type. Thus, our data indicate the importance of zo-2 (tjp-2) gene regulation in ductal cancer development and should help to understand the defects of intercellular interactions, critical for suppressing the malignant phenotype.

Exons↗

Eastern Cooperative Oncology Group Phase I trial of protracted venous infusion fluorouracil plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer: a regimen with unexpected early toxicity.

PURPOSE: We performed a phase I trial of protracted venous infusion (PVI) fluorouracil (5-FU) plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer to determine the maximum-tolerated dose of gemcitabine that could be safely administered. We also sought to identify the toxicities associated with this treatment protocol. PATIENTS AND METHODS: Seven patients with locally advanced pancreas cancer were treated with planned doses of radiation (59.4 Gy) and PVI of 5-FU (200 mg/m(2)/d) with gemcitabine doses of 50 to 100 mg/m(2)/wk. RESULTS: Two of three patients at the 100-mg/m(2)/wk dose level experienced dose-limiting toxicity (DLT), as did three of four at the 50-mg/m(2)/wk dose level. One patient experienced a mucocutaneous reaction described as a Stevens-Johnson syndrome that was attributed to chemotherapy. Three patients developed gastric or duodenal ulcers with severe bleeding requiring transfusion. One patient developed severe thrombocytopenia lasting longer than 4 weeks. Three of the five episodes of DLT developed at radiation doses < or = 36 Gy. CONCLUSION: Based on this experience, we cannot recommend further investigation of regimens incorporating gemcitabine into regimens of radiation with PVI 5-FU. The mechanism of this synergistic toxicity remains to be determined.

Adenocarcinoma↗

Primary gastrointestinal sarcomas: analysis of prognostic factors and results of surgical management.

BACKGROUND: This study was done to review the clinical presentation, surgical management, and prognostic factors for primary gastrointestinal sarcomas. METHODS: We reviewed medical records of 55 patients who were treated for primary gastrointestinal sarcomas from 1981 through 1996. Mean follow-up time was 32 months. RESULTS: Clinical findings included gastrointestinal bleeding (51%), palpable mass (36%), and abdominal pain (33%). The stomach was the most common site of disease (53%), followed by the small intestine (33%). Tumors were high grade in 76% of patients and low-grade in 24% of patients. Complete resection of all gross disease was accomplished in 35 patients (64%), incomplete resection in 17 patients (31%), and biopsy only in 3 patients (5%). Adjacent organ resection was required in 19 patients (35%). Overall actuarial survival was 22% (median survival, 32 months). Unfavorable prognostic factors were incomplete resection, high-grade histologic features, and tumor size of 5 cm or more (P<.05). En bloc resection of contiguous organs did not adversely effect survival. In patients with complete resections, tumor grade was the most important prognostic factor (median survival, 55 months vs 19 months for low-grade vs high-grade tumors; P<.05). CONCLUSIONS: Aggressive surgical resection, including en bloc resection of locally advanced tumors, appears warranted. Despite complete resections, patients with high-grade tumors remain at risk for recurrence.

Adult↗

Esophageal leiomyomatosis in a woman with a history of vulvar leiomyoma and Barrett's esophagus: a case report and review of the literature.

BACKGROUND: The diagnosis and treatment of esophageal pathology remains a challenge despite advances in preoperative endoscopy, radiographic staging, and perioperative care. CASE REPORT: In this article, we present an interesting case of esophageal leiomyomatosis in a woman with a history of vulvar leiomyoma and Barrett's esophagus. This paper represents the first reported simultaneous occurrence of these three pathologic entities in the English literature. CONCLUSIONS: The clinical presentation and characteristic pathologic findings in patients with esophageal leiomyomatosis are reviewed. Diagnostic and therapeutic approaches to esophageal masses are discussed including the indications for esophageal resection.

Adult↗

zo-2 gene alternative promoters in normal and neoplastic human pancreatic duct cells.

We have observed that 2 forms of zonula occludens 2 (ZO-2) protein, ZO-2A and ZO-2C, are expressed in normal human pancreatic duct cells, but only ZO-2C in pancreatic duct adenocarcinoma. We report here partial organization of the zo-2 gene. Transcription of 2 forms of ZO-2 mRNA is driven by alternative promoters P(A) and P(C). Lack of expression of ZO-2A in neoplastic cells is caused by inactivation of the downstream promoter P(A). Analysis of the promoter P(A) sequence and function in normal and neoplastic cells demonstrated that neither structural changes (mutations) nor a change in the pool of transcription factors is responsible for its inactivation. Although hypermethylation was found in a large number of cancer clones, treatment with 5-aza-2'-deoxycytidine did not fully cause the promoter function to recover. We conclude that the initial down-regulation of zo-2 promoter P(A) activity in pancreatic duct carcinomas is due to the structural or functional alteration(s) in the regulatory elements, localized outside the analyzed promoter region. Methylation of P(A) is responsible for the inactivation of the suppressed promoter at the late stages of tumor development.

Base Sequence↗

Tight junction protein ZO-2 is differentially expressed in normal pancreatic ducts compared to human pancreatic adenocarcinoma.

Differential display of hamster mRNA identified a fragment present in normal pancreatic duct cells that is not expressed in pancreatic duct carcinoma cells. Sequence analysis showed an 88% and 82% identity, respectively, to the cDNA of the canine and human tight junction zo-2 gene. Semi-quantitative RT-PCR analysis of human ZO-2 revealed a striking difference in the expression of various regions of the ZO-2 transcript in normal and neoplastic cells and the presence of an abnormality at the 5'-end of mRNA. RACE analysis identified 2 human ZO-2 mRNAs that encode proteins of different lengths, designated as ZO-2A and ZO-2C. The difference between the 2 forms of ZO-2 is the absence of 23 amino acid residues at the N terminus of ZO-2C compared with ZO-2A. Although ZO-2C was expressed in normal pancreatic cells and a majority of neoplastic tissues analyzed, ZO-2A was undetectable except in one case in all of the pancreatic adenocarcinomas analyzed. This suggests the presence of a yet to be identified motif important for cell-growth regulation within the 23-amino acid residue N-terminal peptide of ZO-2A, MPVRGDRGFPPRRELSGWLRAPG.

Adenocarcinoma↗

Results of gastric interposition for reconstruction of the pharyngoesophagus.

BACKGROUND: Free jejunal transfer has become the standard technique for reconstruction of the proximal pharynx and hypopharynx. Gastric tube interposition is an effective alternative when resection extends below the thoracic inlet. This study was done to determine current indications, review morbidity and mortality rates, and to define clinical and pathologic determinants of survival associated with this procedure. METHODS: We reviewed the records of 32 patients who underwent gastric tube interposition for reconstruction of the pharyngoesophagus from 1987 to 1997. RESULTS: The overall complication rate was 50%. Complications were more frequent in the reoperative group (22% vs 66%, P < .05). The overall fistula rate was 31%. The overall mortality rate was 12%. Ultimately, 71% of patients resumed oral feedings. The 5-year actuarial survival rate was 22%. Unfavorable prognostic factors associated with significantly reduced survival (P < . 05) included margin positive resection, positive lymph node involvement, and operations done for recurrent tumor CONCLUSIONS: Reconstruction of the pharyngoesophagus with gastric tube interposition is indicated for primary tumors of the hypopharynx and cervical esophagus with inferior extension below the thoracic inlet and recurrent tumors or benign strictures in which free jejunal transfer is not feasible or has failed. It can be done with acceptable morbidity and mortality and provides reasonable expectations for long-term survival and resumption of oral intake.

Adult↗

Learning sentinel node biopsy: results of a prospective randomized trial of two techniques.

BACKGROUND: Evidence indicates that sentinel node (SN) biopsy can accurately predict axillary nodal status. Debate exists as to the optimal method of SN identification. METHODS: Patients with clinical T1 or T2 tumors and negative axillae were randomized to SN localization with blue dye (B) alone (n = 50) or blue dye plus radioactivity (B+R) (n = 42). Patients undergoing needle localization (n = 47) were assigned to blue dye. RESULTS: The SN was identified in 110 patients (79%) and contained metastases in 28. The SN predicted the axillary nodal status in 96% of cases. The SN identification rate did not differ between B (88%) or B+R (86%) but was significantly lower in patients requiring localization (64%). The time to SN identification also did not differ between B and B+R. The number of cases done by an individual surgeon was a significant predictor of SN identification. A stepwise logistic regression analysis of factors influencing the success of SN identification identified tumor location, needle localization, number of operations, and body mass index as significant predictors. CONCLUSIONS: Our study does not identify any advantage for the use of the more expensive and complex method of SN identification using B+R compared with B alone, even for surgeons learning the techniques.

Axilla↗

Pituitary adenoma and bilateral male breast cancer: an unusual association.

An unusual case is presented of bilateral breast cancer in a male patient with a long history of endocrine dysfunction due to a prolactinoma. The role of abnormal endocrine function in the development of male breast cancer is reviewed. The strongest association between aberrant endocrine function and male breast cancer occurs in patients with Klinefelter's syndrome, who have an approximate 3% lifetime risk of developing breast cancer. Retrospective case-control studies indicate that both estrogen excess and androgen deficiency may be involved in male breast cancer. Clinical studies of estrogen, androgen, and prolactin levels in male breast cancer patients have yielded conflicting results, and the precise nature of the hormonal mechanisms involved in the development of male breast cancer remains to be defined.

Aged↗

Atypical acinar cell foci in human pancreas. Morphological and morphometric analysis.

CONCLUSION: The morphological and quantitative findings of the present study suggest that atypical acinar cell foci are not neoplastic in nature. BACKGROUND: Atypical acinar cell foci (AACF) are rare and unusual lesions in the human pancreas. The biological nature of AACF is poorly understood, and is not clear whether they represent neoplastic or degenerative changes in the acinar cells. METHODS: To further characterize and understand the significance of AACF in relation to acinar cell tumor development, we have examined these lesions by light and electron microscopy and evaluated the growth pattern by measuring cell proliferation and the size of the foci in the pancreas of a 16-yr-old male. RESULTS: The pancreas was grossly unremarkable. AACF were randomly distributed throughout the pancreas, well delineated, and showed minimal variation in sizes. The constituent cells contained uniform nuclei, pale vacuolated cytoplasm, and exhibited low nuclear-cytoplasmic ratio. Electron microscopic examination showed a few zymogen granules and markedly dilated rough endoplasmic reticulum. Proliferative index in AACF (13%) was less than in adjacent uninvolved acinar tissue (19%). Quantitative stereological analysis showed the pancreas to contain approximately 1800 AACF/cm3 with a mean focal diameter of 360 microns.

Adolescent↗

Transgenic technology: an overview of approaches useful in surgical research.

Advances in transgenic science have created powerful tools for the investigation of both genetic and protein regulatory systems. Recently, transgenic animals have been utilized in several vascular and transplantation research laboratories. The ability to specifically mutate genes important in oncologic and cardiovascular research is leading to a greater understanding of the role of gene and protein regulatory systems in cancer and cardiovascular disease. The expanding use of transgenic animals will undoubtedly increase our insight into complex problems in surgical research. This review briefly describes the various techniques utilized to create transgenic animals including: transgene design, gene-transfer utilizing transfection, microinjection and retroviral infection, as well as the use of embryonic stem cells, and methods for screening transgenic offspring.

Animals↗

Gastric cancer. Radiologic staging.

CT scan and EUS play complementary roles in staging gastric cancer. CT scan is initially performed to detect local and distant metastases. Depending on institutional expertise, EUS may be considered for local staging. Laparoscopic staging may also be helpful in select patients. It is hoped that further improvements in these techniques will improve the ability to stage gastric cancer and thereby optimize patient treatment and outcome.

Combined Modality Therapy↗

Initial results of a phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): an Eastern Cooperative Oncology Group study.

PURPOSE: A prospective clinical trial was performed to assess the response and toxicity associated with the use of high dose radiation therapy, 5-fluorouracil, and cisplatin in patients with anal cancer. METHODS AND MATERIALS: Patients with anal cancer without distant metastasis were eligible for this study. Radiation therapy consisted of 59.4 Gy in 33 fractions; a 2 week break in treatment was taken after 36 Gy had been given. A treatment of 5-fluorouracil, 1,000 mg/m2 per day intravenously, was given for the first 4 days of radiation therapy, and cisplatin, 75 mg/m2 intravenously, was given on day 1 of radiation therapy. A second course of 5-fluorouracil and cisplatin was given after 36 Gy of radiation, when the radiation therapy was resumed. RESULTS: Nineteen patients entered this study and received treatment. Thirteen (68%) had a complete response, 5 (26%) had a partial response, and 1 (5%) had stable disease. The patient with stable disease and one of the patients with a partial response had complete disappearance of tumor more than 8 weeks after completion of radiation therapy. Fifteen patients had toxicity of Grade 3 or higher: the worst toxicity was Grade 3 in eight patients, Grade 4 in six patients, and Grade 5 in one patient. The most common form of toxicity of Grade 3 or higher was hematologic. The one lethal toxicity was due to pseudomembranous colitis, which was a complication of antibiotic therapy for a urinary tract infection. CONCLUSION: Radiation therapy, cisplatin, and 5-fluorouracil resulted in an overall response rate of 95%. Significant toxicity occurred, an indication that this regimen is near the maximal tolerated dose. A Phase III clinical trial is planned in which radiation therapy, cisplatin, and 5-fluorouracil will be used as an experimental arm.

Antineoplastic Combined Chemotherapy Protocols↗

Cystic neoplasms of the pancreas. A clinicopathologic study, including DNA flow cytometry.

OBJECTIVE: To review the classification, clinical behavior, and appropriate therapy for cystic neoplasms of the pancreas. We examined patient demographics, clinical parameters, preoperative imaging modalities, histologic findings, and tumor DNA content to determine which best predict outcome. DESIGN: Case series and survey of pathologic specimens. SETTING: Tertiary care center. PATIENTS: Twenty-two patients with cystic neoplasms of the pancreas treated at affiliates of Northwestern University Medical School, Chicago, Ill. MAIN OUTCOME MEASURES: Predictive value of preoperative testing, tumor DNA content, patient survival. RESULTS: In 20 patients undergoing computed tomographic scan, the tumor was visualized in every case. All other imaging studies evaluated were less likely to demonstrate the lesion. Eight of 10 patients with serous cystadenomas were alive with no evidence of disease at the time of this report; one patient was alive with local recurrence, and a second patient had died of unrelated causes. All patients with mucinous cystadenomas were alive with no evidence of disease. Three of seven patients with cystadenocarcinomas had aneuploid, high S-phase tumors, and one had a diploid, high S-phase tumor; all four died (mean survival, 4.8 months). Two patients with cystadenocarcinomas had diploid, low S-phase tumors; both were long-term survivors but died of their disease at 8.6 and 9.3 years. CONCLUSIONS: (1) Computed tomographic scan is the most valuable diagnostic imaging study for preoperative evaluation of these patients. (2) Precise preoperative determination of tumor type is not possible. (3) DNA flow cytometry may help identify patients with aggressive tumors who may benefit from adjuvant chemoradiation.

Actuarial Analysis↗