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D Klimstra

Publications and source records attributed to D Klimstra.

30 records · Page 2Linked to original sources
PubMed1996

Management of adenocarcinoma of the body and tail of the pancreas.

OBJECTIVE: The authors examined the resectability, operative morbidity mortality, and survival of patients with pancreatic adenocarcinoma of the body and tail compared with lesions in the head. SUMMARY BACKGROUND DATA: Adenocarcinoma of the body and tail of the pancreas is characteristically thought of as a disease that presents late and rarely is operable or resectable. METHODS: In an 11-year period, 1981 patients were admitted and entered into a prospective database at Memorial Sloan-Kettering Cancer Center with a diagnosis of peripancreatic cancer, 1363 of whom had adenocarcinoma of the pancreas, 75% with lesions in the head and 25% with lesions in the body and tail. RESULTS: Of 271 patients resected, 237 (23%) had lesions in the head and 34 (10%) had body and tail lesions. Perioperative mortality was 4% for patients with pancreatic lesions in the head and 0% for patients with pancreatic lesions in the body and tail. Five-year actuarial survival for body and tail lesions was projected at 14% for 5 years. Actual survival was 19%, with three patients alive for more than 5 years. CONCLUSIONS: Adenocarcinoma of the body and tail of the pancreas, although less likely to be resectable at presentation than lesions in the pancreatic head, have similar postresection survival.

Adenocarcinoma↗
PubMed1996

p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases.

PURPOSE: To determine whether p53 protein expression is similar within primary colorectal cancer (CRC) and synchronous regional and distant metastases and to assess whether p53 nuclear protein expression could predict outcome in patients with synchronous unresectable liver metastases treated by hepatic artery infusional (HAI) chemotherapy. MATERIALS AND METHODS: Paraffin sections from tumor and corresponding normal mucosa representative of 50 consecutive advanced CRC cases were examined for p53 nuclear protein expression by immunohistochemistry using the monoclonal antibody PAb 1801. Patterns of p53 nuclear expression were correlated with standard clinicopathologic variables and outcome, including response to HAI and survival. In a subset analysis, the pattern of nuclear p53 immunoreactivity was compared between primary CRC and lymph node and liver metastases. RESULTS: Positive nuclear immunoreactivity for p53 protein was found in 72% of cases. The pattern of p53 protein expression in lymph node and liver metastases was identical to that of the primary tumor. The median survival time was 21.0 months in patients with p53-positive tumors and 53.2 months in patients with p53-negative tumors (Wilcoxon test P = .038). Two-year survival rates were 41.7% and 78.6%, respectively (P < .01). No significant difference was found in the response rates to HAI chemotherapy between the two groups. By multivariate analysis, p53 protein status was the single best predictor of survival, with a relative risk of 6.312. CONCLUSION: Our results indicate that nuclear p53 protein status in primary CRC is similar to that in metastatic sites and may be the dominant predictor of survival in patients with advanced hepatic metastases.

Adult↗
PubMed1996

Neoadjuvant therapy of high-risk gastric cancer: a phase II trial of preoperative FAMTX and postoperative intraperitoneal fluorouracil-cisplatin plus intravenous fluorouracil.

PURPOSE AND METHODS: We identified patients with gastric cancer at high risk for recurrence before therapy using endoscopic ultrasonography (EUS). Neoadjuvant therapy using the fluorouracil, doxorubicin, and metrotrexate (FAMTX) regimen was given for three courses before planned laparotomy with the intention to perform curative resection. Postoperatively, intraperitoneal (IP) cisplatin and fluorouracil (FU) and intravenous (i.v.) FU were administered to patients undergoing resection. RESULTS: Fifty-six assessable patients were treated. Preoperative FAMTX therapy was tolerable, with the major toxicity being neutropenic fever. One treatment-related death was seen. Eighty-nine percent of patients underwent surgical exploration and 61% had potentially curative resections. There were two postoperative deaths. Comparison of pathologic tumor (pT) stage with EUS-predicted tumor stage showed apparent downstaging in 51% of patients. Postoperative IP chemotherapy was delivered to 75% of eligible patients. Toxicity was acceptable. There was no increase in operative morbidity or mortality compared with concurrent nonstudy patients undergoing a similar operative procedure and not receiving preoperative therapy. With a median follow-up time of 29 months, the median survival duration was 15.3 months. For patients who underwent potentially curative resections, the median survival duration was 31 months. Peritoneal failure was seen in 16% of patients. CONCLUSION: Chemotherapy with the FAMTX regimen is tolerable in patients with locally advanced gastric cancer, without an increase in operative morbidity or mortality. IP therapy can be successfully delivered to most resected patients. The intraabdominal failure pattern appears to be decreased compared with expected. This approach is an appropriate investigational arm to pursue in future studies.

Adenocarcinoma↗
PubMed1995

Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer.

The development of cisplatin-based induction chemotherapy followed by surgical resection or radiation has improved the poor prognosis of stage III non-small cell lung cancer (NSCLC). In vitro studies indicate that p53 can modulate cisplatin-induced cytotoxicity, but the molecular genetic features determining response or resistance to cisplatin in vivo must be defined. For this reason, tumor specimens from 52 patients with stage IIIA NSCLC entered in a prospective clinical trial of cisplatin-based induction chemotherapy followed by surgical resection were examined for p53 expression by immunohistochemical staining before and after induction chemotherapy. p53 expression was correlated with clinical and pathological response using Fisher's exact test. No correlation was established between p53 expression and clinical response because 47 of the 52 patients studied had a major response. However, a significant association was observed between aberrant p53 expression and resistance to chemotherapy as assessed by pathological response. Only 3 of the 20 patients whose tumors exhibited a high level (+ + to + + + +) of p53 staining experienced a major (+ + + to + + + +) pathological response to chemotherapy. Only 7 of 52 cases examined before and after chemotherapy treatment exhibited a change in the level of p53 expression after cisplatin-based chemotherapy. These results indicate that cisplatin alters p53 expression infrequently and suggest a direct link between aberrant p53 expression and resistance to cisplatin-based chemotherapy in NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Aberrant expression of p53 or the epidermal growth factor receptor is frequent in early bronchial neoplasia and coexpression precedes squamous cell carcinoma development.

New strategies are needed for the detection and treatment of lung cancer and must derive from a fuller understanding of lung carcinogenesis. Frequent molecular genetic abnormalities occur in non-small cell lung cancer (NSCLC), but little is known about which of these precede an invasive carcinoma. We examined the expression of p53, epidermal growth factor receptor (EGFR), and transforming growth factor alpha, the most common molecular genetic abnormalities in NSCLC, in preneoplastic bronchial lesions. Primary NSCLC and associated bronchial lesions were identified by retrospective review of resected tumors at this center. Expression in the invasive carcinomas, the associated bronchial lesions, and normal lung were contrasted using immunohistochemistry. Thirty-four NSCLC associated with 62 bronchial lesions were identified. The invasive tumors included 15 squamous cell carcinomas (SCCs) and 19 non-SCCs. Bronchial lesions included areas of squamous metaplasia (n = 14), inflammatory atypia (n = 19), dysplasia (n = 17), and carcinoma in situ (n = 12). Nineteen (56%) NSCLC and 10 (16%) bronchial lesions exhibited aberrant p53 immunostaining, whereas 18 (53%) NSCLC and 30 (48%) bronchial lesions showed abnormal EGFR immunostaining. Positive staining for transforming growth factor alpha was seen in 16 (47%) NSCLC but occurred inconsistently in the bronchial lesions and in normal bronchial epithelium. Only bronchial lesions associated with squamous cell carcinomas exhibited staining for p53. Aberrant EGFR expression was not associated with a specific type of invasive carcinoma or with specific preneoplastic lesions, although there was a trend toward increased expression in dysplasia and carcinoma in situ relative to metaplasia and atypia. All but one of the NSCLC simultaneously showing aberrant p53 and EGFR staining were SCC. We conclude that: (a) transforming growth factor alpha is variably expressed in normal respiratory epithelium as well as reactive and preneoplastic bronchial lesions; (b) p53 expression is seen in preneoplastic bronchial lesions but is not present in reactive or metaplastic epithelium; (c) aberrant EGFR expression occurs in both reactive and preinvasive bronchial lesions and may be an early marker of neoplastic transformation; and (d) the simultaneous aberrant expression of EGFR and p53 occurs predominantly in SCC and their associated bronchial lesions. These findings indicate that aberrant expression of p53 or the EGFR is frequent in bronchial neoplasia, and coexpression may predispose to the development of squamous cell carcinomas of the lung.

Bronchial Neoplasms↗
PubMed1995

Factors affecting long-term outcome after hepatic resection for hepatocellular carcinoma.

BACKGROUND: Experience with hepatocellular carcinoma (HCC) is limited in the West and factors affecting outcome after resection are not clearly defined. METHODS: Between 1970 and 1992, 106 patients (including 74 Caucasians, 31 Orientals, and 1 black) underwent hepatic resection for HCC at Memorial Sloan-Kettering Cancer Center. Clinical and histopathologic factors of outcome were analyzed. RESULTS: Cirrhosis was present in 33% and 95% were Child-Pugh A. Operative mortality was 6%, 14% in cirrhotics versus 1% in non-cirrhotics (P = 0.013). Orientals had a higher prevalence of cirrhosis (68% versus 19%) (P < 0.0001) and smaller tumors (mean 8.7 cm versus 11.0 cm) (P = 0.028) compared to Caucasians. Overall survival was 41% and 32% at 5 and 10 years, respectively. By univariate analysis, survival was greater in association with the following: absence of vascular invasion (69% versus 28%, P = 0.002); absence of symptoms (66% versus 38%, P = 0.014); solitary tumor (53% versus 28%, P = 0.014); negative margins (46% versus 21%, P = 0.022); small tumor (< or = 5 cm) (75% versus 36%, P = 0.027); and presence of tumor capsule (69% versus 35%, P = 0.047). Ethnic origin, cirrhosis, necrosis and grade did not affect survival. By multivariate analysis, only vascular invasion predicted outcome (P = 0.0025, risk ratio 2.9). CONCLUSIONS: One third of patients resected for HCC can be expected to survive long-term. Except for a higher incidence of cirrhosis in Orientals, no major histopathologic or prognostic differences were noted between Orientals and Caucasians undergoing resection. Early cirrhosis (Child-Pugh A) did not adversely affect survival. Vascular invasion predicted long-term outcome.

Adolescent↗
PubMed1993

Sarcoidosis of the pancreas.

We report a case of pancreatic sarcoidosis in a patient with radiographic and clinical findings suggestive of pancreatic cancer. Clinically apparent involvement of the pancreas is uncommon in patients with known sarcoidosis and is distinctly unusual as the initial presentation of disease. Sarcoid involvement of the pancreas can mimic adenocarcinoma and should be considered in the differential diagnosis of a pancreatic mass in a patient with symptoms suggestive of sarcoidosis.

Aged↗
PubMed1992

Hard metal interstitial pulmonary disease associated with a form of welding in a metal parts coating plant.

We describe two cases of hard metal pulmonary disease (one fatal) in workers employed in the same area of a metal coating plant using the detonation gun process for applying a durable metal surface to metal parts. In this form of welding, a mixture of powdered metals, including tungsten carbide and cobalt, is heated by ignition of a flammable gas and propelled from the end of the "gun" at high temperature and velocity to form a welded metal coating. This process is done in an enclosed chamber and with each application, large volumes of fine aerosols are created. Inhalation exposure to hard metal may occur during the mounting and removal of the metal parts between applications, in spite of engineering controls and industrial hygiene surveillance. One of the cases presented with minimal chest x-ray abnormalities and an obstructive pattern on pulmonary function testing, although subsequent open lung biopsy showed diffuse interstitial pulmonary fibrosis. The fact that two cases of hard metal pulmonary interstitial disease occurred where thorough exposure control procedures and a surveillance program for cobalt were in place may indicate the need for revisions of the current technology used when hard metal is applied in the detonation gun process.

Adult↗
PubMedDate not supplied

Gastric carcinomas of intestinal type concur with distant changes in the gastric mucosa. A multicenter study in the Atlantic basin.

Population studies in the Pacific Basin showed that gastric carcinomas of intestinal type often concur with distant mucosal changes (DMCs). In the present work, the presence of DMCs was investigated in populations dwelling in the Atlantic Basin. A total of 1737 gastrectomy specimens were reviewed: 627 in New York, 435 in Reykjavik, 198 in Buenos Aires, 186 in Florence, 174 in London and the remaining 117 in Stockholm. A total of 17,282 sections were carefully scrutinized. The following DMCs were investigated: intramucosal glandular cysts, gastric cells with ciliated metaplasia, with large or small mucus negative vacuoles, and extensive intestinal metaplasia (IM). The highest frequencies of DMCs were found in Florence for specimens with intestinal type carcinoma: 41.3% had intramucosal cysts, 22.4% had cells with ciliated metaplasia, 12.9% cells with large vacuoles, and 50.9% had high IM. The highest frequency of gastric cells with small vacuoles was recorded in New York (9.1%), also in specimens with intestinal type carcinoma. Significantly lower DMCs percentages were found in specimens with carcinomas of diffuse type, and miscellaneous gastric diseases. The occurrence of DMCs was not influenced to a significant degree by the number of sections available per gastrectomy. Since environmental factors trigger the evolution of intestinal type carcinomas and as DMCs also occurred in specimens without carcinoma-although at a significantly lower rate--it is conceivable that DMCs are also evoked by environmental factors (before a gastric carcinoma ensues). DMCs were found in specimens having intestinal carcinomas either in the cardia, the corpus or the antrum. Thus, DMCs seem to provide the adequate "soil" for the development of gastric carcinomas of intestinal type, independently of the future localization of that tumor in the stomach.

Adenocarcinoma↗
PubMedDate not supplied

High levels of transforming growth factor beta 1 correlate with disease progression in human colon cancer.

Several genes have identified that play a role in colon cancer development. However, less is known about factors that increase the rate of progression of colon cancers to metastasis. One candidate is transforming growth factor beta 1 (TGF beta 1), which can enhance the aggressiveness of human colorectal cell lines in vitro and in vivo. The amount of TGF beta 1, TGF beta 2, and TGF beta 3 protein isoforms expressed in primary site colorectal cancers were measured to determine whether any correlation existed between protein levels and disease recurrence in a series of Memorial Sloan-Kettering Hospital patients who underwent potentially curative resections. Intense staining for TGF beta 1 correlated significantly (P < 0.0013; odds ratio, 18) with disease progression to metastasis and was independent of nodal status and the degree of differentiation of the primary tumor. Therefore, in this study, patients with high TGF beta 1 protein levels in their primary site colorectal cancer were 18 times more likely to experience recurrence of their disease than were patients whose tumors exhibited low levels of TGF beta 1. In this case-control study, patients whose cancer recurred and those remaining cancer free were age and sex matched. The disease recurred at a mean of 26.8 +/- 4.3 (SE) months, whereas the mean follow-up time in patients whose disease did not recur was over twice as long, 57.3 +/- 6.6 months. Ninety-four % of the patients in each group were node positive at the time of resection, with equal mean numbers of positive nodes per patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗