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Biomedical subjects

A L Warshaw

Publications and source records attributed to A L Warshaw.

At least 19 recordsLinked to original sources
PubMed2001

Ten-year experience with 733 pancreatic resections: changing indications, older patients, and decreasing length of hospitalization.

HYPOTHESIS: Experience with pancreatic resection for the last 10 years has resulted in new trends in patient characteristics and, for pancreaticoduodenectomy (PD), a decrease in the length of stay (LOS). This decrease is due in part to the implementation of case management and clinical pathways. DESIGN: Retrospective case series of patients undergoing pancreatic resection. SETTING: A university-affiliated, tertiary care referral center. PATIENTS: The study comprised 733 consecutive patients undergoing pancreatic resection for benign or malignant disease at the Massachusetts General Hospital in Boston from April 1990 to March 2000. INTERVENTIONS: Of the 733 pancreatic resections, 489 were PD; 190, distal pancreatectomy; 40, total pancreatectomy; and 14, middle-segment pancreatectomy. MAIN OUTCOME MEASURES: Length of stay; occurrence of delayed gastric emptying, pancreatic fistula, reoperation, readmission, or other complications; mortality; and comparison of patients in 3 periods according to the implementation of case management (July 1995) and clinical pathways (September 1998). RESULTS: For PD, patients in group 1 (April 1990 to June 1995) were significantly younger (mean +/- SD, 57 +/- 15 years) than those in group 2 (July 1995 to August 1998; mean +/- SD, 62 +/- 13 years) and group 3 (September 1998 to October 2000; mean +/- SD, 65 +/- 13 years)(P <.01). Over time, the proportion of PD for cystic tumors increased from 9.9% to 20% (P =.01), and the proportion of PD for chronic pancreatitis decreased from 23% to 10% (P <.01). Use of pylorus-preserving PD decreased from 45% to 0% (P <.001). Delayed gastric emptying decreased from 17% to 6.1% (P <.01). Pancreatic fistula, reoperation, and mortality were unchanged. Length of stay for PD decreased from 16.1 +/- 0.6 to 9.5 +/- 0.4 days (mean +/- SE) (P <.001). Multivariate analysis showed that period, case volume, pylorus-preserving PD, and presence of complications are all independent predictors of LOS (P <.05 for all). For distal pancreatectomy, patients in groups 2 and 3 were older than those in group 1 (mean +/- SD, 57 +/-14 vs 52 +/- 17 years) (P <.05). Resections for cystic tumors increased from 26% to 52% (P <.05), and resections for chronic pancreatitis decreased from 32% to 14% (P =.06). Median LOS decreased from 9 days to 6. For total pancreatectomy, resections for cystic tumors increased from 18% to 43%. Median LOS decreased from 14.5 days to 11. For all resections, case volume increased from 4 resections per month in 1990 to 5.8 in 1995 and 12 in 2000 (r = 0.83; P <.001). CONCLUSIONS: Older patients are increasingly being selected for pancreatic resection. This reflects an increasing frequency of operations performed for cystic tumors and fewer for chronic pancreatitis. With the exception of delayed gastric emptying, complications and mortality have remained the same or decreased slightly during the past 10 years. However, there has been a significant decrease in LOS; this is the result of implementation of case management and clinical pathways, increasing case volume, decreasing incidence of delayed gastric emptying, and decreasing use of pylorus-preserving PD.

Adenocarcinoma↗
PubMed2001

Biological implications of tumor cells in blood and bone marrow of pancreatic cancer patients.

BACKGROUND: Patients with pancreatic cancer often have tumor recurrence despite curative resection. Cancer cells detected in blood or bone marrow at the time of diagnosis may relate to tumor stage and to prognosis. Recent research emphasis has centered on tumor cells in bone marrow aspirates, but whether these represent early micrometastases or blood-borne cells in transit is unknown. PATIENTS AND METHODS: We developed a specific immunocytochemical assay that evaluated more than 5.3 x 10(6) extracted mononuclear cells per sample of blood and bone marrow and that could identify a single tumor cell in that population. The assay was applied to samples of blood and bone marrow from 105 patients with pancreatic cancer and 66 controls. The prevalence of isolated tumor cells was compared with Union Internationale Contre le Cancer (UICC) stage. A multivariate Cox regression analysis for survival was performed. RESULTS: Pancreatic cancer cells were detected in 26% of blood samples and in 24% of bone marrow specimens. Specificity for cancer was 96%. The prevalence of isolated tumor cells in patients with proven resectable cancer was 9% in blood and 13% in bone marrow. The prevalence increased with UICC tumor stage in blood (P =.04) but not in bone marrow (P =.52) and correlated in blood with resectability (P =.02), progression of disease (P=.08), and peritoneal dissemination (P =.003). While survival correlated significantly with tumor stage (P <.001) and isolated tumor cells in blood correlated with tumor stage, the finding of cancer cells in blood or bone marrow, or both, was not independently associated with survival in patients with pancreatic cancer. CONCLUSIONS: Isolated tumor cells in blood but not bone marrow reflect the stage of growth and spread of pancreatic cancer, particularly in the peritoneal cavity. The findings are consistent with cells in bone marrow aspirates being in transit, not implanted. These disseminated cancer cells may be the consequence, rather than the cause, of progression.

Aged↗
PubMed2001

Linkage of oxidative and nonoxidative ethanol metabolism in the pancreas and toxicity of nonoxidative ethanol metabolites for pancreatic acinar cells.

BACKGROUND: Alcohol abuse is a major cause of pancreatic damage. Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative ethanol metabolites, injure pancreatic acinar cells. Linkage between oxidative and nonoxidative metabolism of ethanol in the pancreas may contribute to increased FAEE levels. METHODS: To study the association between oxidative and nonoxidative ethanol metabolism, FAEE concentration and FAEE synthase activity in rat pancreatic and liver homogenates incubated with ethanol were evaluated with and without inhibitors of oxidative ethanol metabolism. For toxicity studies, trypsinogen activation peptide synthesis as a measure of pancreatic cell injury was quantitated in unstimulated and cerulein-stimulated isolated pancreatic acinar cells incubated with ethanol or FAEE. RESULTS: Inhibition of oxidative ethanol metabolism results in a 2- to 3-fold increase in nonoxidative ethanol metabolism to FAEE in pancreas and in liver. Both ethanol and FAEE induce increased intracellular trypsinogen activation by more than 50% in the presence of physiologic concentrations of cerulein in vitro. CONCLUSIONS: These findings demonstrate that the inhibition of oxidative ethanol metabolism results in an increase in flux through the nonoxidative pathway and support the proposition that alcohol-induced pancreatic injury is mediated at least in part by FAEE, which are important products of pancreatic ethanol metabolism.

Acyltransferases↗
PubMed2001

Regional effects of nafamostat, a novel potent protease and complement inhibitor, on severe necrotizing pancreatitis.

BACKGROUND: We evaluated the effect of the novel protease inhibitor nafamostat on rat necrotizing pancreatitis through different routes of administration. METHODS: Three hours after the induction of severe pancreatitis, the rats received intravenous gabexate or intravenous or local mesenteric intra-arterial nafamostat. At 9 hours, ascites and bronchoalveolar lavage fluid were collected for the evaluation of capillary leakage (Evans blue extravasation). Pancreas and lung were excised for histologic features, myeloperoxidase, and trypsinogen activation peptide. Twenty-four hour survival was evaluated. RESULTS: Only the intravenous infusion of nafamostat significantly reduced myeloperoxidase (11.7 +/- 2.3 vs 18.3 +/- 1.8 mU/mg; P <.05) and capillary leakage in lungs (Evans blue dye, 1.6 +/- 0.3 vs 2.6 +/- 0.3; P <.05). Only intra-arterial infusion of nafamostat significantly diminished capillary peritoneal leakage (Evans blue dye, 3.6 +/- 0.9 vs 9.4 +/- 0.4; P <.01). Typsinogen activation peptide levels were significantly reduced in all groups, but only intra-arterial infusion did so to baseline. Histologic inflammation in the pancreas was most significantly reduced after intra-arterial infusion (0.92 +/- 0.08 vs 2.91 +/- 0.06; P <.05). No form of protease inhibition reduced mortality rates. CONCLUSIONS: The effects of protease inhibition depend on the route of administration. Nafamostat has maximal effects on the pancreas and peritoneal capillary leakage when delivered by way of local intra-arterial infusion, and shows a greater reduction of lung leukocyte infiltration and capillary leakage by the intravenous route. Nafamostat is more effective than gabexate.

Animals↗
PubMed2001

Expression of the adhesion molecules Mac-1 and L-selectin on neutrophils in acute pancreatitis is protease- and complement-dependent.

OBJECTIVE: To examine the effect of pancreatic proteases on the expression of the adhesion molecules Mac-1 and l-selectin on neutrophils, and the role of complement activation in this process. SUMMARY BACKGROUND DATA: Sequestration of neutrophils in the pancreatic and pulmonary microvasculature characterizes acute pancreatitis. METHODS: Serum was collected from inbred rats after induction of necrotizing pancreatitis; trypsinogen activation peptide was measured to quantify trypsin activation. Normal rat serum was also collected and subjected to limited trypsin digestion with and without the addition of complement inhibitor. Both groups of sera were incubated in vitro with healthy leukocytes. Expression of Mac-1 and L-selectin on neutrophils was measured quantitatively by flow cytometry. To assess the consequences of these events in vivo, trypsinated serum with or without complement inhibition or control serum was infused intravenous into rats. Soybean trypsin inhibitor was added to serum before injections to block residual trypsin activity. Pancreatic and pulmonary injury was quantitated by histology, measurement of edema, and myeloperoxidase activity. RESULTS: Mac-1 expression on neutrophils incubated with pancreatitis serum was increased compared with controls, whereas L-selectin was decreased. Neutrophils incubated with trypsinated serum also showed upregulation of Mac-1 and downregulation of L-selectin, particularly with trypsin at 10(-4) mol/L. Addition of soluble complement receptor 1 abrogated both Mac-1 upregulation and L-selectin downregulation. Lungs of animals injected with trypsinated serum showed increased edema and myeloperoxidase activity, which were reduced by soluble complement receptor 1. CONCLUSIONS: Trypsin-generated complement activation participates in the upregulation of Mac-1 and shedding of L-selectin on neutrophils in acute pancreatitis. Protease or complement inhibition may be effective in preventing leukocyte migration and subsequent local and remote organ injury.

Analysis of Variance↗
PubMed2001

Promoting effect of a high-fat/high-protein diet in DMBA-induced ductal pancreatic cancer in rats.

OBJECTIVE: To investigate whether a high-fat/high-protein diet (HFPD) acts as a promoter of the natural course of cancer growth in the 7,12-dimethylbenzanthracene (DMBA)-induced ductal pancreatic cancer model in rats. SUMMARY BACKGROUND DATA: DMBA implantation to the rat pancreas induces ductal adenocarcinoma. Information regarding the effects of diet and the presence of K-ras mutation in this model is not available. METHODS: Rats were randomly assigned to regular rat chow or a diet with a 30% content in fat and protein (HFPD). The presentation of cancer, the histologic spectrum of neoplasia at 1 and 9 months, and the prevalence of cancer in relation to diet were assessed. Histologic specimens comprising normal ducts, hyperplasia, dysplasia/carcinoma in situ, or carcinoma were designated by a pathologist and microdissected. Genomic DNA was extracted, and K-ras and H-ras gene mutations were determined by a mutant-enriched polymerase chain reaction assay and direct sequencing. RESULTS: Rats fed HFPD increased their weight significantly compared with controls. DMBA induced characteristic stages of neoplasia at the implant site but not elsewhere. Macroscopic cancers of the pancreatic head presented regularly with common bile duct and gastric outlet obstruction. The prevalence of K-ras mutations was proportional to the degree of epithelial abnormality. K-ras mutations were significantly more frequent in cancer than in normal and hyperplastic ducts. H-ras mutations were not found. At 1 month in the HFPD-fed rats, the prevalence of cancer (16%) and dysplasia (16%) was not significantly different from the prevalence of cancer (29%) and dysplasia (8%) in the chow-fed rats. At 9 months the prevalence of cancer in the HFPD-fed rats increased to 29%, whereas that in the chow-fed rats decreased to 17%. The combined prevalence of cancer and dysplasia at 9 months in the HFPD-fed rats (34%) significantly exceeded that in the chow-fed rats. CONCLUSIONS: DMBA induces characteristic stages of neoplasia in the evolution of ductal pancreatic cancer in rats. K-ras mutations occur progressively in the ladder of oncogenesis, as in human pancreatic neoplasms. The addition of a diet with a high fat and protein content acts as a promoter of carcinogenesis, possibly by interfering with repair mechanisms and natural regression of early lesions.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Telomerase activity in periampullary tumors correlates with aggressive malignancy.

OBJECTIVE: To determine the presence of telomerase activity in a variety of periampullary malignancies and pancreatic diseases and quantify its activity to establish any association with the stage or aggressiveness of malignancy. SUMMARY BACKGROUND DATA: Progressive shortening of telomeres, repetitive DNA sequences at the ends of chromosomes, plays a role in cell senescence. Telomerase catalyzes conservation of telomeric repeats and may promote cell immortality and hence malignancy. It is absent in normal tissues but upregulated in more than 80% of cancers. METHODS: Fresh specimens of 62 periampullary tumors were snap-frozen in liquid nitrogen and adjacent tissue was formalin-fixed for histopathology. The telomerase repeat amplification protocol (TRAP) was used to obtain telomerase DNA products. These were separated with gel electrophoresis, stained with SYBR green, and quantified by densitometry. Findings were confirmed with a fluorometric TRAP assay in which fluorescent primers specific for telomerase were selectively amplified in its presence. RESULTS: Telomerase activity was upregulated in 26 of 33 periampullary malignancies (79%): 17 of 21 pancreatic adenocarcinomas (81%), 2 of 2 cholangiocarcinomas, 2 of 2 duodenal carcinomas, and 5 of 8 ampullary carcinomas (63%). Poorly differentiated periampullary tumors had significantly higher telomerase activity than well-differentiated tumors, and tumors larger than 2 cm had significantly higher telomerase activity than those 2 cm or smaller. Pancreatic ductal adenocarcinomas with lymph node metastases had significantly greater activity than node-negative cancers. Two of 11 intraductal papillary mucinous tumors were positive for telomerase activity, but only in foci of invasive carcinoma. Chronic pancreatitis (n = 7), serous cystadenomas (n = 5), benign mucinous cystic neoplasms (n = 4), neuroendocrine cancer (n = 1), and acinar cell carcinoma (n = 1) had no detectable telomerase activity. CONCLUSION: Telomerase activity is common in periampullary carcinomas. The magnitude of activity correlates with aggressiveness in pancreatic adenocarcinoma and may prove useful as a molecular index for biologic staging.

Adenocarcinoma↗
PubMed2001

Evaluation of morphology and microcirculation of the pancreas by ex vivo and in vivo reflectance confocal microscopy.

BACKGROUND: Near-infrared reflectance confocal microscopy (CM) provides non-invasive real-time images of thin virtual horizontal tissue sections with high resolution and contrast. AIM: Aim of the study was to characterize morphology, microcirculation and leukocyte-endothelial interaction (LEI) in normal pancreas by in vivo and ex vivo CM. METHODS: For CM we used water immersion objective lenses of high numerical aperture and near-infrared wavelengths. Experimentally measured lateral optical resolution is 0.5-1 micron and the axial resolution is 3-5 microns. The maximum depth of resolution was 300-400 microns. For ex vivo imaging, freshly excised pancreatic tissue from rats was studied by reflectance CM and conventional histopathology. For in vivo CM, the pancreatic head was exteriorized on a specially constructed stage for imaging the microcirculation and LEI. Images were obtained in real time at rates of 30 frames/s and later analyzed off-line to evaluate LEI and functional capillary density (FCD). RESULTS: CM allowed high resolution visualization of normal pancreas acinar cells, ducts, islets, capillaries and LEI in postcapillary venules. Histological images and optical sections from ex vivo CM can be correlated. Cellular morphology is better analyzed by conventional histology, but angioarchitecture and connective tissue structure are better evaluated by CM. FCD (265.7 +/- 16.6 cm-1) and LEI (rolling leukocytes 5.3 +/- 1.6/100 microns/sticking leukocytes 1.5 +/- 0.9/100 microns) were evaluated by in vivo CM in the normal pancreas. CONCLUSIONS: CM findings in tissues ex vivo correlate with those of classical histology but add informative details of connective tissue structure and angioarchitecture. Potential future applications for in vivo CM include real-time analysis of microcirculation, leukocyte-endothelial interaction and angiostructure in inflammatory and malignant pancreatic diseases.

Animals↗
PubMed2001

Cystic neoplasms of the pancreas.

Cystic tumors of the pancreas have become increasingly prevalent. In large series, more than 90% of pancreatic cystic neoplasms are accounted for by mucinous cystadenomas and cystadenocarcinomas, serous cystadenomas, and intraductal papillary mucinous tumors. Differentiating cystic neoplasms from pseudocysts can almost always be accomplished by clinical and radiological means, but in doubtful cases, when observation is contemplated, or when it is important to determine preoperatively the type of cystic neoplasm, cyst fluid analysis is useful. This can be readily obtained by endoscopic ultrasound, and analysis of enzymes, viscosity, cytology and a variety of tumor markers allows for a better differential diagnosis.

Cystadenoma, Mucinous↗
PubMed2000

Impact of laparoscopic staging in the treatment of pancreatic cancer.

HYPOTHESIS: Staging laparoscopy in patients with pancreatic cancer identifies unsuspected metastases, allows treatment selection, and helps predict survival. DESIGN: Inception cohort. SETTING: Tertiary referral center. PATIENTS: A total of 125 consecutive patients with radiographic stage II to III pancreatic ductal adenocarcinoma who underwent staging laparoscopy with peritoneal cytologic examination between July 1994 and November 1998. Seventy-eight proximal tumors and 47 distal tumors were localized. INTERVENTIONS: Based on the findings of spiral computed tomography (CT) and laparoscopy, patients were stratified into 3 groups. Group 1 patients had unsuspected metastases found at laparoscopy and were palliatedwithout further operation. Group 2 patients had no demonstrable metastases, but CT indicated unresectability due to vessel invasion. This group underwent external beam radiation with fluorouracil chemotherapy followed in selected cases by intraoperative radiation. Patients in group 3 had no metastases or definitive vessel invasion and were resection candidates. MAIN OUTCOME MEASURE: Survival. RESULTS: Staging laparoscopy revealed unsuspected metastases in 39 patients (31.2%), with 9 having positive cytologic test results as the only evidence of metastatic disease (group 1). Fifty-five patients (44.0%) had localized but unresectable carcinoma (group 2), of whom 2 (3.6%) did not tolerate treatment, 20 (36.4%) developed metastatic disease during treatment, and 21 (38.2%) received intraoperative radiation. Of 31 patients with potentially resectable tumors (group 3), resection for cure was performed in 23 (resectability rate, 74.2%). Median survival was 7.5 months for patients with metastatic disease, 10.5 months for those receiving chemoradiation, and 14.5 months for those who underwent tumor resection (P = .01 for group 2 vs. group 1; P<.001 for group 3 vs group 1). CONCLUSIONS: Staging laparoscopy, combined with spiral CT, allowed stratification of patients into 3 treatment groups that correlated with treatment opportunity and subsequent survival. Among the 125 patients, laparoscopy obviated 39 unnecessary operations and irradiation in patients with metastatic disease not detectable by CT. Laparoscopic staging can help focus aggressive treatment on patients with pancreatic cancer who might benefit.

Aged↗
PubMed2000

Laparoscopy and peritoneal cytology in the staging of pancreatic cancer.

Staging laparoscopy in patients with pancreatic cancer allows identification of metastatic disease which is beyond the resolution of computed tomography. Laparoscopic ultrasound, dissection, and/or peritoneal cytology may be used to enhance the sensitivity of the staging procedure. Our experience at Massachusetts General Hospital with staging laparoscopy and peritoneal cytology over the past 8 years (N = 239) reveals that approximately 30% of patients without metastases by computed tomography harbor occult metastatic disease at laparoscopy. Additionally, published series demonstrate accurate determination of resectability in greater than 75% of patients after staging laparoscopy. Staging laparoscopy in patients with pancreatic cancer allows optimization of resources and avoidance of unnecessary surgery.

Adult↗
PubMed2000

Cystic lesions in the pancreas: when to watch, when to resect.

The diagnosis of cystic lesions in the pancreas is becoming more common, largely due to the increases in diagnostic imaging done for other reasons. This review considers pseudocysts, mucinous cystic neoplasms, intraductal papillary mucinous tumors, and serous cystadenomas in some detail. The emphasis is on the fact that, through a careful history, physical examination, radiologic studies, and, often, cyst fluid analysis, a diagnosis can be reached expeditiously. This pursuit is important because two thirds of pancreatic cystic neoplasms are malignant or premalignant and should be resected, whereas pseudocysts and serous cystadenomas are benign, and, depending on the case, may be treated through observation, resection, or, for pseudocysts, by internal drainage.

Diagnosis, Differential↗
PubMed2000

Outcome of pancreaticoduodenectomy with pylorus preservation or with antrectomy in the treatment of chronic pancreatitis.

OBJECTIVE: To compare the short- and long-term results of pancreaticoduodenectomy with pylorus preservation (PPPD) or with antrectomy (Whipple procedure) in the treatment of selected patients with chronic pancreatitis. BACKGROUND: PPPD may be preferred over Whipple because of its purported nutritional advantages and the reduced likelihood of postgastrectomy syndromes. METHODS: A retrospective review was performed of 72 consecutive patients undergoing pancreaticoduodenectomy for chronic pancreatitis between 1991 and 1997. RESULTS: PPPD was performed in 39 patients and Whipple in 33. The two patient populations had similar characteristics. Short-term complications included (PPPD vs. Whipple): pancreatic or biliary fistulas (5.1% vs. 15%), delayed gastric emptying (33% vs. 12%), cholangitis (2.6% vs. 6.1%), and death (0 vs. 3%). Delayed gastric emptying was not associated with other complications and resulted in longer hospital stays for PPPD than for Whipple patients (15 vs. 12 days). The duration of follow-up averaged 41 +/- 24 months. Long-term weight status was similar, with body-mass indices of 22.1 and 22.9 after PPPD and Whipple, respectively. Postoperative enzyme supplementation (63% vs. 77%) and new-onset diabetes (10% vs. 12%) did not differ significantly between the PPPD and Whipple groups. Dumping, bile gastritis, or peptic ulcer disease occurred in three patients after PPPD and in three after Whipple. Complete or partial pain relief was attained in 60% and 70% of patients after PPPD and Whipple, respectively. Multivariate analysis of preoperative variables revealed that site-specific pathology in the head of the pancreas was the only independent factor associated with successful pain relief after pancreatic resection. CONCLUSION: PPPD results in higher frequencies of postoperative delayed gastric emptying compared with the Whipple procedure. Both operations achieve comparable long-term nutritional results, cause new insulin dependence in surprisingly few patients, and provide equivalent pain relief to 65% of selected patients. Patients with disproportionate pathology in the head of the pancreas have a higher likelihood of successful pain relief.

Adult↗
PubMed2000

Effect of matrix metalloproteinase inhibition on pancreatic cancer invasion and metastasis: an additive strategy for cancer control.

OBJECTIVE: To investigate the effect of a matrix metalloproteinase (MMP) inhibitor, BB-94, on the viability, invasion, and metastases of pancreatic cancer. SUMMARY BACKGROUND DATA: Inhibitors of MMPs, enzymes that degrade extracellular matrix, have been tested as single chemotherapeutic agents for pancreatic cancer. METHODS: Capan1 and AsPC1 cell lines were studied. BB-94 cytotoxicity was evaluated by cell proliferation assays. Production of MMP2 and MMP9 in conditioned media was demonstrated by gelatin zymography. The in vitro effect of BB-94 on cell invasion was assayed using invasion chambers. Hepatic metastases from pancreatic cancer were induced by intrasplenic injections of Capan1 or AsPC1 cells in nude mice. The in vivo effect of BB-94 on liver metastases was evaluated by comparing animals receiving BB-94 treatment with controls receiving vehicle alone. Variables measured included death rate and tumor burden (liver-to-body weight ratio). RESULTS: BB-94 was not cytotoxic between 3 and 3,000 ng/mL. Zymography demonstrated production of MMP2 and MMP9 by both cell lines, with complete inhibition of these enzymes by BB-94 at 48 ng/mL. Invasion chamber assays showed that BB-94 (48-400 ng/mL) impeded cell invasion in vitro compared with untreated controls. In vivo, BB-94 prevented death or reduced the death rate from hepatic metastases in animals injected with Capan1 or AsPC1 cells. BB-94 treatment resulted in significant reductions in hepatic tumor burden compared with untreated controls. CONCLUSIONS: Inhibition of MMP reduces both growth of pancreatic cancer metastases and the death rate. These actions do not reflect cytotoxicity but rather result from impaired cancer cell attachment, migration, and organ invasion. MMP inhibitors may provide an additive effect to cytotoxic agents in multidimensional treatment regimens for pancreatic cancer.

Animals↗