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K Lewandrowski

Publications and source records attributed to K Lewandrowski.

18 recordsLinked to original sources
PubMed1995

Late histopathologic changes and healing in an improved rodent model of acute necrotizing pancreatitis.

Studies of experimental pancreatitis have generally focussed on early time points rather than the stages of healing and resolution or scarring. We recently characterized a new pancreatitis model of moderate severity by combining intraductal infusion of very low concentrations of glycodeoxycholic acid with intravenous caerulein. This study evaluates late histopathologic changes and gross complications in this pancreatitis model compared to the traditionally used high-dose bile salt model in rats. After 14 days, histopathologic features of caerulein pancreatitis were not different from saline controls. High-dose intraductal bile salt infusion resulted in widespread chronic inflammation, acinar dilation and atrophy, marked reactive stromal proliferation, and ductular budding with periductal fibrosis. In contrast, animals receiving low-dose intraductal bile salt infusion combined with intravenous caerulein demonstrated a moderate degree of chronic inflammation and acinar atrophy along with an intermediate degree of periductal fibrosis and stromal reaction. We conclude that due to its moderate degree of injury, this model may be useful for the study of tissue injury and repair following acute pancreatitis.

Acute Disease↗
PubMed1995

Cyst fluid analysis in the differential diagnosis of pancreatic cysts: a new approach to the preoperative assessment of pancreatic cystic lesions.

Pancreatic cysts include pseudocysts, serous tumors, and mucinous tumors, some of which are malignant. The clinical and radiologic features of these lesions may not permit a preoperative diagnosis. Analysis of percutaneous cyst fluid aspirates for cytologic findings, tumor markers, enzymes, and viscosity has been proposed as an aid to differential diagnosis. The combination of cytologic findings, carcinoembryonic antigen level, and viscosity will usually differentiate mucinous from nonmucinous cysts, whereas cytologic findings and levels of tumor markers CA 15-3 and CA 72-4 are useful to predict malignancy. Pseudocysts can be identified by a combination of cytologic features; levels of tumor markers, including NB/70K; and levels of enzymes, including amylase isoenzymes and leukocyte esterase. Serous tumors are a diagnosis of exclusion, although in 50% of cases the cytologic findings will indicate a serous tumor. When compared with conventional methods of differentiating pancreatic cysts, cyst fluid analysis is a promising new approach to the evaluation of these diagnostically difficult lesions.

Amylases↗
PubMed1994

Utilization and cost analysis of bedside capillary glucose testing in a large teaching hospital: implications for managing point of care testing.

PURPOSE: To study the use and cost of bedside capillary glucose testing in a large teaching hospital. PATIENTS AND METHODS: In a prospective study of 40 inpatient units and 10 outpatient units at Massachusetts General Hospital, records were maintained by each unit of the date, time, operator, and results of patient and quality control tests. Cost analysis was performed using data from time studies, test tallies in logbooks, and hospital administration records. RESULTS: The number of glucose meters in the hospital increased from 10 to 54 over a 2-year period. In 1992, 67,596 tests were performed by the bedside method, representing 30.7% of all glucose measurements performed in the institution. The majority of tests (94.7%) were performed on inpatients, and 10.2% of all hospital admissions underwent bedside glucose testing. The impact on the number of glucose tests performed in the clinical laboratories was minimal, indicating that bedside glucose testing was added as an extra test rather than as a substitute for laboratory-based glucose measurements. The cost of bedside glucose testing was $4.19 per test compared with $3.84 in the clinical laboratory. The cost varied from one unit to another (median $5.52, range $3.08 to $48.16), an effect largely attributed to the difference in the volume of tests performed by different units. In seven high-volume units the cost per test was lower than the corresponding value in the laboratory. The cost of bedside glucose testing included labor (80.2%) and supplies (19.8%). The percent of costs attributed directly to patient testing was 57.7%, whereas the costs for all other related activities (training, quality control, and quality assurance) was 42.3%. CONCLUSIONS: Bedside capillary glucose testing is a rapidly expanding technology and is performed on a significant percentage of hospital admissions. Bedside glucose testing is not inherently more expensive than centralized laboratory measurements but implementation on inefficient care units with low utilization can add substantially to the cost. Much of the excess cost of the bedside method can be attributed to the high costs of quality control and quality assurance, training, and documentation.

Blood Glucose↗
PubMed1994

Failure of pentoxifylline to ameliorate severe acute pancreatitis in the rat: results of a prospective, randomized, controlled study.

OBJECTIVE: To investigate the benefit of pentoxifylline in severe experimental pancreatitis. DESIGN: Prospective, randomized, controlled study. SETTING: Experimental animal laboratory in a University hospital. SUBJECTS: Forty-two adult male Sprague-Dawley rats. INTERVENTIONS: Acute pancreatitis was induced by supramaximal stimulation with cerulein plus a pressure and volume controlled 10 min intraductal infusion of 10-mM glycodeoxycholic acid. Thirty minutes after pancreatitis was induced, animals were randomized to receive pentoxifylline (60 mg/kg over 2.5 hrs), or saline. All animals received fluid resuscitation with lactated Ringer's solution (8 mL/kg/hr), and surviving animals were killed at 24 hrs. MEASUREMENTS AND MAIN RESULTS: There was a progressively significant decrease in mean arterial pressure after pancreatitis was induced, with no difference between pentoxifylline-treated rats and controls. Hematocrit increased significantly in both groups at 6 hrs, and returned to baseline values at 24 hrs. Ascites volume and levels of trypsinogen activation peptide in plasma and ascites were similar in both groups. Twenty-four hour mortality was 47% for the pentoxifylline group and 52% for the control group. Histologic scores for necrosis, edema, inflammation, and hemorrhage showed no significant differences between the two groups. CONCLUSION: Treatment with pentoxifylline failed to improve outcome in a model of severe acute pancreatitis in the rat.

Acute Disease↗
PubMed1994

Pancreatic cystic islet-cell tumors. Clinical and pathologic features in two cases with cyst fluid analysis.

Cystic islet-cell tumors are rare neoplasms that may be confused with more familiar cystic pancreatic lesions, such as pseudocysts, serous cystadenoma, and mucinous tumors. Analysis of aspirated cyst fluid for tumor markers (carcinoembryonic antigen [CEA], CA-125, and CA-15.3), enzymes (amylase and lipase), viscosity, and cytology has been proposed as an aid to preoperative differential diagnosis. These tests will distinguish mucinous from nonmucinous cysts and usually help in determining malignancy. However, cyst fluid parameters from rarer types of pancreatic cystic tumors have not been described. We report the clinical and pathologic features of two cystic islet-cell tumors including cyst fluid parameters in one of the cases. Two cases of cystic islet-cell tumors were identified by clinical history, histopathologic, and immunohistochemical techniques. Cyst fluid was aspirated intraoperatively from one case and analyzed for CEA, CA-125, CA 15.3, insulin, amylase, viscosity, and cytology. Cyst fluid analysis showed low values for CEA, CA-125, and CA-15.3, low viscosity, and variable amylase content. This spectrum of findings is similar to that of serous cystadenomas. Cyst fluid cytologic examination was positive for neuroendocrine-type epithelial cells and insulin levels were elevated, observations indicative of an islet-cell tumor. Analysis of fluid from cystic islet-cell tumors may aid in the preoperative differentiation of these tumors from more common pancreatic cystic lesions. These findings represent the first report of the characteristics of the fluid in these uncommon tumors.

Adenoma, Islet Cell↗
PubMed1993

Resection margins in carcinoma of the head of the pancreas. Implications for radiation therapy.

A retrospective review of the pathology and clinical course of 72 patients undergoing resection of carcinoma of the head of the pancreas was undertaken to identify the frequency of tumor involvement at standard surgical transection margins (stomach, duodenum, pancreas, and bile duct) as well as the peripancreatic soft tissue margin and the potential clinical significance of these findings. Of 72 patients undergoing resection, 37 patients (51%) were found to have tumor extension to the surgical margins. The most commonly involved margin was peripancreatic soft tissue (27 patients) followed by pancreatic transection line (14 patients) and bile duct transection line (4 patients). For 37 patients with tumor present at a resection margin, there were no survivors beyond 41 months. No difference in survival or local control was seen between 14 patients receiving postoperative radiation therapy and 5-fluorouracil (5-FU) compared with 23 patients not receiving additional treatment. In contrast, the 5-year actuarial survival and local control of 35 patients undergoing resection without tumor invasion to a resection margin was 22% and 43%, respectively. The 5-year survival and local control of 16 patients receiving adjuvant radiation therapy and 5-FU was 29% and 42%, respectively, whereas these figures were 18% and 31% for 19 patients not receiving adjuvant therapy (p > 0.10). Because residual local tumor after resection is common, preoperative radiation therapy may be beneficial in this disease. It should minimize the risk of dissemination during operative manipulation and facilitate a curative resection by promoting tumor regression. Because local failure rates approach 60% after resection and adjuvant therapy even in cases having clear resection margins, intraoperative radiation therapy to the tumor bed at the time of resection also might be considered. Protocols evaluating the feasibility and efficacy of preoperative radiation therapy and resection with intraoperative radiation therapy for patients with pancreatic cancer are underway.

Actuarial Analysis↗
PubMed1992

Are there patients with stage I rectal carcinoma at risk for failure after abdominoperineal resection?

The clinical courses of 64 patients undergoing abdominoperineal resection for Stage I lower rectal carcinoma (tumors confined to the muscularis propria without lymph node involvement) were reviewed to identify subsets at risk for failure. Twelve of 12 patients with tumors limited to the submucosa remained disease free without evidence of recurrence. Of the 52 patients with muscularis propria involvement, there have been eight failures with three patients having local failure only, three patients with local failure and distant metastases, and two patients with distant metastases only. The 6-year actuarial disease-free survival, local control, and freedom from distant metastases rates for patients with tumors invasive of the muscularis propria were 80%, 84%, and 88%, respectively. Patients with tumors exhibiting vascular/lymph vessel involvement were at even higher risk for failure. Although adjuvant treatment is infrequently advised for these patients, the use of radiation therapy and chemotherapy should be reconsidered for patients with Stage I lower rectal carcinoma, specifically for patients with tumors invasive of the muscularis propria with vascular/lymph vessel involvement.

Abdomen↗
PubMed1992

Histopathologic correlates of serum amylase activity in acute experimental pancreatitis.

The association of serum amylase activity with the extent of pancreatic injury in acute pancreatitis is unclear. To clarify this relationship, we induced acute pancreatitis ranging from mild to lethal in 118 Sprague-Dawley rats (350-450 g). This was achieved by controlled intraductal infusion of low- or high-dose bile salt, with or without enterokinase, followed by intravenous cerulein or saline for 6 hr. Serum amylase was measured at baseline and 6 hr. Pancreatic histopathology was evaluated by two blinded pathologists employing total surface scoring (N = 118) and morphometric 20-field documentation (N = 22). Serum amylase correlated best with edema (r = 0.61) and fat necrosis (r = 0.58), less well with acinar necrosis (r = 0.53) and inflammation (r = 0.50), and poorly with hemorrhage (r = 0.33) and perivascular infiltrate (r = 0.31). Inasmuch as edema and fat necrosis are not important determinants of severity, these observations could explain the poor prognostic value of serum amylase activity in patients with acute pancreatitis.

Acute Disease↗
PubMed1992

Implementation of capillary blood glucose monitoring in a teaching hospital and determination of program requirements to maintain quality testing.

PURPOSE: To study the implementation of bedside capillary glucose monitoring using a hospital-wide quality control (QC) program. METHODS: A prospective study of QC performance in 7 outpatient and 39 inpatient treatment units was performed in a large teaching hospital over a 2-year period. Approximately 800 nurses were trained to perform bedside capillary glucose monitoring (Accu-Chek II, Boehringer-Mannheim, Indianapolis, IN). An eight-point QC program was instituted including proficiency testing, instrument maintenance, performance of daily controls, storage of reagent strips and supplies, instrument calibration, and documentation procedures. RESULTS: Comparison of laboratory and bedside test results (split-sample proficiency testing) revealed Y = 1.004X + 7.26, r = 0.95, with a mean percent difference of -4.2% (p < 0.001). Less than 7% of results fell outside +/- 20% of the laboratory results. QC scores (0 = worst to 4 = best), based on adherence to the QC program, improved from 0 on the first inspection to 3.7 +/- 0.17 by the 11th inspection. The most common QC deficiencies were failure to perform split-sample testing (41.4%) and failure to perform instrument maintenance (30.2%). Significant differences were noted in the QC performance of different types of medical services. During the 2-year study period, the total number of glucose assays performed in the clinical laboratories decreased by 22.2% concurrent with initiation of bedside testing. The number of instruments in the hospital increased from 10 to 46. CONCLUSIONS: Bedside capillary glucose assays can be widely implemented in large hospitals with an acceptable degree of accuracy. QC programs with frequent inspections are necessary to identify units that function inadequately, and a formal disciplinary policy is required to ensure compliance with the program.

Blood Glucose↗
PubMed1992

Trypsinogen-activation peptides in experimental rat pancreatitis: prognostic implications and histopathologic correlates.

Intrapancreatic activation of trypsinogens is believed to occur either as a cause or a consequence of acute pancreatitis and to be associated with the more severe forms of the disease. Trypsinogen-activation peptides (TAPs) were measured in plasma, urine, and ascites of rats (n = 54) assigned to different pancreatitis-inducing regimens reproducing the entire spectrum of severity. Compared with survivors, nonsurvivors at 9 hours had significantly higher TAP levels in plasma at 3 hours (P = 0.0001), urine (peak, 1-4 hours) (P = 0.004), and ascites (P = 0.0001) after death. Stepwise discriminant analysis showed that TAP in urine and plasma were the most accurate predictors of outcome (88.2% of animals) compared with other routine laboratory parameters. Morphometric analysis showed that the best histopathologic correlates of TAP elevation were acinar necrosis and intrapancreatic hemorrhage. In a second series of experiments using a homogeneous technique of induction producing pancreatitis with a mortality of 55% at 48 hours, plasma TAP level at 3 hours (cutoff, 0.5 nmol/L) and/or urinary TAP level (peak, 1-6 hours; cutoff, 25 nmol/L) accurately predicted outcome in 85% of animals. It is concluded that the TAP assay gives an accurate early prediction of outcome in different pancreatitis models and correlates best with acinar necrosis and hemorrhage.

Acute Disease↗
PubMed1992

Macrocystic serous cystadenoma of the pancreas: a morphologic variant differing from microcystic adenoma.

The term "microcystic adenoma" of the pancreas has gained nearly universal acceptance among pathologists owing to the characteristic gross and microscopic features of this tumor. The possible existence of macrocystic variants of serous cystadenoma has been largely ignored in the literature. We report five cases of macrocystic serous cystadenoma of the pancreas, two of which were of the unilocular type. These tumors exhibited distinctly different macroscopic features from microcystic adenoma, which created diagnostic difficulties for both the radiologist and pathologist. Computed tomography scans on all five cases were thought to represent either mucinous cystic neoplasms or pseudocysts and the tumors were misclassified in two of three cases on which intraoperative frozen sections were performed. In our opinion, microcystic and macrocystic serous tumors represent morphologic variants of the same benign pancreatic neoplasm and we suggest that the term "serous cystadenoma" be used to encompass all variants of this benign neoplasm.

Adenoma↗
PubMed1992

A better model of acute pancreatitis for evaluating therapy.

Existing models of acute pancreatitis have limitations to studying novel therapy. Whereas some produce mild self-limited pancreatitis, others result in sudden necrotizing injury. The authors developed an improved model providing homogeneous moderately severe injury by superimposing secretory hyperstimulation on minimal intraductal bile acid exposure. Sprague-Dawley rats (n = 231) received low-pressure intraductal glycodeoxycholic acid (GDOC) at very low (5 or 10 mmol/L) concentrations followed by intravenous cerulein. Cerulein or GDOC alone caused only very mild inflammation. However, GDOC combined with cerulein was uniformly associated with more edema (p less than 0.0005), acinar necrosis (p less than 0.01), inflammation (p less than 0.006), and hemorrhage (p less than 0.01). Pancreatic injury was further increased and death was potentiated by increasing volume and duration of intraductal low-dose GDOC infusion. There was significant morphologic progression between 6 and 24 hours. The authors conclude that (1) combining minimal intraductal bile acid exposure with intravenous hyperstimulation produces homogeneous pancreatitis of intermediate severity that can be modulated at will; (2) the injury is progressive over at least 24 hours with finite mortality rate; (3) the model provides superior opportunity to study innovative therapy.

Acute Disease↗
PubMed1992

Generation and possible significance of trypsinogen activation peptides in experimental acute pancreatitis in the rat.

Trypsinogen activation peptides (TAP) were quantified by radioimmunoassay in blood, urine, and peritoneal exudate of rats with experimental pancreatitis. Forty-four animals were studied, comprising a control group and four different induction techniques (cerulein, cerulein plus either 2- or 10-min intraductal glycodeoxycholic acid [GDOC] infusion, and cerulein plus intraductal GDOC with enterokinase [EK]). Significantly higher TAP concentrations were found at 6 h (or at death) in plasma and ascites of all pancreatitis groups compared with controls. TAP quantitation in hourly urine samples demonstrated significantly higher concentrations from the third hour onward in the most severe groups and from the fourth hour onward in the cerulein-treated rats. All nonsurviving rats had a plasma TAP of greater than 2.5 nM/L, whereas only 1 of 34 surviving animals had such a concentration (p less than 0.001). A significant stepwise increase in total TAP in ascites was found when comparing the cerulein group, the two GDOC groups, and the EK group (p less than 0.001). Chromatography of samples with a high TAP content demonstrated comigration with synthetic TAP. We conclude that free TAP are present in blood, urine, and peritoneal exudate of rats with experimental pancreatitis of different pathogenesis and that the amount of TAP may be indicative of the severity of the disease process.

Acute Disease↗
PubMed1992

Investigation of N-methyl-D-glucamine buffer for assay of alkaline phosphatase in serum.

We evaluated N-methyl-D-glucamine (MEG) as a buffer for assay of alkaline phosphatase (ALP; EC 3.1.3.1) and compared the MEG-based assay with the current International Federation of Clinical Chemistry Reference Method for ALP (IFCC/RM/ALP), in which 2-amino-2-methyl-1-propanol (AMP) is the pH buffer. The ALP assay in MEG at 30 and 37 degrees C shows excellent correlation with the IFCC/RM/ALP at 30 degrees C, but yields proportionately higher ALP activities (8.2% at 30 degrees C and 57% at 37 degrees C). ALP is unstable in both MEG and AMP at 37 degrees C. Serum incubated in MEG undergoes a pH-dependent biphasic loss of ALP activity: an initial rapid 5% loss after 1 min of incubation and a 10% loss per hour thereafter. A similar pattern was seen for incubation with AMP. The use of a serum-initiated reaction (no preincubation of enzyme with buffer) eliminated the early loss in activity. The addition of the metal ion buffer N-hydroxyethylethylenediaminetriacetic acid, along with low concentrations of Zn and Mg, as used in the IFCC/RM/ALP, reduced the slow loss in activity over time, as did decreasing the reaction temperature to 30 degrees C, but had no effect on the early rapid decay in activity seen in the first minute. Moderate transphosphorylation (45%) and nonenzymatic hydrolysis (3.3 U/L) were observed with MEG under the conditions of the assay (37 degrees C). A comparison of different lots of MEG from two manufacturers showed no significant difference in ALP activities.

Alkaline Phosphatase↗
PubMed1990

Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients.

Within a 12-year period we treated 67 patients (49 women, 18 men; mean age, 61 years) with cystic neoplasms of the pancreas, including 18 serous cystic adenomas, 15 benign mucinous cystic neoplasms, 27 mucinous cystadenocarcinomas, 3 papillary cystic tumors, 2 cystic islet cell tumors, and 2 cases of mucinous ductal ectasia. Mean tumor size was 6 cm (2 to 16 cm). In 39% the patients had no symptoms, and in 37% the lesions had been misdiagnosed as a pseudocyst. Computed tomography was useful for detection, for distinguishing the microcystic subgroup of serous cystadenoma, and for showing rim calcification (all 7 cases were malignant) but was not reliable for distinguishing neoplasm from pseudocyst, serous from mucinous tumors, or benign from malignant. Arteriography showed hypervascularity in 4 of 10 serous adenomas, 3 of 11 mucinous carcinomas, and 1 of 1 papillary cystic tumors. Endoscopic pancreatography showed no communication with the cyst cavity in 37 of 37 cases of cystic neoplasms but opacified the ectatic ducts in 2 of 2 cases of mucinous ductal ectasia. Stenosis or obstruction of the pancreatic duct indicated cancer. The tumor was resected by distal pancreatectomy in 25 patients, by proximal resection in 29, and by total pancreatectomy in one, with no operative deaths. Forty-four per cent of the tumors were malignant. In 10 cases the tumor was unresectable because of local extension or distant metastases, and those patients died at a mean of 4 months. Seventy-five per cent of those resected for cure are alive without evident recurrence. Because the epithelial lining of the tumor was partially (5% to 98%) absent in 40% to 72% of cases of the major tumor types, and the mucinous component comprised only about 65% of mucinous cystadenoma lining, misdiagnoses on frozen and even permanent sections were made. Mitoses and histologic solid growth correlated with malignancy. Neuroendocrine elements were seen in 87% of benign and 47% of malignant mucinous tumors. It is recommended that the terms macrocystic and microcystic be abandoned in favor of the histologic designations serous and mucinous. Incomplete examination of the cyst wall can be misleading, however. It is suggested that mucinous ductal ectasia be recognized separately from cystic tumors and that all of these lesions be resected, with the possible exception of asymptomatic confirmed serous cystadenomas.

Adenocarcinoma, Mucinous↗
PubMed1982

Macrophage surface component gp160: sensitivity to plasmin and other proteases.

The correlation between activation of macrophages and increased secretion of plasminogen activator suggests that macrophages are exposed to the protease plasmin. Incubation of 125I-labeled, caseinate-elicited guinea pig peritoneal macrophages with plasmin cleaves a surface protein, gp160, characterized previously by its sensitivity to trypsin. The gp160 fragments produced by plasmin (fr85 and fr71), which remain disulfide-bonded in the membrane, comigrate with the fragments produced by trypsin, indicating close or identical cleavage sites. No other detectable 125I-labeled surface component is cleaved by plasmin. Neither gp160 nor any other detectable 125I-labeled surface component was cleaved by a series of other proteases associated with inflammation including thrombin, collagenase, pancreatic elastase, leukocyte elastase, cathepsin G, and urokinase. Analysis with the use of homogeneous plasmin from guinea pig plasma shows that concentrations as low as 50 micrograms/ml cause measurable cleavage of gp160 in 30 min.

Animals↗