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Andrew L Warshaw

Publications and source records attributed to Andrew L Warshaw.

At least 37 records · Page 2Linked to original sources
PubMed2005

Endoscopic ultrasound guided fine needle aspiration biopsy of autoimmune pancreatitis: diagnostic criteria and pitfalls.

Autoimmune pancreatitis (AIP) is a benign inflammatory disease of the pancreas that mimics pancreatic malignancy both clinically and radiologically. The fine needle aspiration biopsy (FNAB) features of AIP have not previously been documented. We report our experience with AIP, highlight pitfalls, and perform a comprehensive analysis of the cytomorphologic features of this condition. We identified 16 patients with AIP, initially evaluated by endoscopic ultrasound (EUS)-guided FNAB, 11 of whom subsequently underwent a pancreatoduodenectomy. We compared these to a cohort of EUS-guided aspirates from ductal carcinoma of the pancreas (n = 16) and chronic pancreatitis, not otherwise specified (NOS) (n = 19). On all 51 cases, we semiquantitatively evaluated presence and atypia of ductal cells, presence and cellularity of stromal fragments, and inflammatory cells, type and distribution. Fifty percent (8 of 16) of the AIP cases presented as obstructive jaundice. EUS and CT scan showed mass lesions in 10 and 6 cases, respectively. There were three false-positive cytologic diagnoses, an adenocarcinoma, a solid-pseudopapillary tumor and a mucinous neoplasm. Ductal epithelium was inconspicuous and was seen in 6 cases. The FNAB samples showed background lymphocytes in three AIP cases, a feature absent in the control cohort. Stromal fragments with embedded lymphocytes (greater than 30 per 60x) were seen in 37.5% of AIP cases and only rarely with adenocarcinoma (12.5%) and pancreatitis, NOS (0%). The cellularity of stromal fragments was significantly higher in AIP than in the control group. The presence of stromal fragments of high cellularity with a lymphoid infiltrate in conjunction with clinical and radiology findings could potentially both establish a diagnosis of AIP and exclude carcinoma, thus preventing pancreatic resection.

Adenocarcinoma↗
PubMed2005

Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer.

SUMMARY BACKGROUND DATA: To analyze the effects of a treatment program of intraoperative electron beam radiation therapy (IOERT) and external beam radiation therapy and chemotherapy on the outcome of patients with unresectable or locally advanced pancreatic cancer. METHODS: From 1978 to 2001, 150 patients with unresectable and nonmetastatic pancreatic cancer received IOERT combined with external beam radiation therapy and 5-fluorouracil-based chemotherapy for definitive treatment. RESULTS: The 1-, 2-, and 3-year actuarial survival rates of all 150 patients were 54%, 15%, and 7%, respectively. Median and mean survival rates were 13 and 17 months, respectively. Long-term survival has been observed in 8 patients. Five patients have survived beyond 5 years and 3 more between 3 and 4 years. There was a statistically significant correlation of survival to the diameter of treatment applicator (a surrogate for tumor size) used during IOERT. For 26 patients treated with a small-diameter applicator (5 cm or 6 cm), the 2- and 3-year actuarial survival rates were 27% and 17%, respectively. In contrast, none of the 11 patients treated with a 9-cm-diameter applicator survived beyond 18 months. Intermediate survival rates were seen for patients treated with a 7- or 8-cm-diameter applicator. Operative mortality was 0.6%, and postoperative and late complications were 20% and 15%, respectively. CONCLUSIONS: A treatment strategy employing IOERT has resulted in long-term survival in 8 of 150 patients with unresectable pancreatic cancer. Survival benefit was limited to patients with small tumors. Enrollment of selected patients with small tumors into innovative protocols employing this treatment approach is appropriate.

Adult↗
PubMed2005

Gastrointestinal complications in patients undergoing heart operation: an analysis of 8709 consecutive cardiac surgical patients.

INTRODUCTION: Gastrointestinal (GI) complications following heart operation may be life-threatening. Systematic analysis of risk factors to allow early identification of patients at risk for GI complication may lead to the development of strategies to mitigate this complication as well as to optimize management after its occurrence. METHODS: Of 8709 consecutive patients undergoing heart operation during 7 years (1997-2003), 46 (0.53%) developed GI complications requiring surgical consultation. Preoperative, intraoperative, and postoperative predictors of complication and death were identified and compared with a control group. RESULTS: Significant (P < 0.05) preoperative predictors of complication were prior cerebrovascular accident (CVA), chronic obstructive pulmonary disease (COPD), type II heparin-induced thrombocytopenia, atrial fibrillation, prior myocardial infarction, renal insufficiency, hypertension, and need for intra-aortic balloon counter-pulsation. The most frequent serious GI complication was mesenteric ischemia, which developed in 31 (67%) patients. Twenty-two (71%) of these patients were explored, and 14 (64%) died within 2 days of heart operation. Of the 9 patients with mesenteric ischemia who were not explored, 7 (78%) died within 3 days of heart operation. Other complications included diverticulitis (5), pancreatitis (4), peptic ulcer disease (4), and cholecystitis (2). The mortality rate in this group of other diagnoses was lower (40%), and death occurred later (32 days) after heart operation (P = 0.03 compared with mesenteric ischemia). Predictors of death from GI complication included New York Heart Association (NYHA) class III and IV heart failure, smoking, chronic obstructive pulmonary disease, history of syncope, aspartate aminotransferase (AST) >600 U/L, direct bilirubin >2.4 mg/dL, pH < 7.30, and the need for >2 pressors. CONCLUSIONS: The most common catastrophic GI complication after cardiac surgery is mesenteric ischemia, which is frequently fatal. This complication may be a result of atheroembolization, heparin-induced thrombocytopenia, or hypoperfusion. Techniques to reduce the occurrence of and/or preemptively diagnosis postcardiotomy mesenteric ischemia are necessary to decrease its associated mortality.

Adult↗
PubMed2005

Serous cystadenoma of the pancreas: tumor growth rates and recommendations for treatment.

OBJECTIVE: To define the natural history and optimal management of serous cystadenoma of the pancreas. SUMMARY BACKGROUND DATA: Serous cystadenoma of the pancreas is the most common benign pancreatic neoplasm. Diagnostic criteria, potential for growth or malignancy, and outcomes are not well defined. As a result, management for patients with serous cystadenomas varies widely in current practice. METHODS: A total of 106 patients presenting with serous cystadenoma of the pancreas from 1976-2004 were identified. Hospital records were evaluated for patient and tumor characteristics, diagnostic workup, treatment, and outcome. Twenty-four patients with serial radiographic imaging were identified, and tumor growth curves calculated. RESULTS: Mean age at presentation was 61.5 years and 75% of patients were female. The most common symptoms were abdominal pain (25%), fullness/mass (10%), and jaundice (7%); 47% were asymptomatic. Mean tumor diameter was 4.9 +/- 3.1 cm, which did not vary by location. Tumors <4 cm were less likely to be symptomatic than were tumors > or =4 cm (22% vs. 72%, P < 0.001). The median growth rate in the patients who had serial radiography was 0.60 cm/y. For tumors <4 cm at presentation (n = 15), the rate was 0.12 cm/y, whereas for tumors > or =4 cm (n = 9), the rate was 1.98 cm/y (P = 0.0002). Overall, 86 patients underwent surgery, with one perioperative death. CONCLUSIONS: Large (>4 cm) serous cystadenomas are more likely to be symptomatic. Although the median growth rate for this neoplasm is only 0.6 cm/y, it is significantly greater in large tumors. Whereas expectant management is reasonable in small asymptomatic tumors, we recommend resection for large serous cystadenomas regardless of the presence or absence of symptoms.

Aged↗
PubMed2004

Autoimmune pancreatitis: imaging features.

PURPOSE: To retrospectively determine imaging findings in patients with autoimmune pancreatitis. MATERIALS AND METHODS: Twenty-nine patients (25 male and four female; mean age, 56 years; range, 15-82 years) with histopathologic diagnosis of autoimmune pancreatitis were examined. Data were reviewed by two radiologists in consensus. Imaging findings for review included those from helical computed tomography (CT), 25 patients; magnetic resonance (MR) imaging with MR cholangiopancreatography (MRCP), four patients; endoscopic ultrasonography (US), 21 patients; endoscopic retrograde cholangiopancreatography (ERCP), 19 patients; and percutaneous transhepatic cholangiography, one patient. Images were analyzed for appearances of pancreas, biliary and pancreatic ducts, and other findings, such as peripancreatic inflammation, encasement of vessels, mass effect, pancreatic calcification, peripancreatic nodes, and peripancreatic fluid collection. Follow-up images were available in nine patients. Serologic markers such as serum immunoglobulin G (IgG) and antinuclear antibody levels were available in 12 patients. RESULTS: CT showed diffuse (n = 14) and focal (n = 7) enlargement of pancreas. Seven patients had minimal peripancreatic stranding, with lack of vascular encasement, calcification, or peripancreatic fluid collection. Nine patients had enlarged peripancreatic lymph nodes. MR imaging showed focal (n = 2) and diffuse (n = 2) enlargement with rimlike enhancement in one. MRCP revealed pancreatic duct strictures in two and sclerosing cholangitis-like appearance in one. Endoscopic US showed diffuse enlargement of pancreas with altered echotexture in 13 patients and focal mass in the head in six. ERCP showed stricture of distal common bile duct in 12 patients, irregular narrowing of intrahepatic ducts in six, diffuse irregular narrowing of pancreatic duct in nine, and focal stricture of proximal pancreatic duct in six. Serologic markers showed increased IgG and antinuclear antibody levels in seven of 12 patients. At follow-up, CT abnormalities and common bile duct strictures resolved after steroid therapy in three patients. CONCLUSION: Features that suggest autoimmune pancreatitis include focal or diffuse pancreatic enlargement, with minimal peripancreatic inflammation and absence of vascular encasement or calcification at CT and endoscopic US, and diffuse irregular narrowing of main pancreatic duct, with associated multiple biliary strictures at ERCP.

Adolescent↗
PubMed2004

Membrane-bound ICAM-1 is upregulated by trypsin and contributes to leukocyte migration in acute pancreatitis.

In acute pancreatitis, ICAM-1 is upregulated in various organs and contributes to the development of organ injury. To investigate the effects of pancreatic proteases on ICAM-1 expression and their role in the early process of leukocyte migration, human umbilical vein endothelial cells (HUVECs) were incubated with serum subjected to limited trypsin digestion and Wistar rats were injected with trypsin. Significant upregulation of membrane-bound ICAM-1 was seen on HUVECs incubated with trypsinated serum. Likewise, soluble ICAM-1 increased in the supernatant of HUVECs. Changes of membrane-bound ICAM-1 and soluble ICAM-1 were maximal with high concentrations of trypsin. HUVECs incubated with TNF-alpha (positive control) showed similar changes. In the pancreas and lungs of animals infused with trypsin, ICAM-1 and leukocyte sequestration were increased compared with controls. Reflecting the relevance of protease-induced ICAM-1 expression in leukocyte migration, leukocyte-endothelium interaction, as assessed by intravital microscopy, was markedly increased by trypsin. Inhibition of ICAM-1 ameliorated these changes significantly. In conclusion, trypsinated serum induces the upregulation of both membrane-bound ICAM-1 on endothelial cells and soluble ICAM-1. These changes contribute to the early steps of leukocyte migration in acute pancreatitis. The role of soluble ICAM-1 remains to be investigated.

Acute Disease↗
PubMed2004

Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study.

BACKGROUND & AIMS: Cysts of the pancreas display a wide spectrum of histology, including inflammatory (pseudocysts), benign (serous), premalignant (mucinous), and malignant (mucinous) lesions. Endoscopic ultrasonography (EUS) may offer a diagnostic tool through the combination of imaging and guided, fine-needle aspiration (FNA). The purpose of this investigation was to determine the most accurate test for differentiating mucinous from nonmucinous cystic lesions. METHODS: The results of EUS imaging, cyst fluid cytology, and cyst fluid tumor markers (CEA, CA 72-4, CA 125, CA 19-9, and CA 15-3) were prospectively collected and compared in a multicenter study using histology as the final diagnostic standard. RESULTS: Three hundred forty-one (341) patients underwent EUS and FNA of a pancreatic cystic lesion; 112 of these patients underwent surgical resection, providing a histologic diagnosis of the cystic lesion (68 mucinous, 7 serous, 27 inflammatory, 5 endocrine, and 5 other). Receiver operator curve analysis of the tumor markers demonstrated that cyst fluid CEA (optimal cutoff of 192 ng/mL) demonstrated the greatest area under the curve (0.79) for differentiating mucinous vs. nonmucinous cystic lesions. The accuracy of CEA (88 of 111, 79%) was significantly greater than the accuracy of EUS morphology (57 of 112, 51%) or cytology (64 of 109, 59%) (P < 0.05). There was no combination of tests that provided greater accuracy than CEA alone (P < 0.0001). CONCLUSIONS: Of tested markers, cyst fluid CEA is the most accurate test available for the diagnosis of mucinous cystic lesions of the pancreas.

Biomarkers, Tumor↗
PubMed2004

Cytokeratin 19 is a powerful predictor of survival in pancreatic endocrine tumors.

The prediction of the behavior of pancreatic endocrine tumors (PETs) is a difficult exercise. CK19, a marker of pancreatic ductal cells, does not stain normal islet cells. Our aim was to evaluate the prognostic value of traditional parameters, including the Capella classification, as well as CK19. We evaluated the clinicopathologic features of 101 curatively resected PETs. The influence on survival of size, functional status of tumor, growth pattern, nuclear grade, mitoses (>2/10 HPF), vascular and perineural invasion, and necrosis was determined. Immunohistochemistry for Ki-67 and CK19 was performed in 45 and 54 cases, respectively. Cases were categorized as per the Capella classification as: benign, borderline, low-grade, and high-grade malignant. The different variables were tested by standard univariate and multivariate analyses. Mitoses (P = 0.03), solid pattern (P = 0.04), necrosis (P = 0.01), vascular invasion (P = 0.003), perineural invasion (P = 0.02), CK19 staining (P = 0.0008), and Ki-67 (P = 0.02) were significant prognostic indicators by univariate analysis while the Capella classification was not significant. By multivariate analysis, only CK19 was significant (P = 0.0008). None of the CK19-negative cases died of disease, while 10 of 28 CK19-positive cases died of disease and 3 are alive with disease. The Capella classification includes malignant tumors in its benign and borderline categories. CK19 is a powerful predictor of survival and can potentially segregate benign and malignant PETs. We suggest that all PETs with any one of the following features be diagnosed as malignant: presence of necrosis, vascular invasion, perineural invasion, or CK19 positivity. We hypothesize that a subgroup of PETs may share a common histogenesis with pancreatic adenocarcinomas.

Adolescent↗
PubMed2004

Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection.

OBJECTIVE: To describe clinical characteristics and outcomes of a large cohort of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas affecting the main pancreatic duct. SUMMARY BACKGROUND DATA: IPMNs are being diagnosed with increasing frequency. Preoperative determination of malignancy remains problematic, and reported results of long-term survival following resection are conflicting. METHODS: The combined databases from the Massachusetts General Hospital and the Pancreatic Unit of the University of Verona were analyzed. To avoid confusing overlap with mucinous cystic neoplasms, only patients with tumors of the main pancreatic duct (with or without side branch involvement) were included. A total of 140 tumors consecutively resected between 1990 and 2002 were classified as either benign (adenoma and borderline tumors) or malignant (carcinoma in situ or invasive cancer) to compare their characteristics and survival. RESULTS: Men and women were equally affected (mean age 65 years). Seven patients (12%) had adenomas, 40 (28%) borderline tumors, 25 (18%) carcinoma in situ, and 58 (42%) invasive carcinoma. The median age of patients with benign IPMN was 6.4 years younger than those with malignant tumors (P = 0.04). The principal symptoms were abdominal pain (65%), weight loss (44%), acute pancreatitis (23%), jaundice (17%), and onset or worsening of diabetes (12%); 27% of patients were asymptomatic. Jaundice and diabetes were significantly associated with malignant tumors. Five- and 10-year cancer-specific survival for patients with noninvasive tumors was 100%, and comparable survival of the 58 patients with invasive carcinoma was 60% and 50%. CONCLUSIONS: Cancer is found in 60% of patients with main-duct IPMNs. Patients with malignant tumors are 6 years older than their benign counterparts and have a higher likelihood of presenting with jaundice or new onset diabetes. No patients with benign tumors or carcinoma in situ died of their disease following resection, and those with invasive cancer had a markedly better survival (60% at 5 years) than pancreatic ductal adenocarcinoma. These findings support both the concept of progression of benign IPMNs to invasive cancer and an aggressive policy of resection at diagnosis.

Aged↗
PubMed2003

Pylorus-preserving pancreaticoduodenectomy in the treatment of chronic pancreatitis.

The pylorus-preserving pancreaticoduodenectomy (PPPD) is an alternative to the standard Whipple resection in the treatment of chronic pancreatitis. The operation is safe and can be performed with a low mortality rate. The most common early complication is delayed gastric emptying, which occurs in 25% to 30% of patients, and generally results in longer hospital stays than the standard Whipple procedure. Follow-up studies show that both operations are equally effective in relieving pain in approximately 75% of selected patients. In the long term, the PPPD successfully preserves physiologic gastric emptying, but at the cost of a higher marginal ulceration rate. The purported nutritional advantages of the PPPD over the classic Whipple resection have not been clearly established. At present, the PPPD is the procedure of choice for patients with chronic pancreatitis requiring panceraticoduodenectomy. Based on available information, this recommendation appears to arise form the fact that the PPPD is less radical than the regular Whipple procedure, and some surgeons find it technically easier. Our experience fails to show a distinct superiority of the PPPD over the Whipple operation.

Chronic Disease↗
PubMed2003

Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis.

Hedgehog signalling--an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer--may also be an important mediator in human pancreatic carcinoma. Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx-Shh mice (in which Shh is misexpressed in the pancreatic endoderm) develop abnormal tubular structures, a phenocopy of human PanIN-1 and -2. Moreover, these PanIN-like lesions also contain mutations in K-ras and overexpress HER-2/neu, which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signalling remains active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signalling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. These data suggest that this pathway may have an early and critical role in the genesis of this cancer, and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis.

Adenocarcinoma↗