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Suresh T Chari

Publications and source records attributed to Suresh T Chari.

At least 19 recordsLinked to original sources
PubMed2007

Renal involvement in patients with autoimmune pancreatitis: CT and MR imaging findings.

PURPOSE: To retrospectively evaluate computed tomographic (CT) and magnetic resonance (MR) imaging renal findings at clinical presentation, during treatment, and at follow-up in patients with autoimmune pancreatitis (AIP). MATERIALS AND METHODS: This HIPAA-compliant study received institutional review board approval. All patients included had previously consented to the use of their medical records for the purpose of research. Forty-five patients (38 male and seven female patients; mean age, 64 years) with diagnosis of AIP were included. Forty patients underwent CT or MR imaging at clinical presentation; 33 patients (including five without imaging at presentation) underwent follow-up. CT and MR images were reviewed in consensus by two radiologists for the presence of renal involvement. Various features were evaluated. Clinical characteristics at presentation were compared between patients with and patients without renal involvement. RESULTS: Of the 40 patients who underwent imaging at presentation, 14 (35%) had renal involvement (12 with parenchymal involvement and five with extraparenchymal involvement). Renal parenchymal lesions showed decreased enhancement and appeared as small peripheral cortical nodules, round or wedge-shaped lesions, or diffuse patchy involvement. Thirteen patients with renal involvement at presentation underwent a follow-up study. Renal lesions in 10 patients regressed (in nine, after steroid treatment) but progressed in three patients without steroid treatment. Renal lesions were found in two other patients during follow-up. No significant difference in the clinical characteristics was found between patients with and patients without renal involvement. CONCLUSION: Renal involvement in patients with AIP is relatively common and predominantly involves the cortex of the kidney. The lesions improve after steroid treatment but can progress without steroid treatment.

Adolescent↗
PubMed2007

Current concepts in the treatment of autoimmune pancreatitis.

Autoimmune pancreatitis is a recently described chronic inflammatory disease of the pancreas which appears to be part of a systemic disorder characterized by a lymphoplasmacytic infiltrate in affected organs that is rich in IgG4 positive cells. The inflammatory component of the disease appears to resolve with steroid treatment, though relapses do occur. Here we briefly discuss the role of steroid therapy in the management of autoimmune pancreatitis.

Autoimmune Diseases↗
PubMed2006

Endoscopic retrograde cholangiopancreatography-induced severe acute pancreatitis.

BACKGROUND/AIMS: There is scant information in the literature about the outcomes of endoscopic retrograde cholangiopancreatography (ERCP)-induced severe acute pancreatitis (ESAP). Compared to other causes, higher morbidity and mortality have been reported in ERCP-induced acute pancreatitis. We undertook this study to determine the differences between ESAP and SAP due to other causes (OSAP). METHODS: We retrospectively identified all cases of SAP admitted to our institution during the years 1992-2001. We reviewed the medical records of all SAP patients to obtain information on demographics, interventions, local and systemic complications and outcomes. RESULTS: We identified 207 patients with SAP, of whom 16 (7.7%) had ESAP and 191 OSAP. There was no difference between ESAP and OSAP with regard to demographics, clinical interventions, local and systemic complications and outcomes. Both groups had a similar mortality (25 vs. 18%). CONCLUSION: ESAP has a similar morbidity and mortality compared to OSAP.

Acute Disease↗
PubMed2006

Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma.

Regulator of G-protein signaling-GAIP-interacting protein COOH terminus (GIPC) is involved in protein trafficking, endocytosis, and receptor clustering and is associated with insulin-like growth factor I receptor (IGF-IR), a receptor important for proliferation and anchorage-independent growth. Here, we described GIPC expression in different human pancreatic adenocarcinoma (PCA) cell lines and we examined the role of GIPC in the regulation of IGF-IR protein levels in PCA. Interestingly, inhibition of GIPC expression by RNA interference led to reduced IGF-IR protein levels and a subsequent decrease in proliferation of PCA cells. We also determined that the PDZ domain of GIPC is essential for the post-translational regulation and the binding of IGF-IR. The importance of GIPC in pancreatic cancer development and progression is supported by tissue microarray data of 300 pancreatic cancer specimens where GIPC is highly expressed in PCA. Taken together, our data suggest that GIPC is a central molecule for the stability of IGF-IR and could be a target for future therapy.

Adaptor Proteins, Signal Transducing↗
PubMed2006

IgG4-positive plasma cell infiltration in the diagnosis of autoimmune pancreatitis.

Autoimmune pancreatitis typically produces an enlarged pancreas with narrowing of the pancreatic duct, and can mimic carcinoma. Autoimmune pancreatitis usually responds to corticosteroid treatment, making it important to differentiate from pancreatic ductal adenocarcinoma. Affected patients often have an elevated serum IgG4. It has been proposed that increased numbers of IgG4-positive plasma cells in tissue might be a marker for the condition. We investigated the role of IgG4 staining in the diagnosis of autoimmune pancreatitis, first in resected pancreas specimens (29 autoimmune pancreatitis, nine chronic alcoholic pancreatitis and 25 pancreatic cancer), then in pancreatic needle biopsies. Immunohistochemical stains for IgG4 were scored as none, mild, moderate or marked, according to published criteria. Moderate to marked numbers of IgG4-positive plasma cells were seen in 21/29 autoimmune pancreatitis patients, and were distributed in and around ducts, in interlobular fibrous tissue and in peripancreatic fat. In contrast, eight of nine examples of chronic alcoholic pancreatitis and 22/25 ductal adenocarcinomas had scores of none or mild. When we subdivided autoimmune pancreatitis into the histologic subtypes lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-destructive pancreatitis, 16/17 lymphoplasmacytic sclerosing pancreatitis had moderate to marked staining, compared to five to 12 idiopathic duct-destructive pancreatitis. Needle biopsies from nine patients suspected of having autoimmune pancreatitis had increased numbers of IgG4 cells. We conclude that pancreatic tissue from patients with autoimmune pancreatitis often shows moderate or marked infiltration by IgG4-positive plasma cells (>10/HPF). This is particularly so in the subtype we have designated lymphoplasmacytic sclerosing pancreatitis. We rarely see IgG4 staining in patients with chronic alcoholic pancreatitis and pancreatic ductal adenocarcinoma. IgG4-positive plasma cells are a useful marker for the tissue diagnosis of autoimmune pancreatitis.

Adenocarcinoma↗
PubMed2006

Aberrant nuclear accumulation of glycogen synthase kinase-3beta in human pancreatic cancer: association with kinase activity and tumor dedifferentiation.

PURPOSE: We have shown recently that glycogen synthase kinase-3 (GSK-3) beta regulates nuclear factor-kappaB (NF-kappaB)-mediated pancreatic cancer cell survival and proliferation in vitro. Our objective was to determine the localization of GSK-3beta in pancreatic cancer cells and assess the antitumor effect of GSK-3 inhibition in vivo to improve our understanding of the mechanism by which GSK-3beta affects NF-kappaB activity in pancreatic cancer. EXPERIMENTAL DESIGN: Immunohistochemistry and cytosolic/nuclear fractionation were done to determine the localization of GSK-3beta in human pancreatic tumors. We studied the effect of GSK-3 inhibition on tumor growth, cancer cell proliferation, and survival in established CAPAN2 tumor xenografts using a tumor regrowth delay assay, Western blotting, bromodeoxyuridine incorporation, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. RESULTS: We found nuclear accumulation of GSK-3beta in pancreatic cancer cell lines and in 62 of 122 (51%) human pancreatic adenocarcinomas. GSK-3beta nuclear accumulation is significantly correlated with human pancreatic cancer dedifferentiation. We have found that active GSK-3beta can accumulate in the nucleus of pancreatic cancer cells and that inhibition of GSK-3 kinase activity represses its nuclear accumulation via proteasomal degradation within the nucleus. Lastly, we have found that inhibition of GSK-3 arrests pancreatic tumor growth in vivo and decreases NF-kappaB-mediated pancreatic cancer cell survival and proliferation in established tumor xenografts. CONCLUSIONS: Our results show the antitumor effect of GSK-3 inhibition in vivo, identify GSK-3beta nuclear accumulation as a hallmark of poorly differentiated pancreatic adenocarcinoma, and provide new insight into the mechanism by which GSK-3beta regulates NF-kappaB activity in pancreatic cancer.

Adenocarcinoma↗
PubMed2006

Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience.

BACKGROUND & AIMS: The Japan Pancreas Society criteria for diagnosis of autoimmune pancreatitis (AIP) mandate presence of characteristic imaging (diffuse pancreatic enlargement with diffusely irregular, narrow pancreatic duct). AIP has unique histologic features associated with infiltration of tissues of affected organs with abundant IgG4-positive cells. We propose expanded diagnostic criteria for AIP with a cohort of histologically confirmed AIP. METHODS: We reviewed the pancreatic imaging findings on computed tomography scans, serum IgG4 levels, other organ involvement, and response to steroids in 29 consecutive patients who met histologic criteria for AIP. RESULTS: Computed tomography scans (n = 22) showed diffuse pancreatic enlargement in 6 (27%) patients; the rest had focal enlargement, distinct mass, normal pancreas, or focal acute pancreatitis. Serum IgG4 level was elevated in 15 of 21 (71%) patients, and other organ involvement (eg, intrahepatic biliary strictures) was noted in 11 of 29 (38%) patients. All 17 patients treated with steroids exhibited resolution/marked improvement of pancreatic/extrapancreatic manifestation. On the basis of this experience we propose that diagnosis of AIP can be made in patients with > or =1 of these criteria: (1) diagnostic histology, (2) characteristic imaging on computed tomography and pancreatography with elevated serum IgG4 level, or (3) response to steroid therapy of pancreatic/extrapancreatic manifestations of AIP. Twenty additional patients met expanded diagnostic criteria for AIP, and their demographic and clinical profile was similar to that of the 29 patients meeting histologic criteria. CONCLUSIONS: AIP defined by histological criteria shows a wide spectrum of radiologic features, with characteristic imaging seen only in a minority. Incorporation of additional features into current diagnostic criteria can identify the full spectrum of clinical presentations of AIP.

Adolescent↗
PubMed2005

Defective DNA mismatch repair in long-term (> or =3 years) survivors with pancreatic cancer.

BACKGROUND/AIMS: Defective DNA mismatch repair (MMR) in pancreatic cancer, reported in up to 13% of sporadic pancreatic cancers, may predict a good prognosis. To determine if long-term survival in pancreatic cancer could be attributed to defective DNA MMR, we ascertained its prevalence in 35 pancreatic cancer patients who survived > or =3 years after surgery. METHODS: We performed immunohistochemistry (IHC) for MMR proteins hMLH1, hMSH2, and hMSH6 in all 35 tumors and microsatellite instability (MSI) studies in 34/35 tumors using 10 microsatellite markers in paired normal and tumor DNA. Defective DNA MMR was defined as absence of protein expression on IHC and/or MSI in > or =30% of markers studied. RESULTS: On IHC, 3/35 (8.6%) tumors had defective DNA MMR. All 3 had absent expression of a DNA MMR protein (hMLH1 in 2 and hMSH2) and 2/3 also had MSI; the third could not be tested. Definitely 2, and probably all 3 patients had hereditary nonpolyposis colon cancer as determined by clinical and genetic profiles. CONCLUSION: Defective DNA MMR is uncommon in long-term survivors of pancreatic cancer and does not account for the survival benefit in those with sporadic pancreatic cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Beta-cell function and insulin resistance evaluated by HOMA in pancreatic cancer subjects with varying degrees of glucose intolerance.

BACKGROUND/AIMS: To gain insights into pathogenesis of pancreatic cancer-associated diabetes. METHODS: Using homeostasis model assessment (HOMA), we estimated beta-cell function (BCF) and insulin resistance (IR) from fasting plasma glucose (FPG) and insulin in 67 normoglycemic controls and 62 age- and BMI-matched normoglycemic pancreatic cancer patients. In addition, we studied 73 pancreatic cancer subjects with glucose intolerance; 21 had impaired FPG and 51 had diabetes. RESULTS: BCF was similar in controls and normoglycemic pancreatic cancer subjects (64 +/- 5 vs. 78 +/- 9, p = ns), while IR was higher in pancreatic cancer subjects with normal FPG (1.6 +/- 0.6 vs. 1.1 +/- 0.1, p = 0.002). Among pancreatic cancer subjects, those with impaired FPG had markedly decreased BCF compared to those with normal FPG (44 +/- 5 vs. 78 +/- 9, p < 0.02) without significant difference in IR (1.9 +/- 0.2 vs. 1.6 +/- 0.6, p = ns). In cancer subjects, those with diabetes had markedly increased IR compared to those with impaired FPG (3.2 +/- 0.3 vs. 1.9 +/- 0.2, p < 0.0001), while the BCF was similar (37 +/- 4 vs. 44 +/- 5). CONCLUSION: Diabetes associated with pancreatic cancer is likely due to a combination of marked decline in BCF and increased insulin resistance.

Aged↗
PubMed2005

Autoimmune pancreatitis.

The list of diseases associated with autoantibodies against tissues, cells, or specific autoantigens is growing, and many organs in the body are known to be affected by autoimmune injury. Until recently, the most well-known pancreatic autoimmune disorder was type 1 diabetes mellitus, where there is selective destruction of beta cells in the islets of Langerhans. Although an autoimmune process affecting the exocrine pancreas was suspected over four decades ago, it is only in the past 10 years or so that autoimmune chronic pancreatitis has been recognized as a distinct entity. Here we review the clinical, serologic, radiologic, and histologic features of autoimmune pancreatitis.

Acute Disease↗
PubMed2005

Ectopic expression of VAV1 reveals an unexpected role in pancreatic cancer tumorigenesis.

Herein, we show that the hematopoietic-specific GEF VAV1 is ectopically expressed in primary pancreatic adenocarcinomas due to demethylation of the gene promoter. Interestingly, VAV1-positive tumors had a worse survival rate compared to VAV1-negative tumors. Surprisingly, even in the presence of oncogenic KRAS, VAV1 RNAi abrogates neoplastic cellular proliferation in vitro and in vivo, thus identifying Vav1 as a growth-stimulatory protein in this disease. Vav1 acts synergistically with the EGF receptor to stimulate pancreatic tumor cell proliferation. Mechanistically, the effects of Vav1 require its GEF activity and the activation of Rac1, PAK1, and NF-kappaB and involve cyclin D1 upregulation. Thus, the discovery of prooncogenic pathways regulated by Vav1 makes it an attractive target for therapeutic intervention.

Adenocarcinoma↗
PubMed2005

Quality-of-life after total pancreatectomy: is it really that bad on long-term follow-up?

While selected pancreatic diseases may be best treated by total pancreatectomy (TP), the anticipated sequelae of pancreatic insufficiency make TP an undesirable alternative. Our aim was to determine if patients undergoing TP have a worse quality of life (QoL) than age- and gender-matched controls and poor long-term glycemic control. Ninety-nine patients undergoing TP from 1985 through 2002 were identified. The 34 survivors with no recurrent malignancy were surveyed with the Short Form-36 (SF-36), the Audit of Diabetes Dependent QoL (ADD QoL), the European Organization for Research and Treatment in Cancer Pancreas 26 (EORTC PAN 26), and our institutional questionnaire. Operative morbidity and mortality were 32% and 5%, respectively. Three late postoperative deaths (3%) were attributed to hypoglycemia. Of the 34 surviving patients, 27 (79%) agreed to participate at a mean of 7.5 years postoperatively. Seven patients had required 12 hospitalizations for poor glycemic control. Per the SF-36, two domains (role physical and general health) were decreased compared with an age- and gender-matched national population (P < .05). The ADD QoL demonstrated an overall decrease in QoL related specifically to the diabetes mellitus (P < .01), but comparison with insulin-dependent diabetics from other causes showed no significant difference in QoL. The EORTC PAN 26 instrument also showed measurable effects on QoL. Total pancreatectomy can be performed safely. QoL after TP is decreased compared with age- and gender-matched controls but not with diabetes from other causes; however, the changes are not overwhelming. TP should remain a viable option but in selected patients.

Adult↗
PubMed2005

Probability of pancreatic cancer following diabetes: a population-based study.

BACKGROUND & AIMS: Although diabetes occurs frequently in pancreatic cancer, the value of new-onset diabetes as a marker of underlying pancreatic cancer is unknown. METHODS: We assembled a population-based cohort of 2122 Rochester, Minnesota, residents age > or =50 years who first met standardized criteria for diabetes between January 1, 1950, and December 31, 1994, and identified those who developed pancreatic cancer within 3 years of meeting criteria for diabetes. We compared observed rates of pancreatic cancer with expected rates based on the Iowa Surveillance Epidemiology and End Results registry. In a nested case control study, we compared body mass index (BMI) and smoking status in diabetes subjects with and without pancreatic cancer. RESULTS: Of 2122 diabetic subjects, 18 (0.85%) were diagnosed with pancreatic cancer within 3 years of meeting criteria for diabetes; 10 of 18 (56%) were diagnosed <6 months after first meeting criteria for diabetes, and 3 were resected. The observed-to-expected ratio of pancreatic cancer in the cohort was 7.94 (95% CI, 4.70-12.55). Compared with subjects without pancreatic cancer, diabetic subjects with pancreatic cancer were more likely to have met diabetes criteria after age 69 (OR = 4.52, 95% CI, 1.61-12.74) years but did not differ significantly with respect to BMI values (29.2 +/- 6.8 vs 26.5 +/- 5.0, respectively). A larger proportion of those who developed pancreatic cancer were ever smokers (92% vs 69%, respectively), but this did not reach statistical significance. CONCLUSIONS: Approximately 1% of diabetes subjects aged > or =50 years will be diagnosed with pancreatic cancer within 3 years of first meeting criteria for diabetes. The usefulness of new-onset diabetes as marker of early pancreatic cancer needs further evaluation.

Age Distribution↗
PubMed2005

EUS-guided trucut biopsy in establishing autoimmune pancreatitis as the cause of obstructive jaundice.

BACKGROUND: The diagnosis of autoimmune pancreatitis can be difficult and often requires a larger specimen than can be provided by FNA alone to determine if the tissue sample obtained with EUS trucut biopsy (TCB) is sufficient to allow adequate histologic review to establish the diagnosis of autoimmune pancreatitis. METHODS: EUS TCB was performed in patients presenting with obstructive jaundice who were suspected of having autoimmune pancreatitis based on their clinical, laboratory and imaging studies. The charts were retrospectively reviewed to determine the feasibility of TCB. RESULTS: Between August 2002 and June 2004, 3 patients with obstructive jaundice and suspected autoimmune pancreatitis (AIP) underwent EUS TCB. In each case, a diagnosis of pancreatic cancer also was considered, and surgical resection was the planned therapy before the patient underwent EUS TCB. Histologic review of the TCB specimens established the diagnosis of AIP in two patients and identified nonspecific changes of chronic pancreatitis in the third patient. EUS-guided FNA was performed in two of the 3 patients and failed to establish the diagnosis in either patient. Other than mild transient abdominal pain (n = 1), no complications were identified. CONCLUSIONS: This preliminary study suggests that EUS TCB can safely establish the diagnosis of AIP. Doing so helps guide management and may help to avoid unnecessary surgery. Prospective studies are needed to verify these findings and to more clearly define the role of EUS TCB in these patients.

Aged↗
PubMed2005

Endoscopic ultrasound-guided trucut biopsy of the cyst wall for diagnosing cystic pancreatic tumors.

BACKGROUND & AIMS: Nonoperative methods for diagnosis of pancreas cysts often lack sufficient accuracy. Accurate diagnosis is needed to determine prognosis and guide clinical management. The aim of this study was to determine whether the tissue obtained by endoscopic ultrasound-guided trucut biopsy (EUS TCB) is sufficient for histologic diagnosis of cystic pancreatic tumors (CPTs). METHODS: EUS TCB was performed in patients with a suspected CPT. A dedicated gastrointestinal pathologist reviewed the core biopsies. The final diagnosis was based on clinical, laboratory, imaging, and biopsy findings, and resected specimens when available. RESULTS: EUS TCB was performed in 10 patients with a suspected CPT. Final diagnoses included serous cystadenoma (SCA, n=5), islet cell tumor (n=2), mixed seromucinous lesion (n=1), polycystic disease of the pancreas (n=1), and pseudocyst (n=1). EUS TCB was nondiagnostic in 3 of 10 patients. Among the other 7 patients, TCB diagnosed 4 SCAs, obviating the need for planned surgery in 3 patients. In the fourth patient with an SCA, the TCB result ruled out metastatic disease from locally recurrent lung cancer, allowing a narrowed radiation field. EUS TCB confirmed the need for surgery in 2 patients with an islet cell tumor. In 1 patient, EUS TCB findings were "partially" diagnostic, leading to previously unplanned surgery. CONCLUSIONS: This report establishes the capability and safety of EUS TCB to collect sufficient tissue for diagnosing CPTs. The results might help guide clinical management.

Adenoma, Islet Cell↗