Pancreatic Carcinoma Patients Research Articles

Serum Amyloid A (SAA) in Patients with Pancreatic Carcinoma

9649 Background: New biomarkers are essential for the diagnosis and monitoring of human pancreatic carcinoma. In our previous study, sera collected from nude mice implanted in the pancreas with human pancreatic cancer cells were analyzed by Surface Enhanced Laser Desorption Ionization (SELDI) mass spectrometry. The progressive growth of the tumors directly correlated with the level of Serum Amyloid A (SAA). In the present study, we determined whether plasma levels of SAA correlated with the stage of pancreatic carcinoma in patients. Methods: Plasma was collected from 113 normal volunteers and 134 patients with pathologically confirmed pancreatic adenocarcinoma. The plasma level of SAA was determined by enzyme linked immunosorbent assay (ELISA). Results: The concentration of SAA in plasma of pancreatic cancer patients was significantly higher than that in normal volunteers (mean value: 180.1 vs 27.9 mg/L; P<0.01), and had a tendency to increase in later stages of the disease. Specifically, the level of SAA in stage IV B patients was significantly higher than that in stage I patients and normal volunteers (282.9 vs 17.8 and 27.9 mg/L; P<0.01). Immunohistochemical analysis of pancreatic tumor specimen revealed intense expression of SAA in the malignat epithelium of the carcinomas with less intense staining of desmoplastic fibroblasts. Conclusions: SAA may be a useful biomarker for monitoring of patients with advanced pancreatic cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech; Novartis Pharma

Hemophagocytic syndrome associated with clostridial infection in a pancreatic carcinoma patient

This report describes the autopsy case of a 71-year-old man presenting with clostridial infection and hemophagocytic syndrome (HS). The patient underwent pancreatoduodenectomy for a pancreatic tumor, and a histological examination revealed an invasive ductal adenocarcinoma. Multiple peritoneal metastases were noted when laparotomy was performed because of postoperative ileus 2 months after the initial operation. Then, acutely progressive anemia associated with fever developed in the patient before death. The autopsy revealed advanced cancer dissemination and HS. In addition, systemic spread of clostridium, confirmed by the polymerase chain reaction method, had resulted in generalized bleb formation. The clostridial infection appeared to be responsible for the HS. This case indicates that HS may occur as a result of clostridial infection.

Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients

A randomized phase II, open-label multicenter study evaluating oxaliplatin alone (OXA), infusional 5-fluorouracil alone (5-FU) and an oxaliplatin/infusional 5-FU combination (OXFU) in untreated, advanced pancreatic carcinoma (APC). Chemotherapy-naïve patients with advanced or metastatic, histologically/cytologically proven pancreatic carcinoma with measurable disease, received OXA [130 mg/m2, 2-h intravenous (i.v.) infusion] alone, OXA combined with 5-FU (1000 mg/m2/day, continuous i.v., days 1-4), or 5-FU alone, every 3 weeks. Sixty-three patients (42 males/21 females) were treated: 17 patients/52 cycles OXA, 31 patients/ 175 cycles OXFU, 15 patients/41 cycles 5-FU, with a median of three, six and two cycles/patient, respectively. Patient characteristics were similar in all arms. Median age was 57 years (range 21-75), and 83% of patients had PS 0-1. Most patients (62%) had moderate to well-differentiated tumors, 90% had metastatic disease, 81% with liver metastases. All responses (three partial responses; WHO) occurred in the OXFU arm (10% response rate). Five of 32 patients evaluable for clinical benefit were responders (OXA, 14%; OXFU, 21%). Median time to progression and overall survival were higher in the combination arm (4.2 and 9.0 months, respectively) than either single-agent arm (OXA, 2.0 and 3.4 months; 5-FU, 1.5 and 2.4 months, respectively). Moderate hematotoxicity without morbidity was seen in all arms. Two OXFU patients had grade 3 oxaliplatin neurosensory toxicity. With a 10% response rate, median overall survival of 9 months and an encouraging safety profile, the OXFU combination is effective, appears superior to infusional 5-FU and warrants further studies in APC patients.

FDG-PET scanning in the diagnosis of gastrointestinal cancers

This review deals with the current, well-established indications for two-([Formula: See Text]F)-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scanning in patients with gastrointestinal cancers. FDG-PET is a non-invasive, functional imaging technique. FDG exploits the native glucose transporter to enter the cell. Since many tumours have enhanced glucose uptake, FDG is readily accumulated in malignant cells and can be detected by a PET camera. FDG-PET has been established as an important diagnostic tool in clinical oncology. This review deals with the current, well-established indications for FDG-PET scanning in patients with gastrointestinal cancers. In the current practice, FDG-PET is most commonly used to stage oesophageal carcinoma, to detect and stage recurrence of colorectal carcinoma and to differentiate between benign and malignant pancreatic lesions. The benefit of FDG-PET scanning in patients with oesophagus carcinoma is best established in stage IV disease, as the diagnostic accuracy to detect metastatic disease is higher compared to the combination of computed tomography (CT) and endoscopic ultrasound (EUS). In patients with a history of colorectal carcinoma, FDG-PET scanning is particularly effective in diagnosing recurrent disease, especially in those with a rising carcinoembryonic antigen without a suspect lesion on conventional imaging. Large series have indicated that the sensitivity and specificity for detecting recurrent colorectal carcinoma are in the range of 87%-100% and 66%-100%, respectively. Equally, FDG-PET has a high sensitivity (68%-96%) and specificity (78%-100%) in detecting pancreatic carcinoma in patients with a suspicious-looking pancreatic mass on CT scan. Lastly, we focus on the use of FDG-PET as a modality for early monitoring of treatment response in patients with gastrointestinal stromal cell tumours. Without doubt, future developments will further establish the diagnostic role of the FDG-PET scan in the care of patients with gastrointestinal cancers.

Needle Tract Implantation of Hepatocellular Carcinoma and Pancreatic Carcinoma after Ultrasound‐guided Percutaneous Puncture: Clinical and Pathologic Characteristics and the Treatment of Needle Tract Implantation

Tumor implantation along the needle tract following percutaneous procedures under ultrasonographic guidance for hepatocellular carcinoma (HCC) and pancreatic carcinoma (PC) has been well documented. The purpose of the present study was to investigate the correlation between the procedure, the pathologic differentiation of the primary tumor, and the treatment after implantation. Between July 1992 and March 2000, HCC patients (n=372) who underwent biopsy, percutaneous ethanol injection (PEI) therapy and percutaneous microwave coagulation therapy (PMCT) and PC (n=73) patients who underwent biopsy were retrospectively studied. Needle tract implantation was found in six of the HCC patients (1.6%) and one of the PC patients (1.4%). The interval to diagnosis ranged from 5 to 25 months (mean +/- SD 11.2 +/- 7.6 months) in the HCC patients. The needle tract implantation was evident for all procedure types in these patients (two after PEI alone, two after both biopsy and PEI, and one after PMCT) and for each degree of pathologic differentiation of the primary tumors (well differentiated in one, moderately differentiated in two, and poorly differentiated in one). Each implanted tumor was surgically resected, with no recurrence at the focal lesion. These results suggest that needle tract implantation develops regardless of the procedure or the pathologic differentiation of the primary tumor, and that surgical resection might be effective for controlling these implanted lesions.

Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death.

Pancreatic cancer is resistant to almost all cytotoxic drugs. Currently, gemcitabine appears to be the only clinically active drug but, because of pre-existing or acquired chemoresistance of most of the tumor cells, it failed to significantly improve the outcome of pancreatic carcinoma patients. The current study examined the relevance of nuclear factor kappaB (NF-kappaB) and PI3K/Akt in the resistance of five pancreatic carcinoma cell lines towards gemcitabine. Treatment for 24 h with gemcitabine (0.04-20 micro M) led to a strong induction of apoptosis in PT45-P1 and T3M4 cells but not in BxPc-3, Capan-1 and PancTu-1 cells. These resistant cell lines exhibited a high basal NF-kappaB activity in contrast to the sensitive cell lines. Furthermore, gemcitabine showed a dose-dependent induction of NF-kappaB. At a dose of 0.04 micro M, gemcitabine still induced apoptosis in the sensitive cell lines, but did not induce NF-kappaB. In addition, NF-kappaB inhibition by MG132, sulfasalazine or the IkappaBalpha super-repressor strongly diminished the resistance against gemcitabine (0.04-20 micro M). In contrast to this obvious correlation between basal NF-kappaB activity and gemcitabine resistance, PI3K/Akt seems not to be involved in gemcitabine resistance of these cell lines. Neither did the basal Akt activity correlate with the sensitivity towards gemcitabine treatment, nor did the inhibition of PI3K/Akt by LY294002 alter gemcitabine-induced apoptosis. These results indicate that constitutive NF-kappaB activity confers resistance against gemcitabine and that modulation of this activity by pharmacological or genetic approaches may have therapeutical potential when combined with gemcitabine in the treatment of pancreatic carcinoma.

A prospective pancreatographic study of the prevalence of pancreatic carcinoma in patients with diabetes mellitus

BACKGROUND The correlation between diabetes mellitus and pancreatic carcinoma is well documented, but no criteria have been established for the efficient selection of a high-risk group among patients with diabetes mellitus. METHODS Eighty-seven patients were selected prospectively from outpatients with diabetes and underwent endoscopic retrograde pancreatography (ERP) according to the authors' original criteria, including the onset of diabetes after age 55 years, deterioration of diabetes or loss of body weight despite strict medical control, elevation of serum amylase and/or CA19-9 levels, and pancreatobiliary abnormalities on routine ultrasonography. The patients were divided into two groups according to the time from the onset of diabetes to ERP: Patients in Group A had recent-onset diabetes (within 3 years), and Group B patients had diabetes for > 3 years. RESULTS A total of 86 patients (excluding 1 patient with unsuccessful ERP who had undergone previous Billroth-2 gastrectomy) were enrolled. There were 33 males and 53 females, age 40–90 years, with a mean age of 65.1 years. ERP demonstrated pancreatic carcinoma, although it was advanced disease in all patients, at an extremely high rate of 7.0% (6 of 86 patients) with no serious complications. The prevalence of pancreatic carcinoma in Group A (13.9%; 5of 36 patients) was significantly greater compared with Group B (2.0%; 1 of 50 patients; P = 0.0442). ERP with an indwelling balloon catheter and subsequent pancreatic juice sampling was performed in 49 patients, yielding positive cytology in 1 patient with pancreatic tail carcinoma, whereas measurements of carcinoembryonic antigen and CA19-9 levels in pancreatic juice were of no use in the diagnosis of pancreatic carcinoma. CONCLUSIONS Selective ERP in patients with diabetes who were at high risk did not lead to the early diagnosis of pancreatic carcinoma, although this study showed that the 3-year period after the onset of diabetes was critical. A more aggressive diagnostic approach within this period in diabetic patients with the authors' criteria may contribute to the earlier diagnosis of pancreatic carcinoma. Cancer 2002;94:2344–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10493

A prospective pancreatographic study of the prevalence of pancreatic carcinoma in patients with diabetes mellitus.

The correlation between diabetes mellitus and pancreatic carcinoma is well documented, but no criteria have been established for the efficient selection of a high-risk group among patients with diabetes mellitus. Eighty-seven patients were selected prospectively from outpatients with diabetes and underwent endoscopic retrograde pancreatography (ERP) according to the authors' original criteria, including the onset of diabetes after age 55 years, deterioration of diabetes or loss of body weight despite strict medical control, elevation of serum amylase and/or CA19-9 levels, and pancreatobiliary abnormalities on routine ultrasonography. The patients were divided into two groups according to the time from the onset of diabetes to ERP: Patients in Group A had recent-onset diabetes (within 3 years), and Group B patients had diabetes for > 3 years. A total of 86 patients (excluding 1 patient with unsuccessful ERP who had undergone previous Billroth-2 gastrectomy) were enrolled. There were 33 males and 53 females, age 40-90 years, with a mean age of 65.1 years. ERP demonstrated pancreatic carcinoma, although it was advanced disease in all patients, at an extremely high rate of 7.0% (6 of 86 patients) with no serious complications. The prevalence of pancreatic carcinoma in Group A (13.9%; 5 of 36 patients) was significantly greater compared with Group B (2.0%; 1 of 50 patients; P = 0.0442). ERP with an indwelling balloon catheter and subsequent pancreatic juice sampling was performed in 49 patients, yielding positive cytology in 1 patient with pancreatic tail carcinoma, whereas measurements of carcinoembryonic antigen and CA19-9 levels in pancreatic juice were of no use in the diagnosis of pancreatic carcinoma. Selective ERP in patients with diabetes who were at high risk did not lead to the early diagnosis of pancreatic carcinoma, although this study showed that the 3-year period after the onset of diabetes was critical. A more aggressive diagnostic approach within this period in diabetic patients with the authors' criteria may contribute to the earlier diagnosis of pancreatic carcinoma.

Hepatic and extrahepatic malignancies in primary sclerosing cholangitis

Background/Aims : To assess the risk of hepatic and extrahepatic malignancies in a large cohort of Swedish primary sclerosing cholangitis (PSC) patients compared with that of the general Swedish population. Methods : The study cohort comprised 604 PSC patients identified between 1970 and 1998. Follow-up was provided through linkages to the Swedish Cancer and Death registries. Cumulative incidence of malignancies and standard incidence ratio were calculated with the incidence rates in the Swedish population, taking into account: sex, age and calendar year as comparison group. Results : Median time of follow-up was 5.7 years (range 0–27.8). Seventy-nine percent had concomitant inflammatory bowel disease. The cause of death was cancer in 44%. The frequency of hepatobiliary malignancies was 13.3% (81/604). Thirty-seven percent (30/81) of all hepatobiliary malignancies were diagnosed less than 1 year after the diagnosis of PSC. The risk for hepatobiliary malignancy was increased 161 times, for colorectal carcinoma 10 times and for pancreatic carcinoma 14 times, compared with that of the general population. Conclusions : In this national-based study including the largest cohort of PSC patients ever presented, the frequency of cholangiocarcinoma is 13%. The risk of hepatobiliary carcinoma is constant after the first year after PSC diagnosis with an incidence rate of 1.5% per year. The risk of pancreatic carcinoma is increased 14 times compared with the general Swedish population. These results are suggestive of an increased risk of pancreatic carcinoma in patients with PSC.

Changes in circulating dendritic cells in metastatic or locally advanced pancreatic carcinoma patients during chemotherapy

Changes in circulating dendritic cells in metastatic or locally advanced pancreatic carcinoma patients during chemotherapy

Clinical observations of pancreatic diabetes caused by pancreatic carcinoma, and survival period.

Pancreatic carcinoma is often associated with diabetes mellitus. The interrelationship between them is very interesting and important for clinical examination and treatment. We examined diabetes mellitus in our patients with pancreatic carcinoma, especially those with invasive ductal pancreatic carcinoma, who were admitted to the National Kyushu Cancer Center between 1972 and 1998, in relation to secondary (pancreatic) diabetes, obstructive pancreatitis, angiopathies, treatment, and prognosis. Diabetes mellitus was found at a high frequency (53.1%) in patients with invasive ductal pancreatic carcinoma and was mostly thought to be secondary diabetes (45.9%), caused, in part, by obstructive pancreatitis following pancreatic tumor recognized on the first admission. Control of blood glucose with insulin was sometimes difficult, but was indispensable for the treatment of pancreatic carcinoma. Diabetic angiopathies are usually not seen in patients with pancreatic diabetes caused by pancreatic carcinoma, because the survival period of patients with pancreatic carcinoma has been limited. Furthermore, in spite of the absence of angiopathies, the survival period was significantly lower in pancreatic carcinoma patients with diabetes than in those without diabetes. Diabetes in patients with invasive ductal pancreatic carcinoma is usually secondary diabetes, occurring in part as a consequence of obstructive pancreatitis shown at the beginning of the clinical course. The duration of diabetes is too short for marked diabetic angiopathies to develop, and the survival period in patients with invasive ductal pancreatic carcinoma with diabees is also short compared with that of those patients without diabetes.

A case of pancreatic carcinoma diagnosed by intraductal US after lithotripsy for pancreatolithiasis

There are a number of reports of the occurrence of pancreatic carcinoma in patients with chronic calcific pancreatitis, 1–4 but the relationship between the two diseases remains controversial. 5,6 The diagnosis of pancreatic carcinoma coexisting with chronic pancreatitis is difficult, and serum carbohydrate antigen (CA19-9) determinations and fine-needle aspiration biopsy each have been recommended for the purpose.5 But even with these methods, early detection and correct diagnosis cannot be ensured.

Molecular Testing of Urine: Catching DNA on the Way Out

There has been much recent interest in the potential diagnostic use of DNA in plasma and serum for cancer testing (1), prenatal diagnosis (2), and transplantation monitoring (3). It has also been demonstrated that circulating DNA appears to be cleared very rapidly from the circulation (4). The exact mechanism of clearance, however, has remained incompletely understood. In this issue of the Journal, Botezatu et al. (5) describe interesting results indicating that the kidney plays a role in the clearance of plasma DNA and that, excitingly, a proportion of the DNA is excreted in sizes detectable by molecular techniques such as PCR. Botezatu et al. (5) began their investigation by demonstrating that mice injected with either purified bacteriophage DNA or irradiated Raji cells excreted detectable amounts of DNA derived from the injected materials. They went on to show that their observations could also be extended to humans by demonstrating the presence of male DNA in the urine of women transfused with male blood and in women pregnant with male fetuses (5). These authors continued their line of investigation by showing that tumor-associated K- ras mutations were detectable in the urine of pancreatic and colorectal carcinoma patients. Overall, their results have opened up the possibility that urinary DNA analysis may have diverse clinical applications, ranging …

Gangliosides as targets for immunotherapy for pancreatic adenocarcinoma

Pancreatic adenocarcinoma cells express gangliosides and sialyl Lewis (sLe) antigens. It is not known whether these carbohydrate antigens can be targeted by immunotherapy. The authors measured the expression of GM(2) and sLe antigens on the surface of pancreatic carcinoma cells and the serum levels of total gangliosides, GM(2), and antiganglioside antibodies in patients with pancreatic carcinoma. Cell surface GM(2) and sLe antigens were measured by cell suspension enzyme linked immunoadsorbent assay (ELISA) in four pancreatic carcinoma cell lines. Sera from 20 pancreatic carcinoma patients and 20 age- and gender-matched healthy volunteers were analyzed for antiganglioside and anti-sLe immunoglobulin (Ig) M titers by ELISA. Serum levels of total gangliosides and GM(2) also were measured. All cell lines expressed GM(2) and sLe antigens. When compared with age- and gender-matched volunteers, patients had significantly higher serum levels of total gangliosides (25.6 +/- 9.0 mg/dL vs. 15.6 +/- 2.7 mg/dL; P < 0.001), GM(2) (0.278 +/- 0.415 mg/dL vs. 0.013 +/- 0.018 mg/dL; P = 0.02), ELISA units of anti-GM(2) IgM antibody (368 +/- 95 vs. 155 +/- 25; P = 0.04) and anti-GD(1b) IgM antibody (351 +/- 91 vs. 138 +/- 26; P = 0.03), but not anti-sLe(x) IgM (1389 +/- 345 vs. 1081 +/- 224; P = 0.46) or anti-sLe(a) IgM antibody (1097 +/- 253 vs. 1200 +/- 315; P = 0.80). Patients with unresectable tumors had higher serum levels of total gangliosides compared with patients with resectable tumors, and a serum level > 25 mg/dL was found to correlate significantly with poor overall survival (P < 0.02). Increased serum levels of total gangliosides and GM(2) may reflect shedding or release of gangliosides from the surface of tumor cells. Production of IgM antibody against GM(2) and GD(1b) indicates that these gangliosides are immunogenic antigens that may be potential targets for effective active immunotherapy.

Relationship between anal occult blood and hepatobiliary pancreatic carcinoma screening.

Cotton swab anal smear instead of stool occult blood test can not only be used as a mass screening method for colorectal cancer, but is an auxiliary way to screen hepatobiliary pancreatic carcinoma. Two hundred and twenty-three cases of hepatobiliary pancreatic carcinoma patients received anal occult blood test, of which 121 were positive (54.3%). The screening test was performed in 14,645 healthy people aged 40-60 years; 511 persons (3.4%) were positive for anal blood. Among these, six cases of digestive tract cancer were found (one oesophageal carcinoma, one gastric cardia carcinoma, two gastric carcinomas, two liver carcinomas). This suggests that when anal occult blood is positive, the patient should be scanned by ultrasonic means to rule out hepatobiliary pancreatic tumour.

Molecular detection of metastatic pancreatic carcinoma cells using a multimarker reverse transcriptase-polymerase chain reaction assay.

The diagnosis of pancreatic carcinoma is often associated with a poor prognosis, because most patients already have advanced disease. A highly sensitive assay to detect the progression of pancreatic carcinoma would be of significant clinical utility. The authors developed multiple tumor mRNA markers for reverse transcriptase-polymerase chain reaction (RT-PCR) to detect metastatic tumor cells in the blood and tissue of patients with American Joint Committee on Cancer (AJCC) Stage II/III or IV pancreatic carcinoma. An RT-PCR plus Southern blot assay was used to detect mRNA of tumor markers in blood and tissues. mRNA expression of the tumor progression markers MET (hepatocyte growth factor receptor gene c-met), GalNAc-T (beta1,4- N-acetyl-galactosaminyl-transferase), and beta-hCG (beta-human chorionic gonadotropin) was evaluated in 9 pancreatic carcinoma cell lines, 13 tumor biopsy specimens, 5 nonmalignant pancreatic tissue specimens, and blood from 33 pancreatic carcinoma patients and 32 healthy donors. The detection limit of the assay was 1 rhog, 10 rhog, and 10 rhog for MET, GalNAc-T, and beta-hCG mRNA expression, respectively. The pancreatic carcinoma cell lines expressed all three mRNA markers. Of blood specimens from 17 patients with AJCC Stage IV pancreatic carcinoma, 82%, 65%, and 76% were MET, GalNAc-T, and beta-hCG mRNA positive, respectively. Of blood specimens from 16 patients with AJCC Stage II/III disease, 88% were positive for at least 1 mRNA marker. A multiple molecular marker assay was developed to detect cancer cells in blood and tissue from patients with different stages of pancreatic carcinoma. The detection of cancer cells in the blood may be used as a marker of pancreatic tumor progression and may be useful in monitoring response to therapy.

Expression of cytokeratin 20 in the blood of patients with disseminated carcinoma of the pancreas, colon, stomach, and lung

Cytokeratins are constituents of the intermediate filaments of epithelial cells that are expressed in various combinations depending on the epithelial type and the degree of differentiation. The recently identified cytokeratin 20 (CK-20) was found to be expressed in colonic, gastric, and pancreatic carcinoma tumor tissues. A low rate of incidence of expression of CK-20 was found in tumor tissue from lung carcinoma but no expression was found in blood even with the sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) method. The objective of the current study was to examine whether CK-20 expression in the blood can be used as a biomarker for the detection of dissemination in patients with carcinoma of the colon, stomach, and pancreas. In the current study, RT-PCR was used to determine the expression of CK-20 in the blood cells from patients with metastatic colon carcinoma (n = 22), metastatic pancreatic carcinoma (n = 28), metastatic gastric carcinoma (n = 18), metastatic lung carcinoma (n = 13), no metastatic colon carcinoma (n = 13) and no known malignant diseases (n = 22). RNA was extracted from cell pellets and analyzed by RT-PCR using primers for CK-20. In the group of 22 patients with metastatic colon carcinoma, 14 were found to be CK-20 positive (sensitivity of 63.6% and specificity of 92.3%), 22 of the 28 pancreatic carcinoma patients showed positive CK-20 expression, and 12 of 18 patients with gastric carcinoma showed positive CK-20 expression. All patients with metastatic lung carcinoma except 1 were negative (12 of 13 patients), and 12 of 13 patients with colonic carcinoma with no known metastases also were negative. Negative CK-20 results were obtained in all 22 patients with no known malignant diseases. The results of the current study indicate that because of its high sensitivity, RT-PCR of CK-20 is a potential biomarker for detecting metastases in blood samples from patients with carcinoma of the colon, stomach, and pancreas.

Tumor-Associated Transforming Growth Factor-β and Interleukin-10 Contribute to a Systemic Th2 Immune Phenotype in Pancreatic Carcinoma Patients

In this study, we report coexpression of transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) in pancreatic carcinoma tissue associated with significantly elevated levels of both cytokines in the sera of pancreatic carcinoma patients. Using conditioned media (CM) of pancreatic carcinoma cells, we further demonstrate that tumor cell-derived TGF-beta and IL-10 inhibited in an additive fashion both proliferation and the development of Th1-like responses in peripheral blood mononuclear cell (PBMC) preparations derived from normal donors. The antiproliferative and Th1-suppressive activities contained in CM of pancreatic carcinoma cells were due primarily to IL-10 and/or TGF-beta, as shown by the capacity of cytokine-specific neutralizing antibodies to reverse these effects. Finally, as compared to normal controls, PBMC derived from pancreatic carcinoma patients displayed a Th2-like cytokine expression pattern upon activation with either anti-CD3 antibody or Staphylococcus aureus strain Cowan I. Taken together, these results suggest that aberrant production of TGF-beta and IL-10 in pancreatic tumor patients skews T-cell cytokine production patterns in favor of a Th2 immunophenotype.

Assessment of resectability of pancreatic carcinoma by color Doppler sonography.

This study was undertaken to evaluate the role of color Doppler sonography in the preoperative assessment of vascular involvement in patients with pancreatic carcinoma. Twenty-six pancreatic carcinomas were investigated with color Doppler sonography and angiography, and the results of these examinations were compared with those of surgical findings. Color Doppler sonography was more sensitive than angiography in depicting vascular involvement of carcinoma. Thus, it seems rational to perform a preoperative assessment in suspected pancreatic carcinoma patients initially with color Doppler sonography to improve patient management.

K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance.

Previous studies have demonstrated the presence of K-ras mutations in the plasma of patients with pancreatic carcinoma. However, the diagnostic utility and the prognostic significance of this finding have never been addressed. Forty-four consecutive patients with histologically confirmed primary pancreatic ductal adenocarcinoma were included. A control group of 37 patients with chronic pancreatitis, 10 patients with other tumors of the pancreatic area, nine patients with acute pancreatitis, and four healthy volunteers was also included. Plasma DNA was isolated and K-ras codon-12 mutations were analyzed by means of restriction fragment length polymorphism-polymerase chain reaction and single-strand conformation polymorphism techniques. Patients were followed up to establish their clinical outcome. The mutant-type K-ras gene was found in plasma DNA samples of 12 (27%) of 44 patients with pancreatic ductal adenocarcinoma; this finding was related to the tumor stage (P = .05), mainly in the presence of distant metastases (P = .02). In addition, K-ras mutations were detected in the plasma DNA of two (5%) of 37 patients with chronic pancreatitis. In the subset of patients with pancreatic masses, the sensitivity and specificity of plasma K-ras analysis for pancreatic adenocarcinoma were 27% and 100%, respectively. Finally, pancreatic carcinoma patients with the mutant-type K-ras gene in plasma DNA exhibited a shorter survival time than patients with the wild-type gene (P<.005), and plasma K-ras mutations were identified as the only independent prognostic factor (odds ratio, 1.51; 95% confidence interval, 1.02 to 2.23). Plasma K-ras analysis is a highly specific, low-sensitivity approach that has diagnostic and prognostic clinical implications in patients with pancreatic carcinoma.