Interferon receptor alpha/beta is associated with improved survival after adjuvant therapy in resected pancreatic cancer.

AIM: Interferons (IFNs) are known to have antiproliferative and immunoregulatory activities that are modulated through specific cell surface ligands, known as IFN-alpha, -beta, and -gamma receptors. The presence of these receptors and their impact on response to adjuvant therapy in patients with pancreatic cancer has not been determined. PATIENTS AND METHODS: Slides were prepared from 46 patients with pancreatic adenocarcinoma. Immunohistochemistry (IHC) was subsequently used to determine the expression of IFN- alpha/beta receptor-chain 2 (IFN-alpha/betaR) and IFN-gamma receptor-chain 1 (IFN-gammaR). The correlation between IFN receptor expression, tumor characteristics, and the overall patient response to adjuvant therapy were determined analytically. RESULTS: The IHC performed for pancreatic adenocarcinoma demonstrated a high IFN-alpha/betaR expression in 4% (2/46) of patients, moderate expression in 20% (9/46) of patients, and faint or no expression in 76% (35/46) of patients. IHC confirmed a high expression of IFN-gammaR in 52% (24/46) of patients, moderate expression in 35% (16/46) of patients, and faint or no expression in the remaining 13% (6/46) of patients. Thirty-two (69.7%) patients received adjuvant therapy. Clinicopathological survey did not demonstrate any significant correlation between IFN-alpha/betaR and IFN-gammaR expression with regard to tumor size, vascular invasion, perineural invasion, lymph node metastases, or stage of disease. Use of adjuvant therapy was associated with increased survival in patients with IFN-alpha/betaR-positive tumors compared with patients with IFN-alpha/betaR-negative tumors (24 months versus 14.7 months in log rank test, p=0.012). The expression of IFN-gammaR, however, had no impact on patient survival (20 months vs 17 months; p=0.656, log rank test). CONCLUSION: IFN-alpha/betaR is associated with improved survival for patients with resectable pancreatic cancer who received adjuvant therapy.

Expression of interferon receptors in pancreatic cancer: identification of a novel prognostic factor.

OBJECTIVES: Interferons (IFNs) are known to have antiproliferative and immunoregulatory activities that are modulated through specific cellular-surface ligands, known as IFN-alpha, -beta, and -gamma receptors. The presence of these receptors and their impact on survival in patients with pancreatic cancer has not been determined. METHODS: Slides were prepared from 46 patients with pancreatic adenocarcinoma. Immunohistochemistry (IHC) was used subsequently to determine the expression of IFN-alpha/beta receptor-chain 2 (IFNalpha/betaR) and IFN-gamma receptor-chain 1 (IFNgammaR). The correlation among IFN-receptor expression, characteristics of neoplasms, and overall patient survival were determined analytically. RESULTS: The IHC performed for pancreatic adenocarcinoma demonstrated a high IFNalpha/betaR expression in 4% (2/46) of patients, moderate expression in 20% (9/46), and faint or no expression in 76% (35/46). IHC confirmed a high expression of IFNgammaR in 52% (24/46) of patients, moderate expression in 35% (16/46), and faint or no expression in the remaining 13% (6/46). A clinicopathologic survey failed to demonstrate any significant correlation between IFNalpha/betaR and IFNgammaR expression with regard to size of neoplasm, vascular or perineural invasion, lymph node metastases, or stage of disease. Kaplan-Meier survival analyses demonstrated a survival advantage in those patients whose neoplasms expressed moderate to high IFNalpha/betaR expression, compared with those with faint or no IFNalpha/betaR expression (22 vs 13 months; P = .012, log-rank test). The expression of IFNgammaR, however, had no impact on patient survival (20 months vs 17 months; P = .66, log-rank test). CONCLUSIONS: The IFNalpha/betaR is an independent prognostic factor in patients with pancreatic cancer.

Interferon receptors and the caspase cascade regulate the antitumor effects of interferons on human pancreatic cancer cell lines.

BACKGROUND: Interferons (IFNs) have antiproliferative effects on tumor cells. The apoptotic effects and sensitization to chemotherapy conferred by IFN therapy, however, are not clearly understood. The aims of the present study were to explore the apoptotic effects of IFNs in human pancreatic cancer cell lines and to attempt to define their ability to synergistically enhance sensitivity to 5-fluorouracil (5-FU) and gemcitabine, a mechanism that depends on the expression of IFN receptors. METHODS: Human pancreatic cancer cells were cultured alone or in combination with the chemotherapeutic agents 5-FU and gemcitabine. Differential dosages of IFN-alpha, -beta, and -gamma were also added to the cell lines concomitantly during a period of 24 to 96 hours. The cell line viability and effects of treatment were examined using the methylthiazol tetrazolium assay and single-stranded DNA apoptosis assay. The expression of IFN receptors was determined using immunohistochemistry. Caspase-8 inhibitor was used to block the caspase cascade. RESULTS: The antiproliferative and apoptotic effects of IFNs were most profoundly demonstrated on those cells that expressed the respective IFN receptor. The apoptotic effects provided by the interferons, however, were blocked by caspase-8 inhibition. The addition of IFNs significantly enhanced the cytotoxic effects of 5-FU and gemcitabine in those cell lines that expressed the corresponding IFN-alpha, -beta, or -gamma receptors. CONCLUSIONS: This study on pancreatic cancer cell lines has demonstrated that IFNs mediate apoptosis through IFN receptors and the caspase cascade. Enhanced cytotoxicity occurred when IFNs were combined with 5-FU and gemcitabine.

Is there a role for palliative gastrectomy in patients with stage IV gastric cancer?

Patients with metastatic gastric cancer are currently not considered operative candidates and are most often offered systemic therapy. Palliative resection of the primary tumor has been considered irrelevant to the outcome and has been recommended only for palliation of symptoms. We have examined the role of palliative gastrectomy and its impact on survival in patients with stage IV gastric cancer at initial diagnosis between 1990 and 2000. A total of 105 patients with stage IV disease were identified during this period; 81 of them (77.1%) had no resection, and 24 (22.9%) underwent palliative gastric resection. Mean survival in those without resection who received chemotherapy (with or without radiation) treatment was 5.9 months (95% confidence interval 4.2-7.6). For those with resection and adjuvant therapy, mean survival time was 16.3 months (95% confidence interval 4.3-28.8 months). Kaplan-Meier survival analysis showed significantly better survival in those with resection and adjuvant therapy (log-rank test, P = 0.01). Mortality and morbidity rates associated with palliative resection were 8.7% and 33.3%, respectively, which did not differ statistically from the 3.7% and 25.3% in patients who underwent curative gastrectomy during same period of time. However, the length of hospitalization (22 versus 16 days) was significantly higher compared with those without stage IV disease. These data suggest that palliative resection combined with adjuvant therapy may improve survival in a selected group of patients with stage IV gastric cancer. Palliative gastrectomy plus systemic therapy should be compared with systemic therapy alone in a randomized trial.

Intrahepatic cholangiocarcinoma masked as fever of unknown origin.

Intrahepatic cholangiocarcinoma is a rare malignancy that often presents in an advanced stage. For many patients, early diagnosis is often delayed, secondary to vague symptoms and a lack of physical findings. Herein, we report an unusual case of fever of unknown origin secondary to intrahepatic cholangiocarcinoma.

Nonsentinel lymph node status after positive sentinel lymph node biopsy in early breast cancer.

Axillary dissection is the current standard of care for patients with breast cancer who are diagnosed with metastasis to axillary sentinel lymph nodes (SLNs). Recently, that concept has come under increasing scrutiny because not all women with a positive SLN will need further dissection. The purpose of this study was to look at nonsentinel lymph node status in patients with breast cancer and axillary SLN metastasis in an effort to determine tumor variables that can guide further treatment if there are additional axillary nodes involved. A retrospective chart review was performed on patients with breast cancer who underwent SLN biopsy between July 1998 and April 2003. Chi2 analysis, Student t test, and multivariate analysis were used to determine the significance of tumor size, grade, location, estrogen receptor (ER) and progestrone receptor (PR) receptor status, angiolymphatic invasion, stage, and number and size of SLNs in predicting the status of nonsentinel lymph nodes. During the study interval, 116 patients were identified who underwent SLN biopsy and 34 (29.3%) had positive SLNs. All of these patients underwent complete axillary node dissection and 11 patients (32.3%) had non-SLN metastasis. The presence of palpable breast mass (P = 0.03), tumor size (P = 0.04), angiolymphatic invasion (P = 0.03), and extracapsular extension of SLN metastasis (P = 0.001) were the variables that predicted non-SLN involvement. Micrometastasis was inversely related to non-SLN involvement. In patients with breast cancer and SLN metastasis, the presence of a palpable breast mass, tumor size, angiolymphatic invasion, and extracapsular node extension increase the likelihood of identifying additional node metastasis on subsequent axillary dissection.

Resection of central hepatic malignant lesions.

Tumors within the central hepatic region can be managed by various operative techniques. The aim of hepatic resection should be to render the patient free of disease while limiting the excision of functioning parenchyma. Technical feasibility, improved anatomical understanding, and advanced support services have enabled access to lesions previously considered unresectable. Various surgical options and outcomes from a single surgeon's experience are presented. Thirty-three patients underwent surgical resection for central hepatic lesions adjacent to the anterior hilar plate from 1980 to 2001. The mean patient age was 55.7 years (range 34-82). The mean lesion size was 7.7 cm (2-21). Malignant lesions were most commonly encountered in segments IV and V (43%). The most common resection performed was a central hepatic resection (55%) followed by right trisegmentectomy (27%). Resections were primarily performed for metastatic colon cancer (48%), cholangiocarcinoma (25%), and hepatocellular carcinoma (15%). The 5-year survival was 45 per cent for metastatic colon cancer, 20 per cent for cholangiocarcinoma, and 66 per cent for hepatocellular carcinoma. The overall morbidity was 43 per cent, and there was a single mortality. The size, location, and extension of hepatic tumors are important factors that may predict the extent of hepatic resection. Small centrally located focal lesions are amenable to central hepatic resection with biliary reconstitution hence limiting extensive resections. Valuable 5-year patient survival and a low mortality rate were achieved.

Scholarly activities--essential to surgical education.

Research and scholarship are an integral part of a surgical residency program. A concerted effort by a Director of Surgical Research and a Residency Program Director at the community hospital were successful in addressing this very important part of medical education. A questionnaire was designed and data gathered on the attitudes and involvement toward research activities of graduates over the past 6 years. Increased research and scholarly activity resulted from a requirement of completing 2 research projects on time for residents. Over the period of this study, the number of published full-length papers, number of resident names as authors, number of attending surgeon's names as authors, and numbers of presentations made in-hospital, and at local, national, and international meetings all increased dramatically. Most strikingly, in 1996, there were 4 publications, whereas in 2000, there were 20. Presentations during this period included orals, posters, and videos. Each former resident did an average of about 3 research projects, of which just over 1 was published. Satisfaction with amount and quality of scholarship was over 70%. More than 85% of residents fulfilled the criteria for graduation, and more than 50% were satisfied with the requirement. On average, each graduate had 1 paper published since graduation. Seventy-five percent thought their scholarship had improved their career. It is essential in a community hospital residency program that resident surgeons be trained in the techniques of research and scholarship. In our program, research activity and scholarship have been dramatically improved over the past 6 years.