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Biomedical subjects

R Lenzi

Publications and source records attributed to R Lenzi.

At least 37 records · Page 2Linked to original sources
PubMed1998

RT-PCR quantitation of cytokine responses in vivo from specimens containing small numbers of cells during bioimmunotherapy.

A Standard Template method has been developed to carry out semiquantitative RT-PCR analysis on mRNA extracted from small specimens that contain low yields of RNA. Using easily prepared templates (made from previously tested reference specimens), standard calibration curves were generated for each of two cytokine products of interest, specifically IL-10 and IFN-gamma. Also, internal standardization was accomplished by quantitating a well-characterized housekeeping gene (GAPDH). Simple densitometry of the RT-PCR product did not demonstrate sufficient reliability for quantitation since a logarithmic relationship was shown between product and template input. Peritoneal exudate cell specimens that were obtained from ovarian cancer patients during intraperitoneal immunotherapy were utilized for the demonstration of IL-10 and IFN-gamma transcript in vivo. Briefly, this method consists of: (1) template preparation: a PCR product for the cytokine of interest is generated from a previously identified positive specimen, purified and stored at -20 degrees C. (2) RT-PCR: cDNAs are produced from RNA extracted from patient specimens. Replicates of each cDNA and serial dilutions of the corresponding template are amplified with primers specific for each cytokine of interest. (3) Quantitation: photographs are made of the PCR products displayed on an agarose gel and are analyzed by densitometry. Determinations of fold-differences in cytokine transcript expression are normalized to the mRNA content of each specimen (based on the expression of GAPDH).

Ascitic Fluid↗
PubMed1998

Presenting symptoms in patients referred to a multidisciplinary clinic for bone metastases.

Symptom control is the goal of palliative irradiation. Approximately 1 month is required before symptomatic relief is accomplished with radiotherapy. However, many patients with cancer-related pain do not receive adequate analgesics, and opioids are often not prescribed until patients fail to respond to palliative irradiation. The presenting symptoms of 108 patients who were referred to a multidisciplinary clinic for bone metastases were evaluated with the Wisconsin Brief Pain Inventory (BPI). This validated instrument evaluates the severity of pain using a 0-10 scale; 10 represents the worst pain imaginable. The population comprised 65 men (60%) and 43 women whose ages ranged from 33 years to 81 years; median age was 55 years, and 69% of patients were less than 65 years of age. Despite the presence of metastatic disease, 21% of patients were working full-time outside the home, and 6% were employed part-time outside the home; 13% were homemakers. Only 17 patients (16%) were unemployed. The time since diagnosis ranged from 2 weeks to 23 years; the median time since diagnosis was 22 months, and 30% of patients had been diagnosed with the past 6 months. Pain was a presenting symptom in 74% (N = 80) of patients at diagnosis. At its worst, the pain was rated as severe (levels 7-10) by 78% and intolerable (level 10) in 22% of the patients in the 24 hr prior to the clinic appointment. On average, the pain was rated moderate to severe (levels 4-10) in 79% and severe in 23% of patients. Only 45% of patients experienced good relief from the prescribed analgesics, and 23% of patients indicated that the prescribed analgesics were ineffective. This survey demonstrates that bone metastases incur significant pain that is often undertreated with analgesics before antineoplastic therapy is administered.

Adult↗
PubMed1998

Detection of primary breast cancer presenting as metastatic carcinoma of unknown primary origin by 111In-pentetreotide scan.

Women with isolated metastatic carcinoma or adenocarcinoma involving axillary lymph nodes are a well-recognized group of unknown primary carcinoma (UPC) patients with a favorable prognosis. This group of patients are generally treated based on the assumption that they have occult breast cancer. However, to facilitate patient access to the whole spectrum of therapies available for patients with breast cancer, including strategies involving the use of high-dose chemotherapy, a precise diagnosis is increasingly important. In this clinical case we report the detection of a primary breast cancer by 111In-pentetreotide scanning in a woman who presented with metastatic carcinoma in axillary nodes, no palpable breast lesion, a nondiagnostic mammogram, and negative breast ultrasonography. Previous outcomes analysis of patients with UPC have emphasized the value of identifying women with breast cancer. This report suggests that the 111In-pentetreotide scan can contribute specific, clinically useful information in the evaluation of women presenting with metastatic carcinoma in axillary nodes and an occult primary and deserves prospective study in women with UPC presenting with isolated axillary metastases.

Algorithms↗
PubMed1998

Differential expression of cytokine transcripts in human epithelial ovarian carcinoma by solid tumour specimens, peritoneal exudate cells containing tumour, tumour-infiltrating lymphocyte (TIL)-derived T cell lines and established tumour cell lines.

T cell lines derived in low concentrations of recombinant IL-2 (rIL-2) from TIL of patients with epithelial ovarian carcinoma (EOC) often exhibit specific cytotoxicity against autologous tumour cells. However, the ability of T cells at the tumour site to respond to ovarian carcinoma cells may be affected by the production of cytokines by the various cell types present. Using reverse transcriptase-polymerase chain reaction (RT-PCR) we investigated cytokine transcripts in: (i) established EOC tumour cell lines; (ii) solid tumour specimens or peritoneal exudate cells (PEC) from ascites or peritoneal washings of patients with EOC; and (iii) CD4+ TCRalphabeta+ and CD8+ TCRalphabeta+ TIL-derived T cell lines developed in rIL-2. We have found that (i) established EOC tumour cell lines expressed transcripts for transforming growth factor-beta 2 (TGF-beta2) (7/7), but not IL-10 (0/7) or interferon-gamma (IFN-gamma) (0/7) and rarely IL-2 (1/7); (ii) PEC expressed transcripts for IL-2 (12/13), IL-10 (9/13), and TGF-beta2 (12/13), and less often, IFN-gamma (3/13), whereas solid tumour specimens from eight patients with EOC expressed transcripts for IL-2 (4/8), TGF-beta2 (4/8), and IL-10 (5/8), but not for IFN-gamma (0/8); (iii) CD4+ TCRalphabeta+ T cell lines expressed transcripts for IFN-gamma (4/4), IL-2 (4/4) and IL-10 (3/4), whereas CD8+ TCRalphabeta+ T cell lines expressed transcripts for IFN-gamma (5/5), IL-2 (1/5) and IL-10 (2/5). None of these T cell lines expressed TGF-beta2 transcripts. The frequency of IL-2 and TGF-beta2 transcripts in solid tumours was significantly lower than in the PEC (P = 0.0475). CD4+ or CD8+ T cell lines expressing IFN-gamma, IL-2 and IL-10 transcripts were derived in culture with rIL-2 from the TIL of specimens that did not necessarily express these cytokines in the absence of rIL-2. The frequency of cytokine transcripts in T cell lines compared with these same transcripts in the PEC was significantly higher for IFN-gamma (P = 0.0005) and lower for TGF-beta2 (P = 0.0001). An association was observed between the expression of cytokine transcripts in vivo or by TIL-derived cell lines and functions exhibited by either production of cytokines or in vitro cytotoxicity.

Adenocarcinoma↗
PubMed1998

Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma.

PURPOSE: To evaluate the toxicities, radiographic and pathologic responses, and event-free outcomes with combined modality treatment that involves preoperative rapid-fractionation chemoradiation, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with radiographically resectable localized adenocarcinoma of the pancreatic head were entered onto a preoperative protocol that consisted of a 2-week course of fluorouracil (5-FU) 300 mg/m2 daily 5 days per week and concomitant rapid-fractionation radiation 30 Gy, 3 Gy daily 5 days per week. Radiographic restaging was performed 4 weeks after chemoradiation, and patients with localized disease underwent pancreaticoduodenectomy with EB-IORT 10 to 15 Gy. RESULTS: Thirty-five patients were entered onto the study and completed chemoradiation, 34 (97%) as outpatients. Three patients (9%) experienced grade 3 nausea and vomiting; no other grade 3 or 4 toxicities were observed. Of the 27 patients taken to surgery, 20 patients (74%) underwent pancreaticoduodenectomy with EB-IORT. All patients had a less than grade III pathologic response to preoperative chemoradiation. At a median follow-up of 37 months, the 3-year survival rate in patients who underwent combined modality therapy was 23%. CONCLUSION: Combined modality treatment with preoperative rapid-fractionation chemoradiation, pancreaticoduodenectomy, and EB-IORT is associated with minimal toxicity and excellent locoregional control. This represents one approach to maximize the proportion of patients who receive all components of combined modality therapy and avoids the toxicity of pancreaticoduodenectomy in patients found to have metastatic disease at the time of restaging.

Adenocarcinoma↗
PubMed1998

Unknown primary tumors metastatic to liver.

PURPOSE: The objectives of this study were to identify prognostic factors for unknown primary tumor (UPT) patients with hepatic metastases, determine the common primary tumors identified, assess the yield of specific diagnostic studies, and evaluate the impact of therapy on survival. PATIENTS AND METHODS: The 1,522 patients analyzed were referred from January 1, 1987 through June 30, 1995. Clinical data from these patients were entered into a computerized database for storage, retrieval, and analysis. Survival was measured from the time of diagnosis; survival distribution was estimated by the product limit method. Multivariate survival analyses were performed by proportional hazards regression. RESULTS: Five hundred UPT patients had liver metastases. Primary tumors, usually lung, colorectal, or pancreatic neoplasms, were identified in 135 patients (27%). The remaining 365 unknown primary carcinoma (UPC) patients with liver involvement had a higher death rate than those without liver involvement (hazards ratio, 1.63; P < .0001). Neuroendocrine carcinoma patients had a lower death rate than patients without this histology (hazards ratio, 0.29; (P < .0001). Two hundred sixteen of 365 patients with UPC and liver metastases received chemotherapy. Chemotherapy-treated patients had a lower death rate than those who were not treated with chemotherapy (hazards ratio, 0.52; P < .0001). The effect of chemotherapy was most pronounced in patients with adenocarcinoma. CONCLUSION: Hepatic metastases in UPC patients portend a generally poor prognosis. However, subsets of patients with more favorable outcomes can be identified by available clinical and pathologic data. Chemotherapy may be beneficial for the large subset of UPC patients with adenocarcinoma that involves the liver.

Adenocarcinoma↗
PubMed1998

Intraperitoneal immunotherapy of peritoneal carcinomatosis.

Carcinomas that originate in the ovary or from different sites in the gastrointestinal tract frequently develop metastases that involve the peritoneal and serosal surfaces. Carcinomatous involvement of the peritoneum is a significant cause of morbidity and mortality. Advances in our understanding of the immunobiology of the peritoneal cavity and the availability of technically advanced immunotherapeutic agents are providing an important opportunity for the intraperitoneal delivery of these agents. This review describes newer concepts in tumor immunology that have a bearing on the further development of intraperitoneal immunotherapy; delivery systems for and issues to be resolved in intraperitoneal immunotherapy, and results of studies with recombinant interferons alpha and gamma and interleukin (IL)-2, cellular therapies including lymphokine-activated killer cells, tumor-infiltrating lymphocytes, monoclonal antibodies, and intraperitoneal radioimmunotherapy. New trials of intraperitoneal immunotherapy employing novel agents, including IL-12 and genetically modified tumor vaccines, are discussed, as are issues related to the integration of immunotherapy with standard chemotherapy agents. A number of immunotherapy agents have been tested intraperitoneally and have shown promising clinical activity with acceptable toxicity. Complete responses have been documented at surgical restaging, and intraperitoneal treatments with these agents may soon be included in the therapeutic armamentarium for patients with peritoneal carcinomatosis.

Carcinoma↗
PubMed1997

Improving physician-patient communication in cancer care: outcome of a workshop for oncologists.

BACKGROUND: Physicians caring for cancer patients receive little formal training in difficult communications such as breaking bad news, discussing life support, and addressing patients' emotional concerns. METHODS: The authors conducted a three-day workshop in communication skills for nine oncology attendings and three fellows. Topics for the workshop were selected by participants by a pre-workshop questionnaire. Small groups of four to five participants interviewed simulated patients who role-played scripts based on the selected topics. Sessions on self-awareness and one on planning for continuing the work of the group after the workshop were included. RESULTS: Responses to pretest and posttest questionnaires showed that the workshop increased the participants' confidence in a number of communication areas and also in managing physician burnout. Process issues such as patient death and expectations for cure were also discussed. CONCLUSION: Interactive workshops offer a promising way of teaching communication skills and aspects of the physician-patient relationship to oncologists. Conclusions regarding outcome, however, are preliminary and tentative, and long-term results are uncertain.

Cancer Care Facilities↗
PubMed1997

Poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown origin: favorable subsets of patients with unknown-primary carcinoma?

PURPOSE: The objectives of this study were to assess clinical outcomes and prognostic factors in unselected, consecutive patients with poorly differentiated carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA). PATIENTS AND METHODS: The 1,400 patients analyzed were referred to our unknown-primary tumor (UPT) clinic from January 1, 1987 through July 31, 1994. Clinical data from these patients were entered into a computerized data base for storage, retrieval, and analysis. Survival was measured from the time of diagnosis; survival distribution was estimated using the product-limit method. Multivariate survival analyses were performed using proportional hazards regression and by recursive partitioning. RESULTS: Nine hundred seventy-seven patients were diagnosed with unknown-primary carcinoma (UPC) and 337 of these patients had PDC or PDA. No clinical differences were identified among patients with PDC, PDA, or UPC patients with other carcinoma or adenocarcinoma subtypes. PDC patients enjoyed better survival than PDA patients. Poor cellular differentiation was not an important prognostic variable. Variables predictive of survival included lymph node metastases, sex, number of metastatic sites, histology (PDC v PDA), and age. Although chemotherapy did not appear to influence survival for the entire group of PDC or PDA patients, a subset of patients with good prognostic features experienced median survival durations of up to 40 months. CONCLUSION: The long median survival and chemotherapy responsiveness of UPC patients with PDC and PDA could not be confirmed. However, subpopulations with prolonged median survival durations could be defined, and the value of chemotherapy in this group remains to be determined. Identification and exclusion of treatable or slow-growing malignancies may account for the poor survival of the PDC and PDA patients reported in this study.

Adenocarcinoma↗
PubMed1996

Merkel cell carcinoma of the skin: imaging and clinical features in 93 cases.

Clinical, pathological and imaging data for 93 patients with Merkel cell carcinoma were reviewed. Median survival duration from the date of diagnosis was estimated using the Kaplan-Meier product-limit method. Survival durations of patients with no metastastic disease, with regional lymph node metastasis only and with distant metastases were compared using the Cox-Mantel log-rank test. The median age for patients with Merkel cell carcinoma was 70 years (range 35-91 years). The tumour occurred in 71 men and 22 women. The most common primary site was the head and neck region (64 patients), followed by the extremities (21 patients) and the trunk (10 patients). Median survival duration for the whole group was 33 months (range 2-140 months). Imaging studies of the primary sites were available for 10 patients and of metastatic sites for seven patients. Sonograms of the primary skin lesions showed single or multicentric hypoechoic nodules arising from the dermis and growing into the subcutaneous tissues. CT scans showed single or multiple minimally enhancing soft tissue nodules, in two instances associated with lytic bone erosion. The metastatic lesions were moderately hypoechoic on sonography and target-shaped with or without ring-enhancement on CT. Imaging studies have a limited role in diagnosis of the clinically evident primary skin lesions, but may be helpful in the assessment of the depth of the invasion and are crucial in the evaluation of regional and distant metastatic disease. If regional adenopathy is found then CT of the chest, abdomen and pelvis may be in order.

Adult↗
PubMed1995

Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin.

PURPOSE: Diagnostic strategies designed to identify the underlying primary malignancies in patients with unknown primary tumors (UPTs) have relied on retrospective analyses. We analyzed 879 consecutive patients referred with suspected UPTs to determine the yield and cost of a limited diagnostic evaluation, assess the contribution of specific studies to diagnosis, and analyze the survival patterns of patients in whom the primary tumor was diagnosed. PATIENTS AND METHODS: Data from patients with a suspected UPT were entered into a computerized data base, and the patients underwent a predefined limited diagnostic evaluation. Primary malignancies were diagnosed by pathologic review alone or by pathologic criteria plus a physical or radiographic finding. Survival was measured from diagnosis, estimated using the Kaplan-Meier method, and compared using the Cox-Mantel log-rank test. RESULTS: A primary tumor was found in 179 of 879 patients (20%). The survival duration of patients in whom the primary tumor was diagnosed was superior to that of patients in whom the primary tumor remained unknown. Specific patient subsets contributed most to the improved survival duration of the group in which the primary tumor was found, including lymphoma patients diagnosed solely by pathologic criteria and female patients with primary breast or ovarian cancer. The cost of diagnosis was mostly due to the extensive use of computed tomography. Except for ovarian cancer, computed tomography rarely identified treatable primary tumors. CONCLUSION: The limited diagnostic evaluation used in this study identified patients with treatable malignancies and increased the survival duration of a population of suspected UPT patients. Primary malignancies with the best survival can be diagnosed through careful pathologic review and focused evaluations for breast and ovarian cancer in women.

Adolescent↗
PubMed1994

Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients.

PURPOSE: To evaluate the natural history, validate previous observations, and identify prognostic factors in patients with unknown primary carcinoma (UPC). PATIENTS AND METHODS: Nine hundred twenty-seven consecutive patients referred to the M.D. Anderson Cancer Center with a preliminary diagnosis of UPC were prospectively identified. A standardized evaluation narrowed the study population to 657 patients with UPC. All data were recorded and computerized for storage, retrieval, and analysis. The primary end point for the study was survival, which was calculated from the first day of patient registration. Survival curves were estimated using the Kaplan-Meier method and compared using the Cox-Mantel log-rank test. To identify important prognostic factors, univariate and multivariate analyses were conducted. RESULTS: The demographics of the UPC patient population mirrored those of the general population of patients referred to our cancer center except for an excess of men among the UPC patients. Most patients had histologic or cytologic evidence of adenocarcinoma and had more than one organ site metastatically involved. Univariate and multivariate analyses identified numerous important prognostic factors with a significant influence on survival, including sex, number of organ sites involved, specific organ sites involved, and pathologic subtypes. CONCLUSION: This study validated previously identified important prognostic factors for survival in UPC. Additional variables that had an impact on survival were identified and the complex interaction of the factors was explored. As patient numbers increase, this database will be able to provide further analyses of patient subsets and potentially relate specific clinical features to the evolving molecular and biochemical understanding of these malignancies.

Adenocarcinoma↗
PubMed1993

Liver carcinogenesis associated with feeding of ethionine in a choline-free diet: evidence against a role of oval cells in the emergence of hepatocellular carcinoma.

In an attempt to clarify the role of oval cells in the emergence of hepatocellular carcinoma, we fed rats a choline-free diet containing 0%, 0.05% or 0.1% ethionine. The incidence and nature of premalignant and malignant hepatic lesions were then related to the degree of oval cell proliferation. Intake of choline-free diet alone for up to 12 mo was associated with minimal oval cell proliferation; cholangiofibrosis, hepatocellular nodules and hepatocellular carcinoma were observed in 55%, 23% and 14% of the animals, respectively. When rats were given the choline-free diet with 0.05% ethionine, proliferation of oval cells was more pronounced; after a 6- to 12 mo feeding period, cholangiofibrosis (57%) was again observed. However, hepatocellular nodules (91%) and hepatocellular carcinoma (74%) were the most common lesions seen with this feeding regimen. Finally, rats fed the choline-free diet with 0.1% ethionine had massive oval cell proliferation and progressive loss of parenchymal liver tissue. Most of these animals died before they had consumed the choline-free diet with 0.1% ethionine for 12 mo. Rats in this group (96%) exhibited large and numerous cholangiofibrotic lesions, but hepatocellular nodules and carcinoma were not detected. In all animals of each experimental group, hyperplastic bile duct cells in areas of cholangiofibrosis and oval cells were positive for cytokeratin 19, an intermediate filament protein present only in bile duct cells in normal liver. Hepatocellular nodules and hepatocellular carcinoma were invariably negative for cytokeratin 19. We interpret these findings to suggest that oval cells are not involved in the histogenesis of hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗