Pancreatic carcinoma and Trousseau's syndrome: experience at a large cancer center.

It is common belief that carcinoma of the pancreas has an inherent and unique ability to induce a hypercoagulable diathesis that leads to clinically significant thrombosis. We evaluated 130 consecutive patients with adenocarcinoma of the pancreas to document the incidence and the predisposing factors related to the postulated increased association of thromboembolic disorder (TED) and pancreatic carcinoma. Only nine such patients (6.9%) demonstrated TED complications of the classical Trousseau syndrome. In these instances, the location of the tumor and its mucin-producing potential were significant predisposing factors. In our series, TED was usually associated with tumors of the body and tail, which had a greater likelihood to be mucinogenic as compared with those localized to the head of the pancreas. Routine tests for hemostasis were not helpful in predicting the development of TED except, perhaps, for decreased platelet counts. Therefore, we believe that the relationship between cancer of the pancreas and TED should be de-emphasized since it is neither unique nor especially common to pancreatic carcinoma and since it may be frequently encountered in other varieties of visceral malignancies of the cancer patient population.

The prognosis of Hodgkin's disease in older adults.

This investigation was undertaken to assess the apparent poor survival of older patients with Hodgkin's disease. The clinical course of Hodgkin's disease in 136 patients, 60 to 79 years of age, was compared with that of 223 patients, 40 to 59 years of age. The patients registered from November 1977 through December 1983 had not been previously treated, and were treated at eight cancer centers. When the prognosis of all patients was examined by age, a definite change in the pattern of survival first appeared in the 60- to 69-year-old cohort. The entire older group (60 to 79 years) experienced twice the risk of dying from Hodgkin's disease and four times the risk of dying from other causes than did the younger group. In both groups, stage of disease was the strongest factor in predicting adjusted survival. Delay in treatment and advanced stage at presentation were not characteristic of Hodgkin's disease in older patients as has been postulated. Older patients responded to therapy with a similar complete remission rate (84% v 88% in the younger group, P = .24). From this study, we conclude that (1) Hodgkin's disease in the older adult does not have a different natural history, its major risk factors are similar to those known in other age groups, and thus should be amenable to existing therapeutic approaches; and (2) the prognosis of older patients with Hodgkin's disease has been obscured in previous studies by the inclusion of deaths due to other causes in survival estimates.

p53 immunohistochemical staining predicts residual disease after chemoradiation in patients with high-risk rectal cancer.

This study was conducted to investigate the value of p53 immunohistochemical staining of pretreatment biopsy specimens in predicting the response of rectal cancer to chemoradiation. The study group comprised 42 patients with high-risk rectal cancer treated between July 1990 and July 1995 with a preoperative chemoradiation regimen of 45 Gy of external-beam irradiation and continuous-infusion 5-fluorouracil followed by surgical resection. p53 immunohistochemical staining was performed on pretreatment biopsy specimens. p53 immunohistochemical staining pattern and standard clinical and pathological parameters were correlated with extent of residual cancer in the surgical specimen. Twenty tumors were positive for p53 on immunohistochemical staining, 19 were negative, and 3 were focally positive. Thirteen patients experienced a complete response to chemoradiation. Aberrant p53 protein accumulation, as measured by immunohistochemical staining, correlated inversely with a complete pathological response to chemoradiation (P = 0.005; correlation coefficient = -0.43) and directly with an increased likelihood of residual cancer in the lymph nodes of surgical specimens (P = 0.02; correlation coefficient = 0.39). p53 immunohistochemical staining of pretreatment biopsy specimens correlates with the extent of residual disease after chemoradiation in patients with high-risk rectal cancer.

Absence of a relationship of size of primary colon carcinoma with metastasis and survival.

This retrospective study analysed the relationship of tumor size to regional and systemic metastasis and to survival according to stage of disease. Colon cancers (391 cases) that were treated surgically at M. D. Anderson Hospital from 1955 to 1975 were reviewed. Staging of disease was based on the Astler-Coller modification of Dukes' staging classification. The mean diameters (cm +/- s.e.m.) of Dukes' B1, B2, C2 and D tumors were 4.47 +/- 0.34 (n = 46), 6.61 +/- 0.29 (n = 147), 5.39 +/- 0.23 (n = 71) and 5.78 +/- 0.24 (n = 120), respectively. The mean diameter of Dukes' B2 tumors was significantly greater than C2 (P less than 0.001) and D (P less than 0.05) tumors. Within stage B and C, size of the primary tumor showed no relationship to five year adjusted survival. Our findings suggest that colon carcinoma metastasis and survival are independent of tumor size. Because tumor burden does not account for distant disease, specific tumor cell phenotypes and biological processes are probably more important in determining metastatic disease.

Medroxyprogesterone acetate reduces the in vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients.

Medroxyprogesterone acetate (MPA) is widely used in oncology both in the treatment of hormone-related cancers and as supportive therapy in anorexia/cachexia syndrome (ACS), but conclusive data are not yet available to explain its anticachectic effect. ACS is characterised by weight loss, changes in metabolism, reduction of appetite, nausea and vomiting. Several cytokines, mainly interleukin (IL)-1, IL-2, IL-6 and tumour necrosis factor alpha (TNF alpha), are involved in the pathogenesis of ACS. Additionally, nausea and vomiting can be mediated by factors inducing serotonin (5-HT) production and/or release by pleiotropic cells including activated T lymphocytes. In the present study, we report the effect of MPA on peripheral blood mononuclear cells (PBMC) from 10 cancer patients in advanced stage of disease (6 head and neck, 2 colon, 1 lung and 1 ovary). The proliferative response of PBMC to PHA, anti-CD3 monoclonal antibody (MAb) or recombinant IL-2 (rIL-2), the production of IL-1 beta, IL-2, IL-6, TNF alpha and 5-HT by PHA-stimulated PBMC and the expression of lymphocyte membrane-bound IL-2 receptor (IL-2R) subunities (CD25 and CD122) were studied. The addition of MPA significantly reduced the PBMC proliferative response to PHA and anti-CD3 MAb but not to rIL-2. MPA 0.2 microgram/ml was also capable of reducing the levels of IL-1 beta, IL-6, TNF alpha and 5-HT produced in culture by PHA-stimulated PBMC, whereas it did not induce any change in the percentage of PBMC expressing either CD25 or CD122 or both molecules after stimulation with PHA or anti-CD3 mAb.

Fractionated total body irradiation in allogeneic bone marrow transplantation in leukemia patients: analysis of prognostic factors and results in 136 patients.

BACKGROUND AND PURPOSE: The results of a single-institution series of patients with chronic and acute leukemias are analyzed with regard to literature-reported predictor variables. MATERIALS AND METHODS: Between 1985 and 1994, 136 patients, 82 patients with chronic myeloid leukemia (CML) and 54 with acute leukemia (AL), received a uniform preparatory regimen of fractionated total body irradiation (TBI; 12 Gy in 3 days) plus different chemotherapy regimens before bone marrow transplantation. Eighty-six patients were considered to be in early phase of disease (CML in chronic phase or AL in first complete remission) and 50 in advanced phase (all those beyond first remission or first chronic phase). Ninety-five patients received unmanipulated allogeneic BM, and 41 T-lymphocyte-depleted BM. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) of the whole series were 43% and 31%, and median survival was 43 and 10 months, respectively. A Cox proportional hazard model identified variables related to overall and disease-free survival. For OS, graft versus host disease (GVHD) was the first independent variable (P < 0.0001), followed by age (P < 0.001), T-depletion (P < 0.01), disease status (P < 0.05) and type of leukemia (P < 0.05). With regard to DFS, only T-depletion (P < 0.0001), disease status (P < 0.01) and GVHD (P < 0.01) resulted predictor factors. Early complications after BMT were reported in 59 patients, TBI-induced delayed toxicity in 9 patients, and 16 patients suffered late complications. CONCLUSIONS: Our results confirm the curability of early phase leukemias with standard fractionated TBI-induced Allogeneic bone marrow transplantation (ABMT). With an homogeneous fractionated TBI schedule as employed in our series, T-cell depletion negatively affected the outcome.

Typical and atypical bronchopulmonary carcinoids. A clinicopathologic and flow cytometric study.

The clinicopathologic and flow cytometric characteristics of 47 bronchopulmonary carcinoids were assessed, relative to patient survival. Aneuploidy was associated more often with tumor size of greater than or equal to 3.0 cm (P less than 0.004) and lymph node (P less than 0.013) or vascular involvement (P less than 0.004). Also, an aneuploid DNA content was seen significantly more often in histologically atypical (79%) than in typical carcinoid neoplasms (18%) (P less than 0.0001). Cox proportional hazard model analysis revealed that the histologic category (typical vs. atypical) and ploidy pattern were important prognostic indicators. Size of the primary tumor and the presence of vascular involvement were also significant predictors of outcome. Histologically atypical carcinoids with diploid DNA content pursued a less aggressive course than did their aneuploid counterparts.

Pelvic exenteration for locally advanced rectal carcinoma: factors predicting improved survival.

BACKGROUND: The purpose of this retrospective review was to determine whether a number of clinicopathologic factors (age, gender, type of exenteration, tumor extent, adjuvant therapy, tumor DNA ploidy, and S-phase fraction) that could be determined before operation were useful in predicting survival in patients undergoing pelvic exenteration for rectal cancer. METHODS: Between 1983 and 1992, 40 patients (15 male and 25 female) at our institution underwent pelvic exenteration for rectal adenocarcinoma in which tumor-free pathologic margins were obtained. Twenty-nine patients presented with primary tumors; 11 had recurrent disease. A total exenteration was performed in 20 patients, posterior exenteration in 18 patients, and an anterior exenteration in 2 patients. RESULTS: By multivariate (Cox proportional hazards regression) analysis, age, preoperative chemoradiation therapy, and an S phase of 10% or greater were found to be significant predictors of survival. Age older than 55 years was associated with a relative risk for cancer-related death (RR) of 0.13 (p = 0.02), and chemoradiation had an RR of 0.05 (p = 0.01), indicating their beneficial effect. An S-phase fraction of 10% or greater had an RR of 16.97 (p = 0.03), indicating a poor survival. The clinicopathologic factors listed above were used to derive a prognostic index (PI). A PI of less than 1.37 was associated with a 5-year survival rate of 65% (low risk), whereas patients with a PI of 1.37 or greater had a 5-year survival rate of 20% (high risk) (p = 0.005). CONCLUSIONS: These results indicate that adjuvant chemoradiation may significantly improve survival in patients who require pelvic exenteration for resection of locally advanced rectal carcinoma. An S-phase fraction of 10% or greater is also predictive of a poor outcome. Use of these factors allowed the generation of a PI that identifies high- and low-risk patients. Consideration of the ability to deliver chemoradiation and the determinates of the tumor S-phase fraction in patients requiring pelvic exenteration for rectal cancer may be helpful in predicting outcome and planning therapy.

Osseous metastases secondary to renal cell carcinoma.

We present the distribution of metastases and clinical course of 252 patients with osseous metastases secondary to renal cell carcinoma. Symptoms of the metastases were the presenting complaint in 48 per cent of patients (including 37 with pathologic fractures); the axial skeleton was the most commonly involved site. Despite earlier reports that nephrectomy lengthened survival for patients with osseous metastases, our data showed this to be true only for patients with a solitary osseous metastasis. Patients with multiple osseous metastases had survival rates no better than patients with soft tissue or mixed lesions-whether or not nephrectomy was performed.

Untreated prostatic carcinoma is not associated with frequent thrombohemorrhagic disorders.

We conducted an evaluation of the hemostatic integrity of patients with untreated cancer of the prostate. Of 60 patients analyzed retrospectively, only 1 had a mild case of disseminated intravascular coagulation, possibly associated with concomitant estrogen therapy, and in 1 patient mild deep vein thrombosis developed preoperatively, also possibly associated with multiple medications for concurrent disorders. Of 16 other patients prospectively evaluated on admission, only 1 had frankly abnormal levels of fibrinopeptide A unaccompanied by other coagulation abnormalities. Occasional individuals had minimal, negligible deviations of partial thromboplastin times, thrombin time, or antithrombin III values. In none of these patients did hemostatic complications develop during their hospital stay. These results demonstrate that although an occasional coagulation abnormality may occur in patients with cancer of the prostate (albeit with a lower incidence than in other neoplasms), this malignancy does not require increased precautions with respect to those given to the patient population at large.

Role of nuclear grading in stage I renal cell carcinoma.

Through a retrospective histologic analysis of 55 cases of Stage I renal cell carcinoma, we evaluated the usefulness of the nuclear grading system (Fuhrman, Lasky, Limas) in identifying those tumors that will eventually metastasize and kill the patient. The difference in five-year survival rates between patients with combined nuclear grade 1-3 tumors (n = 50, 91%) and grade 4 tumors (n = 5, 9%) was significant (P less than 0.0046). Other predictors of death due to renal cell carcinoma included: tumor size greater than 8 cm (P less than 0.001) and mitoses greater than one per 10 high-power field (P less than 0.01). Within Stage I tumors, therefore, nuclear grade is an important morphologic variable for predicting long-term survival. Identification of nuclear grade 4 neoplasms may become prognostically indispensable to determine the metastatic potential of early-stage tumors and thereby to institute appropriate systemic therapy.

Survival factors in 186 patients younger than 40 years old with colorectal adenocarcinoma.

BACKGROUND: We sought to determine the clinical factors and tumor characteristics associated with the reported poor prognosis in young patients with carcinoma of the colon and rectum. STUDY DESIGN: A retrospective review was performed of 186 patients younger than 40 years of age who were treated for primary colorectal adenocarcinoma. The median age was 34.3 years, and the median follow-up period was 9.4 years. Clinical and tumor histopathologic parameters were analyzed. RESULTS: Regional lymph node metastases, distant metastases, or both, were seen at first examination in 65.6 percent of young patients. Histopathologic indicators of more aggressive tumor biology were present at a significantly higher frequency in young patients compared with patients older than 40 years (p < 0.001). Poorly differentiated tumor grade was present in 41.0 percent, signet-ring cell tumors were found in 11.1 percent, and infiltrating tumor leading edges were present in 69.0 percent of young patients. Among young patients with stage II disease, vascular invasion was a significant negative prognostic variable (p < 0.05). CONCLUSIONS: We have demonstrated an increased incidence of three biological indicators of aggressive and potentially metastatic tumor biology in 186 young patients with carcinoma of the colon and rectum: signet-ring cell carcinoma, infiltrating tumor edges, and aggressive histologic grade in the primary adenocarcinoma. The increased incidence of these three histologic measures of more aggressive carcinoma of the colon and rectum in part accounts for the higher rate of advanced disease at presentation in patients younger than 40.

On the use of pediatric phantoms in the dose evaluation during computed tomography (CT) thorax examinations.

This paper presents the dosimetric results obtained during computed tomography (CT) thorax examinations, carried out using two different techniques, i.e., sequential CT (SQCT) and helical CT (HECT). The radiological examinations have been carried out on pediatric phantoms expressly designed and realized. Four different phantoms have been realized, according to the children shapes of 0, 2, 6, and 12 years old. The dosimetric measurements have been carried out using thermoluminescent dosimeters. The comparison of the dosimetric data obtained using the two different techniques shows that there is not any relevant difference between them as far as the entrance dose and the doses received by the critical organs are concerned.

The prognostic implications of location for scalp melanoma.

The clinical and pathologic records of 95 patients with primary cutaneous melanoma isolated to the scalp and regional lymph nodes treated at the MD Anderson Cancer Center between 1976 and 1985 were reviewed to assess the effect of lesion location on the prognosis of scalp melanoma. The scalp was defined as an area bounded by the supraorbital ridges, superior nuchal line, zygoma, and mastoid, thereby including a large non-hair-bearing area. Patients were grouped according to lesion location: hair-bearing or non-hair-bearing; anterior or posterior to the mid-tragal line; and parietal versus frontal, temporal, or occipital. There was a similar distribution of prognostic factors between the anatomic subsites. Analysis by univariate and multivariate methods demonstrated that, in a hair-bearing area, in an area posterior to the mid-tragal line, or in the parietal region, lesion location was highly predictive of the patient's survival. For example, the 5-year, melanoma-specific survival rate was 65% overall, 86% for patients with lesions located in non-hair-bearing regions and 47% for those with lesions in hair-bearing regions (p = 0.0019).

Clinical, pathologic, and economic parameters of laparoscopic colon resection for cancer.

BACKGROUND: The appropriateness of laparoscopic colon resection (LCR) as treatment for malignancy has been questioned. METHODS: From 1992 to 1997, 91 patients were entered into a prospective study of LCR for cancer. Clinical, pathologic, and economic parameters of LCR were compared in a cohort of patients matched for age, tumor stage, and type of colectomy who underwent open colon resection (OCR) during the same time period. RESULTS: With a median follow-up of 26 months, there were no significant differences in survival rate for patients in the LCR, converted colon resection, and OCR groups. There were no port-site recurrences and the number of lymph nodes harvested was similar among the procedures. Hospital stay was significantly shorter if laparoscopic resection was successful. Total hospital costs were similar for LCR and OCR; however, the costs were significantly higher for converted colon resection. CONCLUSIONS: LCR is a sound oncologic procedure that can be performed with costs similar to OCR.

Treatment of chronic idiopathic urticaria with topical preparations: controlled study of oxatomide gel versus dechlorpheniramine cream.

A controlled and completely randomized study was carried out with the aim of assessing the efficacy and safety of oxatomide gel in comparison with another preparation for topical use, dechlorpheniramine. Twenty-seven patients (sixteen F, eleven M) aged between 21 and 72 years (mean age 39) suffering from chronic idiopathic urticaria were treated for 15 days with oxatomide gel at 5% or dechlorpheniramine cream at 1%; 15 days of follow-up without therapy were then observed. Both the treatments allowed significant control of cutaneous symptoms. In particular, in the group treated with oxatomide there was a more marked reduction in itching and in the number of weals (p less than 0.01 between times), and in the dechlorpheniramine group in the severity of erythema (p less than 0.01 between times). During the follow-up period, a distinct flare-up of symptoms was observed only in the dechlorpheniramine group. Acceptability and safety, both clinical and biological, were good for both products.

[Effects of Hodgkin cytotoxic serum on electrophoretic mobility of normal and Hodgkin peripheral blood lymphocytes. (author's transl)]. / Effetto del siero citotossico di pazienti con malattia di Hodgkin sulla mobilità elettroforetica di linfociti periferici normali e hodgkiniani

The effect of Hodgkin patient cytotoxic sera on the electrophoretic mobility of normal and Hodgkin peripheral blood allo-lymphocytes has been studied. Contact with cytotoxic serum determined a significant decrease in the electrophoretic mobility of lymphocytes, due to the presence of cytotoxic antibody on the lymphocyte surface. The antibody seems to be directed against T-lymphocytes. The results are discussed in the light of the preceding data by the authors on the role of anti-T-autoantibodies in Hodgkin's disease.

Peripheral blood lymphocyte response to exogenous interleukin 2 by PHA-prestimulated and non-PHA-prestimulated cells in patients with cancer.

The study aims were to assess the response of peripheral blood lymphocytes (PBL) of cancer patients to exogenous Interleukin 2 (IL 2) either by PHA-prestimulated or non PHA-prestimulated PBL, and to carry out preliminary experiments for a direct quantitative evaluation of endogenous IL 2 production by PBL cultures of cancer patients in order to define the actual role of IL 2 in the disease. Analysis of PBL subsets was also carried out with monoclonal antibodies in a selected group of patients. A total of 134 patients entered the study. Cancer sites were: larynx 32, breast 36, lung (NSC) 24, colorectal 17 and gynecologic 25. In the former 3 cancer sites staging showed localized or only locally advanced disease, and in the last 2 sites disseminated disease. Our results provided evidence that cancer patients exhibit a T-cell functional immunodepression, which progresses during tumor growth, so that the localized disease shows a low-grade defect, and advanced disease a high-grade defect. Our data also clearly suggested that the factor involved with a primary role in this functional immune impairment is the IL 2 deficiency. A perspective may be drawn on the therapeutic administration in vivo of IL 2 and IL 2-activated lymphokine-activated killer cells in controlled clinical trials of selected groups of cancer patients.

[Effects of Hodgkin cytotoxic serum on blast transformation of normal and Hodgkin human peripheral blood lymphocytes]. / Effetto del siero citotossico di pazienti con malattia di Hodgkin sulla PHA-responsività in vitro di linfociti periferici umani

The PHA-resposiveness of normal and Hodgkin patient human peripheral blood lymphocytes has been studied before and after incubation with Hodgkin cytotoxic sera. The following conclusions have been reached: (a) Hodgkin cytotoxic serum is capable of decreasing the PHA-responsiveness of normal lymphocytes and of furtherly impairing the already defective PHA-responsiveness of Hodgkin lymphocytes. (b) The impaired PHA-responsiveness can be restored to the original levels by eluting the cytotoxic antibody. Control experiments in which normal and Hodgkin lymphocytes were put in contact with normal and Hodgkin non-cytotoxic serum showed no decrease of PHA-responsiveness. These data are in agreement with the hypothesis that the presence of serum cytotoxin is at least partly responsible for the immuno-incompetence of T-lymphocytes characteristic of Hodgkin's disease.

Prolonged treatment with acrivastine for seasonal allergic rhinitis.

In a double-blind, placebo-controlled multicentre study, the antihistamine acrivastine, was used over prolonged periods for the treatment of seasonal allergic rhinitis. After the initial treatment period of 10 days, 8 mg acrivastine three times daily was significantly superior to placebo in controlling the symptoms of sneezing, itchy nose, running nose, watery eyes, itchy eyes and itchy throat. The benefit from acrivastine was also apparent in the second (14 days) and third (28 days) treatment periods, although the difference no longer reached statistical significance. This was probably due to the large proportion of non-responders in the placebo group who withdrew from the study owing to lack of efficacy. The investigators rated symptom control with acrivastine to be 'good' in comparison to 'poor' control with placebo treatment (P = 0.01) for all three periods. There were no significant differences between acrivastine and placebo in the incidence of adverse experiences at the end of each treatment period. Acrivastine is effective and well tolerated over prolonged periods (up to 52 days) for the treatment of seasonal allergic rhinitis.