Analysis of long-term survival in patients with endometrial carcinoma depending on selected clinical factors

In the period from 1980 to 1990 491 women operated for the cancer of the body of the uterus (stage I, II, III) underwent radiotherapy in the Department of Oncology and Radiotherapy and in Regional Oncological Centre in Bydgoszcz. The patients were at the age from 34 to 78. In the paper the patients' clinical condition was described and assessed according to FIGO/1972 and FIGO/1988 classifications the stages of progression of neoplasms were compared. The distant results of treatment depending on neoplasm's stage, histological type and the method of postoperative radiotherapy were presented.     

Prognostic factors for survival in patients with brain metastases from renal cell carcinoma

BACKGROUND: Patients presenting with brain metastases from renal cell carcinoma portend a poor prognosis, with a reported median survival of 4-6 months. Given their short life expectancy, these patients generally have been excluded from clinical trials that assess the efficacy of medical treatments. However, clinical impression suggests that some patients may achieve long term palliation. METHODS: The clinical features of 68 patients who were treated at the Institut Gustave Roussy for brain metastases from renal cell carcinoma were collected retrospectively. Using univariate and multivariate analyses, a prognostic model based on independent prognostic factors was established. An external data set of 57 patients was used to validate the model. RESULTS: The median survival was 7 months. On univariate analysis survival was related significantly to the following adverse prognostic factors: no initial nephrectomy, left side and temporal location of brain metastases, presence of fever or weight loss, erythrocyte sedimentation rate > 50 mm/h, and time from initial diagnosis to brain metastases < or = 18 months. Multivariate analyses identified the previous variable as well as the presence of other visceral metastases as independent prognostic factors. Forty-four patients (65%) with no or 1 adverse prognostic factor (average risk group) had a median survival of 8 months and a 26% 1-year survival rate. Twenty-four patients (35%) with 2 adverse prognostic factors (poor risk group) had a median survival of 3 months and a 1-year survival rate of 9%. This model proved to be discriminant in an external data set; the median survival of patients assigned to the average risk group was 11 months (46% 1-year survival rate) compared with 4 months (9% 1-year survival rate) for patients assigned to the poor risk group. CONCLUSIONS: Patients presenting with brain metastases from renal cell carcinoma and poor risk prognostic factors are highly unlikely to benefit from medical treatments except symptomatic procedures. Conversely, the enrollment of patients with average risk prognostic factors into clinical trials dealing with chemotherapy or immunotherapy may be considered.     

Peptide growth factors: clinical and therapeutic strategies

Total internal reflection fluorescence microscopy has been used to investigate the binding of the soluble extracellular domain of mouse Fc gamma RII (sFc gamma RII) to an anti-trinitrophenyl monoclonal mouse IgG2b (GK14.1) specifically bound to substrate-supported planar membranes composed of dipalmitoylphosphatidylcholine (DPPC) and trinitrophenylaminocaproyldipalmitoylphosphatidylethanolamine (TNP-cap-DPPE). The equilibrium dissociation constants for sFc gamma RII at GK14.1-coated TNP-cap-DPPE/DPPC planar membranes containing 0.5-25 mol% TNP-cap-DPPE were approximately 1 microM. Total internal reflection with fluorescence photobleaching recovery was used to examine the dissociation kinetics. The fluorescence recovery curves were better described as a sum of two exponentials rather than by one exponential; the rates and fractional recoveries were approximately 1 s-1 (65%) and approximately 0.1 s-1 (35%). The similarity between the values of these equilibrium and kinetic parameters to those previously measured for the binding of IgG in solution to intact mouse Fc gamma RII reconstituted into planar membranes suggests that conformational changes which may occur when IgG is constrained to a membrane surface do not significantly affect the equilibrium or kinetics of IgG-mouse Fc gamma RII binding. The stoichiometry of sFc gamma RII-GK14.1 binding was 1:4, indicating that a significant fraction of the membrane-bound antibodies were not accessible for receptor binding. Possible mechanisms that might underlay the observed heterogeneity in sFc gamma RII-IgG binding kinetics are discussed.     

Changing clinical, pathologic, therapeutic, and survival patterns in differentiated thyroid carcinoma

Records of 792 patients with differentiated thyroid carcinoma seen at the Lahey Clinic Foundation over a 40-year period were analyzed; 631 patients had a minimum followup period of 15 years. Differentiated types currently constitute nearly 90% of thyroid carcinomas. The clinical presentation has improved substantially through the years, and the results of treatment generally have improved. The per cent of patients with primarily incurable and locally unresectable disease or distant metastases has decreased from 7% before 1950 to 1% currently, and this group resulted in almost one third of the total fatalities and one half of fatalities within the first 5 years after treatment. Clear relationships were demonstrated between older age, men, extraglandular extension, blood vessel invasion, major capsular involvement, multifocal disease, and higher mortality rates. Lymph node metastases were found to exert a protective effect in all categories of disease analyzed, and this effect was directly related to the number of lymph node metastases present such that no deaths occurred in those patients who had more than 10 node metastases. Surgical treatment recommended is subtotal thyroidectomy for patients at high risk of death from disease as defined by combinations of age, sex, and extraglandular extension. Patients at low risk or with small carcinomas can be treated satisfactorily by lobectomy. Lymph node resections should be of a limited type or a modified neck dissection and should be performed only therapeutically. No improvement, as judged by mortality or recurrence rates, could be demonstrated by the use of radio therapy after surgery, and its use should be discouraged. Thyroid hormone administered for suppression of endogenous thyroid-stimulating hormone production improved mortality rates significantly in patients with papillary and mixed forms of carcinoma in all age groups but did not affect survival in patients with follicular carcinoma of the thyroid.20     

Cardiac tamponade as first clinical manifestation of small cell carcinoma

A 69 year old man was diagnosed of cardiac tamponade. At surgery a large hemopericardias was evacuated, cardiac and pericardial metastasis of an oat cell carcinoma was demonstrated. The patient died 4 weeks later. A review of the literature is done about patients with cardiac tamponade as the first manifestation of a neoplastic process.     

A case of small cell carcinoma of the lung associated with hypertrophic pulmonary osteoarthropathy

AIM: To investigate the mechanisms of anti-inflammatory effect of matrine (Mat), its effects on mouse splenocyte proliferation, and release of interleukin-1 (IL-1) and interleukin-6 (IL-6) from mouse peritoneal macrophages. METHODS: Splenocyte proliferation was assayed by [3H] TdR incorporation. IL-1 and IL-6 activities were measured by thymocyte proliferation assay and B9 cell proliferation MTT colorimetric method, respectively. RESULTS: Mat (125-500 mg.L-1) obviously inhibited concanavalin A (Con A, 5 mg.L-1)- and lipopolysaccarides (LPS, 10 mg.L-1)-induced splenocyte proliferation and LPS-induced release of IL-1 and IL-6 from mouse peritoneal macrophages. CONCLUSION: Mat inhibited splenocyte proliferation and release of IL-1 and IL-6 in vitro.     

Hepatocellular carcinoma cases with five-year survival and prognostic factors affecting the survival time

Between 1980 and 1994, 178 patients were confirmed to have hepatocellular carcinoma (HCC) in our hospital. The 5-year survival rates in patients with HCC of stage I, II and IVA were 38.1%, 31.8% and 3.9%, respectively. No patient in stage III or IVB survived for more than four years. The 5-year survival rates of the patients treated by hepatic resection, ultrasonically guided percutaneous ethanol injection and transcatheter hepatic arterial embolization were 53.7%, 38.7% and 13.5%, respectively. The logrank test showed a significant difference in cumulative survival rates obtained in patients with HCC according to the tumor stage (p < 0.001) or principal treatment procedure (p < 0.001). Twelve patients survived for more than five years. We employed a Cox's proportional hazards model to estimate the factors significantly affecting the survival time. Variables with statistical significance were the clinical stage (p < 0.001), tumor size (maximal tumor diameter) (p < 0.001) and patient's age (p < 0.05). Conclusively, patients in the early stage of HCC associated with mild liver cirrhosis have a significantly better chance for long survival.     

Gestational squamous cell carcinoma of the breast: an unusual mammary tumor associated with aggressive clinical course

We report two cases of squamous carcinoma of the breast detected during the gestational period. One woman was post-partum and lactating; one was in the first trimester of pregnancy. The lesions were clinically palpable, multifocal, and measured more than 5 cm in their largest dimension; both had a cystic appearance. They were treated with radical mastectomy. One patient received pre-operatory chemotherapy. Histologically, the tumors were poorly differentiated squamous cell carcinomas. No areas of ordinary duct differentiation were seen. Lymph nodes contained metastatic squamous carcinoma in both cases. Tumor cells were negative for estrogen and progesterone receptors. Also, they expressed a high proliferative index and several markers of tumor progression, including cErb-B2, p53 protein, bcl-2, and epidermal growth factor receptor. One patient died of tumor 5 months following breast surgery and had extensive metastases proven at autopsy. The other patient had evidence of pulmonary metastases: following cisplatin therapy, she underwent clinical remission. This study shows that squamous carcinoma of the breast may occur in pregnant or lactating women: it appears clinically distinguishable from the non-gestational type that is usually associated with a better prognosis and occurs in peri- or postmenopausal women.     

Undifferentiated small cell carcinoma (oat-cell type) of the colon. Prognostic and therapeutic implications

AIM: This report reviews the clinical and pathologic features of four patients with small-cell anaplastic carcinoma (SCAC) of the colon and describes in detail their histological and immunohistochemical characteristics. METHODS: Four patients with a SCAC of the colon diagnosed by conventional light microscopy, immunohistochemistry and ultrastructure were reviewed; clinical presentation, tumor location and spread, surgical procedure, adjuvant therapy and clinical outcome were recorded. RESULTS: There were two women and two man, with an average age of 55 (range, 40-66) years. Two tumors were located in the sigmoid and two in right colon. Cases 1, 3 and 4 were removed at laparotomy by segmental resection along with lymph nodes. All cases had liver metastases. Pathologic study identified out-cell subtype in all cases and two histopathologic patterns: pure SCAC (cases 2 and 4) and mixed exocrine-SCC differentiation (cases 1 and 3). Three patients were treated with cyclophosphamide, cisplatin and etoposide. Two patients (cases 2 and 4) died of widely metastatic disease; cases 1 and 3 had partial remission lasting 9 and 3 months, respectively. CONCLUSIONS: Due to extremely aggressive behavior of colon SCAC with early metastatic spread, CT scans of the chest-abdomen and radionuclide bone scan should be performed. In the presence of metastatic disease, multiagent chemotherapy with combined etoposide and cisplatin should be instituted.     

Gastrointestinal hemorrhage and small cell carcinoma

Despite widespread dissemination of primary lung carcinoma by lymphangitic and hematogenous routes, acute gastrointestinal signs and symptoms are rarely presenting symptoms for bronchogenic carcinoma. We present a patient with small cell carcinoma of the lung who came to medical attention because of a lower gastrointestinal hemorrhage. In the absence of radiographically apparent pulmonary disease, the correct diagnosis was suggested by the biopsy specimens of the colon.     

Functioning and nonfunctioning adrenocortical carcinoma: clinical presentation and therapeutic strategies

Adrenocortical cancers are relatively rare endocrine tumors that usually present when hormonally active or after they have become large and metastasis has occurred. Consequently, the 5-year survival rate is 20% to 35%. Surgical removal remains the only form of therapy proven to prolong survival. Mitotane is the most accepted form of chemotherapy. For the approximately 20% to 25% of patients whose tumors respond to mitotane, survival is prolonged.     

Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival

We report the electrophysiologic findings of myoclonus in a patient with Huntington's disease (HD). This patient was studied postoperatively after a bilateral fetal cell transplant in his striatum. Incomplete transient improvement was seen in the myoclonus, followed by gradual deterioration. The myoclonus itself had a cortical correlate and was associated with an enlarged somatosensory evoked potential (SEP), consistent with the presence of cortical reflex myoclonus. An enlarged SEP has not been previously reported in myoclonus associated with HD. The postulated mechanisms for myoclonus, when it occurs in HD, have differed in the literature. The reason for the transient improvement of the myoclonus following transplantation is unclear, but this case raises the possibility that basal ganglia circuits may modulate cortical myoclonic activity.     

Significant prognostic factors for 5-year survival after curative resection of renal cell carcinoma

The aim of this study was, (1) to characterize the serum protein binding of lerisetron, a new 5-hydroxytryptamine (5-HT3) receptor antagonist under investigation as an antiemetic agent, and (2) to measure the percentage of unbound lerisetron in cancer patients. The binding parameters were determined in human serum albumin (HSA), alpha1-acid glycoprotein (AAG) and in pooled serum from six healthy volunteers. Concentrations of lerisetron ranging from 50 ng/ml to 2 microg/ml were used. The serum protein binding of 14C-lerisetron (2 microg/ml) was determined by ultrafiltration in three groups of individuals. Group I comprised healthy subjects (n = 11), group II comprised cancer patients undergoing radiotherapy (n = 9), and group III comprised cancer patients receiving chemotherapy (n = 18). The unbound concentration of lerisetron was measured in all samples by liquid scintillation counting. Concentrations of both AAG and HSA were also measured in all serum samples. The drug was extensively bound in pooled serum, involving a nonsaturated process. In HSA, lerisetron was also highly bound (4.04+/-0.8% unbound) and the protein binding was essentially unchanged within the studied concentration range of lerisetron. The extent of binding to AAG was high but significantly lower than in serum and in HSA and was also independent of lerisetron concentration. The unbound lerisetron was significantly decreased in group II cancer patients when compared with group I subjects (2.38+/-0.64% vs 3.70+/-0.70%; P < 0.001). No significant changes in lerisetron binding were observed in group III patients. HSA was diminished in both groups of patients and AAG was only significantly increased in group II. Unbound lerisetron was correlated with AAG in group II and with HSA in group III.     

Prognostic factors in surgically treated small cell cervical carcinoma followed by adjuvant chemotherapy

BACKGROUND: Small cell carcinoma of the uterine cervix is an uncommon tumor associated with high mortality even among patients with early stage disease. The role of adjuvant chemotherapy after surgery has been suggested by regimens used for small cell lung carcinoma. During the years 1980-1997, 19 cases in which various adjuvant chemotherapies were given after hysterectomy were reported in the literature published in English. METHODS: Adjuvant chemotherapy was administered consecutively to 23 patients with Stage Ib-II small cell cervical carcinoma who had been primarily treated with radical hysterectomy and had adequate bone marrow, renal, and hepatic functions. A combination of vincristine, doxorubicin, and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE) was administered to 14 patients during the years 1988-1996 according to a prospective study protocol. A combination of cisplatin, vinblastine, and bleomycin (PVB) was administered to 8 patients, and another regimen was administered to 1 patient during the years 1984-1988. Prognostic factors were evaluated by analyzing both the data on these 23 patients and the pooled data on the cases retrieved from the literature and our own files. RESULTS: Ten of the 14 patients who received VAC/PE had no evidence of disease during a median follow-up of 41 months, whereas 3 of the 9 who received PVB or another regimen survived. Of the 10 patients who died of their disease, all died of distant metastasis within 10 months after recurrence. Meta-analysis of the pooled data showed that 68% of patients who received regimens containing VAC or PE survived, whereas 33% of patients who received regimens not containing VAC/PE survived (P = 0.0078, log rank test). Seventy percent of patients with no lymph node metastasis at hysterectomy and 35% with lymph node metastasis survived (P = 0.05). All patients who died of disease had extrapelvic metastasis. CONCLUSIONS: Chemotherapies containing VAC or PE are favorable regimens for patients with early stage small cell cervical carcinoma after radical hysterectomy.     

The influence of p53 and associated factors on the outcome of patients with oral squamous cell carcinoma

Radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis. However, the procedure is not widely used because of concerns about leakage of radiopharmaceuticals from the treated joints. Leakage can be minimized by selecting particles of an appropriate size. In this study, we labelled microspheres with 188Re and analysed its biodistribution after intra-articular injection in rabbits with antigen-induced arthritis. Gamma camera imaging was performed to quantify the mean retention of 188Re in the knees. The mean retention of 188Re was 98.7, 94.6 and 93.6% at 1, 24 and 48 h, respectively. The biodistribution data revealed very low radioactivity in all organs at different times, which suggests the leakage of radiotracer from the knee was negligible. Our preliminary results indicate that 188Re microspheres are a potentially effective radiopharmaceutical for radiation synovectomy.     

Control of Schwann cell survival and proliferation: autocrine factors and neuregulins

Postnatal rat Schwann cells secrete factors that prevent the programmed cell death (PCD) of low-density Schwann cells in serum-free culture. These autocrine survival signal(s) do not promote Schwann cell proliferation. Moreover, while NRG and bFGF, which promote proliferation, both rescue a subpopulation of neonatal Schwann cells from PCD, they do not rescue freshly isolated Schwann cells from older animals; other known protein factors tested also do not mimic the autocrine signal. These results suggest that Schwann cells switch their survival dependency around the time of birth from axonal signals such as NRG to autocrine signals. Such an arrangement would be advantageous for the regeneration of peripheral axons following injury. We also compared NRG-induced Schwann cell proliferation using autocrine signals or serum to promote survival. The autocrine signals increase the rate of NRG-stimulated proliferation of low-density Schwann cells in serum-free medium, whereas serum inhibits proliferation by inhibiting both the production of survival signals and the expression of erbB2 and erbB3 receptors; these inhibitions are all reversed by forskolin. In contrast, forskolin has no effect on proliferation when the cells are exposed to high levels of autocrine factors.     

Verrucous squamous cell carcinoma of the larynx: diagnostic and therapeutic considerations

Certain prostaglandins acting as inflammatory mediators have been implicated in the aetiology of perennial allergic rhinitis (PAR). Inhibition of prostaglandin synthesis in the nasal mucosa might therefore influence the symptoms associated with PAR. A randomised, doubleblind, placebo-controlled cross-over trial using 0.1% Diclofenac eye-drops has been conducted to investigate this hypothesis. Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), reduces prostaglandin synthesis through the inhibition of the cyclo-oxygenase pathway. Twenty-five patients with significant PAR and positive skin tests to relevant perennial allergens were recruited and two drops of the given preparation were administered bilaterally q.d.s.. Thirteen patients completed the study. Nasal symptom score (itch, rhinorrhoea, sneezing, and blockage), smell test score, saccharin transit time, total nasal airflow resistance, and nasal inspiratory peak flow measurements were obtained at each of three study visits. No significant treatment effects were found. The daily nasal symptom score over the entire study period showed no significant variation. Adverse effects such as local invitation, dry nose or throat were rare. No untoward changes in haematological, biochemical profiles and urinalysis occurred. In conclusion, topical 0.1% Diclofenac eye-drops applied nasally have no significant effect on PAR. Prostaglandins alone may not play a major role in mediation of symptoms in this condition.     

Advanced endocrine cell carcinoma of the gallbladder: a patient with 12-year survival

Gallbladder carcinoid is a rare disease. In previous reports, classical carcinoid, an entity with a good prognosis, has not been distinguished from endocrine cell carcinoma, a tumor associated with marked cell atypia and mitosis, and a poor prognosis. The patient was a 66 year old woman who presented to our hospital with a chief complaint of jaundice. Pre-operatively, she was diagnosed as having advanced gallbladder carcinoma invading the liver and the hepatic hilus. The patient underwent right hepatic trisegmentectomy with en bloc resection of the caudate lobe and extrahepatic bile ducts, extended lymph node clearance and left hepaticojejunostomy. Histopathological examination showed positive Grimelius staining, marked mitosis, and intense atypism, hence, the tumor was diagnosed as an endocrine cell carcinoma. Twelve years after surgery, the patient is healthy, without any sign of recurrence. We present this novel case of long-term survival and review the literature.     

Biological characteristics of esophageal squamous cell carcinoma associated with contiguous intraepithelial carcinoma

To evaluate the biological significance of esophageal squamous cell carcinoma that is associated with contiguous intraepithelial carcinoma, we analyzed 95 patients with operated esophageal carcinoma. Of these 95 patients, eight had in situ carcinoma. Among 87 cases in which the tumo had invaded more deeply than the lamina propria, there were 42 cases (48.3%) of contiguous intraepithelial carcinoma associated with the main tumor. The biological characteristics (proliferative activity of cells, as revealed by immunostaining with the Ki-67 monoclonal antibody) of 45 tumors without contiguous intraepithelial carcinoma (group A) were compared with those of 42 tumors with contiguous intraepithelial carcinoma (group B). The more advanced was the main lesion, the lower was the incidence of contiguous intraepithelial carcinoma. The mean Ki-67 score of the main tumors in group A was 51.6% and that of the main tumors in group B was 45.9%. The mean Ki-67 score of the main tumors in group B was very similar to that of the contiguous intraepithelial carcinomas that were associated with the main tumors (44.4%, P = 0.682). Furthermore, the mean Ki-67 score of contiguous intraepithelial carcinomas associated with main tumors was very similar to that of carcinomas in situ (41.2%, P = 0.529). From our results, it is suggested that tumors with high proliferative activity may be assumed to grow rapidly and, as a result, the region of intraepithelial carcinoma may develop into an invasive tumor. By contrast, tumors with low proliferative activity may grow slowly and, in such cases, the carcinoma may remain in the epithelium around the invasive tumor.