Abdominal pain with anorexia in patients with breast carcinoma

Breast cancer is the second commonest primary tumour responsible for gastrointestinal metastases after malignant melanoma. The real incidence of gastrointestinal metastases in breast cancer patients is probably underestimated owing to the non-specific presenting symptoms and death of patients caused by other more obvious metastases. The predominant histological subtype of gastrointestinal metastases of breast cancer is invasive lobular carcinoma and the median interval from diagnosis of primary breast cancer to gastrointestinal metastases is five years. We report two cases of disseminated breast cancer with gastrointestinal involvement with a rather long survival.     

Intradural parenchymal involvement in the spinal subarachnoid space associated with primary lung cancer

BACKGROUND: Intradural parenchymal involvement (IPI) in the spinal subarachnoid space associated with primary lung cancer is rare. A retrospective study was undertaken to investigate the clinical and pathologic features of IPI. METHOD: A total of 1215 cases of primary lung cancer were studied at autopsy; the results were reviewed retrospectively. RESULTS: Twenty (1.65%) of the cases revealed IPI in the spinal subarachnoid space. The histologic diagnoses were small cell carcinoma in ten cases, adenocarcinoma in eight cases, and squamous cell carcinoma in two cases. In 14 (70%) cases, the IPI was located between the lumbar and cauda equina of the spinal cord. However, no metastases were observed in the cervical spinal cord. Brain metastasis, vertebral metastasis, and meningeal carcinomatosis were seen in 70%, 60%, and 40% of the 20 cases, respectively, suggesting that these metastases may be related to the metastatic pathway to the spinal cord. Most patients had neurologic symptoms or signs referable to IPI; IPI could be diagnosed before death in only one patient by magnetic resonance imaging. The median interval between diagnosis of lung cancer and development of IPI and median survival after the onset of neurologic symptoms referable to IPI were 415 days and 110 days, respectively. CONCLUSION: The authors retrospectively received 1215 autopsies of patients with primary lung cancer and found 20 (1.65%) with IPI.     

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.     

Simultaneous detection of genetic and immunological markers in non-small cell lung cancer: prediction of metastatic potential of tumor

The restriction fragment length polymorphism of c-Ha-ras-1 and L-myc genes and expression of cell surface effector molecules were studied to determine their potential utility as markers for assessing risk of metastasis in 84 lung cancer patients. We performed a comparative study of primary lung carcinomas, metastases, adjacent tissues and blood samples in a group of patients with lung cancer of different histological types, grade of differentiation and presence of regional and distant metastasis. No differences in the frequency of c-Ha-ras-1 rare alleles were found between lung cancer patients and unaffected controls. The detection of common a4-allele seems to be associated with metastasis and low differentiation of lung carcinomas. S-allele of L-myc was observed in 82.6% of patients with metastatic lesions. Homozygosity of L-allele patients was not evidence for distant metastasis and only 17.4% of these patients have metastatic lesions of the lymph nodes. The expression of HLA class I and receptor of transferrin (TrRec) were tested immunohistochemically in the same patients. In the group of squamous cell carcinomas with regional metastases the expression of HLA class I antigens was decreased [7/21 (33.3%) positive staining tumors versus 13/20 (65.0%) in the group without metastases]. The opposite situation was observed for TrRec. The data of restriction fragment length polymorphism of oncogenes and expression of two cell surface effector molecules, identified in the same patients, were combined. The registration of more than one poor marker, tested in individuals with squamous cell carcinoma, closely correlated with dissemination and advanced stage of the disease. Nearly 90% (20/22) of patients with well and moderately differentiated tumor revealed metastatic lesions versus 6.6% (1/15) of patients with manifestation of a single poor marker. Finally, proposals could be made for the development of a risk group that incorporates both clinical and molecular biology features in the prediction of metastasis.     

Carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and other prognostic indicators in squamous cell lung cancer

Multivariate models of survival have been established for both small cell and non-small cell lung cancers. So far, no study has focussed on squamous cell types. Previous demonstrations of the prognostic value of the tissue polypeptide antigen (TPA) and, partially, of the carcinoembryonic antigen (CEA) are based on univariate analyses of survival. These analyses do not account for the other prognostic factors. In the present study, we report the combined influence of various clinical and biological characteristics on the survival duration of 360 patients with a newly diagnosed squamous cell carcinoma of the lung. The study comprised 29 variables, including age, sex, smoking habit (SH), symptoms at diagnosis, the Karnofsky performance status (KPS), weight loss (WL), radiological findings, various disease extent parameters (DEP), CEA and TPA. Preliminary univariate analyses showed that 20 variables were survival-related. The Cox proportional hazards regression analysis selected stage of disease, KPS, TPA, WL, the existence of bone metastases, and SH as independent factors of prognosis (global chi-square: 122.40, P = 0.0000). A second multivariate analysis, performed with the same covariates but excluding DEP, revealed previous pulmonary diseases and CEA to be, in addition to KPS, TPA, SH, and WL the next most influential prognostic determinants. Also in squamous cell lung cancer, classifications based on the Cox's prediction equation may improve individual counseling and patient selection for therapeutic trials. In this malignancy, TPA shows an independent and strong prognostic significance while CEA shares informations of diverse other prognostic factors and seems to be less important.     

Surgical results of T3 lung cancer with combined resection

Forty six patients with T3 lung cancer underwent pulmonary resection in our institutes. The actual survival rate of lung cancer patients with invasion in pericardium at five years is significantly higher than that in parietal pleura and chest wall (63.5% vs 13.2%, 11.1%). The survival rate of patients with large cell lung cancer is significantly lower than that with squamous cell lung cancer and small cell lung cancer (0.0% vs 39.9%, 16.7%). It is suggested that T3 large cell lung cancer patients might be contraindication of pulmonary resection. The five-year survival rate of patients with n0, n1, n2 disease are 35.5%, 66.7%, 6.7% respectively. There are significant differences in survival rate between patients with n0 + n1 and n2 disease.     

Nitric oxide synthase activity in human lung cancer

Nitric oxide synthases (NOS) exist in human tumor cell lines and solid tumor tissues, and it has been suggested that NO may play important roles in growth, progression or metastasis of tumors. We investigated the activity and distribution of NOS in a series of human cancer and normal lung tissues. Seventy-two primary lung cancer samples (44 cases of adenocarcinoma, 18 of squamous cell carcinoma, 4 of large cell carcinoma, 2 of small cell carcinoma, 2 of adenosquamous carcinoma, and 2 of carcinoids) and corresponding normal lung samples were obtained from surgically treated patients. In normal lung tissues, little NOS activity was observed with no correlation between the patient's age and NOS activity. The total NOS activities in lung adenocarcinoma samples were significantly higher than those in other types of lung cancers of normal lung samples (P < 0.05). Analysis by tumor grade of the adenocarcinoma samples revealed no significant difference of NOS activity between grades. TNM classification showed that, although T stage did not correlate with NOS activity, cancer tissues from patients with N2 disease tended to have lower activity than those from patients with NO or N1 disease. Immunohistochemical studies revealed that the intensity of NOS immunoreactivity correlated with NOS activity. These results suggest that NO may play an important role in the metabolism and behavior of lung cancers, especially adenocarcinoma.     

Small giant cell carcinoma of the lung diagnosed preoperatively by transthoracic aspiration cytology. A case report

Giant cell carcinoma (GCC) of the lung is considered an aggressive form of lung cancer. Most patients with GCC have large tumors with widespread metastases on hospital admission. We describe a small GCC in the lower lobe of the right lung. Preoperative aspiration cytology showed numerous bizarre, giant epithelial cells, highly suggestive of GCC. The resected tumor measured 1.2 x 1.0 x 0.7 cm in diameter, with an ill-defined margin. Histologically the tumor was composed of pleomorphic mononucleate or multinucleate giant cells without adenocarcinoma or squamous cell differentiation. The tumor cells were loosely organized and noncohesive or free in the alveolar space. The histology was interpreted as GCC of the lung. The clinicopathologic features of giant cell carcinoma are discussed.     

Antioxidant systems in rat epididymal spermatozoa

Down-regulation of KAI1 mRNA expression has been shown to be associated with the formation of metastases or disease progression in pancreatic cancer. Whether KAI1 possesses similar characteristics in other malignancies of the gastrointestinal tract is not known. Here, we compared the patterns of KAI1 mRNA expression in 41 esophageal cancers and 35 stomach cancers to assess whether KAI1 might also be of biological relevance in the metastatic ability of these tumors. By Northern blot analysis, KAI1 mRNA levels ranged widely in both normal and cancerous esophageal and gastric tissue samples, with no statistical differences. No association between KAI1 mRNA expression and tumor stage or tumor differentiation was seen in these tumors. In addition, KAI1 mRNA expression was similar in primary esophageal and gastric cancer samples with or without metastases. By in situ hybridization, KAI1 mRNA expression was evident in the cytoplasm of most squamous epithelial cells in the normal esophagus and in nonmucosal epithelial cells of the normal stomach. The staining intensity in the esophageal and gastric cancer cells was similar to that in the normal controls. This differential pattern of KAI1 mRNA expression in esophageal and gastric cancers in comparison to pancreatic cancer indicates that KAI1 seems to influence the potential of gastrointestinal cancer cells to metastasize differently. In esophageal and gastric cancers, the formation of metastases is not dependent on the reduction of KAI1 in the cancer cells.     

Complete spontaneous remission in a patient with metastatic non-small-cell lung cancer. Case report, review of the literature, and discussion of possible biological pathways involved

Spontaneous remission of cancer (SR) is defined as a complete or partial, temporary or permanent disappearance of all or at least some relevant parameters of a soundly diagnosed malignant disease without any medical treatment or with treatment that is considered inadequate to produce the resulting regression. We report the case of a 61-year-old man who presented with extensive metatastic disease five months after pneumonectomy for poorly differentiated large cell and polymorphic lung cancer. A vast metastatic tumour mass of the abdominal wall was confirmed histolologically and there was clinical and radiographic evidence of liver and lung metastases. Eight months later, the patient was operated on for a hernia, which had developed in the inguinal biopsy scar and the surgeon confirmed complete clinical SR of the abdominal wall metastases. Again five months later there was no longer any radiologic evidence of liver and lung metastases. Complete remission has persisted more than five years. Histology of the primary and of the abdominal metastases were reviewed by several independent pathologists. SR is an extremly rare event in lung cancer. This is the first documented case of clinically evident visceral metastases of a bronchiogenic adenocarcinoma developing after complete resection of the primary and then showing complete SR. The epidemiology of SR is reviewed and possible mechanisms involved in SR are discussed.     

Preliminary results of fine needle aspiration biopsy histology in upper gastrointestinal submucosal tumors

To elucidate the characteristics of lung cancer complicated by pneumoconiosis, we compared the clinical features of complicated and uncomplicated lung cancer cases. The average age at onset was higher for patients with pneumoconiosis than for those without. Because pneumoconiosis presents various respiratory symptoms, subjective symptoms were less important than objective symptoms in detecting lung cancer complicated by pneumoconiosis. Although fiberoptic bronchoscopy was the predominant diagnostic method, it could not be used with the pneumoconiosis patients. Diagnoses of lung cancer complicated by pneumoconiosis were made more after by percutaneous needle aspiration cytology. Squamous cell carcinoma is the most frequent form of cancer in patients with pneumoconiosis, which suggests that the inhalation of carcinogens may play a role in the pathogenesis of lung cancer. With respect to the smoking index (SI), histological specimens indicated that the incidence of squamous cell carcinoma in patients with pneumoconiosis was significantly higher in heavy smokers (SI > or = 600) than in light smokers (SI < 600) or nonsmokers. It is suspected that smoking affects carcinogenesis of pneumoconiosis. No differences in the distribution of lung cancer (right-left, hilar-peripheral) distinguished the 2 groups. Many of the patients with peripheral-type lung cancer and pneumoconiosis had tumors in the lower lung lobes. These findings underline the importance of encouraging pneumoconiosis patients to avoid lung cancer by not smoking, and to have lung cancer detected in its early stages by undergoing regular medical exams.     

Metastases of the heart and pericardium

Tumours metastasizing to the heart are one of the least investigated subjects in clinical oncology. Nevertheless, this problem holds great practical significance in relation to the operability and type of treatment of neoplastic patients. Of 4769 patients autopsied at the Institute of Pathological Anatomy of Trieste from 1994 through 1995, 1148 males (42%) and 780 females (38%) had a primary tumour. Among them, 162 subjects had cardiac metastases (8.4%) of all cancers), with a significant decrease in frequency in elderly patients. Mesothelioma, melanoma and lung cancer showed the highest frequency of heart involvement in males (100, 50 and 31%, respectively). Melanoma, lung tumours and renal neoplasms had the highest percentages of secondary heart lesions in females (45, 26 and 20%, respectively). In lung cancer, anaplastic small-cell carcinoma (37%) and adenocarcinoma (33%) showed the most frequent heart involvement in males, while squamous carcinoma (43%) and anaplastic small-cell carcinoma (29%) had the highest frequency of heart metastases in females. Adenocarcinoma (82%) and anaplastic small-cell carcinoma (74%) of the lung, mesothelioma (100%) and breast tumours (73%) had the highest frequency of metastases to the pericardium. A particularly high frequency of myocardial involvement was observed in squamous cell carcinoma of the lung (62%), urinary tract tumours (60%) and melanoma (45%).     

Metastases from testicular carcinoma. Study of 78 autopsied cases

The necropsy records of 78 patients with histologically proved germ cell tumors of the testis, who died as a direct result of their malignant disease, were reviewed to determine the usual modes of spread, distribution of metastasis, the histologic characteristics of the metastatic foci as compared with the morphology of the primary tumor and the specific cause of death. The sites of metastases in order of decreasing frequency for all cases were lung, retroperitoneal lymph nodes, liver, mediastinal lymph nodes, brain, kidney, gastrointestinal tract, bones, adrenals, peritoneum and spleen. The absence of metastases solely in the anterior mediastinum without involvement of other mediastinal nodes (middle/posterior) strongly supports the premise for a primary extragonadal origin whenever the anterior mediastinum alone is involved with malignant disease having the histologic appearance of a primary germ cell tumor. The histologic features of the metastatic lesions were usually similar in nature to those of the primary tumor except for seminoma in which the metastatic lesions proved to be of a different histologic pattern in almost one third of the patients dying from the disease. It should be axiomatic that whenever a patient with seminoma fails to respond appropriately to radiotherapy that his treatment be immediately discontinued and that appropriate biopsies be obtained to substantiate the histologic pattern present.     

Pulmonary hypertrophic osteoarthropathy and clubbing of fingers in patients with lung cancer

We examined clinical characteristics of patients with primary lung cancer associated with clubbing of the fingers or pulmonary hypertrophic osteoarthropathy. Clubbing was observed in 12.5% of patients with lung cancer. Squamous cell carcinoma was frequently associated with clubbing. Clubbing was found in all clinical stages. PaO2 and PaCO2 were normal in patients with lung cancer, which suggests that neither hypoxemia nor hypercapnia caused the clubbing in these patients. Pulmonary hypertrophic osteoarthropathy was found in three patients with lung cancer (two men and one woman, mean age 49 years). The incidence was 2.9% among lung cancer patients with clubbing, 0.22% in all lung cancer patients, and was apparently lower than those in reports from outside Japan. One of these patients has stage IIIA squamous cell carcinoma, one had stage IV large cell carcinoma, and one had stage IV adenocarcinoma. In all cases bone scans were useful for diagnosis and for following the clinical course.     

Spontaneous regression of pulmonary metastases from transitional cell carcinoma

Spontaneous regression of metastatic cancers occurs rarely and has been reported only once for pulmonary metastases from transitional cell carcinoma. Two cases of spontaneous complete regression of lung metastases from transitional cell carcinoma are presented. In one case, regression occurred after a course of radiation to the primary bladder cancer, but in the other patient, lung lesions disappeared without treatment to the primary or metastatic cancers. The factors that alter the tumor-host relationship to allow spontaneous regression of cancers are unknown, but observation of these phenomena may help reveal parameters that influence tumor progression in the majority of cancer patients.     

Clinically significant, isolated metastatic disease to the thyroid gland

Despite being second only to the adrenal glands in terms of relative vascular perfusion, the thyroid gland is a rare site of metastatic disease; but when thyroid metastases occur, long-term survival has been reported to be dismal. To determine the incidence and management of isolated, metastatic disease to the thyroid, we reviewed our clinical experience. Between June 1986 and August 1994 ten patients underwent thyroidectomy for isolated, metastatic disease of nonthyroidal origin (mean +/- SD age 58 +/- 6 years, 30% female). The primary tumors were renal cell carcinomas (RCCs) (n = 5), esophageal adenocarcinoma (n = 1), pulmonary squamous cell carcinoma (n = 1), gastric leiomyosarcoma (n = 1), lingual squamous cell carcinoma (n = 1), and parotid gland carcinoma (n = 1). Three patients underwent preoperative fine-needle aspiration (FNA), all of which were suggestive of metastatic disease. The mean time from resection of the primary tumor to thyroid metastases was 3.5 +/- 6.0 years (range 0-19.5 years). Total thyroidectomy (n = 5) or lobectomy (n = 5) was performed without morbidity or mortality. After a median follow-up of 5.2 years six patients are alive and two are free of disease. Moreover, no patients have had recurrent disease in the neck. Thus carcinomas metastatic to the thyroid represent a rare cause of clinically significant thyroid disease, with RCCs comprising 50%. Most thyroid metastases (80%) present within 3 years of primary tumor resection, but with RCC they can occur as late as 19 years. The diagnosis of metastatic disease should be suspected in patients with even a remote history of cancer, especially RCC, and an FNA revealing clear cell or spindle cell carcinoma. Contrary to previous reports, long-term survival can be achieved after resection of the metastatic tumor. Furthermore, thyroidectomy may also palliate/prevent the potential morbidity of tumor recurrence in the neck.     

Halothane acts on many potassium channels, including a minimal potassium channel

Three patients who had genitourinary cancer combined with lung cancer are reported. One patient had pulmonary adenocarcinoma and bladder transitional cell carcinoma, one had small cell lung cancer and squamous cell carcinoma of the penis, and one had large cell lung carcinoma and prostatic adenocarcinoma. In Japan, where society is aging rapidly, cases of multiple primary cancer with lung and genitourinary cancers are expected to increase considerably in the future.     

Cholecystokinin-B/gastrin receptor: a novel molecular probe for human small cell lung cancer

The brain-gut hormones, gastrin and cholecystokinin, have a trophic effect on the gastrointestinal mucosa in vivo and promote the growth of several neoplastic cell lines. In this study, cholecystokinin-B/gastrin receptor has been demonstrated to provide a novel molecular marker for the diagnosis of small cell lung cancer by using biopsy specimens. Physiological expression of the receptor mRNA is detectable in particular areas of the human brain, stomach, and pancreas but not in the lung. The receptor mRNA was detected selectively in all small cell lung cancer (10 cases) with a RT-PCR assay. By contrast, it was detectable in only 1 of 13 squamous cell carcinomas or 21 adenocarcinomas of the lung. Thus, the cholecystokinin-B/gastrin receptor could be an attractive therapeutic target for small cell lung cancer.     

Successful treatment of solitary extracranial metastases from non-small cell lung cancer

BACKGROUND: Recurrence after resection of non-small cell lung carcinoma is generally associated with a poor outcome and is treated with either systemic agents or palliative irradiation. Recently, long-term survival has been reported after resection of isolated brain metastases from non-small cell lung carcinoma, but resection of other metastatic sites has not been explored fully. METHODS: We have identified 14 patients who had solitary extracranial metastases treated aggressively after curative treatment of their non-small cell lung carcinoma. The histology was squamous carcinoma in 5, adenocarcinoma in 8, and large cell carcinoma in 1. Initially, 3 patients had stage I, 5 stage II, and 6 stage IIIa disease. RESULTS: The sites of metastases included extrathoracic lymph nodes (six), skeletal muscle (four), bone (three), and small bowel (one). The median disease-free interval before metastases was 19.5 months (range, 5 to 71 months). Complete surgical resection of the metastatic site was the treatment in 12 of 14 patients. Two patients received only curative irradiation to the metastatic site, with complete response. The overall 10-year actuarial survival (Kaplan-Meier) was 86%. To date, 11 patients are alive and well after treatment of their metastases (17 months to 13 years), 1 has recurrent disease, 1 died of recurrent widespread metastases, and 2 died of unrelated causes. CONCLUSION: Long-term survival is possible after treatment of isolated metastases to various sites from non-small cell lung carcinoma, but patient selection is critical.     

CYFRA 21-1 enzyme-linked immunosorbent assay. Evaluation as a tumor marker in non-small cell lung cancer

BACKGROUND: The CYFRA 21-1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21-1 is a sensitive and specific tumor marker for non-small cell lung cancer. METHODS: CYFRA 21-1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21-1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer. RESULTS: The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21-1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21-1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21-1 assay has the highest sensitivity. The median level of CYFRA 21-1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p<0.001). The serum level and sensitivity of CYFRA 21-1 were well correlated with staging and tumor size in squamous cell carcinoma. The CYFRA 21-1 values were measured for monitoring progression of disease in 20 patients with squamous cell carcinoma. There is significant difference in paired observation of CYFRA 21-1 level in patients with progressive disease (Wilcoxon signed-rank test, p<0.05), but no difference was observed in patients with stabilized disease (p>0.1). CONCLUSION: For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.