The Incidence of Cardiac Metastasis in Primary Lung Cancer and the Management of Malignant Pericardial Effusion

The incidence of metastasis to the heart and pericardium was35% in post-mortem studies of 150 cases of carcinoma of thebronchus. Twenty-one patients with malignant pericardial effusion fromcarcinoma of the bronchus were treated at the National CancerCenter Hospital during the last three years. Fifteen patientswere treated by creating a pericardial window through a subxiphoidapproach without complications or mortality, in these 15 patientscardiac compression caused by pericardial effusion was promptlyrelieved by the creation of the pericardial window. There wasno reaccumula tion of the effusion in five of six patients treatedby the pericardial window procedure with intrapericardial instillationof chemotherapeutic agents and eight of nine patients treatedby creating the window without local chemotherapy. On the otherhand cardiac tamponade was controlled in one of three patientsby repeated pericardiocenteses. The median survival periodsfrom the initiation of treatment for the effusion up to deathwere 4 mo in six patients treated by the pericardial windowprocedure with intrapericardial instillation of chemotherapeuticagents, 2 mo in nine patients treated by the window techniquewithout local chemotherapy and 0.8 mo in six patients in whoma pericardial window was not created. The median survival of15 patients treated by the pericardial window procedure (2 nio)was not significantly longer than that of six patients not sotreated. We have come to the conclusion that the creation of a subxiphoidpericardial window is a safe, effective and reliable treatmentprocedure for the manage ment of malignant pericardial effusion,but the prognosis for survival in patients with malignant pericardialeffusion may depend principally on the extent of the primarytumor and the performance status of patients at the initiationof treatment for the effusion.     

Phase II Study of 7-N-(p-Hydroxyphenyl)-Mitomycin C (KW2083) in Patients with Advanced Non-Small Cell Carcinoma of the Lung and Metastatic Pulmonary Tumors

Twenty-six patients with non-small cell carcinoma of the lungand 25 with metastatic pulmonary tumors were treated by intravenousinjection of 7-N-(p-hydroxyphenyl)-mitomycin C (KW2083), a derivativeof mitomycin C, either at a single 70-mg/m² dose or at a doseof 20–30 mg/m² once a week for 3 weeks. Two patients withadenocarcinoma among 21 evaluable patients with non-small cellcarcinoma of the lung, and one with embryonal cell carcinomaamong 21 patients with metastatic pulmonary tumors achievedpartial response lasting 5 to 7 weeks. In these three patients,KW2083 was administered by a single 70-mg/m² dose, and no patientswho received a dose of 20–30 mg/m² weekly achieved objectiveresponse. Myelosuppression, primarily thrombocytopenia, waspronounced with either treatment regimen and it was the majordose-limiting toxicity.     

HISTOCHEMICAL STUDY ON OXIDATIVE ENZYME ACTIVITY IN THE BRAIN, PARTICULARLY OF ASTROCYTES, IN SPONTANEOUSLY HYPERTENSIVE RATS

Hanakita J., Hazama F., Amano S., Yamada E. & Handa H. (1980)
Neuropathology and Applied Neurobiology 6, 471–482
Histochemical study on oxidative enzyme activity in the brain, particularly of astrocytes, in spontaneously hypertensive rats
In order to obtain indirect information concerning brain oedema or increased vascular permeability under hypertensive conditions, the enzyme responses of astrocytes in the brains of spontaneously hypertensive rats were histo-chemically investigated. Reactions for oxidative enzymes, such as NADH₂-, NADPH2-tetrazolium reductases and succinate dehydrogenase were performed on SHR brains of various ages. In the hypertensive rats, proliferation, hypertrophy and increased enzyme activity were observed in astrocytes, particularly in the white matter. This activation of astrocytes appeared at 12 13 weeks-of-age and increased with advancing age. These findings suggest that increased vascular permeability of the materials in the smaller molecules begins in the early stage of the development of hypertension before the breakdown of the blood-brain barrier. Many degenerating astrocytes, showing clasmatodendritic changes, were observed in severely oedematous regions or around cystic foci in the white matter. The changes in astrocytic function seem to be related to the development of the parenchymal changes, particularly of the white matter in the chronic hypertensive state.     

Suspected acute encephalopathy with symmetrical abnormal signal areas in the basal ganglia,thalamus, midbrain and pons diagnosed by magnetic resonance imaging

A 4-year-old boy was admitted with disturbed consciousness following a convulsion. He developed bilateral pyramidal tract signs and showed a decerebrate posture. Laboratory findings revealed severe liver dysfunction and disseminated intravascular coagulation. On the eighth day eight in hospital he developed parkinsonism. However, 5 months from onset he had recovered almost completely. Brain CT on admission showed low density areas in the basal ganglia, thalamus, midbrain and pons. A T2-weighted scan in magnetic resonance imaging (MRI) showed almost symmetrical high signal intensities in both basal ganglia (including putamen, caudate nucleus, globus pallidus), external capsule, internal capsule, thalamus, midbrain, pons and white matter of the peribasal ganglia; but a T1-weighted scan showed low signal intensities in the same regions during all phases. Therefore hemorrhagic lesions or the presence of thalamic methemoglobin were excluded. It was considered that the pathogenesis may be cytotoxic cellular edema due to cytotoxic agents or acute metabolic factors. Clinical presentation, laboratory findings and radiological findings were most suggestive of acute necrotizing encephalopathy. As differential diagnoses, acute disseminated encephalomyelitis and brainstem encephalitis were considered.     

Pulmonary Toxicity Induced by Pepleomycin 3-[(S)-l'-Phenylethylamino] Propylamino-Bleomycin

Chemotherapy regimens containing pepleomycin, a derivative ofbleomycin, were used for 81 patients with advanced primary lungcancer and 32 patients with metastatic pulmonary tumors. Amongthe patients with non-small cell carcinoma of the lung, partialresponses were observed in three of 27 patients treated withpepleomycin + carbazilquinone and four of 26 patients treatedwith pepleomycin + mitomycin C (published in Cancer TreatmentReports, 1983). Five partial responses (primary organ: larynx,esophagus, lung, pancreas and uterus; one patient each) in 23evaluable patients with metastatic pulmonary tumors were observedduring treatment, for an overall response rate of 21.7%. Inpatients with primary lung cancer, no correlation between theincidence of the decrease in partial arterial oxygen tension(PaO₂) during treatment and age was observed. Decrease in PaO₂during treatment was found more frequently in patients withabnormal pulmonary function before treatment than in patientswith normal pulmonary function, but the mean lowest values ofPaO₂, in the two groups were the same. Intravenous weekly injectionof pepleomycin is less likely to result in a decrease in PaO₂,than two daily intramuscular injections. Definite pulmonarytoxicity occurred in seven of the 113 patients (6.2%). Eachof the seven received a total dose of over 60 mg and their ageswere over 60 yr, although no correlation between the incidenceof pulmonary fibrosis and total cumulative dose of pepleomycinwas observed. Six of the seven patients died of pulmonary fibrosisin spite of prednisone treatment. Clinical, radiologic and histopathologicfindings associated with pepleomycin were the same as thoseof bleomycin pulmonary toxicity. Further studies are neededto determine the appropriate dose schedule and route of administrationof pepleomycin with regard to its benefit and toxicity.     

Serum RNase Activity in Patients with Malignancy and Nonmalignant Diseases

One hundred seventeen patients with malignancy, 104 patientswith non-malignant diseases and 50 healthy subjects were evaluatedwith respect to serum RNase (EC 3.1.4.22 [EC] , ribonuclease I:ribonucleate3'-pyrimidino-oligo-nucleotidohydrolase) levels. The patientswith malignancy had no proved distant metastasis and proceededto surgery. Elevated activity of this enzyme in serum was associatedwith hepatocellular carcinoma (77.8%), carcinoma of the lung(40.0%) and carcinoma of the stomach (33.3%). One patient withpancreatic carcinoma had a normal value. Few correlations werefound between the activities of RNase and other enzymes in serumin malignancy. Some patients with nonmalignant diseases suchas chronic pancreatitis, chronic hepatitis and pulmonary tuberculosisalso had abnormal values. Thus, serum RNase cannot be used asa specific marker for any malignancy, but it may have practicaldiagnostic value because of its high positivity in hepatocellularcarcinoma and to a lesser extent in the other malignancies.     

Further studies on the resolution of human mercapt- and nonmercaptalbumin and on human serum albumin in the elderly by high-performance liquid chromatography

High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on Asahipak GS-520 showed at least two peaks, the principal component corresponding to human mercaptalbumin (HMA) and the secondary one to nonmercaptalbumin (HNA). HPLC analysis of HSA on Asahipak ES-520 N showed three peaks, the principal component corresponding to HMA, the secondary one to HNA having mixed disulfide with cysteine or glutathione and the tertiary one to HNA oxidized higher than mixed disulfide. Two kinds of rapid HPLC for the resolution of HSA into HMA and HNA were developed by the present authors. Using these HPLC, the present authors found a significant decrease in the fraction of HMA in the elderly.     

Epidemiology of genotypes of hepatitis C virus in Japanese patients with type C chronic liver diseases: A multi-institution analysis

Sixteen medical institutions in Japan collaborated in this study of the epidemiology of hepatitis C virus (HCV) genotypes. A total of 4176 patients with type C chronic liver disease, from the four main islands of Japan, were evaluated. Of those evaluated, 2794 had chronic hepatitis, 727 had liver cirrhosis and 655 had hepatocellular carcinoma. The HCV genotype of the patients was determined by an enzyme-linked immunosorbent assay based on serological genotype 1- and 2-specific recombinant peptides (SG-1 and SG-2, respectively) of the NS4 region. The prevalence of SG-1 and SG-2 HCV was similar in the four main islands of Japan. SG-1 HCV predominated in each disease category (69–76%). The percentage of patients with SG-1 HCV increased by 7%, while that of patients with SG-2 HCV decreased by 7%, as liver disease progressed in severity from chronic hepatitis to carcinoma (P < 0.001). Patients with either SG-1 or SG-2 had a similar mean age and history of blood transfusion. In conclusion, SG-1 HCV was found to predominate in Japan, and the HCV genotype was found to be related to the stage of hepatitis C disease.     

Coexistence of proguanylin (1–15) and somatostatin in the gastrointestinal tract

In order to identify proguanylin-secreting cells, we have raised an antiserum against the synthetic fragment of human proguanylin (1–15) and have examined the proguanylin-positive cells in the human and rat gastrointestinal tract by immunohistochemical methods. Numerous proguanylin (1–15)-immunoreactive cells were found in the gastrointestinal tract. They were either pyramidal or spindle shaped in the stomach. Spindle-shaped cells, frequently possessing long slender processes, were located at the base of the pyloric epithelium and did not extend to the lumen. In the duodenum and jejunum, these cells were mostly pyramidal in shape and often had a slender process towards the lumen. The immunostaining was completely blocked by the human proguanylin (1–15) fragment. Paneth and goblet cells were negative against this antiserum. The number of serotonin-positive cells was much larger than that of proguanylin-positive cells in all the segments tested. The number of proguanylin-positive cells decreased from the jejunum to the ileum and very few cells were observed in the colon. In contrast to serotonin-positive cells, most somatostatin-positive cells were also positive for proguanylin. Thus, proguanylin (1–15) or its related protein appears to coexist with somatostatin in intestinal endocrine D cells which may be a source of circulating proguanylin. Proguanylin, like somatostatin, may also regulate intestinal function as a local regulator.