[Local advanced lung cancer invaded thoracic vertebral bodies with unruptured cerebral aneurysm].

A 57-year-old man presented with the chief complaint of left shoulder pain in June 2001, and paridrosis of left upper trunk and left upper limb in July 2001. Head magnetic resonance imaging (MRI) showed 8 mm sized unrupture aneurysm of left middle cerebral artery, and chest computed tomography (CT) showed the lung tumor invaded thoracic vertebral bodies. The local advanced lung carcinoma (cT4N0M0) and unrupture aneurysm of left middle cerebral artery was diagnosed. The prevented clipping of unrupture aneurysm was performed at 11th September 2001, and left upper lobectomy, hemivertebrectomy and reconstruction of thoracic vertebral body (Th 3-5) with Modul' ICS at 12th October 2001. The pathological findings revealed squamous cell carcinoma. The staging was pT4N0M0, IIIB. The postoperative course was uneventful. After the radiotherapy (50 Gy), chemotherapy (gemcitabine and vinorelbine) was performed. But the radiation pneumonia was occurred and chemotherapy was intermitted. The steroid was administrated due to the radiation pneumonia, and the complication was improved. He discharged at 17th April 2002 and had no recurrence. The prevented clipping of unrupture cerebral aneurysm and the reconstruction of thoracic vertebral body (Th 3-5) with Modul' ICS were useful for the radical operation of the local advanced lung cancer.

Parathyroid hormone-related peptide producing cholangiocellular carcinoma with a marked psammoma formation.

Humoral hypercalcemia caused by parathyroid hormone-related peptide (PTHrP), associated with cholangiocellular carcinoma (CCC), has rarely been documented. There have been no reports of CCC associated with extensive calcification of the tumor with psammoma body formation. A 66-year-old man was admitted with a large calcified tumor in the liver detected on an abdominal X-ray. An ultrasound-guided fine needle biopsy specimen of the liver tumor showed evidence of adenocarcinoma. He had hypercalcemia with an elevated PTHrP level. The patient died because of disseminated intravascular coagulation and progressive hepatic failure. A postmortem examination revealed a large poorly differentiated CCC in the liver. Immunohistochemical examination showed the presence of PTHrP-positive tumor cells. The calcified lesion consisted of a number of accumulated psammoma bodies. We present a case of PTHrP producing CCC with a marked psammoma formation.

Right-sided pedunculated hepatocellular carcinoma: a form of adrenal metastasis.

Pedunculated hepatocellular carcinoma (HCC) or extrahepatic growth of HC C is an uncommon but not rare pathological form, but its genesis is unknown. Right-sided adrenal metastases of HCC that were abutting on or about to fuse with the right hepatic lobe were resected in three patients. The masses seemed to have originated in the para-adrenal tissue, leaving the adrenal gland intact. They were partially supplied by the hepatic artery as well as by the suprarenal artery. Four cases of autopsied pedunculated HCC of the right lobe were also studied. The mass was protruding caudad from the noncancerous parenchyma of the right lobe. Postmortem angiography carried out on one liver showed that only a small portion of the mass toward the liver was supplied from the hepatic artery. These observations suggest that some, perhaps most, of the right-sided pedunculated HCCs represent fusion of the right lobe and para-adrenal or adrenal metastatic HCC. This phenomenon may be explained by possible transport of cancer cells toward the right adrenal gland through the so-called adrenohepatic fusion, a relatively common anatomical change in advanced age.

Case report: right-sided periadrenal metastasis supplied by the hepatic artery. Clue to the genesis of pedunculated hepatocellular carcinoma.

The adrenal is the second most common site of haematogenous metastasis of hepatocellular carcinoma (HCC). The right adrenal is much more frequently affected than the left, but no reason has been offered for this difference. An aetiological connection has never been suggested between adrenal metastasis and pedunculated HCC. Hepatocellular carcinoma was resected in two patients who subsequently developed right-sided adrenal metastasis diagnosed by imaging. The adrenal mass was enhanced by hepatic arteriography and took up lipiodol injected into the hepatic artery. Reoperation was performed to remove the adrenal mass, which was abutting on the liver but was readily separable. Histopathologically, the adrenal gland was compressed by a metastatic HCC that developed in the immediate periadrenal tissue or adrenal capsule. By conventional imaging, the adrenal gland could not be recognized and the mass was thought to have arisen within the adrenal gland. In conclusion, periadrenal growth of HCC is a hitherto unrecognized type of metastasis and must have been mistaken either for an adrenal metastasis or a pedunculated HCC in the past. If left unresected, it would have fused with the liver and grown into a pedunculated HCC. Cancer cell invasion through an adrenohepatic fusion is the most likely mode of periadrenal metastasis; it explains the arterial communication between the mass and the liver.

Beneficial treatment with methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside in a patient with primary myelofibrosis.

We attempted treatment with methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a novel nitrosourea derivative, in a 55-year-old man with advanced-stage primary myelofibrosis. MCNU was given intravenously at a dose of 50 mg once a month. Following MCNU treatment, his anemia and splenomegaly improved markedly. An increased dose of MCNU (100 mg, once a month) was even more effective for relieving the symptoms. Severe side effects resulting from this therapy, such as leukocytopenia or thrombocytopenia, were never observed. These observations indicate that MCNU treatment may be a beneficial management of advanced-stage primary myelofibrosis.

[State III large cell carcinoma of the lung cured by radiotherapy--a case report].

Presented is the case of a 61-year-old male whose chief complaints were hoarseness, cough, and bloody sputum. Chest radiography demonstrated a left hilar mass with mediastinal widening, a peripheral localized infiltrate and the elevation of the left hemidiaphragm. By means of a mediastinoscopy, a biopsy was done on the enlarged mediastinal lymph node and a histological diagnosis of a large cell carcinoma was confirmed. He was graded as in Stage III (T2N2M0) and was placed under radiotherapy with 60Co. Complete response was obtained after a total dose of 6150 cGy. Following this radiotherapy, he was given multiple courses of mild chemotherapy and the disease as of this report has been under control for 7 years. This case may be unusual, but suggests the possibility of a cure of lung cancer by irradiation under certain conditions.

[A case of a small hepatoma with multicentric development in precirrhotic fibrosis].

Multicentricity of hepatocellular carcinoma (HCC) is considered, especially in patients with liver cirrhosis. This paper describes an operative case of a male patient with probable multicentric development of HCC in precirrhotic fibrosis. The main tumors inside the capsule were completely necrotic due to transarterial embolization (TAE). Histologic examination disclosed discrete tiny nodules of HCC that were not detected grossly. They showed highly differentiated trabecular arrangements: Edmondson I. A scirrhous type was noted in the center of the tumors. At the borders of the tumors the carcinoma cells exhibited replacing growth patterns and it was thought that they developed multicentrically. Partial resection must be performed as extensively as possible in a case such as the present one.

Alpha 1-acid glycoprotein and hepatic fibrosis.

The relationship between alpha 1-acid glycoprotein (alpha 1-AG) and liver fibrosis was studied. Immunoperoxidase staining of liver specimens from patients with chronic hepatitis showed large amounts of alpha 1-AG to be located primarily in hepatocytes adjacent to areas of piecemeal necrosis, bridging fibrosis and fibrous septa. In patients with severe chronic active hepatitis, hepatocytes throughout the liver stained similarly to those adjacent to areas of piecemeal necrosis. In cell cultures of human embryonal lung (HEL) fibroblasts, addition to the culture medium of alpha 1-AG promoted cell growth. It is known that alpha 1-AG is also produced in the liver. It thus appears likely that alpha 1-AG is a promoter of hepatic fibrosis in chronic hepatitis.

99mTc-methylene diphosphonate uptake by ossifications and calcifications of non-osseous metastatic tumors.

Two cases of extra-osseous uptake of 99mTc-methylene diphosphonate (MDP) by non-osseous metastatic tumors are reported. One was a metastasis with ossification in the abdominal wall from carcinoma of the sigmoid colon and the other was a metastasis with calcification from an ovarian carcinoma. The mechanism of extra-osseous uptake of 99mTc-MDP is discussed. Bone scintigraphy can be a potential means to assess tumor spread with ossifications and calcifications.

An autopsy case of miliary tuberculosis and review of autopsy cases in Japan.

Presented is an autopsy case of a 79 year-old male who died of miliary tuberculosis. The patient was admitted to the University Hospital with an unknown fever and suspicion of leukemia. He expired on the 13th day of hospitalization. Postmortem examination revealed generalized miliary tuberculosis. The diagnosis of tuberculosis was established only after autopsy. Difficulty in diagnosis of miliary tuberculosis is discussed. Also discussed is a probable association of acute interstitial nephritis with chemotherapy or miliary tuberculosis. Leukemoid reaction is thought to be associated with miliary tuberculosis. The present case reminds us that miliary tuberculosis should never be forgotten when treating a patient having a fever of unknown origin. Cases with tuberculosis were compiled from the Annual of Pathological Autopsy Cases in Japan during 1974 through 1981. There were 3,242 cases of tuberculosis (1.4%) out of 235,095 autopsies recorded in the Annual of Pathological Autopsy Cases in Japan during the above 8 years. Of 3,242 cases 618 were miliary tuberculosis. The latter figure indicates 19.0% of all tuberculosis and 0.26% of all autopsies. Although all age groups were not spared, the 7th and 8th decades were more affected than the others. Tuberculosis has markedly declined since the advent of antituberculous antibiotics. But, autopsy cases with tuberculosis have not recently decreased in number. Clearly, increased awareness of the continuing presence of tuberculosis is needed.

Studies on carcinogenesis of human prostate. II. Long-term explant culture of normal prostate and benign prostatic hyperplasia: light microscopy.

Light microscopic and histochemical changes in normal human prostate and benign prostatic hyperplasia (BPH) during long-term explant culture were characterized. Normal human prostate obtained at immediate autopsy of young adults or BPH obtained at the time of surgery were maintained in explant culture as long as 24 weeks. Morphologic alterations in glandular epithelium and stroma in response to culture conditions were assessed by light microscopy and histochemistry of mucosubstances. The histologic and histochemical responses of normal prostate and BPH to in vitro conditions were essentially identical. Within 1 week, secretory epithelial cells became necrotic and sloughed into acinar lumina. Remaining epithelial cells proliferated, repopulated acinar structures, and migrated onto explant surfaces forming a new well-differentiated epithelium characterized by synthesis and secretion of neutral and acidic mucosubstances. During subsequent periods in vitro, synthesis and secretion of mucosubstances gradually diminished whereas the stroma and deep glandular structures became necrotic. Our observations suggest that cells comprising the new epithelium in cultured explants of normal human prostate and BPH are derived from prostatic basal cells.

Studies on carcinogenesis of human prostate. III. Long-term explant culture of normal prostate and benign prostatic hyperplasia: transmission and scanning electron microscopy.

Ultrastructural changes in normal human prostate and benign prostatic hyperplasia (BPH) during long-term explant culture were compared. Explants of normal prostate obtained at immediate autopsy of young adults of BPH obtained at the time of surgery were maintained as long as 24 weeks in vitro. Ultrastructural changes occurring in epithelial cells during culture were monitored by transmission and scanning electron microscopy. Essentially identical results were found for normal prostate and BPH. During the first week of culture, secretory epithelial cells degenerated and sloughed into the acinar lumen, resulting in an accumulation of necrotic debris. During this period, however, epithelial cells with ultrastructural characteristics of basal cells remained viable, repopulated glandular structures, migrated from glands and ducts, and epithelialized adjacent cut surfaces, eventually covering the explant. On explant surfaces, these basal cells initially were squamous-like, but they later became typically cuboidal, polygonal, or sometimes columnar and formed an epithelium, two cells or more thick. Epithelium with similar features lined acini within explants. Epithelial cells at the surface or within explants were distinguished by the presence of microvilli, junctional complexes, multiple Golgi complexes, well-developed rough endoplasmic reticulum, polyribosomes, nuclei with prominent nucleoli, orthodox mitochondria, scattered tonofilaments, and a basal lamina. Some epithelial cells extended from the lumen to the basal lamina; others were oriented along the basal lamina and did not extend to the lumen. By 1--2 weeks in vitro, these epithelial cells began synthesis of mucus-like material. At later intervals of culture, microvilli were shortened and mucosubstances were reduced. During culture, the stroma became progressively hypocellular and necrotic. In summary, explant-cultured epithelial cells of normal human prostate or BPH were similar ultrastructurally and were found to originate from basal cells, which alone survive culture conditions.

Aryl hydrocarbon hydroxylase in human prostate.

Aryl hydrocarbon hydroxylase (AHH) was present in explant cultures of human prostate obtained from surgery of benign prostatic hyperplasia and was inducible by benz[a]anthracene (BA). The induction of AHH ranged from 14- to 150-fold when compared with control values and 10-fold variation of AHH inducibility among individuals was observed. Epithelial cells grown from human prostate tissue also contained measurable AHH activity and AHH was inducible by BA and 7,12-dimethylbenz[a]anthracene (DMBA). Inducibility of AHH by BA ranged from 2- to 63-fold. The inducibility of AHH by DMBA was always less than that by BA. In cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), there were no changes in AHH activity. These findings support the view that the human prostate is susceptible to environmental polycyclic hydrocarbon carcinogens and that environmental and occupational factors might contribute to the etiology of human prostatic carcinoma.

Cell surface changes in preneoplastic and neoplastic epithelium.

Reviewed are studies on alterations of the plasma membrane of neoplastic epithelial cells. Changes in the plasma membrane are probably of unique importance in the major clinical manifestations of cancer. Discussed are sequences in cell membrane changes in vivo and in vitro in both human tumors and chemical-induced animal models of carcinogenesis. Emphasis is placed on alterations in specializations of the plasma membrane, including cell junctions, antigenic and enzyme markers, intramembranous components, ion regulation, and the cytoskeleton. In general, the plasma membrane of neoplastic cells is less specialized than the cell of origin. In mammalian bladder, pleomorphis microvilli may occur concomitant with neoplastic transformation. Cell junctions in tumor cells may be reduced in number of functional characteristics compared to normal cells, which may affect cell-cell communication. Such alterations may be related to tumor cell invasion and metastasis. Normal membrane antigens may be lost or new ones gained in neoplasia. Thus, ABO blood group antigens may be lost in the case of human bronchus and bladder, while carcinoembryonic antigen occurs de novo in tumors of the colon and lung. Similarly, several marker enzymes may be reduced in activity, or appear de novo. Alterations in the number and pattern of distribution of intramembranous particles have been observed in bladder tumors, possibly related to changes in membrane function. Shifts in ion ratios (Na+/K+/Ca++) within neoplastic cells may result in abnormalities in cell shape, cell movement, and cell-cell communication. Many of these changes may reflect defects in function of the Golgi apparatus, which synthesizes components of the plasma membrane. Alterations in one or more components of the cytoskeleton may adversely affect cell shape, mobility of membrane proteins, cell-cell adhesion, etc., and play a major role in malignant cell behavior.

Studies on carcinogenesis of human prostate. IV. Comparison of normal and neoplastic prostate during long-term explant culture.

Morphologic responses of neoplastic human prostate to long-term explant culture were monitored at serial intervals by LM, TEM and SEM, and compared to normal prostate. Explants were cultured at 37 degrees C in CMRL-1066 supplemented with fetal calf serum and antibiotics. At 0-time culture, normal prostate of young adult males obtained at immediate autopsy, consisted of glandular spaces and ducts lined by columnar to cuboidal secretory epithelial cells and basal cells embedded in fibromuscular stroma. Neoplastic tissue was obtained surgically by transurethral resection (TUR), and consisted of stroma widely infiltrated by well-to moderately-differentiated tumor cells arranged in variable sized, gland-like structures. Secretory activity was evident; basal cells were absent in these glands. During early periods of culture up to several weeks, secretory cells of normal prostate became necrotic. Basal cells remained viable, repopulated acinar structures and epithelialized explant surfaces. At these sites, basal cells, or their derivatives, formed a multicellular epithelium. Exaggerated intercellular spaces separated cells, and synthesis of mucus-like material was seen. Epithelial characteristics included microvilli, junctional complexes, and basal lamina. In marked contrast, tumor cells covered explant surfaces forming an irregular, disorganized layer of squamous-like cells with elongated nuclei and prominent nucleoli. Microvilli, junctional complexes, and basal lamina were poorly developed or absent. Intercellular attachments appeared tenous. Some tumor cells accumulated lipid; synthesis of mucus-like material was not seen. At later intervals of culture up to 10 weeks, synthesis of mucus-like material by basal cells, or their derivatives, declined. Surface cells of neoplastic prostate gradually became more anaplastic in appearance; cells contacted neighboring cells with pseudopodia and filopodia.

Accuracy of diagnosis of cancer among autopsy cases: JNIH--ABCC population for Hiroshima and Nagasaki.

The accuracy of death certificate diagnoses of cancer in the fixed population of about 100,000 samples in Hiroshima and Nagasaki was determined for the period 1961 approximately 1970 by comparison with autopsy findings. In general, when the death certificate listed cancer as a cause of death it was found at autopsy in a high proportion of cases. However, cancer was not always reported on death certificates, indicating that cancer occurs more frequently than recorded by official mortality statistics. Older persons, persons who die at home, and persons with certain cancers are more likely not to have cancer named on their death certificates. It is estimated that in the 10,749 deaths occurring at home or in hospital, there were 32% more deaths due to cancer than certified on death certificates (3,095 vs. 2,345) and for persons aged 70 or more dying at home it is estimated there were 55% more stomach cancer (269 estimated vs. 174 listed) and 244% more lung cancer (141 estimated vs. 41 listed) than were certified on death certificates. The death certificate is not a good source of information for cancer of the cervix because many cases of this disease reported on death certificates as cancer of the uterus. This practice needs to be taken into account in the use of mortality data for cervical cancer in Japan.