Biomedical subjects
Publications and source records attributed to O Nakashima.
Neoplastic angioendotheliosis has rarely been described as a respiratory disease. A patient is described with pulmonary vascular involvement induced by neoplastic angioendotheliosis in pulmonary vessels.
Cytokines increase the expression of the inducible (type II) nitric oxide synthase (NOS) in macrophages, liver, and renal epithelial cells. Previously, we found that cultured rat medullary interstitial cells (RMIC) contain high levels of soluble guanylyl cyclase. To determine whether these cells can also produce NO, we studied the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on NO production, NOS II mRNA, and NOS II protein expression. Both TNF-alpha and IFN-gamma, in the presence of a low concentration of the other cytokine, caused dose-dependent increases in NO production. Exposure to TNF-alpha and IFN-gamma stimulated the production of NOS II mRNA, as determined by Northern blotting. Restriction mapping of reverse transcription-polymerase chain reaction products indicated that normal cells contained macrophage NOS II, whereas cytokine-stimulated cells contained primarily vascular smooth muscle NOS II and some macrophage NOS II. The appearance of NOS II protein was demonstrated by Western blotting. RMIC cell guanosine 3',5'-cyclic monophosphate accumulation increased 129-fold in response to the cytokines. NOS inhibitors decreased nitrite production. We conclude that 1) TNF-alpha and IFN-gamma induce the expression of vascular smooth muscle NOS II and production of NO in RMIC, and 2) NO acts as an autocrine activator of the soluble guanylyl cyclase in RMIC.
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Some surgically resected small hepatocellular carcinoma (HCC) up to 2 cm in diameter have indistinct margins, and it is sometimes difficult to identify the margins of the cancer nodule in the resected specimen. We classified such tumors as small HCC with indistinct margins and carried out a morphological study to define their characteristics in comparison with small HCC with distinct margins as a control group. We have encountered 27 examples among 86 tumors smaller than 2.0 cm in diameter. The tumors of this type indistinctly retained the basic architecture of the background and were vaguely demarcated. Most tumors were uniformly composed of well-differentiated cancer tissue, which is characterized by increased cell density with increased nuclear/cytoplasm ratio, increased cytoplasmic eosinophilia, and irregular thin-trabecular pattern with occasional pseudoglandular pattern. Portal tracts were included within the cancerous tissue. There was a "replacing" growth pattern at the tumor/nontumor boundary. Four of the 27 lesions had a nodule-in-nodule appearance, and the inner nodules consisted of moderately differentiated HCC without portal tracts. In all of the small HCC with indistinct margins, tumor invasion into the portal vein and intrahepatic metastasis were not found. In a control group, the tumors were well-demarcated, and 53% of them were encapsulated. They were well-differentiated in 9, moderately differentiated in 38 and mixed well and moderately in 12. Tumor invasion into the portal vein and intrahepatic metastasis was found in 16 (27.1%) and 6 (10.2%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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We report a case of a 58-year-old man presenting with a mild attack of upper abdominal pain and who was found to have a swollen pancreatic body and tail. Pathological study of the resected mass revealed cystic lymphangioma. Only 30 cases of lymphangioma of the pancreas, including our case, have been reported to date. Here we present this case in detail and discuss the differential diagnosis of cystic lesions in the pancreas.
A 68-year-old woman presented a one-month history of lower abdominal pain and weight loss, and was admitted to our hospital. On physical examination, a large hard mass was palpated in her right lower abdomen. An ultrasonograph and computed tomographic (CT) scan revealed a right ovarian tumor that measured 6.9 x 4.9 cm in size. A total hysterectomy and bilateral salpingo-oophorectomy were performed. The postoperative diagnosis of the tumor was squamous cell carcinoma (SCC) of the ovary. She died of infection and disseminated intravascular coagulation 5 months after surgery. The clinical and autopsy examinations did not show the primary lesions of SCC except in the right ovary. Mature cystic teratoma, Brenner tumor and endometriosis, which are ordinary regarded as the histogenesis of ovarian SCC, were not found, but a few surface epithelial inclusion cysts with squamous metaplasia were observed in non-cancerous area of the right ovary, and the contiguous transition from the metaplastic cyst wall to SCC was confirmed by stepwise serial sections. The present case suggests that the surface epithelium of ovary could be the fourth possibility in the histogenesis of the ovarian SCC.
Adenomatous hyperplasia (AH) is defined as a discrete nodular lesion showing varying degrees of hepatocyte hyperplasia in chronic liver disease, particularly in liver cirrhosis. Recently, AH has attracted the attention of both clinician and pathologist regarding the possibility of the precursor lesion of hepatocellular carcinoma (HCC) because AH is frequently coexistent with HCC and occasionally contains foci of well-differentiated HCC within a nodule. Of the 60 resected HCCs, smaller than 2 cm in diameter, in case of liver cirrhosis in our hospital, AH was found in the vicinity of HCC of 7 cases (12%). Of the 8 autopsy cases of HCCs, smaller than 2 cm in diameter with liver cirrhosis, AH was found in the vicinity of HCC of 3 cases (37.5%). On the other hand, there was no association of AH in 94 resected HCCs with chronic hepatitis. Furthermore, among 51 autopsy cases of liver cirrhosis, 41 nodular lesions, smaller than 2 cm in diameter, were found and 23 large regenerative nodules (56.1%), 6 AHs (14.6%), 4 AHs containing cancerous foci (9.8%) and 8 HCCs (19.5%). Accordingly, if AH could be a precursor of HCC, it could be said that approximately 12-37.5% of HCC would be multicentric origin and the association of liver cirrhosis would be inevitable for the multicentric occurrence of HCC from the view point of morphologic observation. Together with frequent association of HCC and AH, and the presence of AH containing HCC foci, AH may have a high potency of a precursor lesion, and it is important to conduct a meticulous follow-up for AH.
There have been few reports in the literature concerning lymph node metastasis (LM) in hepatocellular carcinoma (HCC). Nowadays, hepatectomy has become one of the most popular treatments for HCC, and understanding LM in HCC is indispensable at surgery for improving the patient's prognosis. In the present study, the authors verified this using autopsy cases. The clinicopathologic characteristics of LM have been studied in 660 consecutive autopsy cases of HCC at Kurume University Hospital during the past 22 years. LM was noted in 168 (25.5%) of the 660 cases, and was most frequent (66.7%) in HCCs of the pedunculated type. The incidence of LM was significantly higher in the massive type of HCC (30.1%) than the nodular type (19.9%) (P < 0.05). The incidence of LM was also higher in non-cirrhotic (34.8%) than cirrhotic cases (23.5%) (P < 0.05). No metastasis was found in tumors less than 3 cm in diameter. The metastasis rate increased to 40% in tumors larger than 10 cm in diameter. The LM sites were peripancreatic, 13.6%; hepatic hilar, 13.5% and perigastric, 10.8%. The incidence of LM in the perigastric nodes was significantly higher in tumors located in the left hepatic lobe. LM was not found in well-differentiated HCCs but was frequently found in poorly-differentiated HCCs. Extensive LM was found in 60% of HCCs with sinusoidal tumor growth and in 57% of cases showing sarcomatous changes.
A 56-year-old male consulted us because of a palpable mass and pain of the left flank 8 and a half years after resection of hepatocellular carcinoma of the left lobe about 3 cm in diameter. Ultrasound examination of the abdomen demonstrated a tumor about 10 cm in diameter showing a mosaic of hyperechoic and hypoechoic areas on the upper pole of the left kidney. By angiography, the tumor was found to be supplied mainly by the inferior adrenal artery. PIVKA-II was increased. Adrenal metastasis of hepatocellular carcinoma was suspected, and adrenalectomy was carried out. No intrahepatic metastasis was noted. The tumor was histopathologically identified as a pseudo-glandular type of moderately differentiated hepatocellular carcinoma with a trabecular pattern similar to the primary lesion. In this patient, a resectable giant metastasis was observed only in the left adrenal gland and no intrahepatic metastasis was demonstrated 8 and a half years after resection of hepatocellular carcinoma. The patient has survived 10 years after the first operation. This case is considered to be important for evaluation of the treatment for distant metastasis of hepatocellular carcinoma.
We present a rare case of an apocrine adenocarcinoma arising in a mature cystic teratoma of the ovary. The patient, a 41-year-old woman, was admitted to the hospital with low back pain and hypermenorrhea. A unilocular cystic tumor, measuring 5.5 x 5.0 cm in diameter, was found in her right ovary, and was removed. The tumor contained a mural nodule, measuring 8 x 7 mm in diameter. Microscopically, the unilocular cystic tumor was a teratoma consisting of mature cutaneous tissue with numerous hairs. The mural nodule was composed mostly of cords of epithelial cells with an infiltrative fashion and anastomosing tubular structures, which were lined partly by cells with eosinophilic cytoplasm and decapitation secretion. The cytoplasm contained iron granules as well as granules that were stained with periodic acid-Schiff, with and without diastase digestion.
In hepatocellular carcinoma (HCC), it has been strongly suggested that as the tumor increases in size, foci of less-differentiated malignant tissues arise in the well-differentiated tumor and increase until they replace the well-differentiated tumor tissues. It has also been suggested that tumor growth is attributed to such dedifferentiation. In the current study, the individual histologic features of ultrasound-guided fine-needle biopsy specimens, taken from 12 small HCC in an early stage, were compared with those of autopsy to confirm the dedifferentiation of HCC. In all 12 cases, autopsy was performed 6 months or more after the initial biopsy. Dedifferentiation was demonstrated in 9 of 12 cases (75.0%). Most of the biopsy specimens from minute HCC were well-differentiated. All tumors that had been well-differentiated when evaluated by biopsy were found to have become moderately differentiated at autopsy. This comparative study confirmed the dedifferentiation of HCC with tumor growth.
The nodular lesions seen in the noncancerous areas of the 80 consecutively resected small hepatocellular carcinoma associated with cirrhosis were pathomorphologically studied. A total of 51 nodular lesions were found, and they were classified into the following four groups: large regenerative nodule (30 nodules), adenomatous hyperplasia (12 nodules), atypical adenomatous hyperplasia (4 nodules) and adenomatous hyperplasia containing cancerous foci (5 nodules). Grossly, all large regenerative nodules were well demarcated, but some of the adenomatous hyperplasia group were vaguely nodular. Atypical adenomatous hyperplasia and adenomatous hyperplasia containing cancerous foci accounted for 43% of the adenomatous hyperplasia group found in the vicinity of the 16 resected hepatocellular carcinoma (20%) out of 80 cases. The mean size (+/- S.D.) of the adenomatous hyperplasias containing cancerous foci, 15.8 +/- 2.2 mm, was significantly larger than 10.1 +/- 2.6 mm of the adenomatous hyperplasias p less than 0.01). All adenomatous hyperplasias containing cancerous foci and 75% of the atypical adenomatous hyperplasias demonstrated a marked fatty change, but none of the large regenerative nodules were accompanied by any fatty changes. This study demonstrated the morphological transition from adenomatous hyperplasia to hepatocellular carcinoma that was suggestive of multistep hepatocarcinogenesis. As a result, it is predicted that approximately 20% of all hepatocellular carcinomas may have the potential for being of multicentric origin and that approximately 40% of adenomatous hyperplasias may undergo malignant transformation, but it is difficult to estimate the exact number of incidences. The presence of varying degrees of fatty change may be one of the significant morphological markers for a malignant transformation from adenomatous hyperplasia to hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
Pathomorphological and immunohistochemical studies were conducted on cases of hepatocellular carcinoma (HCC) with pale bodies (PB). HCC containing PBs was seen in 6 (5.7%) of 106 consecutively resected HCC cases. It was of interest that varying degrees of sclerotic change were found in 4 of the 6 cases and a certain correlation between PBs and sclerotic change of HCC tissue was suggested. Histologically, PBs were identified as a pale amorphous substance with a distinct margin and most of PBs occupied the entire cytoplasm of the cancer cells. PBs were practically negative for periodic-acid Schiff, and were also negative for phosphotungstic acid hematoxylin and orcein stains. Ultrastructurally, PBs were found to be a mass of granular or fibrillar materials having a single-layered limiting membrane, and dilated rough endoplasmic reticular (rER) were also found in the vicinity of PBs, suggesting the presence of a close relationship between rough endoplasmic reticula and PBs. Most PBs were found to be strongly positive for anti-fibrinogen antibody and some of them were weakly positive for anti-albumin, but were solely negative for other antibodies such as anti-HBs antigen, anti-alpha-1-antitrypsin, and anti-ferritin. According to those findings, PBs were thought to be fibrinogens accumulating in cystic rER due to a defective intracellular transport or an excretion disturbance.
In order to clarify the incidence of the delta agent among hepatocellular carcinomas (HCCs) in Kurume, where the hepatitis B infection and its related HCC are most prevalent in Japan, liver tissues from sero hepatitis B surface antigen-positive autopsy cases, with or without HCC, were immunohistochemically investigated for detection of the delta antigen. Only one patient (1.7%) among 58 patients with HCC was found to have delta-antigen in the nuclei in the hepatocytes, which were diffusely distributed throughout the non-cancerous liver. None of 26 patients with liver cirrhosis showed delta-antigen in the liver tissue. The incidence is so low that the delta agent is unlikely to have a role in the development of HCC in our areas.
Two cases of coexisting mature teratoma and thecoma are reported. In Case 1, a 36-year-old woman presented with severe genital bleeding and an ovarian tumor, 12 x 9 cm in size, was found. In Case 2, a 48-year-old postmenopausal woman presented with severe lower abdominal pain and an ovarian tumor, 15 x 11 cm in size, was detected. Macroscopically, the resected tumors of both cases showed a unilocular cystic tumor adjacent to a solid tumor. Microscopically, the cystic tumors were composed of cutaneous tissues and the solid tumors consisted of spindle cells with lipid-rich cytoplasm, arranged in interlacing bundles. The cystic tumor and the solid tumor were completely separate and no transitional features were recognized histologically.
Thirty-eight patients with small hepatocellular carcinomas (HCCs), size less than 20 mm, initially detected by ultrasound (US) and histologically confirmed, were examined by magnetic resonance (MR) imaging, computed tomographic (CT) scan, and angiography. MR imaging demonstrated HCC nodules in nine (75.0%) of 12 patients with tumors less than 10 mm in diameter and in 22 (84.6%) of 26 patients with tumors 10-20 mm in diameter. In total, HCC nodules were detected in 31 of 38 patients (81.6%) by MR imaging. On the other hand, HCC lesions were found on CT scan in 14 of 26 patients (53.8%) and in 27 of 35 patients (77.1%) by angiography. With MR imaging, HCC nodules were demonstrated in 21 of 31 patients on both T1 and T2 weighted images, and 13 of 21 patients (61.9%) were shown to have low intensity areas or iso intensity areas on T1 weighted image, whereas the other eight patients (38.1%) were shown to have high intensity areas. All 21 patients were shown to have high intensity areas on T2 weighted image. Among 15 resected cases, four patients had a high intensity area on T1 weighted image, and a significant fatty change was noted in HCC nodules by histological study of the resected specimen. We suggest that MR imaging is a useful diagnostic imaging modality, even in small HCC of less than 20 mm.
A hyperplastic nodular lesion resembling focal nodular hyperplasia (FNH) was found in the cirrhotic liver of a 50-year-old male patient. A nodule was detected by ultrasonography and hepatic angiography conducted as part of a routine follow-up study for chronic liver disease, and was excised under a diagnosis of suspected hepatocellular carcinoma. Grossly, central stellate scar-like septa subdividing the nodule ware noted. These fibrous septa contained many small arteries and veins, as well as bile ducts. The parenchyma of the nodule also contained many small arteries. Although these findings were similar to those seen in typical FNH, the present lesion was different in that it was encapsulated, occurred against a background of liver cirrhosis, lacked hepatocyte hyperplasia and showed hemosiderin deposition.