Natriuretic peptide receptor A is related to the expression of vascular endothelial growth factors A and C, and is associated with the invasion potential of tongue squamous cell carcinoma.

Natriuretic peptide receptor A (NPRA) is one of the natriuretic peptide receptors. NPRA has been reported to play a role in the carcinogenesis of various tumours, as well as functional roles in renal, cardiovascular, endocrine, and skeletal homeostasis. The clinicopathological significance of NPRA in tongue squamous cell carcinoma (TSCC) was examined in this study. The overexpression of NPRA was more frequent in TSCC (21/58, 36.2%) than in the normal oral epithelium (0/10, 0%) (P<0.05). It was also more frequently observed in cancers with higher grades according to the pattern of invasion (grades 1-2 vs. grades 3-4, P<0.01). Additionally, there was a tendency towards an association between the N classification and NPRA expression (N0 vs. N1-2, P=0.06). Significant correlations were also observed between the expression of NPRA and that of VEGF-A (P<0.001) and VEGF-C (P<0.001). The high-NPRA expression group had a significantly poorer prognosis, with a 5-year disease-specific survival rate of 39.7%, compared to 97.0% in the low-expression group (P<0.001). Multivariate analysis suggested that the overexpression of NPRA may also be an independent prognostic factor (P<0.05). In conclusion, NPRA is associated with VEGF expression levels, invasion, and metastasis, and may be a prognostic factor in TSCC patients.

Experimental study on pathogenesis and histomorphology of early carcinoma of the extrahepatic bile duct in the Syrian hamster.

To elucidate the pathogenesis of carcinomas in the extrahepatic bile duct, we investigated the histomorphological characteristics of adenomas and early carcinomas induced in the extrahepatic bile duct of hamsters. Syrian hamsters underwent a cholecystoduodenostomy along with a dissection of the common duct, while also being administered N-nitrosobis(2-oxopropyl)amine (BOP). The tumors that arose from the extrahepatic bile duct included 10 adenomas and 55 early carcinomas in 56 of the 156 hamsters sacrificed. All the adenomas were found to be polypoid in shape. The early carcinomas, which were restricted within the mucosal layer of the bile duct, showed the following three different growth patterns: (1) protruding type in 41 (75%), consisting of 27 polypoid and 14 papillary tumors; (2) superficial spreading type in 9 (16%); and (3) periductal glandular type in 5 (9%). There were no depressed tumors observed. Carcinomas existing either alone or associated with adenomas were evident in 12 (22%) tumors, and 11 of these were polypoid. Atypical papillary hyperplasia within the tumor mass was noted in 22 early carcinomas (40%) and was particularly prominent in papillary type tumors. These results support the concept of an adenoma-carcinoma sequence in the majority of polypoid tumors of the extrahepatic bile duct. Atypical papillary hyperplasia might also be premalignant, and these precursor lesions should reflect the growth patterns of tumors, at least in the early stage of tumorigenesis.

Comparative histopathological findings in the pancreas of cigarette smokers and non-smokers.

Although a correlation has been suggested between cigarette smoking and pancreatic cancer, studies on pathological changes in the pancreas of smokers are fragmentary. In the present study we examined histopathologically 73 pancreases obtained by autopsy from 42 heavy cigarette smokers and 31 non-smoker patients. One invasive adenocarcinoma (2 cm in diameter) and three small carcinomas (2-5 mm in diameter) were found in smokers and one small carcinoma in a non-smoker patient. Although the incidence of pancreatic cancer in smokers was higher than in non-smokers, the difference was statistically not significant. Of smokers with pancreatic cancer, 2 had lung cancer, 1 skin cancer, 1 colon cancer and 1 was free of any malignancies. Ductal changes, including mucinous or squamous cell metaplasia and papillary hyperplasia, were found with equal frequencies in both groups of patients. The type and the incidence of these ductal alterations were not related to smoking but to the age. Our results do not indicate that cigarette smoking increases the incidence of pancreatic cancer, although, the limited number of the sections of the pancreas examined, as well as exclusion of other important variables, such as alcohol, diet and diabetes weaken the value of this study.

Hepatic inflammatory pseudotumor associated with chronic cholangitis: report of three cases.

We present three cases of hepatic inflammatory pseudotumor associated with chronic cholangitis. In these three cases the inflammatory pseudotumor was solitary, was present in the hepatic hilar region, and had been misdiagnosed as cholangiocarcinoma by imaging modalities and/or gross pathologic examination. Hilar bile ducts were embedded within the tumor. Histologically, these "tumors" consisted of an 2ad-mixed proliferation of lymphocytes, plasma cells, and fibroblasts with variable hyaline fibrosis. The phenotypes of lymphocytes and plasma cells within the tumor were immunohistochemically heterogeneous. Bile ducts and peribiliary glands embedded within these tumors showed nonspecific fibrosis and inflammation, and inflammatory changes of the bile ducts were imperceptibly merged with those of the inflammatory tumor, raising the possibility that these tumors may have arisen in relation to cholangitis. The bile ducts adjacent to the tumor also showed similar but milder nonspecific inflammatory changes. The pathogenesis of cholangitis was unknown in two cases and was speculated to be due to fungal infection in the remaining case. These cases may indicate that biliary tract disease(s) should be explored as the etiology of hepatic inflammatory pseudotumor.

A method for culturing and transplanting biliary epithelial cell from syrian golden hamster.

The present paper describes the establishment of a method for simultaneous culturing of biliary epithelial cells (BECs) from the gall bladder (GB), extrahepatic bile duct (EBD) and intrahepatic bile duct (IBD) of the hamster. GB, EBD and IBD were cut from the biliary tree after collagenase perfusion of the liver. These biliary segments were minced into fragments. The fragments were embedded in collagen gel and cultured in Dulbecco's modified Eagle medium/HamF12 medium containing 10% fetal bovine serum. The various cells subsequently spread from the fragments and formed cellular sheets. After the fragments and flattened cells were removed with the aid of a Pasteur pipette under phase-contrast microscopy, the sheets remaining were found to be composed of cuboidal cells. These cuboidal cells were shown to express gamma glutamyl transpeptidase and cytokeratin 7, which are known to be specific markers of BECs. Ultrastructurally, a large number of microvilli were observed on the luminal surface and junctional complex and interdigitation was identifiable on the lateral surfaces. BEC cultures were subcultured by digestion with collagenase and dispase and then dissociated by subsequent digestion in trypsin and ethylenediaminetetraacetic acid and then maintained on collagen gel for up to 8 weeks. After several passages, the BECs in culture eventually increased in size and showed vacuoles in the cytoplasm. They demonstrated irreversible growth arrest at 9 weeks. The BECs tended to form cystic structures when the BECs with collagen gel were transplanted into the interscapular fat pads of syngeneic hamsters. We established a method for culturing and transplanting biliary cells from syrian golden hamsters. This method may help to clarify the mechanism of hepatobiliary diseases.

Sclerosing encapsulating peritonitis combined with peritoneal encapsulation.

The combined occurrence of idiopathic sclerosing encapsulating peritonitis and peritoneal encapsulation is described. A 52-year-old man presented with intestinal obstruction. The results of preoperative examinations were suggestive of sclerosing encapsulating peritonitis. Laparotomy revealed the concurrence of peritoneal encapsulation and sclerosing encapsulating peritonitis. The thick membrane of sclerosing encapsulating peritonitis was freed with multiple incisions. After operation, the patient reverted to the preoperative state. The condition, however, was alleviated with conservative therapy consisting of intravenous hyperalimentation and nasogastric suction. To our knowledge, the combined occurrence of sclerosing encapsulating peritonitis and peritoneal encapsulation has never before been reported.

Small non-functioning endocrine tumor of pancreas: comparison with solid cystic tumor.

A small non-functioning islet-cell tumor of the pancreas in a 79-year-old man is reported. Ultrasonography showed a solid small mass in the body of the pancreas. All laboratory data, including serum hormones and tumor markers, were within normal limits. A distal pancreatectomy was performed. Cut sections of the specimen revealed a small, hard, solid mass measuring 2.8 x 2.2 x 2.0 cm. Histologically, the tumor consisted of large acidophilic cells with round nuclei, and these cells were similar to those normally found in solid and cystic tumors (SCT) of the pancreas. However, the tumor cells were slightly positive for somatostatin and neuron-specific enolase. Ultrastructural studies revealed clear nuclei with no zymogen but immature neurosecretory granules in the cytoplasm of the tumor cells. These findings were consistent with those of non-functioning islet-cell tumors. We describe the clinical and histological differences between non-functioning islet-cell tumors and SCT based on an analysis of the literature.

Primary hepatic carcinoid tumor.

A primary hepatic carcinoid tumor arising in a 49-year-old woman is reported. The patient was admitted with multiple hepatic tumors and treated by a left lobectomy and cholecystectomy. Cut sections of the specimen revealed a solid and necrotic mass, measuring 10 x 12 x 13 cm, with multiple small satellite nodules. Histologically, the tumor cells had small oval-shaped nuclei and presented with a trabecular arrangement and rosette-like formation. Both Grimelius and Fontana-Mason stainings were positive. The tumor cells were positive for chromogranin A and negative for other antigens. Ultrastructural studies of the tumor cells revealed duct-like formation with microvilli and a cluster of dense small immature neurosecretory granules in the cytoplasm. These findings were consistent with those of carcinoid tumors. Postoperatively, the patient was treated with repeated transcatheter arterial chemoembolization for any remnant tumors. However, she died of the disease 5 years after the initial surgery. The autopsy findings suggested the primary site to be the liver.

Leiomyosarcoma occurring in the ligamentum teres of the liver: a case report and a review of seven reported cases.

We treated a 49-year-old male with leiomyosarcoma of the ligamentum teres of the liver. Preoperative hepatic imagings revealed a mass in the median segment of the liver. The patient underwent surgery, and the mass, measuring 6x5cm in size, was pathologically diagnosed as leiomyosarcoma arising from the ligamentum teres. To our knowledge, only eight cases of this rare tumor have been reported to date in the English literature.

Biliary diverticulum with pancreaticobiliary maljunction.

The case of a 48-year-old Japanese man with a biliary diverticulum (type B by the so-called Alonso-Lej classification) accompanied by pancreaticobiliary maljunction is reported on herein. The patient had epigastric distress, and an ultrasound examination suggested gallstones and adenomyomatosis of the gallbladder. Subsequent endoscopic retrograde cholangiopancreaticography demonstrated a 3 mm biliary diverticulum in the intrahepatic bile duct and pancreaticobiliary maljunction. Intra-operative cholangiography confirmed both the diverticulum and the pancreatiocobiliary maljunction. Cholecystectomy alone was performed. The histological diagnosis of the gallbladder was adenomyomatosis with intramural calculi. Except for continuing mild hyperamylasemia, the patient has been doing well for 18 months following surgery. To our knowledge, only two cases, of type B bile duct dilatation with pancreaticobiliary maljunction, including ours, have been reported in the English and Japanese literature. The size of the diverticulum in our case was smaller than in the other reported case. The relationship between pancreaticobiliary maljunction and type B bile duct dilatation is discussed.

Intra-tumor injection of an angiogenesis inhibitor, TNP-470, in rabbits bearing VX2 carcinoma of the tongue.

A semi-synthetic analogue of fumagillin, TNP-470, has been shown to be a potent angiogenesis inhibitor. In this study, we evaluated the anti-tumor efficacy of TNP-470 on rabbits bearing VX2 carcinoma of the tongue, by comparison of topical, intra-tumor (i.t.) injection with systemic, intra-venous (i.v.) administration. The i.t. injection of the angiogenesis inhibitor produced much stronger anti-tumor effects, and almost complete tumor regression was achieved at doses of 10 mg/kg or 20 mg/kg. TNP-470 injected intra-tumorally significantly reduced expression of proliferating cell nuclear antigen (PCNA) and microvessel density in the VX2 carcinoma of the tongue. TNP-470 also halted the tumor-associated neovascularization in the rabbit cornea assay. These data suggest that i.t. injection of TNP-470 effectively inhibits tumor angiogenesis and disrupts microvasculature development, which may suppress tumor growth. In conclusion, the i.t. injection of TNP-470 provided remarkable anti-tumor effects on the VX2 carcinoma of the tongue and is expected to have promising therapeutic uses for oral cancer.

[Usefulness of bronchoscopy for the diagnosis of atypical pulmonary mycobacteriosis].

In 14 subjects whose chest radiographs showed abnormal shadows during the two years from January 1995 until December 1996, no definite diagnosis could be obtained because sputum, smears and cultures all gave negative results for mycobacteria. Bronchoscopy was therefore performed, revealing atypical mycobacteria in cultures of the bronchial washing fluid for mycobacteria, and the significance of bronchoscopic examinations in cases diagnosed an atypical pulmonary mycobacteriosis was investigated. Most of the subjects (9) were women. Nine subjects had been informed that they had abnormal chest shadows; five had subjective symptoms; bloody sputum, 3 and cough, 2. The characteristics of the shadows were as follows: in the plain radiographs, the main shadows had a mottled or granular appearance in the majority of the patients (9) and there were infiltrative shadows in 3 patients and nodular shadows in another 3. In computed tomograms, the shadows in the vicinity of the pleura appeared as micronodular conglomerates in 12 patients, in 11 of whom bronchiectasis was also present near the shadows. Alveolar infiltrative shadows were present in four cases, and a cavity was seen in only one. Smears of the bronchial washing fluid for mycobacteria were positive in 7 patients, and cultures of this fluid yielded at least 100 colonies in 8 of the 14 subjects for whom the results were positive. By culture, Mycobacterium avium complex (MAC) was identified in 13 patients, but eleven of these in whom the bronchial washing fluid was concurrently tested for MAC by the polymerase chain reaction, only four were MAC-positive. Transbronchial lung biopsies were performed in 11 cases, in which the histological findings of mycobacterial infections showed granuloma in four, and caseation in three. Bronchoscopy is making possible initial-stage diagnosis, which are normally difficult, among the recently growing number of cases of the bronchial form of atypical pulmonary mycobacteriosis and is also useful for reaching definite diagnosis in the early stage.

[Anesthetic management of a Paget's disease patient complicated with Parkinson disease].

Paget's disease is a metabolic disorder of unknown etiology characterized by excessively rapid remolding of bone. We report a case of Paget's disease complicated with Parkinson syndrome. A 69-year-old female patient was scheduled for ventriculo-peritoneostomy due to hydrocephalus. Her manifestations included disability to walk, slight deafness and muscular rigidity of limbs, without symptom of intracranial hypertension. After induction of anesthesia with thiopental and vecuronium, tracheal intubation with Macintosh laryngoscope was attempted but failed because mouth opening was restricted to only 3 cm. Again with Bullard laryngoscope, she was successfully intubated. During neurosurgical operation, the anesthesia was maintained with low concentration of isoflurane (under 0.3%), nitrous oxide and oxygen. The surgery was completed without adverse events such as disorder of autonomic nervous system. However 6-days after operation, ventilatory arrest occurred due to bronchial obstruction with sputum. Immediately, re-intubation was performed without any sequela and tracheostomy was also performed. In conclusion, as reported previously, intubation and postoperative pulmonary dysfunction should be carefully taken care of, and Bullard laryngoscope was useful for this patient.

[Actual situations and problems of patients receiving home IVH--trial use of an assessment chart for outpatients].

In order to improve the quality of life (QOL) and continue nursing, we used an assessment chart to investigate the actual situations and problems of the patients receiving home intravenous hyperalimentation (IVH). From January, 1997 to June, 1999, we investigated 20 patients with home IVH. To 7 patients among them, we asked questions using Kurihara's assessment chart for QOL, plus our original questions concerning IVH. The mean age of the patients was 61 years old, and 19 of them had advanced cancers. Forty percent of the patients maintained the IVH all by themselves and 10% of the patients needed the support of their family. The remaining 50% of the patients left all to their family. There were 9 incidents of trouble during the maintenance of the IVH. Almost all patients from whom informed consent had been received were satisfied with the home IVH. On the contrary, all patients who had not given informed consent were not satisfied with the home IVH. According to the results of the assessment chart, even if the total points were low, the points for the IVH were high in the patients had given informed consent. The main reason for lower QOL was pain. The points for the families were lower than those for the patients. They sometimes complained of uneasiness and dissatisfaction with the support they received. We conclude that therapies to improve symptoms and mental state are necessary to satisfy the patients, and that it is important to support not only the patients but also their families.

[Mandibular movements in dentulous cleft lip and palate patients with lingualized occlusion].

Most dentulous unilateral cleft lip and palate patients show a tendency toward lingualized occlusion in lateral segment teeth. The purpose of this study was to investigate the effect on the stomatognathic function by changing the occlusal contacts of buccal cusps in lateral segment teeth in dentulous unilateral cleft lip and palate patients with lingualized occlusion. Three patients were selected and two types of experimental upper crowns, L crown (with occlusal contact only at the lingual cusp), B crown (with occlusal contacts both at lingual and buccal cusps), were fabricated. The border jaw movements and mandibular movements during chewing an almond were recorded with MMJI-E (Shofu inc.). The results were as follows: 1. By using B crown, the area of border jaw movements in the frontal plane and the amount of maximum opening on the experimental crowns side were increased. 2. By using B crown, mandibular movements in the occlusal phase were converged and stabilized during chewing. 3. It was suggested that favorable mandibular movements during chewing were due to proper occlusal contacts provided in lateral segment teeth.

[Surgical treatment of recurrent thyroid carcinoma after primary resection].

Twenty-six patients who underwent the second operation for recurrent thyroid carcinoma were reviewed. 1) Three surgical interventions; dissection of local lymph nodes, modified neck dissection and extended neck dissection, for the patients with recurrent thyroid carcinoma were performed. Among these patients, recurrence of thyroid carcinoma occurred again in 14 (74%) of 19 patients with dissection of local lymph nodes, 15 (63%) of 24 with modified neck dissection, 2 (22%) of 9 with extended neck dissection. Patients with extended neck dissection had significantly less local recurrence than those with other procedures (p < 0.05). 2) Lymph node recurrence on the resected area occurred in 11 (73%) of 14 patients with dissection of local lymph nodes. Ten (67%) of 15 patients with modified neck dissection had recurrence beyond the dissected area. 3) In well differentiated carcinoma, there was recurrence in 5 (62%) of 8 patients with dissection of local lymph nodes, and in 4 (31%) of 13 with modified neck dissection. In contrast, in poorly differentiated carcinoma, we found recurrence in 8 (89%) of 9, and 10 (100%) of 10, respectively. However, in only one (20%) patient with extended neck dissection, recurrence occurred. We conclude that extended neck dissection should be the procedure of choice in patients with recurrent thyroid cancer whenever feasible.

[Early determination of the effect of preoperative TAE by observation of serum AFP changes in patients with hepatocellular carcinoma].

Serum Alpha-fetoprotein (AFP) was assessed several times after preoperative TAE on 18 patients with hepatocellular carcinoma, and postoperatively the resected specimens were examined histopathologically. Changes in AFP level after TAE showed five typical patterns: AFP continued to rise in spite of treatment (non-effective type); AFP shows regular and equal increases and decreases (undulating type); AFP showed an increase after initially decreasing (increasing after decreasing type); AFP decreased gradually to normal levels (gradually decreasing type); and AFP decreased along a half-value period line to normal levels (half-value period type). These AFP patterns were intimately related to necrosis rate of tumor and other factors such as tumor size and existence of daughter tumors. Even when the AFP level decreased to 1/2 one week after TAE, the tumor showed only about 70% necrosis. Only when the AFP level fell into 1/4 of the original level after one week we could expect complete necrosis. Immuno-histological findings revealed AFP-producing cells in carcinoma but not in necrotic cells. It seems therefore, that the immuno-histological technique is uneffective in determining the viability of tumor cells.

[Morphological studies on the pathogenesis and treatment of hepatolithiasis].

Review of 108 patients with hepatolithiasis showed a recent increase of primary intrahepatic gallstones. 55 per cent of cases with hepatolithiasis had their gallstones in the left intrahepatic bile ducts. Clinicopathological study on the resected hepatic specimens of 33 patients revealed numerous intrahepatic periductal glandular formations. Periductal glandular formations were classified into the intramural and extramural glands. The mucous substances which might had been released from the periductal glands seemed to play a role in the formation of stones in combination with bilirubin pigments, cholesterin, bacterial organisms, cellular debris and other bile component. Intrahepatic gallstones and extramural glands were seen in the intrahepatic segment and area ducts. The defunctionalized atrophic hepatic lobe or segment should be resected in order to remove the calculi completely and to prevent the recurrence.