Frequency and risk factors of thoracic metastases and optimisation of the use of cross-sectional chest imaging in follow-up patients with cervical cancer.

AIM: To optimise cross-sectional chest imaging usage by identifying frequency and risk factors associated with thoracic metastases in cervical cancer patients after initial definitive treatment. MATERIALS AND METHODS: This study, conducted during 2004-2015, examined 361 consecutive patients with histopathologically proven cervical carcinoma with at least 1 year of follow-up. Electronic medical records and all available imaging modes were used to record and assess patient and tumour characteristics and timing of thoracic metastases. Associations with these characteristics and thoracic metastases were assessed using univariate and multivariable Cox proportional hazards modelling. RESULTS: Of the 361 patients, 31 developed thoracic metastases. Multivariate regression results showed that adeno/adenosquamous carcinomas (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.06 to 5.72), other histology (HR, 5.61; 95% CI, 1.81 to 17.42), high International Federation of Gynaecology and Obstetrics (FIGO) stage (HR, 2.84; 95% CI, 1.09 to 7.37), and presence of initial intra-abdominal lymph node metastases (HR, 2.46; 95% CI, 1.02 to 5.90) were associated significantly and independently with thoracic metastases. The second analysis among the subgroup of surgical treatment identified intermediate-high risk classification of recurrence (HR, 5.12; 95% CI, 1.14 to 22.94), high FIGO stage (HR, 2.73; 95% CI, 1.05 to 7.13), and other histology (HR, 11.51; 95% CI, 3.66 to 36.19) as independent predictors of thoracic metastases. Two of the 361 and 2/313 patients with thoracic metastases who did not correspond to the conditions above were in the respective evaluation groups. CONCLUSION: Assessment of negative prognostic factors for thoracic metastases might contribute to reduced need for chest cross-sectional chest computed tomography examinations.

The dipeptidyl peptidase-4 inhibitor vildagliptin has the capacity to repair ß-cell dysfunction and insulin resistance.

The aim of the present study was to determine whether the dipeptidyl peptidase (DPP)-4 inhibitor could repair pancreatic ß-cell dysfunction and insulin resistance. Ten subjects with type 2 diabetes who had never received DPP-4 inhibitor treatment were enrolled in the study. Just before and 3 months after twice-daily administration of vildagliptin (50 mg tablets), insulin secretion and insulin sensitivity were estimated using 2-compartment model analysis of C-peptide kinetics and insulin-modified minimal model parameters, respectively. The first-phase insulin secretion (CS1) was determined as the sum of the C-peptide secretion rate (CSR) from 0 to 5 min (normal range 6.8-18.5 ng/ml/min). The whole-body insulin sensitivity index (SI) was calculated using a minimal model software program (normal range 2.6-7.6×10(-4)/min/µU/ml). After vildagliptin treatment, reductions in mean (± SE) HbA1c were noted (43.28±1.53 vs. 40.98±1.77 mmol/mol; p=0.019). Vildagliptin treatment increased the area under the curve for the C peptide reactivity (CPR) (AUCCPR; 26.66±5.15 vs. 33.02±6.12 ng/ml · 20 min; p=0.003) and CS1 (0.80±0.20 vs. 1.35±0.38 ng/ml/min; p=0.037) in response to an intravenous glucose load. -Vildagliptin treatment significantly increased SI (0.46±0.27 vs. 1.21±0.48×10(-4)/min/µU/ml; p=0.037). The long-term administration of vildagliptin improved CS1 and Si suggesting that this drug has the capacity to repair impairments in pancreatic ß-cell function and insulin resistance in type 2 diabetes.

Nizatidine improves clinical symptoms and gastric emptying in patients with functional dyspepsia accompanied by impaired gastric emptying.

BACKGROUND/AIMS: In this crossover study, we investigated whether nizatidine, a H(2)-receptor antagonist, can alleviate clinical symptoms and gastric emptying in patients with Rome III-based functional dyspepsia (FD) with or without impaired gastric emptying. METHODS: We enrolled 30 patients presenting with FD symptoms (epigastric pain syndrome, n = 6; postprandial distress syndrome, n = 24). Rome III-based FD patients were treated with nizatidine (300 mg/day) or placebo for 4 weeks in a crossover trial. Gastric motility was mainly evaluated with the T(max) value using the (13)C-acetate breath test. Meal-related symptoms were defined as postprandial fullness and early satiation. Gastroesophageal symptom was defined as a burning feeling rising from the stomach or lower chest up toward the neck. Acylated- and desacylated ghrelin levels were evaluated by the ELISA method. Clinical symptoms, gastric emptying and ghrelin levels were evaluated at three different points during the study (pretreatment, after 4 weeks former treatment and after 4 weeks later treatment). The primary end point of this study was to determine whether nizatidine would improve clinical symptoms and gastric emptying in FD patients with or without impaired gastric emptying via affecting ghrelin levels. RESULTS: Meal-related symptoms of the patients treated with nizatidine improved significantly (21/30; 70%) compared to those treated with placebo (3/30; 10%). In addition, nizatidine treatment also significantly improved gastroesophageal symptoms (16/30; 53%) compared to those treated with placebo (0/30; 0%). Nizatidine treatment in patients with FD accompanied by impaired gastric emptying significantly improved clinical symptoms and T(max) value as a marker of gastric emptying (10/11, 91%; 9/11, 82%) compared to placebo therapy, respectively. There were no significant differences in ghrelin levels between nizatidine treatment and placebo therapy. CONCLUSION: Nizatidine administration significantly improved both gastric emptying and clinical symptoms in FD patients with impaired gastric emptying.

The incidence, treatment and prognosis of cervical carcinoma in young women: a retrospective analysis of 4,975 cases in Japan.

OBJECTIVE: To determine the clinical characteristics of patients (young women) with cervical carcinoma aged less than 35 years. METHODS: Data from patients who were treated for cervical carcinomas from 1990 to 2000 in the Kinki District were retrospectively investigated for clinical stage, histologic type, treatment procedure and prognosis. RESULTS: Of a total of 4,975 cases, 441 patients were aged less than 35 years old. The incidence of cervical carcinoma in these women was 7.9% from 1990 to 1995, 9.1% from 1996 to 2000, and 9.5% from 2001 to 2005. FIGO Stage I included 374 cases, followed by, 49 in Stage II, 11 in Stage III, and seven in Stage IV. Squamous cell carcinoma incidence was 80.7% and non-squamous cell carcinoma incidence was 19.3%. Several types of surgery were performed in patients with Stage I and II, while patients with Stage III and IV were treated with radiotherapy and/or chemotherapy without any type of surgery. In patients who underwent lymphadenectomy, 21.1% cases had nodal involvement. The 5-year survival rate was 95% for Stage I disease, 73% for Stage II, 68% for Stage III, and 19% for Stage IV. CONCLUSION: The incidence of cervical carcinoma in young women slightly increased from 1990 to 2005. The prognosis of cervical carcinoma tends to be better in young women than in older patients, especially in Stage III disease.

Effectiveness of a comprehensive oral management protocol for the prevention of severe oral mucositis in patients receiving radiotherapy with or without chemotherapy for oral cancer: a multicentre, phase II, randomized controlled trial.

The aim of this phase II, multicentre, randomized controlled trial was to evaluate the effectiveness of a comprehensive oral management protocol for the prevention of severe oral mucositis in patients with oral cancer receiving radiotherapy alone or chemoradiotherapy. In total, 124 patients with oral cancer were enrolled from five institutions. Of these, 37 patients undergoing radiotherapy were randomly divided into an intervention group (n=18) and a control group (n=19). The remaining 87 patients, who were undergoing chemoradiotherapy, were also randomized into an intervention group (n=42) and a control group (n=45). During radiotherapy, patients in the control group received only oral care, while those in the intervention group additionally received spacers to cover the entire dentition, pilocarpine hydrochloride, and topical dexamethasone ointment for oral mucositis. The primary endpoint was the incidence of severe oral mucositis. The intervention was significantly associated with a decreased incidence of severe oral mucositis in patients receiving radiotherapy alone (P=0.046), but not in those receiving chemoradiotherapy (P=0.815). These findings suggest that an oral management protocol can prevent severe oral mucositis in patients with oral cancer undergoing radiotherapy without concurrent chemotherapy.

Ultrastructural features of large cell carcinoma of the lung with reference to the prognosis of patients.

Epon embedded sections of large cell carcinoma of the lung obtained from 26 patients were examined by light and electron microscopy. On an ultrastructural basis this carcinoma was subclassified into four types: squamous, adenosquamous, adenocarcinomatous, and giant cell types. The giant cell carcinoma was regarded as a special type of squamous or undifferentiated carcinoma. Transition between each of these types was clearly demonstrated. Follow-up study revealed that a close correlation existed between these types and the prognosis of the patients, the squamous type showing a better prognosis and the adenosquamous and adenocarcinomatous types exhibiting equally poor prognoses. The giant cell type invariably pursued a fulminant course. It was suggested that each of the types might represent different stages and directions of differentiation of cancer cells originating from the same ancestry. The authors' view favors the Y construct theory concerning the histogenetic pedigree of pulmonary carcinoma.

Bilateral renal dysplasia, pancreatic fibrosis, intrahepatic biliary dysgenesis, and situs inversus totalis in a boy.

This is a case report of a Japanese newborn infant showing bilateral renal dysplasia, severe pancreatic fibrosis simulating cystic fibrosis, intrahepatic biliary dysgenesis, and situs inversus totalis. The chromosomal analysis was normal. A review of the literature showed that there was another case exactly the same. These two rare cases had no difinite evidence of blood relationship, but occurred in the same town in a remote area.

Relation of fine structure to prognosis for papillary adenocarcinoma of the lung.

Eight cases of papillary adenocarcinoma of the lung were investigated by light and electron microscopy. Prognoses for all but one patient were favorable. Two patients (husband and wife) who underwent tumor resection during the same year experienced no disease-related problems for more than seven years afterward. Microscopic study of the papillary adenocarcinomas revealed columnar, peg-shaped, mucus-secreting tumor cells lining the alveoli. The tumor tissue contained alveolar macrophages, with some multinucleated giant cells, interstitial lymphoid infiltrates, mildly thickened alveolar walls, and a few pneumoconiotic foci. These inflammatory stromal reactions in the tumor tissue might have been associated with the favorable prognoses. Nuclear inclusions were detected in some tumor cells in all cases. Ultrastructurally, the inclusions contained tubular, granular, crystalline, and electron-dense homogeneous structures in addition to unclassifiable nuclear bodies. The tubular structures were in close proximity to inner leaflets of the nuclear membranes. The papillary adenocarcinoma cells had features of totipotential bronchioloalveolar cells, differentiating toward type II pneumocytes, Clara cells, and ciliated epithelial cells.

Lymphoepithelial cyst of the pancreas in a 65-year-old man.

A case of an extremely rare cystic lesion of the pancreas is presented. The multilocular cyst was found adjacent to the upper border of the pancreatic body, and the cyst contained bean curd lees-like substances. Histologically, the cyst wall consisted of mature keratinizing squamous epithelium and surrounding lymphoid tissue stroma, and the cyst was filled with keratinized materials. A histopathologic diagnosis of typical lymphoepithelial cyst of the pancreas, proposed by Truong et al (Am J Surg Pathol 11:899-903, 1987), was made. Its histogenesis is still unknown; however, we hypothesize that it might arise from a benign epithelial inclusion of a peripancreatic lymph node, followed by squamous metaplasia of the epithelial inclusion. We recently found a retropyloric lymph node with a squamous epithelial inclusion, which might support this hypothesis regarding the histogenesis of the cyst.

Reconstitution of shunted mantle in experimental hydrocephalus.

The morphological mechanism of the reconstitution of shunted mantle was studied histopathologically in 22 kaolin-treated hydrocephalic puppies. A remarkable attenuation of cerebral mantle to less than 1 cm in thickness was seen on computerized tomography (CT) scans of four animals sacrificed 1 to 2 months after kaolin treatment (preshunt group). Ventricular shunting resulted in successful recovery of the mantle on repeated CT scans obtained 1 to 2 months after shunting in seven animals (postshunt group). In the remaining 11 animals the cerebral mantle, which had been reduced to 4 mm in thickness prior to shunting, failed to recover even 2 months after the procedure (shunt-refractory group). On gross inspection, the preshunt specimens showed marked thinning of the white matter, with the cortical ribbon well preserved, while the postshunt specimens consisted predominantly of thickened white matter. Histopathological examination of the attenuated white matter of the preshunt specimens showed decreased nerve-fiber density, myelin destruction with myelin regeneration and/or repair of myelin sheaths, and reactive astrocytosis, which were prominent especially in the periventricular white matter. The main findings in the reconstituted white matter of the postshunt specimens were extensive myelin regeneration of residual axons and remarkable astroglial proliferation with mesenchymal reaction, particularly at capillaries. No clear evidence of increased numbers of nerve fibers or axonal regeneration was observed. The shunt-refractory specimens showed remarkable attenuation of cortex, in which reduced numbers of neurons and loss of cortical lamination were noted, with vestigial white matter. The results indicate that astroglial proliferation with mesenchymal reaction and myelin regeneration contribute to the reconstitution of the cerebral mantle volume following ventricular shunting in this model. It is suggested that the critical factor for mantle reconstitution in chronic hydrocephalus is whether cortex is preserved.

Morphological study of experimental syringomyelia with kaolin-induced hydrocephalus in a canine model.

In this morphological study the authors investigated whether spinal cord cavitation, produced in young mongrel dogs that had been rendered hydrocephalic by cisternal injection of kaolin, consists of a dilated central canal or intramedullary cavities. Hydrocephalus was noted in 50 of 56 dogs treated with kaolin. Of the 50 hydrocephalic young dogs, 29 were shown to have central canal dilation that was prominent at the thoracic level and 21 to have cervical intramedullary cavities in the posterior column and/or the posterior horn. In 11 dogs from the latter group these cavities were demonstrated to have no communication with the central canal. This finding could not be explained by the hydrodynamic theory. On histopathological examination, myelomalacia and hemorrhagic infarction following ventricular shunting were noted adjacent to the cervical cavities, which suggested vascular impairment. A perfusion study revealed insufficient blood flow within the cervical cord at the level of the intramedullary cavities. A close correlation between the vascular insufficiency of the cervical cord and the pressure cone resulting from significant hydrocephalus was observed. The latter may cause cervicomedullary compression at the foramen magnum, affecting the venous drainage of the cervical cord below that level, resulting in intramedullary cavitation. Accordingly, vascular impairment was thought to play a significant role in the development of cervical syrinx formation in our kaolin model. The current results may provide a reasonable explanation for the formation of noncommunicating cervical syringomyelia in Chiari I malformation.

Gastric small cell carcinoma with squamous and neuroendocrine differentiation.

A rare gastric carcinoma containing diverse components, that is, neuroendocrine (small cell carcinoma), squamous and gland-like elements in an 82 yr old woman is described. Radiologic examination revealed a large ulcerated tumor, and a Borrmann type II tumor, 6.5 x 5 cm, was found in the resected stomach. Histologically, the tumor was mainly composed of small cells with hyperchromatic nuclei and scant cytoplasm. Argyrophilic granules were seen in these cells. There were also scattered foci of large cells with features of squamous cells, and many intermediate cells with oncocytic cytoplasm. The small cancer cells were positive for chromogranin A and neuron specific enolase. Squamous cell nests were positive for high molecular cytokeratin (CK), and intermediate cells were positive for low molecular CK. Electron microscopic examination revealed secretory granules in the small cells and tonofilaments in the squamous cells. This tumor might have originated from the pluripotential stem cell in the gastric epithelium.

Alveolar rhabdomyosarcoma of the ethmoid sinus.

A case of the alveolar rhabdomyosarcoma originating in the left ethmoid sinus was reported. Despite treatment by radical excision of the tumor, irradiation and chemotherapy, the patient died of generalized metastases of the tumor six months after surgery; however, no local recurrence of the tumor was found at an autopsy. The tumor was further studied by light and electron microscopic procedures.

Meningioma of the parapharyngeal space: a unique extension of intracranial tumor.

A 45-year-old woman with a meningioma growing in the parapharyngeal space is reported. Her initial symptom was a stuffy feeling in the right ear and swelling of the right parapharynx. The parapharyngeal mass was biopsied, and a frozen section diagnosis suggested a paraganglioma. On electron microscopy, however, the tumor cells failed to show secretory granules, and represented a prominent interdigitation of the cytoplasm with occasional desmosomal attachments. Based on these features the tumor was diagnosed as a meningioma. Thereafter a mass lesion in the temporal lobe of the brain was detected by computerized tomography of the brain. The extracranial extension of the meningioma may occur in some occasions, but such cases in which the infiltrative portion in the parapharyngeal space was initially discovered have been rarely reported.

Pruritus and mast cell proliferation of the skin in end stage renal failure.

We studied the relationships between dermal mast cell proliferation and pruritus or hyperparathyroidism in hemodialysis (HD). Skin biopsies were taken from 59 patients in end stage renal failure; 51 were on maintenance HD, and the other 8 were not. As a control, 34 non-renal failure pruritic patients were used. Thirty-one of the 59 end stage renal failure patients (52.5%) had pruritus. The incidences of pruritus found in patients on HD and those not on HD were 56.9% and 25%, respectively. Significantly larger numbers of dermal mast cells were found in HD patients than in the control. There was no clear relationship between dermal mast cell proliferation and serum parathyroid hormone (PTH) levels. We speculated that the cause of pruritus in the patients undergoing maintenance HD was due to an increase of dermal mast cells and a release of histamine as a result of extra-corporeal circulation.

An ultrastructural comparison of sinusoids in hepatocellular carcinoma, adenomatous hyperplasia, and fetal liver.

Transmission and scanning electron microscopic examinations were performed to evaluate the fine-structural differences in sinusoids of hepatocellular carcinoma, adenomatous hyperplasia of the liver, and fetal livers. In cancerous sinusoids, thickened endothelial cells with loss of sieve plates were conspicuous features. In the sinusoids of adenomatous hyperplasia, scanning electron microscopy showed apparent sieve plates, and basement membrane formation (capillarization) was less conspicuous than in carcinoma. In fetal livers, occasional large gaps as well as small fenestrations in the endothelium were noted. Basement membrane materials were not seen. It was concluded that the sinusoids of hepatocellular carcinoma lost the fine-structural nature of normal sinusoids and showed much more prominent capillarizations than the sinusoids of adenomatous hyperplasia, and that the fine structures of cancerous sinusoids were also different from those of the sinusoids in fetal livers.

Minute hepatoma with excessive copper accumulation. Report of two cases with resection.

Minute hepatomas with prominent copper accumulations were resected in two women, aged 60 and 62 years, who had never suffered from jaundice. Mild elevation of serum alpha-fetoprotein level was found in both patients. One tumor was diagnosed by celiac angiography, and the other was determined by an ultrasonic echogram. Microscopically, these two tumors were relatively well-differentiated hepatocellular carcinoma, though having less-differentiated foci. Many cancer cells contained numerous copper granules stained by orcein, Victoria blue, and p-dimethylaminobenzylidene rhodanine. Ultrastructurally, cancer cells contained many secondary lysosomes with an electron-dense material. We concluded that the excessive copper in the cancer cells was aggregated lysosomal copper metallothionein, and that it might not be carcinogenic but stored by an altered metabolism of copper and copper-binding proteins with the neoplastic transformation.

Clinicopathological and immunohistochemical study of basal cell carcinoma with reference to the features of basement membrane.

One hundred and thirty-five cases of basal cell carcinoma (BCC) were investigated, focusing upon factors determining a postoperative prognosis. Out of the 135, nine tumors on the face recurred. All of these nine tumors were insufficiently extirpated at the initial operation, and showed micronodular or infiltrative patterns with stromal fibrosis. Dividing the degree of dermal invasion into four levels, all tumors with recurrence reached levels 3 and 4, the two deeper groups. The immunohistochemical study using anti-laminin and anti-type IV collagen antibodies showed various changes of staining pattern around tumor cell nests, such as attenuation, disruption, and thickening of basement membrane, in contrast with the normal thinly continuous staining around nontumorous control epidermis. The disruption of basement membranes was remarkable around the tumor cells showing a micronodular growth pattern, although the discontinuity of basement membrane was observed in all types of BCCs to a greater or lesser degree. Ultrastructural thickening, multiplication, or discontinuity of basement membranes were found in all 19 cases examined with a greater or lesser degree, although they were most frequently observed around the cell nests showing micronodular growth patterns. It was concluded that deep dermal and marginal invasions were the most ominous signs of recurrence of BCCs. Although the disruption of basement membranes might participate in the local aggressiveness of BCCs, especially in the tumor cells showing micronodular infiltrative growth, other factors may concern the recurrence of BCCs.

Electron microscopical findings with special reference to cancer in rats caused by inhalation of nickel oxide.

A special exposure system was used for the inhalation of nickel oxide (NiO) aerosol by Wistar male rats. The median aerodynamic diameter and the geometric standard deviation were 1.2 µm and 2.2, respectively. A histopathological study of the rats was performed immediately, and at intervals of 12 and 20 mo after a 1-mo expsoure to NiO. Electron microscopy showed that localization of NiO particles was restricted to the lungs and that each particle had been engulfed by the alveolar macrophages. Type II pneumocytes and nonciliated bronchiolar epithelial cells (Clara cells), as well as numerous tubular myelin (surfactant) in the alveoli were prominent. In rats dissected after 12 mo, clusters of NiO particles were still present within the terminal bronchioli, alveolar walls, and lysosomes of the alveolar macrophages. Pools of tubular myelin were observed in the peribron-chial lymphatics. The Clara cells, which project into the lumen of bronchioli, showed active secretion and were filled with smooth en-doplasmic reticulum (SER) in the apical cytoplasm. In the experimental group sacrificed after 20 mo, one rat had papillary adenocarcinoma and two rats showed adenomatosis in the peripheral portion of the lung, but none in the upper respiratory tract.

Biological half-time in rats exposed to nickel monosulfide (amorphous) aerosol by inhalation.

This study reports the biological half-time of amorphous nickel monosulfide(NiS(A)) aerosol retained in rat lungs. Wistar male rats were exposed to NiS(A) aerosols (mass median aerodynamic diameter:4.0 microns) for a single 4 h exposure, or for 7 h/d, 5 d/wk for 1 mo. The average exposure concentrations were controlled at 107 mg/m3 for the single exposure and at 8.8 mg/m3 for the repeated exposures by a dust generator consisting of a continuous fluidized bed with an overflow pipe and a screw feeder. After the exposures, the nickel contents in the rat organs, blood, and urine were measured and histopathological examinations were performed. The biological half time of NiS(A) in rat lungs was 20 h, which was extremely shorter than 21 mo of green nickel oxide (NiO(G)). There were no malignant tumors in any of the exposure groups.