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.

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.

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.

G-protein ß3 subunit 825CC genotype is associated with postprandial distress syndrome with impaired gastric emptying and with the feeling of hunger in Japanese.

BACKGROUND: G-protein dysfunction related alteration of intracellular signal transduction might be linked to various abnormalities of functional gastrointestinal (GI) disorders. Serotonin (5-hydroxytryptamine; 5-HT) as well as G-protein is also key signaling molecule sensorimotor functions in the GI tract. Thus, this study aims to evaluate the correlation between gastric emptying and GNß3 and 5-HTs polymorphisms in functional dyspepsia (FD) as defined by Rome III classification. METHODS: Seventy-four patients presenting with typical symptoms of FD (epigastric pain syndrome: EPS, n=24; postprandial distress syndrome: PDS, n = 51) and sixty-four healthy volunteers were enrolled. Gastric motility was evaluated with the T(max) value using the (13) C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and SRQ-D scores to determine depression status. GNß3-C825T, 5-HT(1A) -C1019G, 5-HT(2A) -G1438A, 5-HT(3A) -C42T, and 5-HT(4A) -G353+6A polymorphisms were analyzed in DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. KEY RESULTS: There was a significant relationship (P=0.045) between GNß3 825CC genotype and PDS patients without gastro-esophageal reflux symptoms with impaired gastric emptying. In Japanese, GNß3 825CC genotype in FD patients was significantly associated (P=0.0485) with the feeling of hunger compared with GNß3 825CT and TT genotypes. CONCLUSIONS & INFERENCES: Our results suggest that the GNß3 825CC genotype is significantly associated with PDS patients without gastro-esophageal reflux with impairments of gastric emptying and also with the feeling of hunger in patients with FD. Further studies are needed to clarify whether the GNß3 825CC genotype is linked to disturbances of gastric emptying via altered signal transduction responses.

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.

Radiosurgical treatment of maxillary squamous cell carcinoma.

The authors report their experience of using the CyberKnife system (Accuray Incorporated, Sunnyvale, California, USA), a new radiosurgical device, as a treatment option for squamous cell carcinoma (SCC) of the maxillary sinus. A 66-year-old man with SCC stage T4 was treated using the CyberKnife system.

[Dystonic movement of the left upper limb in a case of the right pontine hemorrhage].

We report a 69-year-old woman who presented with dystonic movement in the left upper limb. She also had left hemiparesis and sensory disturbance in the right face and the left half of the body, pseudoathetosis in the left hand, and hotness, swelling, and lead-pipe rigidity in the left upper limb. The dystonic movement was presented mainly in the proximal part of the left upper limb, and was induced by voluntary movements; for example, when she was ordered to shake hands, the left shoulder always abducted with the flexion of the left elbow. Brain MRI showed a fresh hemorrhage in the dorsal part of the right middle pons including the base and the tegmentum, old infarctions in the right postero-lateral thalamus, putamen, and right parietal lobe. The dystonic movement persisted for 2 weeks, and hotness and swelling in the left upper limb lasted for 2 months, while the rigidity and pseudoathetosis persisted for 7 months or more despite medication.

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.

Occurrence and antigenic heterogeneity of L-2,4-diaminobutyrate decarboxylase in Acinetobacter species.

We have previously reported that a novel enzyme, L-2,4-diaminobutyrate decarboxylase (DABA DC), which is responsible for the formation of 1,3-diaminopropane, occurs in two Acinetobacter species. The present study extends this observation to additional Acinetobacter species and strains (6 reference strains and 30 clinical isolates). Furthermore, the DABA DC protein was detected in every strain by Western blot analysis with the antiserum against the enzyme purified from A. baumannii ATCC 19606. However, only the DABA DCs in the A. calcoaceticus and Acinetobacter genospecies 3 in addition to A. baumannii strains strongly cross-reacted with the antiserum, suggesting antigenic heterogeneity among the DABA DC proteins in Acinetobacter species. Therefore, immunological testing of the DABA DC protein may provide an additional method for differentiating and identifying Acinetobacter strains.

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.

Giant cell tumor-like cholangiocarcinoma associated with systemic cholelithiasis.

A cholangiocarcinoma of the hepatic hilus with an element of giant cell tumor that occurred in a 59-year-old man is reported. His medical history included systemic cholelithiasis and repeated operations on the biliary passages. Four years after the last operation, which was a hepatic segmentectomy, he was readmitted because of persistent fever. A computed tomography scan showed a low-density area and stones in the hepatic hilus. He died of hepatic failure approximately 1 month later. At autopsy, a fist-sized tumor and gallstones were found at the hepatic hilus. Histologically, the tumor mainly showed sarcomatoid features and some tubular adenocarcinoma. An element of giant cell tumor consisting of many osteoclast-type giant cells also was noted. The results of immunohistochemical studies showed a positive reaction to cytokeratin and vimentin in some of the spindle-shaped sarcomatoid cells. Sarcomatoid bile duct carcinomas are rare, as are those with osteoclast-type giant cells. The authors also discuss the histogenesis of these giant cells.

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.

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.

Hyalinized hemangioma of the liver.

We report the case of a 65-yr-old woman with hyalinized hemangioma of the liver which, on radiological examination, resembled primary or metastatic carcinoma of the liver. She had undergone a partial colectomy for a sigmoid adenocarcinoma, followed by the diagnosis of a hepatic tumor with ultrasonic echogram 5 months later. The tumor was depicted as a low-density mass on plain computed tomography (CT), and an enhancement at the peripheral portion was noted by contrast CT. Hepatic angiography disclosed a faint pooling of contrast medium in segment 8. A subsementectomy of the liver was performed under the diagnosis of metastatic adenocarcinoma or hepatocellular carcinoma. Histologically, the tumor was composed of dense collagenous tissues with marked hyalinization and scattered sclerotic vessels. Elastic fibers were distributed concentrically around the vessels. Totally hyalinized sclerosis of hemangioma is uncommon, and can be erroneously diagnosed as carcinoma by radiologic examination. This unusual hemangioma is reported, with pertinent literature.

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.

A scanning electron microscopic study of postnatal development of rat peribiliary plexus.

Hepatic microcirculation in the developing stages is not fully clarified. This study aimed at clarifying the development of hepatic microcirculation, especially peribiliary vascular plexuses, in neonatal rats by corrosion cast procedures and scanning electron microscopy. Peribiliary vascular plexuses of large bile ducts at the hilus of 1-day-old rats showed a simple capillary network that directly poured into the portal vein. The hepatic artery promptly tapered down into many small branches and ended in sinusoids or capillary plexuses around portal vein branches near the hilus. Neither apparent hepatic artery branches nor peribiliary vascular plexuses were found in the peripheral areas of the liver. On the seventh day, very loose peribiliary vascular plexuses and small hepatic artery branches appeared up to the peripheral portal tracts, and the peribiliary vascular plexuses of large bile ducts were still capillary networks. After the seventh day, peribiliary vascular plexuses of large and medium-sized portal tracts often poured into side branches of the portal vein rather than directly into the portal vein as shown in the rats from the first day mentioned above. Peribiliary vascular plexuses of the large bile duct in 2-week-old rats showed a double layer, that is, an outer layer composed of arteries and veins and an inner layer of capillary vessels, that resembled peribiliary vascular plexuses of adult livers. After nearly 4 wk, hepatic microcirculations had almost fully developed into those of adult rats. It was concluded that the gradual postnatal development of the hepatic arterial system and the peribiliary vascular plexuses occurred in parallel with the maturation of the intrahepatic biliary trees.

Morphological effects of cadmium on proximal tubular cells in rats.

Twenty-four male rats of the Wistar strain divided into four groups were injected s.c. with a dose of 0.8, 1.5, and 3.0 mg Cd/kg body wt as CdCl2 in saline, and saline alone to the control rats, three times a week for 3 wk. Cadmium levels of whole kidney homogenate, supernatant (cytosol), precipitate, and metallothionein (MT) fraction were measured. Histological changes of the renal proximal tubules were investigated by optical and electron microscopy. In the kidneys, Cd levels were increased with the increment of Cd dosage; 80-90% of Cd was contained in cytosol, and 55-75% was in MT fraction. Non-MT-Cd reached a maximum in the 1.5 mg Cd group, whereas that of the 3.0 mg Cd group showed some decline. With increasing Cd doses, the size of nuclei and nucleoli in the cells of proximal tubule showed significant enlargement and also an increase in the number of nucleoli on light microscopy. At higher doses, chromatin condensation of the tubular nuclei and vacuolar degeneration of the tubular cells were evident. On electron microscopy, perichromatin granules of the proximal tubular nuclei were increased in number, especially in the rats of Cd 0.8 mg and 1.5 mg/kg groups. As the Cd doses increased, ring-shaped nucleoli were increased in number and nucleolar segregation was observed more clearly. Moreover, in the 3.0 mg/kg Cd group, nuclear indentation and nucleoli containing compact dense granules were observed. In the cytoplasm, there was an increase of lysosomes, myelin bodies, ring-shaped mitochondria, and vesiculation; ultimate changes were degeneration and cell necrosis. The injured cells were heterogenously distributed in each nephron and this heterogeneity was attributed in the difference in Cd content and cell cycle in each cell of the nephron.

Melanocytic schwannoma in the spinal canal.

A case of melanocytic schwannoma, a rare form of schwannian neoplasm, in the thoracolumbar spinal canal of a 52-year-old man is presented. Histopathologically, the tumor was composed of irregularly interlacing spindle-shaped cells showing cystic degeneration, with occasional pigmented tumor cells. The tumor cells showed a low degree of nuclear pleomorphism without any mitotic figures. These histological features were considered to be consistent with a benign schwannian tumor showing pigmentation. Most of the pigments were considered to be melanin histochemically and immunohistochemically. According to the pathological features of the present tumor and those described previously in the literature, the neoplastic Schwann cells were assumed to have melanogenetic capacity, and the concept of the common neural crest origin of Schwann cells and melanocytes appeared to be demonstrated in the present tumor.