Long-term control of lung metastasis of tongue cancer treated effectively with cetuximab combination chemotherapy.

Generally, systemic chemotherapy is indicated for oral squamous cell carcinoma with distant metastasis and has a poor prognosis. Recently, the advent of molecular targeted drugs, such as cetuximab and immune checkpoint inhibitors, has dramatically improved prognosis, though controlling distant metastasis remains challenging. We report a case of tongue cancer in which lung metastases disappeared in the long term. A 60-year-old Japanese male with squamous cell carcinoma of the tongue underwent preoperative chemoradiotherapy and surgery including subtotal glossectomy, bilateral modified radical neck dissection, and immediate reconstruction with an anterolateral thigh flap. One month after surgery, multiple nodules less than 10 mm in diameter appeared in both lungs on CT imaging. Multiple lung metastases were diagnosed with no local recurrence or regional lymph node metastasis. The patient continues to receive a 4-week treatment course of chemotherapy that included cetuximab every 3 months and the lung metastases were markedly reduced in size or had disappeared. No local recurrence or newly emerged metastases were observed. The patient has been doing well for nine years since the appearance of the lung metastases.

Is the addition of extranodal extension and lymph node yield of pN0 to the lymph node ratio useful as a prognostic parameter for patients with oral squamous cell carcinoma?

We investigated the value of the weighted lymph node ratio (WLNR), a new marker in pN0 patients that incorporates the number of metastatic lymph nodes with extranodal extension and the lymph node yield, for the prognosis and postsurgical management of oral squamous cell carcinoma (OSCC). We designed a retrospective study and enrolled patients with OSCC who were treated by neck dissection (ND). The predictor variable was WLNR, and the outcome variable was overall survival (OS). The Cox proportional-hazards model was used to identify independent prognostic factors. In 133 patients with OSCC, the WLNR cut-off value for predicting OS was 0.0363 (area under the curve 0.723, p<0.001). When stratified according to WLNR, there was a significant difference in OS (88.4% for low WLNR and 63.0% for high WLNR, p<0.001). Univariate analyses showed close associations between OS and age, dissection area, postoperative management, extranodal extension, number of positive lymph nodes, pN stage, WLNR, and nodal disease area. Cox multivariate analysis identified the WLNR as an independent predictive factor for OS (HR 3.273, 95% CI 1.227 to 8.731, p=0.018). As a predictive factor, a high WLNR (≥0.0363) in patients with pN0 disease, which included the addition of extranodal extension and lymph node yield to the LNR, was associated with diminished survival.

Postoperative delirium after reconstructive surgery for oral tumor: a retrospective clinical study.

The aim of this study was to perform a statistical evaluation of the risk factors for postoperative delirium after oral tumor resection and reconstructive surgery. The records of 69 consecutive patients who underwent major head and neck tumor resection and reconstructive surgery, and who received postoperative management in the high care unit (HCU) or intensive care unit (ICU) of Tsukuba University Hospital between January 2013 and December 2017, were analysed retrospectively. Delirium was diagnosed in 23 patients (33.3%) after surgery. There were significant differences in age, sex, history of diabetes mellitus and chronic obstructive pulmonary disease, recent hospitalization history, sedation period, duration of ventilator use, length of ICU/HCU stay, postoperative blood tests (haemoglobin and potassium), and postoperative medication with a major tranquilizer between those with and without delirium. Logistic regression analysis of selected independent variables revealed a hazard ratio (95% confidence interval) of 1.42 (1.09-1.86) for the sedation period. Delirium was hyperactive type in 15 cases, hypoactive type in five, and mixed type in three. There was no obvious difference in postoperative day of onset or delirium period according to subtype. In conclusion, a history of diabetes and the sedation period were found to be related to postoperative delirium. However, this study was small and retrospective, so further investigation is necessary.

Diagnostic accuracy of plasma atrial natriuretic peptide concentrations in cats with and without cardiomyopathies.

OBJECTIVES: Plasma atrial natriuretic peptide (ANP) levels have been reported to be elevated in cats with cardiomyopathy. We investigated the diagnostic accuracy of plasma ANP concentration as an indicator of the severity of cardiomyopathies. ANIMALS: This study included 78 control cats and 83 cats with various types of cardiomyopathy. METHODS: This was a prospective multicentre study. Control cats were determined to have a normal heart, and diseased cats were diagnosed by echocardiography. Diseased cats were divided into asymptomatic cats without left atrial dilation (LAD), asymptomatic cats with LAD, and cats with heart failure. Plasma C-terminal ANP concentrations were measured using chemiluminescence. RESULTS: The median plasma ANP concentration in controls was 43.3 (interquartile range, 33.0-56.3) pg/mL. Plasma ANP values were significantly higher in the cardiomyopathic cats with LAD and heart failure, but the values in cats without LAD were comparable to those in control cats. To distinguish cats with cardiomyopathy from controls, a plasma ANP concentration >77.5 pg/mL afforded sensitivity of 66.3% and specificity of 84.6%. Use of plasma ANP concentration >110.9 pg/mL to identify cats with LAD had a sensitivity of 73.6% and specificity of 93.5%. The areas under the receiver-operating characteristic curve were 0.80 and 0.86. CONCLUSIONS: Plasma ANP concentrations were higher in cats with more advanced cardiomyopathy. Although assaying the ANP concentration alone may not help to diagnose cardiac disease, measuring provides additional information that is useful for assessing the severity of cardiomyopathies.

Bone morphogenetic protein 4 and bone morphogenetic protein receptor expression in the pituitary gland of adult dogs in healthy condition and with ACTH-secreting pituitary adenoma.

The purpose of this study was to investigate the expression of bone morphogenetic protein 4 (BMP4) and its receptors, bone morphogenetic protein receptor I (BMPRI) and BMPRII, in the pituitary gland of healthy adult dogs and in those with ACTH-secreting pituitary adenoma. Quantitative polymerase chain reaction analysis showed that the BMP4 messenger RNA expression level in the ACTH-secreting pituitary adenoma samples was significantly lower than that in the normal pituitary gland samples (P = 0.03). However, there were no statistically significant differences between samples with respect to the messenger RNA expression levels of the receptors BMPRIA, BMPRIB, and BMPRII. Double-immunofluorescence analysis of the normal canine pituitary showed that BMP4 was localized in the thyrotroph (51.3 ± 7.3%) and not the corticotroph cells. By contrast, BMPRII was widely expressed in the thyrotroph (19.9 ± 5.2%) and somatotroph cells (94.7 ± 3.6%) but not in the corticotroph cells (P < 0.001, thyrotroph cells vs somatotroph cells). Similarly, in ACTH-secreting pituitary adenoma, BMP4 and BMPRII were not expressed in the corticotroph cells. Moreover, the percentage of BMP4-positive cells was also significantly reduced in the thyrotroph cells of the surrounding normal pituitary tissue obtained from the resected ACTH-secreting pituitary adenoma (8.3 ± 7.9%) compared with that in normal canine pituitary (P < 0.001). BMP4 has been reported to be expressed in corticotroph cells in the human pituitary gland. Therefore, the results of this study reveal a difference in the cellular pattern of BMP4-positive staining in the pituitary gland between humans and dogs and further revealed the pattern of BMPRII-positive staining in the dog pituitary gland. These species-specific differences regarding BMP4 should be considered when using dogs as an animal model for Cushing's disease.

Denervation-Associated Change in the Palatinus and Levator Veli Palatini Muscles of Dogs with Elongated Soft Palate.

Muscle lesions and decreased numbers of peripheral nerve branches have been reported in the soft palates of dogs presenting with brachycephalic airway obstruction syndrome (BAOS). Myosin adenosine triphosphatase staining was employed to investigate whether muscle lesions in the elongated soft palate (ESP) of dogs with BAOS reflect the presence of denervation. Soft palates were collected from nine brachycephalic dogs during surgical intervention for BAOS and from five healthy beagle dogs as controls. In the control soft palates, myofibres with relatively uniform diameters and a random mosaic pattern of type I and II myofibres were observed in the palatinus muscle (PM), while almost all of the myofibres in the levator veli palatini muscle (LVPM) were of type II. In the ESPs, small group atrophy, large group atrophy and angular-shaped atrophy were observed in myofibres of the PM and rarely in the LVPM. Fibre type grouping and an increase in type IIC myofibres were found only in the PM. Morphometric analysis of ESPs revealed a significant increase in the number of type I and II myofibres in the PM showing atrophy or hypertrophy compared with controls. A significant increase in atrophic type II myofibres was found in the LVPM of affected dogs. Myopathy consistent with denervation was observed in the PM, but rarely in the LVPM, of ESP specimens. The results suggest that the myopathy seen in dogs with ESP may partly reflect atrophy of myofibres resulting from damage to peripheral nerve branches, with subsequent reinnervation of myofibres.

Efficacy and Safety of Salmeterol/fluticasone Combination Therapy in Infants and Preschool Children with Asthma Insufficiently Controlled by Inhaled Corticosteroids.

BACKGROUND: Clinical evidences of inhaled salmeterol/fluticasone propionate combination (SFC) therapy are insufficient in early childhood asthma. OBJECTIVES: To examine the effects of SFC50, a combination product of salmeterol xinafoate (50 µg/day) and fluticasone propionate (100 µg/day), in infants and preschool children with asthma. METHODS: The study was conducted at 31 sites in Japan. 35 patients (6 months to 5 years old) with asthma insufficiently controlled by inhaled corticosteroids (100 µg/day) were initiated to treat with SFC50 twice a day for 12 weeks with pressurized metered dose inhalers. The efficacy of SFC50 was assessed using nighttime sleep disorder score as the primary endpoint and the other efficacy measurements. The safety measurement included the incidences of adverse event (AE). RESULTS: Mean patient age was 3.1 years, and 94.2% had mild-to-moderate persistent asthma (atopic type: 65.7%). Nighttime sleep disorder scores, assessed by a nighttime sleep diary, significantly decreased after treatment with SFC50 throughout the study period (p<0.01). SFC50 also significantly improved other efficacy outcomes including asthma symptom score, frequency of short-acting beta-agonist treatment, frequency of unscheduled visits to clinic, frequency of exacerbation due to virus infection, asthma control score and patient QOL score (p<0.01). AEs of cold, upper respiratory inflammation and asthmatic attack occurred in each of the 3 patients (8.6%); however, these were not regarded as treatment-related AEs. CONCLUSIONS: SFC50 improved nighttime sleep disorder score and other efficacy outcome measures with no safety concerns. The results suggest that SFC50 treatment is useful to control the mild-to-moderate asthma in infant and preschool-aged children.

A magnetic resonance imaging-based classification system for indication of trans-sphenoidal hypophysectomy in canine pituitary-dependent hypercortisolism.

OBJECTIVES: The objectives of this study were to establish a magnetic resonance imaging-based classification system for canine hyperadrenocorticism according to pituitary gland extension, determine indications for trans-sphenoidal hypophysectomy, and clarify the prognosis for each disease grade. METHODS: A 5-point classification system (Grades 1 to 5) was developed based on tumour extension in dorsal and cranio-caudal directions. Cases were then classified as Type A: no arterial circle of Willis or cavernous sinus involvement and Type B: cases in which these blood vessels were involved. RESULTS: Medical records and magnetic resonance imaging data of 37 cases with hyperadrenocorticism were reviewed. Thirty-three cases underwent surgery; 4 Grade 5 cases did not have appropriate indications for surgery, and other therapies were used. Complete resection was achieved for 3, 3, 22 and 1 Grade 1A, 2A, 3A and 3B cases, respectively. Resection was incomplete in 1, 1 and 2 Grade 3A, 3B and 4B cases, respectively. Remission was achieved in 29 cases. Recurrence occurred in 4 cases, all of which were classified as Grade 3. CLINICAL SIGNIFICANCE: Dogs with Type A, Grade 1 to 3 hyperadrenocorticism had a good prognosis following trans-sphenoidal hypophysectomy. Grade 3B, 4 and 5 cases may not be suitable for this surgery.

Salivary Gland Epithelial-Myoepithelial Carcinoma with High-Grade Transformation in a Dog.

An 8-year-old male neutered standard dachshund was presented with a slowly growing mass in the left submandibular salivary gland. Histopathological examination revealed a tumour that was composed of bilayered duct-like structures with an inner layer of ductal cells and an outer layer of clear cells. Both inner and outer cells in the greater part of the tumour exhibited low to moderate atypia and low mitotic activity. However, a focal area towards the periphery showed enhanced cellular atypia and mitotic activity in tumour cells. Immunohistochemically, the outer layer of clear cells expressed myoepithelial markers, while the inner layer cells were positive for a luminal epithelial marker. No local recurrence or lymph node or distant metastasis was observed 18 months following surgery. Based on the morphology and immunohistochemical findings, a final diagnosis of epithelial-myoepithelial carcinoma with high-grade transformation was made.

Histological and immunohistological analysis of degenerative changes in the cranial cruciate ligament in a canine model of excessive tibial plateau angle.

OBJECTIVE: To create a canine model of excessive tibial plateau angle (eTPA) and assess the chondroid metaplasia and extracellular matrix alteration in the cranial cruciate ligament. METHODS: Seven mature female Beagles were included. Cylindrical osteotomy was performed bilaterally in the proximal tibia. The TPA was increased to approximately 40° in the left tibia (eTPA stifle) and left unchanged in the right tibia (control stifle). Exercise stress was started at three months postoperatively, and at 12 months postoperatively the dogs were euthanatized and the cranial cruciate ligaments were collected. The specimens were subjected to haematoxylin and eosin staining to assess the ligamentocyte morphology and immunostaining to assess the type I (COLI), type II (COLII), and type III (COLIII) collagen, and the sry-type HMG box 9 (SOX9) staining. RESULTS: Macroscopic cranial cruciate ligament injury was absent in six dogs but present in the eTPA stifle of one dog, which was excluded from the analysis. The ligamentocyte density decreased and the percentage of round ligamentocytes increased in the eTPA stifles. The COLII, COLIII, and SOX9 staining increased significantly and COLI deposition decreased in the eTPA stifles compared to the control stifle. CLINICAL SIGNIFICANCE: The extracellular matrix changed, COLI deposition decreased, and COLIII and SOX9 staining increased in the cranial cruciate ligament of the eTPA stifles. SOX9 may contribute to COLII synthesis in the extracellular matrix of the cranial cruciate ligament in eTPA stifles, and eTPA may promote chondroid metaplasia and extracellular matrix alteration.

Tibial displacement with stifle joint flexion and cranial cruciate ligament transection in the dog. An ex vivo study using a robotic simulator.

OBJECTIVE: The aim of this study was to investigate the biomechanical effects of cranial cruciate ligament (CrCL) transection on stifle stability at three different stifle joint flexion angles using a robotic system. METHODS: This was an ex vivo biomechanical study. Stifles (n = 6) were collected from the cadavers of Beagles weighing 10.5-12.0 kg. Six stifle joints were dissected, potted, and secured to the manipulator arms of a robotic simulator. With the stifle joint angle maintained at either hyperextension (151°), 135° or 90°, stability was assessed by application of a 50 N load in either the cranial-caudal (CrCd test) or proximal-distal (PD test) directions. The stifle was given a cranial-caudal load of 50 N (CrCd test). A proximal-distal compression load of 50 N was then administered by the manipulator (proximal-distal test: PD test). The change in three-dimensional kinematics of the intact and the CrCL-transected stifles was compared between hyperextension, and 135° and 90° flexion for the CrCd and PD load conditions. A value of p <0.05 was considered statistically significant. RESULTS: The cranial tibial displacements in the PD tests of the CrCL-transected stifles at 135° (8.4 ± 1.2 mm) and at 90° (8.1 ± 1.9 mm) were significantly greater than the displacement at 151.5° (5.1 ± 1.6 mm) (p = 0.004 and p = 0.012 respectively). CLINICAL SIGNIFICANCE: The canine stifle exhibited the most instability when the stifle flexion angle was 135°.

Rapid transition of NESTIN-expressing dividing cells from PROP1-positive to PIT1-positive advances prenatal pituitary development.

We recently reported that the quantitative and qualitative transition of stem/progenitor cells occurs by the acquisition of a novel mechanism in the terminal differentiation during postnatal development of the anterior pituitary. We hypothesised that this novel mechanism is an alteration of a cell supply system accompanying proliferation of the progenitor cells. In the present study, we examined the proliferation activities of progenitor cells by indication of the expression of Nestin, a marker of rapidly dividing progenitor cells, aiming to verify our hypothesis and to resolve another outstanding issue regarding whether the Nestin gene is expressed in the pituitary. We found that NESTIN-positive dividing cells certainly exist in the pituitary through all stages of development. Almost all of the PROP1-positive progenitor cells express Nestin in early embryonic pituitary development. Thereafter, Nestin-expressing dividing cells involved in the cell supply system transfer from PROP1-positive progenitor cells to committed progenitor cells, such as PIT1-positive cells, on neonatal pituitary development. Furthermore, our data, together with the findings of previous studies on cell lineage tracing analyses using Nestin-Cre mice derived by the central nervous system (CNS)-specific Nestin promoter, suggest that at least two regulation systems for Nestin-expression exist in the pituitary, with the majority of these not being CNS-specific.

Plasma IL-6 levels during arm exercise in persons with spinal cord injury.

STUDY DESIGN: Non-randomized study. OBJECTIVES: Previous studies indicated that at least 2-h leg exercise at more than 60% maximum oxygen consumption (VO(2)max) increased plasma interleukin (IL)-6 in able-bodied (AB) subjects. The purpose of the present study was to compare IL-6 response to arm exercise in AB subjects and persons with spinal cord injury (SCI). SETTING: Wakayama Medical University in Japan. METHODS: Six subjects with SCI between T6 and T10 and seven AB subjects performed 2-h arm crank ergometer exercise at 60%VO(2)max. Plasma catecholamines, IL-6, tumor necrosis factor (TNF)-α and high-sensitivity C-reactive protein (hsCRP) were measured before exercise, 60-min exercise, immediately and 2 h after the completion of exercise. RESULTS: Arm exercise increased myoglobin and plasma IL-6 levels in SCI and AB (P<0.01), but there were no differences in them between the two groups throughout the study. Plasma levels creatine kinase, lactate dehydrogenase, TNF-α and hsCRP did not change throughout the study in both groups. CONCLUSION: These findings suggest neither significant muscle damage nor inflammatory response during exercise. The increase in plasma IL-6 in SCI was not unexpected, confirming that moderate intensity and relatively long-arm exercise is safe and beneficial for SCI subjects with regard to IL-6 excretion, as in AB subjects.

Serum hyaluronic acid in dogs with congenital portosystemic shunts.

OBJECTIVES: To compare the serum level of hyaluronic acid in dogs with congenital portosystemic shunt with that in healthy dogs and to investigate the perioperative change in serum hyaluronic acid following shunt attenuation. METHODS: Blood samples were obtained from 29 congenital portosystemic shunt dogs before the operation, and 2 and 4 weeks after the operation from 17 and 7 dogs, respectively. The serum hyaluronic acid level of these dogs was measured and compared with that of 10 healthy beagles. RESULTS: The median preoperative hyaluronic acid level in dogs with congenital portosystemic shunt was significantly elevated compared with that in healthy dogs. Furthermore, the median postoperative hyaluronic acid level significantly decreased compared with the median preoperative levels in congenital portosystemic shunt dogs. CLINICAL SIGNIFICANCE: In the case of dogs with congenital portosystemic shunt, the reduction of intrahepatic portal blood flow might lower the clearance rate of hyaluronic acid in hepatic sinusoidal endothelial cells, so hyaluronic acid clearance could be improved by attenuation of a shunt vessel. Hence, serum hyaluronic acid levels might be useful to evaluate liver function and also have the potential to evaluate successful attenuation of a shunt vessel in dogs with congenital portosystemic shunt. Further investigations are required to clarify whether serum hyaluronic acid offers significant benefits over existing markers such as serum bile acid or ammonia concentrations.

Impaired immune response to voluntary arm-crank ergometer exercise in patients with cervical spinal cord injury.

STUDY DESIGN: Non-randomized study. OBJECTIVE: The mechanism underlying exercise-induced argumentation of natural killer cell cytotoxic activity (NKCA) in humans remains unclear. To address this, NKCA responses were studied during and after exercise in persons with cervical spinal cord injury (CSCI) and dysfunctional sympathetic nervous system. SETTING: Kibikogen Rehabilitation Center for Employment Injuries. METHODS: We examined the NKCA responses to 20-min arm-crank ergometer exercise at 60% of maximum oxygen consumption in eight persons with CSCI (between C6 and C7) and six able-bodied subjects. NKCA, adrenaline, and cortisol were measured before, immediately after exercise, 1 h after exercise, and 2 h after exercise. RESULTS: In able-bodied subjects, NKCA increased immediately after exercise (P<0.01) and then decreased to below the pre-exercise level 1 h after exercise, before recovering to the baseline level at 2 h after exercise. Plasma adrenaline concentrations increased significantly immediately after exercise (P<0.01) and returned to the baseline level 1 h after exercise. The plasma cortisol level did not change throughout the study. In contrast, NKCA, plasma concentrations of adrenaline, and cortisol did not change throughout the study in subjects with CSCI. CONCLUSION: In subjects with CSCI, the lack of response in NKCA throughout the experiment is probably mainly due to a dysfunctional sympathetic nervous system.

Low-echoic lesions underneath the skin in subjects with spinal-cord injury.

STUDY DESIGN: Criterion standard and survey cases. OBJECTIVES: To assess the utility of ultrasonography for detecting deep tissue injury or incipient pressure ulcers and to determine the patterns of development of pressure ulcers in subjects with chronic spinal-cord injury (SCI). SETTING: Ambulatory setting at public hospital. METHODS: The subjects were 43 men with SCI between C5 and L1 (age: 42.6+/-11.6 years, mean+/-s.d.). A total of 129 areas (sacral region and bilateral ischial regions in each subject) were examined by inspection, palpation and ultrasonography. RESULTS: Of the 129 areas, 112 were normal by inspection, palpation and ultrasound imaging. Nine areas were abnormal on ultrasonography alone and six were lesion positive by palpation and ultrasonography. Only two areas were abnormal by all three methods. Ultrasonography always detected a heterogeneous pattern and low-echoic areas directly adjacent to the bone. CONCLUSIONS: Our results indicated that low-echoic lesions, signaling deep tissue injuries or early pressure ulcers, originated in areas near the bone and extended toward the epidermis. The results suggest that ultrasonography is a useful tool for the early detection of deep tissue injuries or pressure ulcers.

Effects of early intervention with inhaled sodium cromoglycate in childhood asthma.

International and Japanese guidelines classify childhood asthma as mild, moderate, or severe, and recommend treatment with "as needed" bronchodilators, inhaled sodium cromoglycate, and inhaled corticosteroids, respectively. Alternatively, some investigators proposed inhaled corticosteroids as first-line therapy to prevent airway inflammatory obstruction. This article describes a clinical study assessing the effect of early intervention with inhaled sodium cromoglycate in childhood asthma. This was a retrospective study of 189 asthmatic children treated with inhaled sodium cromoglycate for five years and whose age of onset of asthma was six year of age or younger. An end-of-study questionnaire completed the examination. Children administered oral or inhaled corticosteroids simultaneously with sodium cromoglycate, were excluded. Asthma scores as defined by the Japanese Pediatric Allergic Committee, were reduced continuously during the five years after the start of sodium cromoglycate treatment. The frequency of emergency department visits and hospitalizations also decreased. Significant between-period intervention differences showed improvement of clinical outcomes for children with severe asthma during the five years of sodium cromoglycate inhalation. The early intervention regime of starting sodium cromoglycate inhalation within two years of the onset of asthma shows a large improvement in the long-term prognosis of childhood asthma, especially for children with severe asthma. It is possible that starting inhaled sodium cromoglycate earlier than the present recommendation of corticosteroids could further improve clinical outcomes, but a prospective study should be performed to verify our results.

Regulation of cholangiocyte bicarbonate secretion.

The objective of this review article is to discuss the role of secretin and its receptor in the regulation of the secretory activity of intrahepatic bile duct epithelial cells (i.e., cholangiocytes). After a brief overview of cholangiocyte functions, we provide an historical background for the role of secretin and its receptor in the regulation of ductal secretion. We review the newly developed experimental in vivo and in vitro tools, which lead to understanding of the mechanisms of secretin regulation of cholangiocyte functions. After a description of the intracellular mechanisms by which secretin stimulates ductal secretion, we discuss the heterogeneous responses of different-sized intrahepatic bile ducts to gastrointestinal hormones. Furthermore, we outline the role of a number of cooperative factors (e.g., nerves, alkaline phosphatase, gastrointestinal hormones, neuropeptides, and bile acids) in the regulation of secretin-stimulated ductal secretion. Finally, we discuss other factors that may also play an important role in the regulation of secretin-stimulated ductal secretion.

[Renal metastasis originating from pulmonary carcinoma: a case report].

A 61-year-old woman, who had undergone total right pneumonectomy 22 months before due to lung cancer (adenosquamous cell carcinoma) was admitted for macroscopic hematuria. Abdominal CT showed two renal tumors in the right kidney. Right radical nephrectomy was performed, because no imaging study showed any other metastasis. Pathological examination revealed adenosquamous cell carcinoma, which was the same pathology as the lung cancer had been. She died of the left lung metastasis 24 months after right radical nephrectomy. Her prognosis was thought to have been prolonged by the operation of right radical nephrectomy.

Regression of cholangiocyte proliferation after cessation of ANIT feeding is coupled with increased apoptosis.

Cholangiocyte proliferation and loss through apoptosis occur in cholestatic liver diseases. Our aim was to determine the mechanisms of apoptosis in an animal model of ductal hyperplasia. Rats were fed alpha-naphthylisothiocyanate (ANIT) for 2 wk and subsequently fed normal chow for 1, 2, and 4 wk. Proliferation was assessed in sections by morphometry and in small and large cholangiocytes by proliferating cellular nuclear antigen immunoblots and measurement of cAMP levels. Apoptosis and reactive oxygen species (ROS) levels were also assessed. ANIT feeding increased small and large cholangiocyte proliferation and apoptosis. Cessation of ANIT feeding was associated with decreased proliferation and a further increase in apoptosis in small and large cholangiocytes. Cholangiocytes from ANIT-fed rats or exposed to ANIT in vitro showed increased apoptosis and ROS generation. ANIT-induced duct injury results in enhanced proliferation and apoptosis in small and large cholangiocytes. The mechanism of ANIT-induced apoptosis may be due to ROS generation induced directly by ANIT. Our model has implications for understanding the pathophysiology of cholangiopathies (characterized by the coexistence of cholangiocyte apoptosis and proliferation).