A case of anaplastic ductal carcinoma of the pancreas with production of granulocyte-colony stimulating factor

We report a case of anaplastic ductal carcinoma of the pancreas with production of granulocytecolony stimulating factor in a 46-year-old man. He underwent distal pancreatectomy, total gastrectomy with Roux-en-Y reconstruction and splenectomy. He recovered uneventfully postoperatively and was discharged from hospital on the 22nd postoperative day. Histological examination showed anaplastic ductal carcinoma (giant cell type) of the pancreas. However, three months after the operation, multiple liver metastases were demonstrated by CT scan and the peripheral leukocyte count rose to 81,800/microL. Serum granulocyte-colony stimulating factor concentration was 155pg/mL (normal 5.78-27.5 pg/mL). Therefore, we diagnosed granulocyte-colony stimulating factor-producing pancreatic cancer. Anaplastic ductal carcinoma of the pancreas with production of granulocyte-colony stimulating factor is very rare. Tumors with production of granulocyte-colony stimulating factor are highly malignant, and this patient died of hepatic failure four months after the operation.     

A new method for isolating colonocytes from naturally evacuated feces and its clinical application to colorectal cancer diagnosis

BACKGROUND & AIMS: The early detection of colorectal cancer is desired because this cancer can be cured surgically if diagnosed early. The purpose of the present study was to determine the feasibility of a new methodology for isolating colonocytes from naturally evacuated feces, followed by cytology or molecular biology of the colonocytes to detect colorectal cancer originating from any part of the colorectum. METHODS: Several simulation studies were conducted to establish the optimal methods for retrieving colonocytes from any portion of feces. Colonocytes exfoliated into feces, which had been retrieved from 116 patients with colorectal cancer and 83 healthy volunteers, were analyzed. Part of the exfoliated colonocytes was examined cytologically, whereas the remainder was subjected to DNA analysis. The extracted DNA was examined for mutations of the APC, K-ras, and p53 genes using direct sequence analysis and was also subjected to microsatellite instability (MSI) analysis. RESULTS: In the DNA analysis, the overall sensitivity and specificity were 71% (82 of 116) of patients with colorectal cancer and 88% (73 of 83) of healthy volunteers. The sensitivity for Dukes A and B was 72% (44 of 61). Furthermore, the sensitivity for cancers on the right side of the colon was 57% (20 of 35). The detection rate for genetic alterations using our methodology was 86% (80 of 93) when the analysis was limited to cases in which genetic alterations were present in the cancer tissue. CONCLUSIONS: We have developed a new methodology for isolating colonocytes from feces. The present study describes a promising procedure for future clinical evaluations and the early detection of colorectal cancers, including right-side colon cancer.     

Analysis of systemic and airway inflammation in obstructive sleep apnea

Purpose

The presence of both systemic and airway inflammation has been suggested in obstructive sleep apnea (OSA) by increased levels of inflammatory biomarkers in the circulation and respiratory specimens. We aimed to investigate the relationship between systemic and airway inflammation in OSA.

Methods

This study was conducted by simultaneously measuring various biomarkers both in serum and induced sputum of 43 patients. We compared the relationships of these biomarker levels with polysomnographic data and obesity measurements and also investigated their interrelationships between systemic and local compartments. We also assessed the relation of inflammatory markers with proximal airway resistance measured by impulse oscillometry.

Results

In multiple regression analyses, each measured serum biomarker [leptin, interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)] significantly correlated with waist circumference or fat area determined by computed tomography. In contrast, regarding airway inflammation, sputum IL-6, IL-8, TNF-α, and VEGF significantly correlated with OSA severity as indicated by the respiratory disturbance index or oxygen desaturation indices. Sputum IL-6, IL-8, TNF-α, and VEGF were significantly related to sputum neutrophil number, and sputum IL-8 and TNF-α were related to proximal airway resistance independently of body mass index. There were no significant interrelationships between the same biomarkers in serum and induced sputum.

Conclusions

Systemic and airway inflammation in OSA might be differently regulated by OSA itself and comorbid obesity, depending on the type of cytokine. Although we did not find apparent interrelationships between systemic and local compartments, further studies are needed to clarify this concept.     

Measurement of dyspnea in patients with obstructive sleep apnea

Purpose

Patients with obstructive sleep apnea (OSA) frequently complain of exertional dyspnea. We aimed to assess its related factors and the significance of its measurement in OSA.

Methods

We evaluated 301 subjects with suspected OSA for dyspnea during activities of daily living using the Medical Research Council (MRC) scale. We analyzed the relationships between MRC grades and various subjective and objective indices. Further, the relationship of disease severity based on the apnea/hypopnea index (AHI) with these indices was examined. Results were compared between those obtained using MRC grades and the AHI.

Results

Of 301 subjects, 265 were diagnosed with OSA. Their MRC scores were worse than in non-OSA patients. Among OSA patients, 125 had MRC grade 1 (mild), 121 had MRC grade 2 (moderate), and 19 had MRC grade 3 or more (severe) dyspnea. Various measurements differed significantly between groups categorized according to the MRC scale although determinants between mild and moderate groups and between moderate and severe groups differed. AHI categorizations were not significantly related to patient-reported measurements such as the Medical Outcomes Study 36-item short form, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale scores, unlike categorization based on the MRC scale.

Conclusions

Dyspnea is an important outcome in OSA although dyspnea in OSA patients is unrelated to the sleep disorder per se. Measurement of dyspnea in patients with OSA might provide further insights into the health of these patients and clinical manifestations of this disease.     

Activin signaling through type IB activin receptor stimulates aromatase activity in the ovarian granulosa cell-like human granulosa (KGN) cells

In addition to a stimulatory effect on FSH production by the pituitary gland, activin is thought to have a paracrine or autocrine role in follicular development in the ovary, where it is produced. Recently, we established a human ovarian granulosa tumor cell line, KGN, which possesses in vivo characteristics of granulosa cells, namely the expression of functional FSH receptors and cytochrome P-450 aromatase. Here, we have demonstrated the activin signaling pathway and its role in KGN cells. A series of transient transfection experiments revealed that activin type IB receptor (ActRIB) is an essential component of the activin signaling pathway in KGN cells. Smad2 was found to act downstream of ActRIB as an intracellular signal transmitter. Smad7, but not Smad6, was an inhibitory Smad in the pathway. Finally, we show that FSH receptor expression and cytochrome P-450 (P-450) aromatase activity was up-regulated by activin stimulation through ActRIB in KGN cells. These results show that we have clarified the signaling mechanisms and the roles of activin in the human granulosa cell line, KGN. Activin signaling mediated by ActRIB-Smad2 system in the ovary may thus be essential for the regulation of follicular differentiation.     

Variability in absorption lag time of pyridoxal phosphate under fasting and pre- and post-meal conditions

Inter-individual variations in the absorption lag time of pyridoxal phosphate were determined after administration of an enteric-coated tablet (EC) or a plain capsule (PC) to 113 healthy volunteers under fasting, pre-meal, and post-meal conditions. The absorption lag time of pyridoxal phosphate was assessed from the urinary excretion of 4-pyridoxic acid after administration of EC and PC. Significantly larger lag times after administration of both formulations were observed under post-meal conditions than under pre-meal conditions (0.477 ± 0.315 h versus 0.081 ± 0.086 h for PC and 1.995 ± 1.345 h versus 1.064 ± 1.327 h for EC), indicating that the mean gastric emptying rates of both a solution and a tablet were delayed after food intake. The lag time for PC showed little inter-individual variation with (0–1.2 h) or without food (0–0. 25 h), whereas that for EC showed markedly large inter-individual variation, from 0.25 to 2.63 h (median, 1.5 h) in the fasting condition, from 0.25 to > 5.5 h (median 0.25 h) under pre-meal conditions, and from 0.25 to > 5.5 h (median 1.25 h) under post-meal conditions. The effect of food on the gastric emptying rate of a solution appears to be almost uniform, whereas that for a tablet is so unpredictable that a reliable absorption rate for an enteric-coated tablet cannot be expected, particularly under pre- and post-meal conditions.     

Surgical management of small bowel metastases from primary carcinoma of the lung

Purpose  

To investigate the treatment and outcomes in a series of seven cases of small bowel metastases from lung cancer.     

Clinical evaluation of bird related hypersensitivity pneumonitis]

We retrospectively evaluated 8 cases of bird related hypersensitivity pneumonitis in Tenri hospital, all of whom underwent surgical lung biopsy. They had a history of contacting with birds and had serological studies using lymphocyte stimulation test to pigeon serum or antibody in serum and bronchoalveolar lavage fluid to pigeon dropping extracts yielded positive results. Computed tomography revealed a radiographic pattern unlike typical UIP. The result of pathological diagnosis of surgical lung biopsy was 'others' or NSIP pattern. Only one case had pathological findings of granuloma. Four cases had an improved or stable course only offer segregation from bird antigens. The other four cases needed corticosteroids and immunosuppressants, and two of the four cases had a progressive course and died of respiratory failure.