Chemotherapy for high-risk early-stage endometrial cancer

PURPOSE OF REVIEW: To discuss the usefulness of chemotherapy in high-risk early-stage endometrial cancer and the best chemotherapy regimen. RECENT FINDINGS: External radiation therapy has been successfully used to prevent local recurrence; however, it does not improve the overall survival and it increases the incidence of late toxicity. A recent randomized study revealed that adjuvant platinum-based combination chemotherapy might be a suitable alternative to radiotherapy for high-risk early-stage endometrial cancer. The optimal regimen is still in question because combinations of doxorubicin-cisplatin and paclitaxel-doxorubicin-cisplatin cause significant toxicity. The combination of paclitaxel-carboplatin may be better than doxorubicin-cisplatin with regard to toxicities. SUMMARY: Radiation treatment following surgery has been the standard adjuvant therapy for endometrial cancer for a long time. Radiotherapy decreases the local recurrence rates; however, a significant impact on the overall survival has not been demonstrated. The usefulness of adjuvant chemotherapy has been demonstrated by only a little evidence. Nonetheless, we are encouraged by a recent randomized study. In light of the excellent outcomes associated with early-stage endometrial cancer, it is important to conduct another large randomized trial based on standardization of high-risk criteria to evaluate the efficacy of adjuvant chemotherapy.     

Effects of deletion-type human hepatocyte growth factor on murine septic model.

BACKGROUND: Sepsis is known to be the main cause of multiple organ failure. The liver especially is vulnerable to the stress of infection. In this study, the effects of deletion-type human hepatocyte growth factor (dHGF) on a murine septic model were studied. MATERIALS AND METHODS: Sepsis was induced in male adult Sprague-Dawley rats by cecal ligation and puncture method (CLP). Controls were given a sham operation. Intravenous injection of 1000 micrograms/kg dHGF or the same volume of vehicle was given every 12 h for 3 days before and/or after the CLP from a central vein catheter inserted 1 week prior to the operation. The daily percentage of survival after CLP was followed up for 1 week, and blood samples and liver specimens were collected from the surviving animals 72 h after CLP or sham operation. RESULTS: The survival rate, the degree of liver damage and liver protein synthesis, and coagulation function were all favorable in the dHGF-treated animals compared to the untreated animals. Immunohistochemical staining showed that dHGF prevented the disappearance of thrombomodulin (TM) in liver sinusoid endothelium. CONCLUSIONS: dHGF appears to prevent liver injury caused by disturbance of microcirculation through preservation of TM expression and the antithrombotic function in the endothelium of sinusoids. dHGF also facilitates repair of damaged hepatic tissue by stimulating regeneration of the cells and by preserving hepatic functions such as protein synthesis. dHGF exerts protective effects on even quiescent hepatocytes, but is most effective on injured but competent hepatocytes.     

Mid-mediastinal parathyroid lesions: Preoperative localization and surgical approach in two cases

Although hyperfunctioning mediastinal parathyroid lesions that require median sternotomy or thoracotomy for removal are occasionally present, the majority are located in the anterior mediastinum closely associated with the thymus. Only eight cases of ectopic hyperfunctioning parathyroid tumors in the middle mediastinum have been reported. We experienced two cases of either persistent or recurrent hyperparathyroidism in which abnormal parathyroid tissue was located in the aorticopulmonary window. One of the patients had a parathyroid adenoma and the other had metastatic lesions of parathyroid carcinoma. In both cases, thallium scanning proved useful in identifying the lesions while computed tomography scan was effective for mediastinal three-dimensional localization. In one case, single photon emission computed tomography imaging with thallium proved beneficial for both identification and localization of the middle mediastinal lesion. The surgical approach used in both cases was different. In one case, left thoracotomy was performed, after which the ligamentum arteriosum was divided, and an adenoma anterior to the left main bronchus and posterior to the left pulmonary artery removed. In the other case, two metastatic tumors of parathyroid carcinoma anterior to the right main bronchus and posterior to the right pulmonary artery were resected through a median sternotomy and opening of the pericardium.     

Evaluation of extensive lymph node dissection for carcinoma of the stomach

We compared the results of curative resection for carcinoma of the stomach in 254 patients who underwent simple resection (SR) and 454 patients who underwent extensive regional lymph node dissection (ELD). The 5-year survival rates of the 2 procedures were significantly different in carcinoma involving the serosa of the stomach; it was 45% in the ELD group and 18% in the SR group (p<0.001). In patients with regional lymph node metastasis we obtained a 5-year survival rates of 39% and 18% by ELD and SR, respectively (p<0.001). The incidence of metastasis to the secondary lymph nodes, removable only by ELD, was higher in cases with carcinomatous invasion of the deeper layers of the gastric wall, and this may have been the reason why ELD proved to be more effective than SR. ELD is discussed in relation to the site of the primary carcinoma and the extent of lymph node metastasis.     

A case of synchronous double primary lung cancer with neuroendocrine features.

We report a case of unique double primary lung cancers with neuroendocrine features in a 63-year-old male smoker. The mass in the left lower lobe (LLL) was a small cell/large cell carcinoma with spindle cell sarcomatous areas and organoid structure. The mass in the left upper lobe (LUL) was a tubular adenocarcinoma with neuroendocrine features including organoid nests showing occasional rosette formation, nuclear palisading in the periphery of the nests and positive immunoreaction for CD56, chromogranin A and synaptophysin. The difference in histological structures between the two masses led us to diagnose double primary lung cancer. The combination of small cell lung carcinoma and spindle cell carcinoma is very uncommon. The relationship between LLL and LUL tumors remains unclear. Multiple lung cancers with neuroendocrine features have only rarely been reported in the literature. The patient in our case died of widespread cancer 2 years and 4 months after the surgery without adjuvant chemotherapy, a longer postoperative survival time than in cases of ordinary extensive small cell lung cancer. Multiple lung cancers with neuroendocrine features are extremely rare and similar cases have not been reported in the literature. Neuroendocrine differentiation has attracted widespread attention and, therefore, examining neuroendocrine features in lung cancers is important.     

Tetrodotoxin secreting glands in the skin of puffer fishes

Unique exocrine glands or gland-like structures were found in the skin of several species of puffer fishes of the genus Takifugu. The glands of T. pardalis and T. vermiculare porphyreum consisted only of secretory cells with a large vacuole. These cells were completely enclosed by epithelial cells with developed microfilaments, except at their opening to the lumen. The contents of the large vacuole in the peculiar secretory cell were forced out when the puffer was stimulated. Exocrine glands or gland-like structures with peculiar secretory cells were also found in the skin of T. poecilonotus, T. niphobles and T. vermiculare radiatum. A high concentration of TTX was detected in the gland contents collected directly from live specimens of T. pardalis. We therefore conclude that these glands are TTX secreting glands.     

Infection of feline lymphoid cells with feline leukemia virus in culture

An in-vitro system for infection of cat T lymphocytes with feline leukemia virus (FeLV) was developed. For establishment of this system, FeLV was inoculated in vitro into concanavalin-A stimulated primary lymphoid cells and long-term cultured T cells grown with interleukin-2 (IL-2) from various feline lympho-hematopoietic organs. During serial cultivation with IL-2, FeLV group-specific antigen (GSA) was detected 5-6 weeks after infection in the primary cultures, and 1 week after infection in the long-term cultures of T cells. The percentage of FeLV-GSA-positive cells gradually increased with passages and reached more than 80% in several cultures of lymphoid cells, that became persistently infected and produced FeLV. These FeLV-infected lymphoid cells expressed T-cell markers, but showed no obvious differences in growth or cytological characteristics from FeLV-free feline lymphoid cells during the observation period of 60 weeks.     

Pulmonary varix clearly demonstrated by 3D-CT before pulmonary angiography

Pulmonary varix is a rare and usually asymptomatic localized dilation of a pulmonary vein. This disease should be distinguished from other pulmonary and mediastinal diseases, particularly pulmonary arteriovenous malformations. Herein, we encountered a case of pulmonary varix clearly demonstrated by 3-dimensional reconstructed computed tomography (3D-CT) which proved useful in its diagnosis. The 3D-CT enabled easy understanding of the vascular connections and confirmation of the absence of an inflow pulmonary artery. We also performed angiography which showed findings consistent with those obtained by the 3D-CT, thus confirming the diagnosis of pulmonary varix. After the diagnosis, the patient was followed up for several years without any treatment and she remained asymptomatic. On follow-up CT, the lesion remained unchanged.     

A prospective analysis of concentration of 25-OHD between northern and southern district in Japan in year-round study

Although osteoporotic patients have already been recognized as having a low-volume vitamin D status, the concentration of active vitamin D precursor has not been studied in detail. This trial aimed to clarify the concentration of 25-hydroxyvitamin D (25-OHD), which is a natural type of vitamin D and compare between 2 separate areas in Japan. To compare and clarify the concentration of 25-OHD between 2 separate areas, Japanese patients who were diagnosed as having osteoporosis based on bone mineral density were studied. We analyzed 2 different hospitals’ patients whose residence is separated into a northern district (Akita city: north latitude 39” 43’) and a southern district (Shizuoka city: north latitude 34” 58’). Both of them have completely different daylight hours. Three-hundred sixty eight patients (174 in Akita, 194 in Shizuoka) were enrolled in this trial to compare the differences of concentration of 25-OHD by Welch’s t t-test. There were significant differences in the concentration of 25-OHD and age between them. Akita patients were significantly higher than that of Shizuoka patients despite Shizuoka having much daylight hours of Akita. In conclusion, there might be no relationship between the concentration of 25 OHD and exposure to sunlight.     

Pentraxin 3 is an adipose tissue‐related serum marker for pancreatic cancer cachexia predicting subsequent muscle mass and visceral fat loss

Cancer cachexia, a paraneoplastic syndrome characterized by ongoing skeletal muscle mass loss, is accompanied by adipose tissue loss and strongly affects chemotherapy endurance. Our aim was to detect a serum marker reflecting pancreatic cancer cachexia and predicting subsequent loss of muscle mass and adipose tissue, focusing on adipose tissue‐secreted proteins. Murine‐derived pancreatic cancer cells were orthotopically injected into the mouse pancreatic tail. After 3 weeks, RNA sequencing of perigonadal fat and orthotopic tumors was carried out. We analyzed stocked sera and clinical data of metastatic pancreatic cancer patients who received chemotherapy. Perigonadal fat weight/body weight decreased in mice with orthotopic tumors compared to those without tumors. By RNA sequencing and real‐time PCR validation, pentraxin 3 (PTX3) was identified as a secreted protein‐encoded gene whose expression was significantly higher in the perigonadal fat of mice with orthotopic tumors than in that of mice without orthotopic tumors and was least expressed in orthotopic tumors. Serum PTX3 levels correlated with PTX3 mRNA levels in perigonadal fat and were higher in mice with orthotopic tumors than in those without tumors. In 84 patients diagnosed with metastatic pancreatic cancer, patients with high serum PTX3 levels showed a greater visceral fat loss/month and skeletal muscle mass index (SMI) decrease/month than those with low serum PTX3 levels. High serum PTX3 was an independent risk factor for visceral fat loss, decreased SMI, and poor prognosis. High serum PTX3 in pancreatic cancer patients predicts visceral fat and muscle mass loss and major clinical outcomes of cancer cachexia.