One-stage surgical case management of a two-year-old Arabian horse affected by male-pseudo hermaphroditism.

A two-year-old Arabian horse presented for abnormal external genitalia and dangerous stallion-like behavior was diagnosed with disorder of sexual development (DSD), also known as intersex/hermaphroditism. Standing 1-stage surgical procedure performed under sedation, and local anesthesia to concurrently eliminate stallion-like behavior, risk of neoplastic transformation of intraabdominal gonads, and to replace ambiguous external genital with a functional, and cosmetically more acceptable anatomy. Step-1) Laparoscopic abdominal exploration and gonadectomy; Step-2) Rudimentary penis resection and perineal urethrostomy. The horse tolerated surgery well (combined surgery time 185 min) with no complications. At macroscopic examination of the gonads, they resembled hypoplastic testis-like tissues. Microscopic examination confirmed presence of seminiferous tubules, Leydig and Sertoli/granulosa cells. Cytogenetic evaluation revealed a 64,XX karyotype, SRY-negative. The stallion-like behavior subsided within days post-operatively. Long-term follow-up revealed the genitoplasty site healed without urine scalding or urethral stricture. The owner satisfaction was excellent and the horse could be used post-surgery as an athlete.

Simultaneous assessment of coronary flow reserve and left ventricular function during vasodilator stress evaluated by 13N-ammonia hybrid PET/MRI.

AIM: To explore changes in left ventricular (LV) function and the relationship of these changes with myocardial blood flow (MBF) evaluated by 13N-ammonia hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) during vasodilator stress in patients with suspected coronary artery disease (CAD). MATERIALS AND METHODS: Fifty-two consecutive patients with suspected CAD, who underwent 13N-ammonia PET/MRI, were enrolled. Vasodilator stress was induced by intravenous injection of adenosine. MBF and coronary flow reserve (CFR) were calculated from dynamic acquisition of 13N-ammonia PET. LV function was evaluated by MRI both at rest and during vasodilator stress. An abnormal perfusion on myocardial images was defined as a summed difference score of ≥4. RESULTS: MRI showed that the LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction (LVEF) remained unchanged during vasodilator stress in all patients (n=52) as well as in the patients with CFR of <2 (n=27), stress MBF of <1.3 ml/g/min (n=28), abnormal myocardial perfusion (n=30), and more than one diseased vessel (n=46). In only four patients, the LVEF measured by MRI decreased by >5% during vasodilator stress. In these four patients, CFR was lower (1.57 ± 0.12 versus 2.18 ± 0.86, p<0.01) and the number of diseased vessels was higher (2.75 ± 0.50 versus 1.48 ± 0.92, p<0.01) than in patients without post-stress LV dysfunction. CONCLUSION: The LV volume and systolic function evaluated by cardiac MRI remained unchanged during vasodilator stress; however, LV dysfunction during vasodilator stress may occur in patients with severe CAD.

Regulatory T cells and M2-polarized tumour-associated macrophages are associated with the oncogenesis and progression of oral squamous cell carcinoma.

Regulatory T cells (Tregs) and tumour-associated macrophages (TAMs) contribute to the tumour microenvironment by inhibiting anti-tumour immune responses. This study was performed to investigate the roles of Tregs and TAMs in oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPL). The expression of Treg markers CD25 and FoxP3 and TAM markers CD163 and CD204 was investigated in 82 OSCC and 45 OEPL specimens, and their associations with clinicopathological parameters were analyzed. Correlations were found among CD25, FoxP3, CD163, and CD204 levels (P < 0.001), and these targets were up-regulated in OSCC compared to OEPL (P < 0.001). In OSCC, infiltration of Tregs and/or M2 TAMs was associated with sex and clinicopathological features, such as tumour size, nodal metastasis, tissue differentiation, stromal reaction, invasive behaviour, and invasive depth. In OEPL, CD25, FoxP3, CD163, and CD204 immunoreactivities were significantly associated with sex, postoperative recurrence, and cancerization to OSCC. This study is novel in showing that the infiltration of Tregs and M2 TAMs is significantly associated with the progression of premalignant lesions to OSCC. This suggests that these cells represent prognostic biomarkers for premalignant lesion progression and that immunotherapeutic approaches to control Treg/M2 TAM numbers could protect against progression to malignancy.

BYSTANDER WI-38 CELLS MODULATE DNA DOUBLE-STRAND BREAK REPAIR IN MICROBEAM-TARGETED A549 CELLS THROUGH GAP JUNCTION INTERCELLULAR COMMUNICATION.

Bi-directional signaling involved in radiation-induced bystander effect (RIBE) between irradiated carcinoma cells and their surrounding non-irradiated normal cells is relevant to radiation cancer therapy. Using the SPICE-NIRS microbeam, we delivered 500 protons to A549-GFP lung carcinoma cells, stably expressing H2B-GFP, which were co-cultured with normal WI-38 cells. The level of γ-H2AX, a marker for DNA double-strand breaks (DSB), was subsequently measured up to 24-h post-irradiation in both targeted and bystander cells. As a result, inhibition of gap junction intercellular communication (GJIC) attenuated DSB repair in targeted A549-GFP cells, and suppressed RIBE in bystander WI-38 cells but not in distant A549-GFP cells. This suggests that GJIC plays a two-way role through propagating DNA damage effect between carcinoma to normal cells and reversing the bystander signaling, also called 'rescue effect' from bystander cells to irradiated cells, to enhance the DSB repair in targeted cells.

BK virus-associated urothelial carcinoma of a ureter graft in a renal transplant recipient: a case report.

BACKGROUND: Urothelial carcinomas of ureter grafts in renal transplant patients are rare. Here we report our experience with a case of BK virus-associated urothelial carcinoma in a ureter graft. CASE REPORT: A 47-year-old man developed chronic renal failure secondary to diabetes mellitus and started maintenance hemodialysis in September 2007. Two months later, the patient received a renal transplant from his 70-year-old mother. The patient developed BK virus-associated nephropathy 1 year after transplantation and presented with a decline in renal function and hydronephrosis in the transplanted kidney 4 years 6 months after transplantation. Cystoscopy and retrograde pyelography revealed an irregular filling defect in the ureter graft. Cytologic diagnosis of his urine revealed a high-grade urothelial carcinoma. Computerized tomography showed a cT2 ureteral tumor and no involvement of other organs. The patient subsequently underwent a transplant nephroureterectomy with bladder cuff resection. Histopathologic findings revealed a high-grade urothelial carcinoma, pT2, in the ureter graft with SV40-positive staining. The patient was closely observed without adjuvant chemotherapy therapy and remained disease free 1 year after surgery. Renal transplant recipients with BK virus infection are at high risk of developing urologic malignancies. Close attention is necessary to diagnose post-transplantation urologica malignancies as early as possible.

Geometric and compositional appearance of atheroma in an angiographically normal carotid artery in patients with atherosclerosis.

BACKGROUND AND PURPOSE: Arterial remodeling may enable atherosclerotic disease without luminal stenosis. We sought to assess the prevalence and characteristics of atherosclerosis in angiographically normal carotid arteries. MATERIALS AND METHODS: Forty-six arteries with 0% stenosis by MRA were evaluated with multicontrast carotid MR imaging at 3T. For each artery, the percentage wall volume (wall volume/[lumen volume + wall volume] x 100%) and the presence versus absence of an LRNC, calcification, IPH, and fibrous cap rupture were recorded. In addition, the relative size of each plaque component (eg, percentage LRNC = LRNC volume/wall volume x 100%), when present, was calculated. RESULTS: The mean of percentage wall volume in arteries with 0% stenosis was 43.0 +/- 6.9% with a range from 31.6% to 60.1%. An LRNC was present in 67.4% (31/46) of arteries, calcification was present in 65.2% (30/46), IPH was present in 8.7% (4/46), and fibrous cap rupture was present in 4.3% (2/46). In arteries with an LRNC (n = 31), the average percentage LRNC volume was 8.8 +/- 7.3% with a range from 1.0% to 31.5%. For calcification (n = 30), the mean percentage calcification volume was 3.8 +/- 4.2% with a range of 0.1%-17.4%. The mean percentage IPH volume (n = 4) was 2.7 +/- 1.7% with a range of 0.5%-4.1%. CONCLUSIONS: These findings indicate that stenosis by MRA may underestimate the presence of carotid atherosclerosis, and they demonstrate the need for improved methods for accurately identifying carotid atherosclerotic plaque severity.

Predictors of surface disruption with MR imaging in asymptomatic carotid artery stenosis.

BACKGROUND AND PURPOSE: Surface disruption, either ulceration or fibrous cap rupture, has been identified as a key feature of the unstable atherosclerotic plaque. In this prospective observational study, we sought to determine the characteristics of the carotid lesion that predict the development of new surface disruption. MATERIALS AND METHODS: One hundred eight asymptomatic individuals with 50%-79% carotid stenosis underwent carotid MR imaging at baseline and at 3 years. Multicontrast imaging criteria were used to determine the presence or absence of calcification, LRNC, intraplaque hemorrhage, and surface disruption. Volume measurements of plaque morphology and the LRNC and calcification, when present, were collected. RESULTS: At baseline, 21.3% (23/108) of participants were identified with a surface disruption. After 3 years, 9 (10.6%) of the remaining 85 individuals without disruption at baseline developed a new surface disruption during follow-up. Among all baseline variables associated with new surface disruption during regression analysis, the proportion of wall volume occupied by the LRNC (percentage LRNC volume; OR per 5% increase, 2.6; 95% CI, 1.5-4.6) was the strongest classifier (AUC = 0.95) during ROC analysis. New surface disruption was associated with a significant increase in percentage LRNC volume (1.7 +/- 2.0% per year, P = .035). CONCLUSIONS: This prospective investigation of asymptomatic individuals with 50%-79% stenosis provides compelling evidence that LRNC size may govern the risk of future surface disruption. Identification of carotid plaques in danger of developing new surface disruption may prove clinically valuable for preventing the transition from stable to unstable atherosclerotic disease.

In-air micro-particle induced X-ray emission analysis of asbestos and metals in lung tissue.

Inhalation of asbestos increases the risk of lung cancer and pulmonary fibrosis. It is difficult to directly assess the distribution and content of inhaled particles in lung tissue sections. The purpose of this study is to employ an in-air micro particle induced X-ray emission (in-air micro-PIXE) system for assessment of the spatial distribution and content of asbestos and other metals in lung tissue. A proton ion-microbeam from this system was applied to irradiate lung tissue of patients with or without asbestosis, tumor tissue from both groups, and asbestos fibers (in vitro). The content of each element composing asbestos and those of other metals were calculated and their distribution was assessed from the characteristic X-ray pattern for each element obtained after irradiation. This in-air micro-PIXE system could identify the location of asbestos bodies composed of Si, Mg, and Fe in lung tissue sections. Macrophage and lymphocytes accumulated in that area. This new system also revealed deposits of titanium, nickel, and cobalt in the lung tissues, in addition to asbestos bodies. The Si and Fe content were higher in lungs with asbestosis than in lungs without asbestosis or in tumor tissue. Analysis of asbestos fibers composed of chrysotile, crocidolite, and amosite showed that the ratios of Si, Fe, and Mg corresponded with those for the chemical structures. In-air micro-PIXE analysis is useful for assessing the distribution and quantities of asbestos bodies and also other metals in lung tissue comparing to immune-related cell localizations, and is also useful for analysis of standard asbestos fibers.

Congenital cytomegalovirus infection following primary maternal infection in the third trimester.

OBJECTIVE: To determine the effect of primary cytomegalovirus (CMV) infection in the third trimester on fetal outcome. DESIGN: Observational study. SETTING: Four perinatal departments in tertiary hospitals in Israel. POPULATION: Twenty-eight women with primary CMV infection acquired after 25 weeks of gestation. METHODS: Prenatal evaluation included amniocentesis and ultrasonographic examinations. Maternal infection was determined from seroconversion and presence of low avidity anti-CMV immunoglobulin G after 25 weeks of gestation. Fetal CMV infection was diagnosed from CMV isolated or CMV DNA amplified from the amniotic fluid. Neonatal infection was established from CMV presence in their urine or anti-CMV IgM was in their peripheral blood immediately after birth. All liveborn neonates underwent cerebral ultrasonography, hearing assessment, and psychomotor development evaluation. Infected neonates were followed up for a median of 36 months (range 6-36 months). MAIN OUTCOME MEASURES: Intrauterine CMV infection and neonatal CMV disease throughout follow up. RESULTS: Vertical transmission of CMV was documented in 21 (75%) of the 28 pregnancies. None of the 20 live infected newborn had symptomatic congenital infection. One pregnancy was terminated at 34 weeks following evidence of prenatal infection. Most of the patients (75%) had CMV serology test due to clinical signs of CMV disease. CONCLUSIONS: Although CMV infection during the third trimester of pregnancy is highly transmissible, sequelae were not found among infected offspring.

Analysis of tissue cadmium distribution in chronic cadmium-exposed mice using in-air micro-PIXE.

This study undertook the analysis of tissue cadmium (Cd) distribution using in-air micro-particle-induced X-ray emission (PIXE) and the examination of the involvement of metal ions in parenteral Cd toxicity. A mouse was injected intraperitoneally with 3 mg/kg body weight of CdCl2 thrice weekly. After 27 wk, the liver and kidney were excised and fixed in 10% formalin solution for 4 h and then embedded in paraffin. Thin paraffin sections were used to analyze trace elements with in-air micro-PIXE and to examine metallothionein protein and histological changes. Cd distribution was determined by micro-PIXE in the liver and renal cortex of the Cd-exposed mouse, and the net Cd count was higher in the liver than in the renal cortex. The net iron (Fe) count was higher in the liver of the Cd-exposed mouse compared to the control, and an opposite tendency was observed in the renal cortex. Wide cellular Cd distribution was demonstrated in the liver and renal cortex of the chronic Cd-exposed mouse compared to the control. Metallothionein staining was increased by chronic exposure to Cd both in the liver and kidney, and nephrotoxicity was more apparent than hepatotoxicity. The modification of tissue Fe and calcium distribution by an intraperitoneal injection of Cd might be involved in Cd-induced toxicity.

[Mucoepidermoid carcinoma in a young man treated by bronchoplasty].

A 17-year-old man in whom mucoepidermoid carcinoma of the left upper lobe bronchus was successfully treated by bronchoplasty. The patient has been suffered from relapsing respiratory infections over the past 2 years. Bronchoscopic examination revealed a tumor at the orifice of the left upper lobe bronchus. Thus, left upper sleeve lobectomy was carried out. The tumor was 18 x 15 x 14 mm in size and obstructed left upper bronchus with mucoid impaction peripherally. Hystological examination confirmed a diagnosis of low grade malignant mucoepidermoid carcinoma without lymph node metastasis. The patient has been well and free from recurrence for 4 years postoperatively.

Demonstration of inter- and intracellular distribution of boron and gadolinium using micro-proton-induced X-ray emission (Micro-PIXE).

Micro-proton-induced X-ray emission (Micro-PIXE) was applied to determine inter- and intracellular distribution of boron (10B) and gadolinium (157Gd), the capture atoms used to kill tumor cells in neutron capture therapy (NCT). Cultured 9L gliosarcoma cells on Mylar film were exposed to sodium borocaptate (BSH) and gadobenate dimeglumine (Gd-BOPTA). To analyze the inter- and intracellular distribution of 10B and 157Gd in 9L gliosarcoma cells, the cells were irradiated using a proton beam of 1.7 or 3 MeV energy collimated to 1 microm diameter and emission X-ray was detected. The distribution of 10B and 157Gd in 9L gliosarcoma cells was then examined. In this study, we could directly analyze the inter- and intracellular distribution of 10B and 157Gd elements in 9L gliosarcoma cells directly using Micro-PIXE. This is the first report on the distribution of 10B employing a method to detect gamma-rays resulting from the nuclear reaction of 10B using particle-induced gamma-ray emission (PIGE). These results show that the distribution of 157Gd elements was correctly measured using micro-PIXE. 157Gd should have the same tendency as 10B in cultured 9L gliosarcoma cells and agree with the distribution in 9L gliosarcoma cells. Further investigation is necessary for a higher spatial resolution and optimization of the measurement time or improvement of the sampling method. In the future, it will be possible to employ this method to analyze the intracellular microdistribution of the capture element and in the development of new drugs for NCT.

[Castleman disease of the inter-lobar lymph node origin].

We report a case of Castleman disease which originated from the inter-lobar lymph node, with a review of literatures. A 19-year-old woman complaining of cough was pointed out to have an abnormal shadow in the left lung field on chest X-ray. Chest computed tomography (CT) and magnetic resonance imaging (MRI) with enhancement revealed a homogeneous mass lesion at the left inter-lobar portion of the lung. Bronchoscopic findings demonstrated mucosal telangiectasis of the left lower bronchus. We performed the usual axillary thoracotomy and succeeded in extirpation of the tumor without large amount of bleeding. The tumor was elastic and hard, and 70 x 55 x 45 mm in size. Her postoperative course was uneventful and she was discharged on the 12th postoperative day.

Non-functional C-cell adenoma in aged horses.

Thyroid tumours occur in older horses, and most such tumours have been considered to be of follicular epithelial origin. However, their immunohistochemical characterization has not been investigated. The purpose of this study was to confirm a suspicion that most of these tumours are in fact parafollicular cell (C cell)-derived adenomas, and to evaluate their pathogenesis and functional state. Thyroid glands from 38 horses aged 10-29 years were evaluated, all tissue samples being examined histologically, immunohistochemically and ultrastructurally. Nodular tumour masses were found in the thyroids of 12 of 38 horses older than 10 years (31.6%), and in nine of 12 horses older than 20 years (75.0%), regardless of sex or breed. Nodular lesions were composed of solid proliferations of polygonal cells with eosinophilic granular cytoplasm. Immunohistochemically, tumour cells were positive for calcitonin and neuron specific enolase, but negative for thyroglobulin. Ultrastructurally, few if any secretion granules were found in tumour cells. On the basis of these results it was concluded that the nodular lesions were C-cell adenomas, not follicular adenomas. It was suspected that the C-cell adenomas were non-functional and unlikely to lead to calcitonin hypersecretion-related diseases.

Extranodal lymphoblastic lymphoma of suspected B-cell lineage in the gingiva of a racehorse, accompanied by mandibular osteolysis.

A mass developed in the mandibular gingiva of a thoroughbred racehorse. When the horse could no longer eat unassisted, it was killed and immediately autopsied. Macroscopically, the mandible exhibited extensive osteolysis, with only a small amount of bone remaining around the tooth roots. The cut surface of the mass around the mandible consisted of neoplastic medullary tissue, in which osteogenesis was observed. The medullary tissue was composed of pleomorphic medium-sized to large cells, interlaced by collagen bundles. These cells had large, pale, round or ovoid, sometimes cleaved nuclei, with one or two prominent nucleoli. Mitoses were numerous. Electron microscopy showed that the cells in the medullary tissues were similar in shape to undifferentiated lymphocytes. Immunohistochemically, these cells were positive for B-cell associated antigen in the pre-B-cell stage. Our findings suggest that the horse had extranodal lymphoblastic lymphoma of suspected B-cell lineage, possibly originating from the lymphatic system of the gingiva. We consider that the osteolysis resulted from activation of osteoclasts by proliferation of the tumour cells.

Hypoxia induces transcription factor ETS-1 via the activity of hypoxia-inducible factor-1.

ETS-1 plays an important role in angiogenesis and cancer invasion, and hypoxia is a common feature in these phenomena. We examined whether hypoxia influenced ETS-1 expression. Hypoxia induced ETS-1 in a human bladder cancer cell line, T24, and promoter analysis revealed that the deletion of -424 to -279 bp from the human ETS-1 promoter decreased the hypoxia-mediated inducibility. This region contained a hypoxia responsive element-like sequence, and HIF-1 bound to it under the hypoxic condition. Double-stranded synthetic oligonucleotides of this sequence as a decoy inhibited the hypoxia-mediated inducibility. These results indicate that hypoxia induces ETS-1 via the activity of HIF-1.

Retinoic acids repress the expression of ETS-1 in endothelial cells.

The transcription factor ETS-1 expressed in endothelial cells (ECs) regulates angiogenesis by inducing MMP-1, MMP-3, MMP-9, u-PA and integrin beta3 in endothelial cells (ECs). Here, we examined whether antiangiogenic retinoic acids affect the expression of ETS-1 in ECs. The expression of ets-1 mRNA was up-regulated in sparse to subconfluent ECs and down-regulated in confluent ECs. When confluent ECs were stimulated with basic fibroblast growth factor (bFGF), ets-1 mRNA was induced. All-trans retinoic acid (ATRA) as well as 9-cis retinoic acid reduced the augmented expression of ets-1 mRNA in both subconfluent ECs and bFGF-treated confluent ECs. This inhibitory effect of ATRA was dose dependent and was evident at a concentration as low as 10(-7) M. ATRA did not alter the stability of ets-1 mRNA. Moreover, promoter analysis indicated that ATRA repressed the expression of ets-1 mRNA at transcriptional level. As a result, ATRA reduced the binding of ETS-1 protein to the ETS binding motif. These results indicate that the anti-angiogenic effect of retinoic acids is mediated at least in part by the transcriptional repression of ets-1 mRNA in ECs.

[Possible inhibitory mechanism of liver regeneration through non-parenchymal cells after combined hepatectomy and pancreatectomy].

BACKGROUND: Recently, simultaneous hepatectomy (Hx) and pancreaticoduodenectomy have been performed in the treatment of biliary tract cancer. Postoperative hepatic failure is a common and potentially fatal complication. The aim of this study was to examine the reduced rate of liver regeneration after 70% Hx alone or in combination with 70% pancreatectomy (HPx). MATERIALS AND METHODS: Male Sprague-Dawley rats underwent Hx or combined Hx and Px. The ratio of liver-body weight, labeling index of hepatocytes in vivo, and DNA synthesis of hepatocytes and/or Kupffer cells in primary culture were analyzed. RESULTS: The ratio of liver-body weight in HPx rats was found to be significantly lower than that in Hx rats from 12 hours to 72 hours after surgery. There was no difference in blood glucose or ALT levels between the two groups. An inhibitory effect on DNA synthesis was observed in cocultured hepatocytes and Kupffer cells when portal plasma obtained one hour after surgery was added. We further observed that conditioned medium of Kupffer cells stimulated by portal plasma obtained one hour after HPx inhibited DNA synthesis by hepatocytes. This effect was abolished after incubation at 56 degrees C for 30 min. CONCLUSIONS: These results clearly indicate the existence of a growth inhibitory factor in portal serum after HPx. This heat-labile growth inhibitory factor was released from Kupffer cells stimulated by portal plasma after HPx and appears to act on hepatocytes in a paracrine manner.

Interleukin-10 induction after combined resection of liver and pancreas.

BACKGROUND/AIMS: Recently in Japan, combined resection of liver and pancreas is being performed in cases of advanced biliary neoplasms. As we previously reported, in the rat model of combined resection of the liver and pancreas, the potential for liver regeneration after this operation was decreased compared to that after hepatectomy only. Moreover, non-parenchymal cells play an important role in the production of inhibitory factors for liver regeneration. The anti-inflammatory cytokine IL-10, downregulates the release of TNF-alpha, and affects the progressive regeneration of the hepatic parenchyma. To investigate the role of IL-10 and TNF-alpha in hepatic regeneration in the rat, we measured the levels of IL-10 and TNF-alpha in the conditioned medium of non-parenchymal cells stimulated with portal plasma. We also investigated the concentration of IL-10 and TNF-alpha in the portal plasma after combined resection of the liver and pancreas. METHODOLOGY: Adult male Sprague-Dawley rats were used. Rats were divided into 3 groups: group I underwent 70% partial hepatectomy only (Hx), group II underwent 70% partial pancreatectomy only (Px) and in group III both procedures were used, Hx plus Px (HPx). Portal plasma was harvested at 1, 3, 6, 12 and 24 hours after surgery and was used to stimulate the culture medium of non-parenchymal cells. Cytokine concentrations in the plasma and in the conditioned medium were measured by ELISA. Northern blot analysis for IL-10 mRNA was performed on liver, pancreas, kidney, lung and spleen at 1, 3 and 6 hours after surgery. RESULTS: The level of IL-10 released by non-parenchymal cells stimulated with HPx portal plasma was 154.1 +/- 20.3 pg/mL and significantly higher than when stimulated with Hx portal plasma, which was 100.1 +/- 6.4 pg/mL (P < 0.05) during the first hour. Also, the level of TNF-alpha released by Kupffer cells stimulated with HPx portal plasma was 86.6 +/- 13.4 pg/mL, significantly less than when stimulated with Hx portal plasma, which was 138.7 +/- 15.1 pg/mL (P < 0.005) during the first hour. Furthermore, the plasma levels of IL-10 in the HPx group remained significantly higher than those of the other groups from 6 hours up to 12 hours. In northern blot analyses, higher IL-10 mRNA expression were detected in the spleen and moderately high levels in the liver at 1 and 3 hours after HPx, in contrast to those after Hx. CONCLUSIONS: IL-10 expression is induced in the spleen and liver remnant just after HPx. IL-10 released by the spleen and liver might downregulate TNF-alpha production, thereby inhibiting the liver regeneration.

Prognostic significance of lymph node metastasis and clear cell histology in ovarian carcinoma limited to the pelvis (pT1M0 and pT2M0).

BACKGROUND: The prognostic significance of lymph node (LN) metastasis in clinically early-stage (pT1M0 or pT2M0) ovarian carcinoma has not yet been fully elucidated. METHODS: From 1988 to 1997, 94 patients with ovarian carcinoma of pT1M0 (n = 78) or pT2M0 (n = 16) classification underwent surgery including systematic pelvic and paraaortic LN dissection. We investigated the prognostic factors of intraperitoneally determined early-stage ovarian carcinoma focusing on LN metastasis. RESULTS: LN metastasis was seen in 5.1% of pT1M0 and in 31.3% of pT2M0 tumors. Univariate analysis of grade, histology (clear cell vs others), size of primary tumor, peritoneal cytology, and LN metastasis revealed that histology (P < 0.01), size of tumor (P < 0.05), and LN metastasis (P < 0.0005) were related to patient survival of early-stage ovarian carcinoma. Peritoneal cytology (P = 0.053) and grade (P = 0.059) had marginal statistical significance. A multivariate Cox regression analysis showed that clear cell histology (P < 0.05) and LN metastasis (P < 0. 005) are significant independent prognosticators of patient survival. Three (two with clear cell adenocarcinoma and one with mucinous adenocarcinoma) of nine patients with LN metastasis had died of the disease by the time of the present analysis. Two of the three deceased patients had recurrent tumors in distant organs (bone and brain/liver), one had pleural and peritoneal carcinomatosis, and no patients had retroperitoneal recurrence. This suggests that LN metastasis indicates that tumor cells may have already spread systemically at the time of treatment and, at the same time, retroperitoneal lymph node dissection (RPLND) may be effective in eradicating retroperitoneal metastasis in some instances of ovarian carcinoma. CONCLUSION: Clear cell histology and LN metastasis are indicators of poor prognosis for patients with tumors limited to the pelvis. Therapeutic significance of systematic RPLND for pT1M0/pT2M0 ovarian carcinomas needs to be further investigated by randomized studies.