Can serum IgE or blood eosinophil count predict postoperative oral corticosteroid response in chronic rhinosinusitis with nasal polyps?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by inflammatory mucosa and polyp formation in the paranasal sinuses. The study's primary objective was to evaluate the outcomes of postoperative oral corticosteroid (OCS) in treating patients with bilateral CRSwNP. The secondary objective was to determine whether preoperative serum IgE levels (sIgE)and/or blood eosinophil count (BEC) correlate with postoperative outcomes following OCS use. METHODS: Patients with bilateral CRSwNP (n=236) who underwent endoscopic sinus surgery (ESS) were randomly assigned to receive 15 mg OCS twice daily or a placebo for 2 weeks. We investigated the treatment effects based on the subjective visual analogue scale (VAS), Sino-Nasal Outcome Test 22 (SNOT-22), and objective Lund-Kennedy Endoscopy Score (LKES) over 6 months; subgroups were stratified preoperatively as follows: sIgE <150 IU/mL, sIgE>=150 IU/mL, BEC <0.39x10(9) cells/L, and BEC>=0.39x10(9) cells/L. RESULTS: A total of 193 participants completed the study up to the 6-month follow-up; no apparent linear relationship was noted between sIgE and BEC. No significant differences in scores were noted upon assessment of the VAS, SNOT-22, and LKES among the follow-up timepoints in the primary analysis. However, in the primary or subgroup analyses with sIgE or BEC, significant differences in the longitudinal scores of sleep dysfunction were observed at the 1-month follow-up. CONCLUSION: Postoperative OCS did not significantly affect bilateral CRSwNP outcomes. sIgE levels and BEC may not be surrogate predictive biomarkers to assess the role of postoperative OCS use. OCS may increase the risk of transient sleep disturbance.

Changes of CCAAT enhancer-binding proteins (CEBPs) in the lung of streptozotocin-induced diabetic rats.

CCAAT enhancer-binding proteins (CEBPs) play key roles in the metabolic regulation, cell transformation, and inflammation. However, the expression and/or functions of CEBPs in rats with hyperglycemia are still unclear. In the present study, we investigated the changes of CEBPs protein in lung of the diabetic rats. The levels of C/EBPß and C/EBPδ protein were decreased in the lung isolated from streptozotocin-induced diabetic rats (STZ-diabetic rats) as compared with that of normal rats. Exogenous insulin at the dose sufficient to normalize the plasma glucose of STZ-diabetic rats reversed the protein levels of C/EBPß and C/EBPδ in lung after a 4-day treatment. Similar results were also observed in STZ-diabetic rats that received the treatment of phlorizin to reverse the plasma glucose level for 4 days. Otherwise, the protein level of C/EBPα in lung of the STZ-diabetic rats was similar as the normal rats. Also, the level of C/EBPα protein in lung of the STZ-diabetic rat was not significantly changed by correction of plasma glucose by exogenous insulin or phlorizin. In addition, we also cultured human lung cells (A-549) and rat lung cells (L2) in varies concentration of D-glucose and L-glucose to identify the effect of glucose in expression of C/EBPs. The obtained results suggest that increase of plasma glucose is related to the lower expression of C/EBPß and C/EBPδ proteins in the lung of STZ-diabetic rats. The changes of expression of C/EBPß and C/EBPδ are not caused by changes of osmolarity but by D-glucose itself.

Indomethacin activates peroxisome proliferator-activated receptor γ to improve insulin resistance in cotton pellet granuloma model.

Inflammation is involved in the development of insulin resistance and diabetes. However, the effectiveness of anti-inflammatory drugs in diabetic therapy remains obscure. In the present study, the possible mechanisms of indomethacin, one of the nonsteroidal anti-inflammatory drugs, in the improvement of insulin resistance were investigated. Indomethacin treatment significantly decreased cotton pellet implantation induced white blood cell count elevation and immune cells infiltration in epididymal white adipose tissue. Also, cotton pellet implantation induced impaired glucose utilization and insulin resistance were improved by indomethacin. The decrement in phosphoinsulin receptor and phospho-Akt levels induced by cotton pellet implantation was improved by indomethacin as well. Moreover, indomethacin decreased cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in epididymal white adipose tissue with a marked reduction of prostaglandin 2 (PGE2) and nitrite/nitrate (NOx) levels in cotton pellet-implanted mice. Furthermore, pretreatment of peroxisome proliferator-activated receptor γ (PPARγ) antagonist, GW9662 not only reversed indomethacin-modified COX-2 and iNOS levels but also reversed indomethacin-improved insulin sensitivity determined by homeostasis model assessment-insulin resistance (HOMA-IR). Taken together, indomethacin might elevate the expression of PPARγ to decrease serum NOx and PGE2 to result in the improvement of insulin resistance.

Outcome of distal gastric cancer with pyloric stenosis after curative resection.

AIMS: Pyloric stenosis usually presents with symptoms, and this may lead patients to consult their physician. We evaluate whether distal gastric cancer patients with pyloric stenosis had a better outcome than those without. METHODS: A total of 551 distal gastric cancer patients who received curative subtotal gastrectomy between January 1988 and December 2003 at Taipei Veterans General Hospital were analyzed. Among them, 174 patients were sorted into the pyloric stenosis group according to obstructive symptoms. Their clinicopathological features, survival and prognostic factors were evaluated. RESULTS: The 5-year overall and disease-free survival rate of distal third gastric adenocarcinoma for the pyloric stenosis group was significantly lower than those without pyloric stenosis. Multivariate analysis revealed the pyloric stenosis group had deeper cancer invasion (relative to pT1, RR of pT2 3.1, p=0.009; pT3 6.1, p<0.001; pT4 16.5, p<0.001), and more lymph node metastasis (RR 3.6; p=0.001). The pyloric stenosis group had a tendency to lymph node metastasis toward the hepatoduodenal ligament, but this did not reach statistical difference. However, the pyloric stenosis group had significantly higher lymph node metastasis in the retropancreatic region (5.17% vs. 0.53%; p=0.001). CONCLUSIONS: Distal gastric cancers with pyloric stenosis have worse biological behavior than those without, and consequently have a poor outcome.

Primary giant cell malignant fibrous histiocytoma of the kidney with staghorn calculi.

Malignant fibrous histiocytomas (MFH) as primary renal tumours are rare, with less than 50 cases described in the literature. We report a case of primary renal MFH of giant cell type in a 56-year-old man, who presented with bilateral dull flank pain, intermittent gross haematuria and body weight loss (6 kg in 3 months). Intravenous urography, computerized tomography (CT) and magnetic resonance image (MRI) showed right ureteral stones with mild hydronephrosis, and a solid mass at the lower pole of the left kidney associated with staghorn calculi, as well as tumour thrombi in the left renal vein and inferior vena cava. Left radical nephrectomy and evacuation of tumour thrombi from the left renal vein and inferior vena cava were performed. Histopathologic examination revealed malignant fibrous histiocytoma (MFH) of giant cell type. To the best of our knowledge, this is the first report of primary renal MFH associated with staghorn calculi.

Synthesis of bicyclic pyrane derivatives via tungsten-mediated [3 + 3] cycloaddition of epoxides with tethered alkynes.

Propargyltungsten compounds bearing a tethered epoxide were prepared in short steps from readily available materials. In the presence of various Lewis acids, BF(3).Et(2)O catalysts (25 mol %) most effectively promote the [3 + 3] cycloaddition of the epoxide with its tethered propargyltungsten group, delivering bicyclic pyranyltungsten compounds in reasonable yields. This cyclization proceeds highly diastereoselectively with tolerance of various functional groups. The stereochemical outcome indicates that the cycloaddition is initiated by the ring opening of the epoxides via an exo-attack of the propargyltungsten group. The resulting pyranyltungsten organometallics were demetalated to yield various bicyclic pyranyl derivatives using different oxidants. This new method provides a short enantiospecific synthesis of bicyclic oxygen compounds if chiral epoxide is used in the cyclization. A mechanistic model is presented to rationalize the reaction pathway of this [3 + 3] cycloaddition.

Comparison of the UICC/AJCC 1992 and 1997 pN categories for gastric cancer patients after surgery.

BACKGROUND/AIMS: UICC/AJCC 1997 classification changes pN category. We evaluated its prognostic impact. METHODOLOGY: A total of 710 patients who underwent a > or = D2 gastrectomy were recruited. Among them, the data of 319 patients who had involved regional lymph nodes and no evidence of distant metastases were used for comparing the 1992 and 1997 pN categories. RESULTS: For 1997 category, 201 patients (64%) were pN1, 75 (23.5%) pN2, and 43 (13.5%) pN3. For 1992 category, 143 patients (44.8%) were pN1, and 147(46.1%) pN2. 29 patients (9.1%) with lymph node metastasis to the hepatoduodenal ligament were distant metastasis. The 1997 pN category was a more powerful prognostic discriminant (relative risk: 2.086) than the 1992 category. Compared to the 1992 stage classification, the 1997 one had a skewed distribution of patients with marked shift of patients of stage IIIA (105-126 patients), IIIB (116-58 patients), and IV (100-122 patients). The survival difference between stage IIIA and IIIB for the 1997 stage classification is narrower than for 1992. CONCLUSIONS: The 1997 pN category allows for estimation of prognosis superior to the 1992 category.

Concomitant chemoradiation treatment in the management of patients with extrahepatic biliary tract recurrence of gastric carcinoma.

BACKGROUND: The aim of this study was to determine the role of concomitant chemoradiation in the alleviation of obstructive jaundice in patients with extrahepatic biliary tract metastases from gastric carcinoma. METHODS: Thirteen patients with good performance status who had obstructive jaundice resulting from extrahepatic biliary metastases after gastrectomy for gastric carcinoma were treated with palliative intent. Treatment consisted of insertion of a percutaneous transhepatic choledochal drainage (PTCD) catheter followed by external radiation up to a total dose of 40-60 grays in combination with chemotherapy (cisplatin 20 mg/m(2)/day, 5-fluorouracil 600 mg/m(2)/day, and leucovorin 90 mg/m(2)/day for 96 hours during the first and fifth weeks) on an outpatient basis. RESULTS: The concomitant chemoradiation produced a good palliative effect in all 13 patients. Hyperbilirubinemia continued to improve after treatment, patients' clay-colored stool resolved within an average of 4 weeks (range, 2-6 weeks), and bilirubin levels returned to normal. The PTCD catheter could be removed after treatment was completed (the seventh week); the mean duration of PTCD placement was 2 months. The entire treatment course was performed on an outpatient basis; hospital admission was necessary only for PTCD insertion and chemotherapy. Ten patients died of their disease, with an average survival of 14.4 months (range, 4-31 months) from the time of PTCD insertion. Three patients are still alive at 16, 21, and 8 months. Biliary tract patency was maintained until death. No serious treatment-related complications occurred, and no endoprothesis or intraluminal brachytherapy was needed in this study. CONCLUSIONS: Satisfactory palliation can be achieved by concomitant chemoradiation for patients with obstructive jaundice resulting from extrahepatic biliary metastases from gastric carcinoma, providing an alternative treatment choice for these patients.

Human gastric cancer kinase profile and prognostic significance of MKK4 kinase.

Alterations of protein tyrosine kinase are often associated with uncontrolled cell growth and tumor progression. Knowledge of the overall expression pattern of tyrosine kinases should prove beneficial in understanding the signaling pathways involved in gastric cancer oncogenesis and in providing possible biomarkers for gastric cancer progression. To establish a general tyrosine-kinase expression profile, degenerated polymerase chain reaction primers designed from the consensus catalytic kinase motifs were used to amplify protein tyrosine kinase molecules from gastric cancer tissues. We observed more than 50 tyrosine and serine/threonine kinases from matching pairs of gastric cancer tissue and normal mucosa. Based on this new kinase profile information, we selected the MKK4 gene for further immunohistochemical studies. Statistical analysis of MKK4 protein expression and clinicopathological features indicated that MKK4 kinase expression could serve as a significant prognostic factor for relapse-free survival and for overall survival. We demonstrated a simple and sensitive method for establishing protein tyrosine-kinase expression profiles of human gastric cancer tissues as well as for discovering novel and useful clinical biomarkers from such kinase expression profiles.

Serum matrix metalloproteinase-9 level associated with stromal reaction in patients with gastric cancer.

BACKGROUND: Matrix metalloproteinase 9 (MMP-9) plays an important role in cancer invasion and metastasis. The relationship between serum MMP-9 levels and clinicopathological factors in gastric cancer patients is not clear. MATERIALS AND METHODS: Preoperative serum was obtained from 170 patients who had undergone gastrectomy for gastric cancer at the Veterans General Hospital-Taipei. The serum MMP-9 level was measured using a sandwich enzyme-linked immunoassay by monoclonal antibodies. RESULTS: The median serum MMP-9 level was 368.6 ng/mL (range: 43.9-1871.3 ng/mL). Univariate analysis showed that stromal reaction and Lauren's histological classification were two factors related to serum MMP-9 levels (p = 0.014 and p = 0.030 respectively). Multivariate analysis revealed that stromal reaction was the only factor independently (odds ratio: 1.695) associated with MMP-9 levels. Patients with a serum MMP-9 level < 368.5 ng/mL had a tendency towards better survival rate (5-year survival rate: 64.4%) than those with > 368.5 ng/mL (58.5%), but this tendency did not reach statistical significance (p = 0.512). CONCLUSION: These data suggests that serum MMP-9 levels are associated with stromal reaction in gastric cancer.

Surgical mortality, survival, and quality of life after resection for gastric cancer in the elderly.

Although there were some studies on clinicopathologic characteristics, operative morbidity, and mortality in elderly patients with gastric cancer, no reports have specifically focused on survival and quality of life after resection. A total of 433 patients aged >/= 65 years (1987-1994) who underwent gastric resection for gastric adenocarcinoma were studied. Two groups were considered: patients aged 65 to 74 years and those > 74 years. Most of the patients (78.1%) had advanced diseases, and nearly half (41. 3%) had associated chronic disease(s). Resections with curative intention were performed in 362 patients (83.6%). The overall operative morbidity rate was 21.7% and mortality rate 5.1%. Although operative procedures were similar in both groups, patients aged >74 years had a higher mortality rate than those aged 65 to 74 years (10. 1% vs. 3.5%; p = 0.034). Age and extent of gastric resection were two independent factors negatively affecting mortality. The cumulative survival rates for patients who underwent curative resection were 86.2%, 72.4%, 67.2%, 62.9%, and 60.0% at 1, 2, 3, 4, and 5 years, respectively. Nearly all patients (96%) after surgery had normal work and daily activities. Some patients appeared to lack energy (16%) or experienced a period of anxiety or depression. There was no statistical difference in survival and quality of life assessed by the Spitzer index after curative resection between the two groups. Therefore resection with curative intention can be performed for the elderly with acceptable morbidity and mortality rates, possible long-term survival, and good quality of life, but a limited operation should be considered in the very elderly patients.

Acute necrotizing otitis media in an infant: a case report.

Acute necrotizing otitis media (ANOM), an uncommon but severe form of bacterial otitis media, frequently causes distressing sequelae if not properly diagnosed and treated. A four-month-old female infant initially became ill with intermittent fever, followed by left facial nerve paralysis and left otorrhea four days later. Microscopic examination of the left ear revealed congestion and swelling of the external ear canal, perforation of the eardrum and erosions on the malleus. Culture of pus from the otic lesion grew Pseudomonas aeruginosa. The patient's condition did not improve despite systemic administration of antibiotics; thus, surgical intervention was arranged. During the operation, near-total perforation of the eardrum, a dislodged incus, cholesteatoma-like matrix around the stapes, and granulation tissue occupying the middle ear and mastoid cavities were noted. Radical mastoidectomy was conducted and pathologic examination of the surgical specimen disclosed necrotic changes in both soft and bony tissues. The patient recovered soon after surgery. Her fever subsided one day after surgery and the patient was discharged in a stable condition 12 days later. However, she still had left facial nerve paralysis six months later.

Factors correlated with number of metastatic lymph nodes in gastric cancer.

OBJECTIVE: We had previously reported a reasonable categorization of the number of positive lymph nodes (LN: 0, 1-4, 5-8, and > 8) as a prognostic indicator. This study was an extension, to see which factors correlated with number of positive lymph nodes. METHODS: A total of 533 patients with gastric adenocarcinoma, who underwent curative surgery between January 1988 and December 1995, were entered into this study. Patients were divided into four groups according to metastatic LN number (0, 1-4, 5-8, and > 8). Their survival and clinicopathological factors were analyzed. RESULTS: A total of 16,457 LNs, with an average of 30.9 per specimen, were removed, of which 1686 (10.2%) showed metastases. The 5-yr cumulative survival rate decreased as the number of metastatic LNs increased, ie., 91.3% for LN 0; 67.4% for LN 1-4; 37.2 for LN 5-8, and 14.1% for LN > 8. Multivariate analyses showed that depth of cancer invasion (odds ratio: 2.4), gross appearance (odds ratio: 1.9), size (odds ratio: 1.9), and location (odds ratio: 1.4) of tumor were four independent factors correlated with the number of metastatic LNs. Number of metastatic LNs increased with advanced Japanese nodal stage and UICC-TNM stage. CONCLUSIONS: Depth of tumor invasion, and gross appearance, size, and location of tumor were four pathological factors independently correlated with number of metastatic LNs in gastric cancer.

Serum progesterone levels in patients with gastric adenocarcinoma before and after gastrectomy.

BACKGROUND: Having observed that progesterone receptors exist in all gastric carcinoma tissues, the authors determined that serum progesterone levels in gastric carcinoma patients were worthy of evaluation. METHODS: Serum progesterone levels were determined in patients with gastric adenocarcinoma and in patients with benign disease who served as controls. All female patients were older than 55 years. The clinicopathologic significance of their serum progesterone levels was determined. RESULTS: In male patients (n = 122), the serum progesterone level (mean +/- standard deviation) was significantly higher than in the male control group (n = 163) (0.264+/-0.261 vs. 0.142+/-0.113 ng/mL; P < 0.001) and showed a tendency to be stage-related (P = 0.029). Serum progesterone levels significantly decreased after gastrectomy in patients with disease at Stage I (n = 27), II (n = 20), and III (n = 32), but not IV (n = 7). In 11 patients who died of recurrence, the serum progesterone levels were decreased when they were disease free but raised when recurrence was clinically evident. Patients with serum progesterone levels > 0.264 ng/mL survived for significantly shorter periods than those with levels < or = 0.264 ng/mL (P = 0.039). However, serum progesterone level was not an independent predictor of survival. Among the female patients (n = 12), the serum progesterone level (mean +/- standard deviation) of patients with gastric carcinoma was 0.427+/-0.428 ng/mL, whereas that of the control group (n = 17) was 0.217+/-0.451 ng/mL; the difference was statistically significant (P = 0.02). In female disease free patients studied postoperatively, the progesterone after gastrectomy showed a tendency to decrease, but this difference was not statistically significant (0.444+/-0.368 vs. 0.175+/-0.150 ng/mL; P = 0.091; n = 7). CONCLUSIONS: These data suggest that serum progesterone level reflects the presence or absence of gastric carcinoma by some unknown mechanism.