Neoadjuvant chemoradiation versus adjuvant chemotherapy for locally advanced adenocarcinoma of the rectosigmoid junction.

AIM: The optimal treatment approach for adenocarcinoma of the rectosigmoid junction remains unclear. The aim of this work was to compare outcomes of neoadjuvant chemoradiation (NCR) and adjuvant chemotherapy (AC) treatment for cancer of the rectosigmoid junction. METHOD: This was a nationwide, retrospective cohort study (2004-2015) using hospital-based cancer outcomes data (National Cancer Database). All patients who underwent resection with curative intent for locally advanced [American Joint Committee on Cancer (AJCC) Stages II and III] adenocarcinoma of the rectosigmoid junction were included. Exclusion criteria were age less than 18 or over 75 years, Charlson-Deyo score > 2, AJCC Stages I and IV and unstaged tumours. Treatment with NCR was compared with treatment with AC, the primary outcome being overall survival. Other end-points were resection margin status, the presence of lymphovascular invasion and postoperative length of stay. RESULTS: A total of 2828 patients were included in this study, of whom 1701 (59.7%) received NCR. NCR was more frequently utilized in patients who were black (10.3% vs 7.6%, P < 0.05) and underwent treatment at academic institutions (37.9% vs 22.5%, P < 0.05). Treatment with NCR did not differentially influence survival following risk adjustment (hazard ratio 1.17, CI 0.98-1.40; P = 0.085). NCR was independently associated with a decreased likelihood of a positive resection margin (OR 0.44, CI 0.33-0.58; P < 0.001) and lymphovascular invasion (OR 0.51, CI 0.40-0.67; P < 0.001). However, treatment with NCR was associated with the need for prolonged hospitalization compared with AC (7.3 days vs 6.5 days; P = 0.015). The study was limited by its retrospective design, external validity and risk of tumour misclassification. CONCLUSION: NCR currently seems to be favoured over AC for the management of locally advanced adenocarcinoma of the rectosigmoid junction. This approach may not be justified as NCR is associated with prolonged hospitalization needs without a clear survival benefit when compared with AC. Prospective studies are warranted to definitively compare outcomes of NCR and AC in this patient population.

Comparison of body composition by bioelectrical impedance analysis and dual-energy X-ray absorptiometry in Hispanic diabetics.

OBJECTIVE: The purpose of this study was to compare Tanita tetrapolar foot-to-foot bioelectrical impedance analysis (Model TBF-310, Tanita Corporation of America, Inc, Arlington Heights, IL; Tanita-BIA) and fan beam dual-energy X-ray absorptiometry (Hologic Discovery A v12.6, Waltham, MA; DXA) in diabetic patients. METHODS: Seventy Hispanic diabetic participants (23 male, 47 female; mean age: 53.03 ± 10.32 yrs; mean weight: 81.45 ± 17.65 kg; and mean body mass index: 31.40 ± 6.80 kg/m(2)) were selected from the Loma Linda University En Balance culturally-sensitive Spanish diabetes education program using the baseline data. RESULTS: DXA vs Tanita-BIA fat mass (FM), percent fat mass (%FM), and fat-free mass (FFM) were compared using Pearson's (FM: 0.96, %FM: 0.91, and FFM: 0.95), and Spearman's rank (FM: 0.94, %FM: 0.91, and FFM: 0.93) correlation coefficients. Bland-Altman analyses were also used to compare the difference (DXA - BIA) vs average of DXA and BIA results and showed general agreement between the two methods. When Tanita-BIA was regressed onto DXA, the adjusted R(2) was: FM=0.91; %FM=0.83; FFM=0.90. Gender combined concordance correlations with 95% confidence intervals were calculated using a bootstrap re-sampling of the data and found high associations [FM: 0.93 (95% CI: 0.89, 0.96)], [%FM: 0.86 (95% CI: 0.79, 0.90)], and [FFM: 0.93 (95% CI: 0.89, 0.96)]. CONCLUSION: Tanita-BIA may provide valid measures of fat, percent body fat and fat-free mass in Hispanic diabetics, and could be a convenient and practical approach for assessment in community-based research.

The role of bile duct reactive change in the pathogenesis of liver fibrosis due to hepatitis C.

The question addressed here is: does the bile duct reactive component of hepatitis C disease progress during the progression of the disease to cirrhosis? The question is important because if the answer to the question is yes, then an important correllated question is: does the bile duct reactive component contribute to the fibrotic change which leads to cirrhosis? The first question is addressed in the present study of a series of liver biopsies taken at the four stages of liver fibrosis in patients with hepatitis C. Sixty-four patients with hepatitis who had been biopsied for staging purposes were reviewed retrospectively. The liver biopsies were routinely stained with antibodies for liver cells, bile duct cells, activated stellate cells and cells in S phase of the cell cycle and histochemical stains for collagen and basement membrane. Selective biopsies were stained for stem cells and oval cells. There was a progressive increase in metaplastic bile ductules but the increase did not reach a significant level until stages III and IV of fibrosis. There was a positive correlation between the number of ductules formed and the stage of liver fibrosis. The incidence of proliferating metaplastic ductules was low and did not change significantly during the progression of the stage of the fibrosis. Stains for oval cells and stem cells were negative. It is concluded that the answer to the question posed is: bile ductule reaction does increase during the development of cirrhosis caused by hepatitis C but the increase is due to bile ductular metaplasia, not due to proliferation.

The effect of Viagra (sildenafil citrate) on liver injury caused by chronic ethanol intragastric feeding in rats.

Rats fed with ethanol and a nutritious diet intragastrically develop liver pathologic changes associated with cyclic elevation of blood and urinary ethanol levels (BAL and UAL cycle). At the peaks of the UAL cycle, the livers are hypoxic. When the liver portal hepatic blood flow is temporarily clamped for 2 min and then released, the livers at the peak UAL fail to recover completely compared to the control livers and the livers at the UAL cycle troughs. Viagra was fed to the ethanol-fed rats to enhance the effects of nitric oxide. Since nitric oxide is known to increase hepatic blood flow, it was anticipated that Viagra would prevent the liver hypoxia at the UAL cycle peaks and also improve the post-clamp recovery from the post-clamp ischemia challenge. Viagra tended to improve the post-clamp recovery of the liver surface pO2 levels of the ethanol-fed rats probably by slowing O2 consumption as result of NO inhibition of mitochondrial cytochrome c oxidase activity. However, Viagra increased the pathology score when fed with ethanol. For this reason, Viagra is a two-edged sword. On the one hand, it tended to be protective in the post-ischemic injury in the ethanol-fed rats and on the other hand, it enhanced the liver injury caused by ethanol. Viagra did not affect the UAL cycle.

Possible association between high-dose fluconazole and adrenal insufficiency in critically ill patients.

OBJECTIVE: Whereas the antifungal azole ketoconazole interferes with steroidogenesis and can cause adrenal insufficiency, fluconazole in standard doses is thought to not interfere with cortisol production. The objective was to evaluate the effect of high-dose fluconazole therapy on adrenal function in critically ill patients in an intensive care setting. DESIGN: Descriptive case reports. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Two patients, a 77-yr-old man (case 1) with esophageal cancer and a 66-yr-old woman (case 2) with multiple organ failure developed reversible adrenal insufficiency temporally related to the institution and withdrawal of high-dose fluconazole. INTERVENTIONS: Short cosyntropin (adrenocorticotropic hormone; ACTH) stimulation tests. MEASUREMENTS AND MAIN RESULTS: Two days after high-dose fluconazole in case 1, the serum ACTH level was 121 pg/mL (normal range is 9-52 pg/mL), and the peak cortisol after ACTH stimulation was 15.5 microg/dL (normal response is >or=18 microg/dL). Eleven days after discontinuation of fluconazole, the peak cortisol level after ACTH stimulation was 43.4 microg/dL. Twenty-four hours after high-dose fluconazole in case 2, an ACTH stimulation test had a low peak serum cortisol of 16.8 microg/dL. Fluconazole was withdrawn, and 5 days later, the peak stimulated cortisol was 20.6 microg/dL. CONCLUSIONS: Although fluconazole is the therapy of choice for patients in the intensive care setting with Candida infections, two patients with multiple organ failure who received high-dose fluconazole appeared to develop adrenal insufficiency. Although preliminary and anecdotal, these data suggest a need to further investigate the possibility that high-dose fluconazole might cause adrenal insufficiency in already compromised critically ill patients.

Novel antineoplastic isochalcones inhibit the expression of cyclooxygenase 1,2 and EGF in human prostate cancer cell line LNCaP.

Experiments were conducted to determine the effects of novel anti-neoplastic isochalcones (DJ compounds), on cyclooxyegenase 1 and 2 (COX-1 and COX-2) enzyme expression in androgen receptor dependent human prostate cancer cell line LNCaP. Results from Western blot analysis and cell flow cytometry showed that DJ52 and DJ53 decreased the steady state levels of COX-1 and COX-2 protein levels in a dose dependent manner. In addition, DJ52 and DJ53 decreased the levels of epidermal growth factor (EGF) in LNCaP cells. In this study, we report that novel isochalcones decreased COX-1, COX-2 and EGF levels as well as LNCaP cellular growth in a dose responsive manner. Our findings indicate that relative decreases in COX-1, COX-2 and EGF expressions might serve as indicators of tumor growth inhibition in prostate neoplasms.

CT findings after uterine artery embolization.

Asymptomatic uterine leiomyoma can be detected on routine computed tomography (CT) of the pelvis. Leiomyomas have been described as low attenuation masses that can disrupt the smooth contour of a normal uterus. Four women underwent uterine artery embolization for the treatment of uterine leiomyoma. CT findings include initial retention of contrast in fibroids the day of the procedure and central necrosis of the fibroid with subsequent cavitation as early as 1 month postprocedure.

Heat-shocked A20 lymphoma cells fail to induce degranulation of cytotoxic T lymphocytes: possible mechanism of resistance.

A20 lymphoma cells were subjected to heat shock for 2 h at 42 and 43 +/- 0.1 degrees C and then evaluated at 37 degrees C for sensitivity to lysis by intact allo-specific cytotoxic T lymphocytes (CTLs), perforin-containing granules isolated from CTLs, and Fas-mediated apoptosis. Heat shock at 42 degrees C caused little change in sensitivity of the lymphoma cell line to lysis by intact CTLs or their isolated cytotoxic granules, but caused increased sensitivity to Fas-mediated apoptosis. However, A20 cells shocked at 43 degrees C declined significantly in sensitivity to lysis by intact CTLs, while remaining very sensitive to perforin granules and to Fas-mediated apoptosis. Expression of the inducible heat shock protein was observed in A20 cells incubated at 43 degrees C, but not in those incubated at 42 degrees C, suggesting a role for heat shock proteins. Furthermore, A20 cells shocked at 43 degrees C did not provoke degranulation and secretion of granzymes by antigen-specific CTLs, although formation of CTL-target conjugates and levels of MHC class I molecules remained unchanged. These observations demonstrate that hyperthermia or febrile conditions may reduce susceptibility of target cells to CTL attack due to failure of antigen presentation and the inability of CTLs to recognize heat stressed targets, thus enabling targets to escape CTL attack.

Successful palliation of Ebstein's malformation on the first day of life following fetal diagnosis.

Severe Ebstein's malformation has a poor prognosis when diagnosed during the neonatal period. Surgical options that have proved successful in older patients have been associated with high mortality and morbidity in neonates. We report here our success with a policy of induction at term and immediate surgical intervention when Ebstein's malformation was diagnosed prenatally.

Uterine artery embolization for the treatment of uterine leiomyomata midterm results.

INTRODUCTION: The authors review their midterm experience with uterine artery embolization for the treatment of uterine fibroids. MATERIALS AND METHODS: Sixty patients were referred for permanent polyvinyl alcohol (PVA) foam particle uterine artery embolization during an 18-month period. Detailed clinical follow-up and ultrasound follow-up were obtained. RESULTS: Bleeding was a presenting symptom in 56 patients and pain was a presenting symptom in 47 patients. All patients underwent a technically successful embolization. One of the patients underwent unilateral embolization. Fifty-nine patients underwent bilateral embolization. Of all patients undergoing bilateral embolization, at last follow-up (mean, 16.3 months), 81% had their uterus and had moderate or better improvement in their symptoms. Ninety-two percent of these patients also had reductions in uterine and dominant fibroid volumes. Overall, the mean uterine and dominant fibroid volume reduction were 42.8% and 48.8%, respectively (mean follow-up, 10.2 months). One infectious complication that necessitated hysterectomy occurred. CONCLUSION: Uterine artery embolization for the treatment of uterine fibroids is a minimally invasive technique with low complication rates and very good clinical efficacy.

Contralateral early blink reflex in multifocal motor neuropathy.

Multifocal motor neuropathy (MMN) is a clinical entity affecting the peripheral nerve system mainly. We present here a Colombian man, 37 year-old, who presented MMN, and interestingly, displayed abnormal responses in the blink reflex after electrical stimulation of the supraorbital nerves. These findings allow us to suggest that the lesion distribution in MMN mostly the subclinical one, seems to be more widespread than usually thought.

Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells.

Although prostate cancer cells are often initially sensitive to androgen ablation, they eventually lose this response and continue to survive, grow and spread in the absence of androgenic steroids. The mechanism(s) that underlie resistance to androgen ablation therapy remain mostly unknown. We have demonstrated that elevated caveolin protein levels are associated with human prostate cancer progression in pathological specimens. Here we show that suppression of caveolin expression by a stably transfected antisense caveolin-1 cDNA vector converted androgen-insensitive metastatic mouse prostate cancer cells to an androgen-sensitive phenotype. Orthotopically grown tumors and low-density cell cultures derived from antisense caveolin clones had increased apoptosis in the absence of androgenic steroids, whereas similarly grown tumors and cells from vector (control) clones and parental cells were not sensitive to androgens. Studies using a representative antisense caveolin clone showed that selection for androgen resistance in vivo correlated with increased caveolin levels, and that adenovirus-mediated caveolin expression blocked androgen sensitivity. Our results identify a new candidate gene for hormone-resistant prostate cancer in man and indicate that androgen insensitivity can be an inherent property of metastatic prostate cancer.

Tyrosine kinase participates in phosphorylation of the Ro60 ribonucleoprotein.

Studies of Ro ribonucleoprotein are important in rheumatology, since anti-Ro antibodies are probably involved in the pathogenesis of congenital heart block and subacute cutaneous lupus erythematosus. In addition, the phosphorylation-dephosphorylation cycle modulates binding of ribonucleoproteins to RNA, a process that might affect the antigenicity and function of the Ro protein. The present study was designed to determine whether Ro can be phosphorylated by tyrosine kinase. To answer this question, synchronized HEp-2 cells were phosphorylated in vivo with exogenous 32P, and Ro ribonucleoprotein previously subjected to metabolic radiolabeling was immunoprecipitated by monoclonal anti-Ro antibodies and examined by SDS-PAGE and autoradiography. The main results were as follows: first, Ro ribonucleoprotein was phosphorylated in vivo; second, Ro was found to have phosphorylable tyrosine residues; third, tyrosine kinase participated in the phosphorylation of Ro; and fourth, phosphorylation did not change the recognition pattern of Ro by anti-Ro antibodies. In conclusion, Ro60 is phosphorylated by tyrosine kinase.

Simultaneous repair of pectus excavatum and congenital heart disease.

Most repair of heart lesions and pectus deformity has been performed in adult patients using long incisions, sternal splits, excision of deformed cartilages, and sternal turnover operations that could result in poor cosmesis and chest growth in children because of sternal devascularization. We performed simultaneous pectus repair and atrial septal defect closure in 2 children using a short longitudinal incision and avoiding a transverse or longitudinal sternal split. After extraperichondrial excision of the deformed cartilages and mobilization of the sternum from the neurovascular bundles, a transverse wedge of sternum was removed at the level of the third cartilages, allowing cephalad retraction of the sternum and providing excellent exposure for the intracardiac operation. The cosmetic appearance remains excellent in both patients at 1 and 4 years postoperatively.

Management of arch hypoplasia after successful coarctation repair.

BACKGROUND: Pronounced arch obstruction can be seen after a well-repaired coarctation, and this probably results from the failure of a somewhat hypoplastic arch to grow or from clamp injury at the time of the initial repair, or from both causes. Because of mediastinal adhesions and minimal collateral circulation, use of extraanatomic bypass grafts appears to be the preferred approach. METHODS: Six children or young adults presented with arch obstruction over a 3-year period. Their mean age was 13.5 +/- 4 years, and the mean interval from the time of the initial repair was 10 +/- 4 years. The mean age of the patients at the time of the initial repair was 3.2 +/- 5 years. Symptoms included exertional headache and chest pain. The mean systolic gradients, as shown by echocardiography and cardiac catheterization, were 34 +/- 7 mm Hg and 33 +/- 6 mm Hg, respectively. Repair was accomplished through a midsternotomy using a polytetrafluoroethylene patch placed in the concavity of the arch, which extended from the ascending to the descending aorta. Dissection was kept close to the aorta and arch to minimize injury to the phrenic and recurrent laryngeal nerves. Cardiopulmonary bypass and moderate hypothermia (25 degrees to 27 degrees C bladder temperature) without circulatory arrest were used. RESULTS: All patients were discharged home 4 to 20 days postoperatively (mean, 7 +/- 6 days). All patients were found to be normotensive at a mean follow-up of 1.3 +/- 1 years. Postoperative echocardiograms, which were obtained in all patients, revealed no residual gradients. Exercise blood pressure was evaluated in 2 patients and found to be normal. CONCLUSIONS: Transsternal arch enlargement using cardiopulmonary bypass and moderate hypothermia without circulatory arrest is an attractive and safe approach for the treatment of arch obstruction after coarctation repair. Unlike the use of extraanatomic bypass grafts, it allows complete relief of the obstruction, unhampered aortic growth, the minimal use of foreign material, and a repair that is protected deep within the mediastinal space.

Recognition and management of obstructed pulmonary veins draining to the coronary sinus.

BACKGROUND: Obstruction of the pulmonary veins in total anomalous pulmonary venous drainage to the coronary sinus is generally considered rare. However, if it is present, the usual treatment of unroofing the coronary sinus will lead to a poor result. METHODS: Four patients with total anomalous pulmonary venous drainage to the coronary sinus with obstruction were identified over a 14-month period. Three patients in whom the diagnosis of obstruction was not made underwent coronary sinus unroofing. Retrospective review of the preoperative echocardiograms and Doppler studies showed the presence of obstruction in the vertical vein in 2 patients and in the branches in the other. In the fourth patient, obstruction in the vertical vein was recognized preoperatively with echocardiography and Doppler study. This patient underwent direct common pulmonary vein-left atrial anastomosis. RESULTS: All 3 patients who had coronary unroofing were seen with obstructed pulmonary veins 2 to 7 months postoperatively. After reoperation, 1 died, and the other 2 have done relatively well 3 1/2 and 15 months postoperatively. The patient who had an anastomosis between the common pulmonary vein and the left atrium is doing well 18 months postoperatively. CONCLUSIONS: Obstruction in total anomalous pulmonary venous drainage to the coronary sinus is not as rare as previously reported. To improve outcome, its presence should be sought using complete echocardiography including Doppler studies. When obstruction is present, transection of the vertical vein and common pulmonary vein-left atrial anastomosis through the superior approach is an attractive technique that also eliminates the right-to-left shunting associated with coronary sinus unroofing and simplifies closure of the atrial septal defect.