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.

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.

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.

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.

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.

Subpopulations of primary sensory neurons show coexistence of neuropeptides and glucocorticoid receptors in the rat spinal and trigeminal ganglia.

The coexistence of the neuropeptides substance P, calcitonin gene-related peptide, galanin, somatostatin and neuropeptide Y with glucocorticoid receptors was studied in neurons of the rat lumbar dorsal root and trigeminal ganglia by means of the double immunofluorescence technique. Based on analysis of microphotographs, about one-third of the populations of nerve cells (small and large) containing substance P or calcitonin gene-related peptide immunoreactivity (IR) showed nuclear glucocorticoid receptor IR. A similar pattern was observed within the dorsal root and trigeminal ganglia. Furthermore, within the lumbar dorsal root ganglia 50% of the small neurons, containing galanin IR, possessed nuclear glucocorticoid receptor IR of moderate intensity. Glucocorticoid receptor IR was not observed in the galanin immunoreactive neurons of the trigeminal ganglion neither in the somatostatin and NPY immunoreactive neurons of both the dorsal root and the trigeminal ganglia. The results provide a chemical anatomical basis for a direct regulation by glucocorticoids of distinct populations of substance P and calcitonin gene-related peptide immunoreactive nerve cells in the lumbar spinal and trigeminal ganglia and of galanin immunoreactive nerve cells of the spinal but not of the trigeminal ganglia.

Adrenalectomy increases the number of substance P and somatostatin immunoreactive nerve cells in the rat lumbar dorsal root ganglia.

Using an immunocytochemical technique we have analyzed changes in substance P, somatostatin, calcitonin gene-related peptide, and galanin immunoreactivity pattern in the rat dorsal root ganglia. After 7 days of adrenalectomy, sham operated rats were compared with adrenalectomized animals either receiving a daily intraperitoneal injection of 10 mg/kg b.wt. corticosterone or vehicle. Three lumbar ganglia from each animal were blocked, serially cut, and immunostained for each neuropeptide by means of the biotin-avidin-peroxidase technique. A systematic sampling of immunoreactive ganglion cells was performed and the sample number of immunoreactive ganglion cells was calculated. After adrenalectomy, the number of substance P and somatostatin immunoreactive ganglion cells markedly increased ((means +/- S.E.M.): 245 +/- 68 versus 123 +/- 12 for sham operated animals, P < 0.01 (substance P) and 42 +/- 8 as compared to 22 +/- 9 for sham operated animals, P < 0.01 (somatostatin)). No significant changes were found in the number of calcitonin gene-related peptide and galanin immunoreactive cells after adrenalectomy. These results suggest that adrenal steroid hormones may reduce the synthesis of both substance P and somatostatin in the dorsal root ganglion cells. Daily treatment with a high dose of corticosterone, mimicking its serum levels after stress, failed to prevent the increase of peptide contents after adrenalectomy. These observations also indicate that a tonic action of corticosterone on mineralocorticoid receptors may be crucial for peptide regulation in the spinal ganglia. These results may be of relevance to adrenalectomy induced changes in sensory mechanisms, neurogenic inflammation and pain transmission and to a role of substance P and somatostatin in these processes.

A technique for converting a needle-catheter jejunostomy into a standard jejunostomy.

The benefits of enteral nutrition for surgical patients have been well documented in the literature, and needle catheter jejunostomy is frequently used at initial surgical exploration. Occasionally, the need arises for prolonged use of the catheter, and problems occur with occlusion of the catheter. A simple technique is described for converting the needle-catheter jejunostomy into a standard-feeding jejunostomy.

The many faces of aortoenteric fistulas.

Aortoenteric fistulas represent a life-threatening complication of abdominal aortic surgery that is becoming increasingly well-recognized. The presentation is often subtle, with a herald bleed followed by a period of grace, followed by an exsanguinating hemorrhage, and resulting in cardiovascular collapse. The diagnosis is often difficult, even with modern modalities of endoscopy, arteriography, and CAT scanning. A high index of suspicion is critical for making a successful diagnosis. The fistulas most commonly occur between the proximal aortic suture line and the duodenum after abdominal aortic surgery for aneurysmal or occlusive disease. Typically they occur years after this procedure. However, over the last several years, we have seen 12 cases with extremely unusual presentations that illustrate the wide spectrum of possible presentations. Included in this group was a primary aortoduodenal fistula, and two fistulas occurring just months after the initial surgery. These cases are reported with attention to the details of the presentation to emphasize the wide range of presentations of this serious complication. A brief review of this literature is also included in the report.

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.

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.

Nutritional improvement of poor urban preschool children. A 1983-1977 comparison.

The nutritional status of preschool children from 1,219 families living in an urban poverty area was surveyed in 1983 and these results were compared with findings from a similar survey of the same community done in 1977. A second comparison was made of children whose families participated in a commodity supplementary food program and those whose families did not participate. Results of the 1983 survey indicated improvements in median serum levels of vitamins A and C, hemoglobin, and red blood cell volume. Nevertheless, 9% to 18% of the children had low or deficient levels of vitamins A, C, B1, and B2, hemoglobin, serum iron, and transferrin saturation. Also a greater number of the preschoolers were categorized as thin. Annual incomes for families had significantly decreased from 1977 when the median value for food recipients was +3,078 to a median of +1,848 in 1983. Considering the decrease in other resources, federal food assistance programs seem to be the only identifiable factor contributing to the improvement in nutritional status over 1977.

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.

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.

Computed tomography scans and negative symptoms in schizophrenia: chronic schizophrenics with negative symptoms and nonenlarged lateral ventricles.

Computed tomography scans of 31 chronic schizophrenics with negative symptoms and 31 age-matched normal volunteers were assessed for ventricular size, cortical atrophies, third ventricle diameter, and cerebellar atrophies. No significant differences were found in the size of the lateral ventricles or third ventricles between the chronic schizophrenics and the controls. The frontal horns in patients did show a tendency toward increased size compared with controls. Sulci width showed significant differences between patients and controls. The clinical variables, except for the memory test, did not correlate with any brain morphology. A meta-analysis was performed on 17 studies that used the planimetric method in order to evaluate the relationships between the size of the lateral ventricles in patients and their respective controls. We found significant differences between the group of studies using normal controls and the group using medical controls.