Increasing the Rates of Complete Response to Neoadjuvant Chemoradiotherapy for Distal Rectal Cancer: Results of a Prospective Study Using Additional Chemotherapy During the Resting Period

OBJECTIVES: Addition of chemotherapy in the resting period between radiotherapy completion and response assessment during neoadjuvant treatment for distal rectal cancer could potentially increase rates of complete tumor regression. The purpose of this study was to evaluate toxicity rates and the impact of an extended neoadjuvant chemoradiation regimen on complete response rates. METHODS: Thirty-four consecutive patients with nonmetastatic distal rectal cancer were prospectively included. Patients were managed by 5,400 Gy of radiation and 5-fluorouracil/leucovorin-based chemotherapy given for three consecutive days every 21 days for six cycles (three cycles concomitant with radiotherapy). Tumor response assessment was performed at ten weeks from radiation completion. Patients with complete clinical response were strictly monitored and were not immediately operated on. Patients with incomplete clinical response were referred to surgery. RESULTS: Twenty-nine patients had completed 12 months of follow-up and were included in this preliminary analysis. Twenty-eight (97%) successfully completed treatment. Fifteen of 16 patients had Grade III toxicities that were skin-related (93%). Median follow-up was 23 months. Fourteen patients (48%) were considered as complete clinical responders sustained for at least 12 months (median, 24 months) after chemoradiation completion by clinical assessment alone. An additional five patients (17%) were considered as complete responders with ypT0 results after full-thickness local excision. Overall, the complete response rate was 65%. CONCLUSIONS: The addition of chemotherapy during the resting period after neoadjuvant chemoradiation is associated with acceptable toxicity and high tolerability rates. The considerably high rates of complete response in this preliminary series requires further follow-up, but they may provide valuable information for future prospective, randomized trials.

Mammography findings following electron intraoperative radiotherapy or external radiotherapy for breast cancer treatment

Radiotherapy following breast cancer conserving surgery decreases the risks of local recurrence. Because 85% of breast cancers relapse in or around the surgical bed there has been some debate on the need for irradiating the whole breast. Electron intraoperative radiotherapy (ELIOT) has been used as a viable alternative for conventional external radiotherapy (RT). While the former requires a single dose of 21 Gy in the tumoral bed, the latter requires 5-6 weeks of irradiation with a total dose of 50 Gy and a boost of 10 Gy that irradiates the surgical bed. Herein, we investigated whether any significant differences exist between the mammography findings obtained from patients submitted to one of the two techniques. Two groups of 30 patients each were included in this study. All patients had mammographies taken at 12 and 24 months after finishing treatment. The mammography findings evaluated were: cutaneous thickening (>2 mm), architectural distortion secondary to fibrosis, edema, calcifications (both benign and malignant), and fat necrosis. For all variables studied, there was no statistical difference between the two groups. This indicates that the mammography findings obtained in either 12- or 24-month follow-up periods after breast cancer conserving surgery are similar, regardless of which of the two radiotherapy techniques (ELIOT or RT) is employed as a treatment for breast cancer. (C) 2010 Published by Elsevier Ireland Ltd.

Long-Term Nutritional Outcome After Gastric Bypass

Weight loss and nutritional status 5 or more years after Roux-en-Y gastric bypass was prospectively documented. The hypothesis was that even after clinical adaptation, imbalances might still occur. Seventy-five consecutive patients (age 49.3 +/- 10.6 years, 89.3% females) were recruited 83.4 +/- 14.3 months after the intervention. Weight loss and nutritional abnormalities were registered. Body mass index (BMI) was 56.5 +/- 10.0 preoperatively, 29.4 +/- 6. 2 by 24 months and 34.4 +/- 14.6 when last seen. Major current deficit occurred for magnesium (32.1% of the patients), hemoglobin (50.8%), iron (29.8%), ferritin (36.0%), zinc (40.5%), vitamin B(12) (61.8%), vitamin D(3) (60.5%), and beta-carotene (56.8%). Low preoperative measurements had already been unveiled for iron, transferrin, zinc, and vitamin B(12). Total drug consumption tended to decrease after operation, and present findings correlated with excess weight loss (EWL). Also presence of diabetes and BMI value were predictors of long-term EWL, along with biochemical profile by 2 years. Multivitamin supplementation and gastrointestinal complaints partially correlated with nutritional results. (1) Good initial weight loss with moderate late regain, anemia, and multiple nutrient deficits was the common pattern. (2) Massive weight loss, frequent vomiting, dumping syndrome, and women in reproductive age were risk factors for hemoglobin or vitamin deficits, whereas superobesity, diabetes, and use of multiple drugs were associated with EWL result. (3) Most laboratory tests became stable by 2 years and along with BMI correlated with late EWL. (4) Two-year nutritional investigation is especially recommended because of its long-term predictive value.

Early and Late Results of Topical Diltiazem and Bethanechol for Chronic Anal Fissure: A Comparative Study

Background/Aims: Late efficacy of medical treatment of chronic anal fissure remains controversial due to high recurrence. This study aimed at analyzing safety and efficacy of topical diltiazem and bethanechol regarding healing and symptoms relief, safety, recurrence, and need for surgery. Methodology: This was a single-center non-randomized trial. Outcomes of 30 patients with chronic anal fissure treated with 2% diltiazem were compared to 30 patients treated with 0.1% bethanechol, both for eight weeks. Patients were assessed after seven days and eight weeks. Results: In diltiazem group, after seven days, 31% were symptomatic; after bethanechol, 71% (p=0.06). After seven days, fissure healing occurred in 19% after diltiazem and in 11% after bethanechol. After eight weeks, in both groups, 64% were asymptomatic; after diltiazem, 53% healed; after bethanechol, 50% (p=0.80). Success was the same for both groups: 63.3%. Groups were similar regarding complications. After diltiazem, 9 (30%) patients were operated on; and 11 (36.7%) after bethanechol (p=0.60). Recurrence occurred in 4 (13.3%) patients in both groups. Median time to recurrence after diltiazem was 15 (10-24) months and 7.5 (2-15) after bethanechol - p=0.15. Conclusions: Both treatments are safe and effective. Diltiazem may be associated to earlier relief and more sustained response.

Two-Year Outcome of Partial Lacrimal Punctal Occlusion in the Management of Dry Eye Related to Sjogren Syndrome

Purpose: To analyze the influence of thermal partial punctal occlusion on the ocular surface of dry eye related to Sjogren syndrome. Material and Methods: Thirty-seven eyes of 19 patients (3 male and 16 female; 49.11 +/- 14.33 years old) with keratoconjunctivitis sicca were enrolled in this study. Superior and inferior partial occlusion were performed in both eyes under topical anesthesia using thermal cautery with a sterile tip to obtain lacrimal punctum smaller than 0.5 mm. Schirmer I, break-up-time, diameter of lacrimal puncta, corneal fluorescein, and rose Bengal staining scores were analyzed before and after 24 weeks and after 24 months of the procedure. All measurements were performed under controlled climate. Results: The average lacrimal punctum diameter before the procedure was 0.65 +/- 0.134 mm. All lacrimal puncta were successfully reduced to less than 0.5 mm after 4 weeks of the procedure. The average Schirmer I test values improved statistically after 24 weeks and maintained stable after 24 months. Average break-up-time, rose Bengal, and fluorescein staining score values improved statistically after 24 weeks and improved even more after 24 months. Average Schirmer I test, break-up-time, rose Bengal, and fluorescein staining scores showed significant improvement (p < 0.0001) after 24 months of partial thermal punctal occlusion. Conclusion: Our study showed that reducing the punctum diameter to 0.5 mm can improve vital staining scores, break-up-time, and Schirmer I test in dry eye related to Sjogren syndrome.

Speech perception in adolescents with pre-lingual hearing impairment with cochlear implants

Profound hearing loss is a disability that affects personality and when it involves teenagers before language acquisition, these bio-psychosocial conflicts can be exacerbated, requiring careful evaluation and choice of them for cochlear implant. Aim: To evaluate speech perception by adolescents with profound hearing loss, users of cochlear Implants. Study Design: Prospective. Materials and Methods: Twenty-five individuals with severe or profound pre-lingual hearing loss who underwent cochlear implantation during adolescence, between 10 to 17 years and 11 months, who went through speech perception tests before the implant and 2 years after device activation. For comparison and analysis we used the results from tests of four choice, recognition of vowels and recognition of sentences in a closed setting and the open environment. Results: The average percentage of correct answers in the four choice test before the implant was 46.9% and after 24 months of device use, this value went up to 86.1% in the vowels recognition test, the average difference was 45.13% to 83.13% and the sentences recognition test together in closed and open settings was 19.3% to 60.6% and 1.08% to 20.47% respectively. Conclusion: All patients, although with mixed results, achieved statistical improvement in all speech tests that were employed.

Acquisition of Serum Antibodies Reactive With Enterohemorrhagic Escherichia coli Virulence-Associated Factors by Healthy Brazilian Children and Adults

Background: Patients with hemorrhagic colitis or hemolytic uremic syndrome due to enterohemorrhagic Escherichia coli (EHEC) develop serum IgM and IgG response to lipopolysaccharide (LPS) and to virulence factors such as intimin. The small numbers of cases of diarrhea associated with EHEC strains in Brazil suggests a pre-existing immunity probably due to previous contact with diarrheagenic E. coli. Our aim was to evaluate the development of the serum antibody repertoire to EHEC virulence factors in Brazilian children and adults. Methods: Serum IgM and IgG antibodies were determined by enzyme-linked immunosorbent assay with LPS O111, LPS O26, and LPS O157 in 101 children between 2 months and 10 years of age and in 100 adult sera, by immunoblotting with protein membrane extracts and purified beta intimin; the ability of adult sera to neutralize Shiga toxin2 was also investigated. Results: Children older than 24 months had IgM concentrations reactive with the 3 LPS equivalent to those seen in the adult group, and significantly higher than the group of younger children (P < 0.05). Anti-O26 and anti-O157 LPS IgG concentrations were equivalent between the 2 groups of children and were significantly different from the adult group (P < 0.05). The anti-O111 LPS IgG levels in older children were intermediate between the younger group, and adults (P < 0.05). Immunoblotting revealed strong protein reactivity, including the conserved and variable regions of beta intimin and more than 50% of the adult samples neutralized Shiga toxin 2. Conclusions: Our results demonstrate an increasing anti-LPS and antiprotein antibody response with age, which could provide protection against EHEC infections.

A longitudinal study on the transmission dynamics of human Leishmania (Leishmania) infantum chagasi infection in Amazonian Brazil, with special reference to its prevalence and incidence

This was a longitudinal study carried out during a period over 2 years with a cohort of 946 individuals of both sexes, aged 1 year and older, from an endemic area of American visceral leishmaniasis (AVL) in Para State, Brazil. The object was to analyze the transmission dynamics of human Leishmania (Leishmania) infantum chagasi infection based principally on the prevalence and incidence. For diagnosis of the infection, the indirect fluorescent antibody test (IFAT) and leishmanin skin test (LST) were performed with amastigote and promastigote antigens of the parasite, respectively. The prevalence by LST (11.2%) was higher (p < 0.0001) than that (3.4%) by IFAT, and the combined prevalence by both tests was 12.6%. The incidences by LST were also higher (p < 0.05) than those by IFAT at 6 (4.7% A- 0.6%), 12 (4.7% A- 2.7%), and 24 months (2.9% A- 0.3%). Moreover, there were no differences (p > 0.05) between the combined incidences by both tests on the same point surveys, 5.2%, 6.3%, and 3.6%. During the study, 12 infected persons showed high IFAT IgG titers with no LST reactions: five children and two adults developed AVL (2,560-10,120), and two children and three adults developed subclinical oligosymptomatic infection (1,280-2,560). The combined tests diagnosed a total of 231 cases of infection leading to an accumulated prevalence of 24.4%.

Leprosy-specific oral lesions: A report of three cases

Leprosy is a chronic infection caused by Mycobacterium leprae, a bacillus that presents a peculiar tropism for the skin and peripheral nerves. The clinical spectrum of leprosy ranges from the tuberculoid form (TT) to the disseminative and progressive lepromatous form (LL). Oral lesions are rare but, when present, occur in the lepromatous form. This article describes the clinical and microscopic findings of three cases of LL with oral manifestations. All patients had the lepromatous form and their leprosy-specific oral lesions occurred in the palate. The diagnosis was based on clinical, serological and histopathological findings, and multidrug therapy for multibacillary leprosy was started and continued for 24 months. All patients completed treatment, but developed reaction episodes which were treated with prednisone and/or thalidomide. The authors emphasize the importance of oral mucosa evaluation by a dental health professional during patient care since oral lesions may act as a source of infection.

C-Peptide Levels and Insulin Independence Following Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus

Context In 2007, the effects of the autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in 15 patients with type 1 diabetes mellitus (DM) were reported. Most patients became insulin free with normal levels of glycated hemoglobin A(1c) (HbA(1c)) during a mean 18.8-month follow-up. To investigate if this effect was due to preservation of beta-cell mass, continued monitoring was performed of C-peptide levels after stem cell transplantation in the 15 original and 8 additional patients. Objective To determine C-peptide levels after autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM during a longer follow-up. Design, Setting, and Participants A prospective phase 1/2 study of 23 patients with type 1 DM(aged 13-31 years) diagnosed in the previous 6 weeks by clinical findings with hyperglycemia and confirmed by measurement of serum levels of anti glutamic acid decarboxylase antibodies. Enrollment was November 2003-April 2008, with follow-up until December 2008 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirao Preto, Ribeirao Preto, Brazil. Hematopoietic stem cells were mobilized via the 2007 protocol. Main Outcome Measures C-peptide levels measured during the mixed-meal tolerance test, before, and at different times following HSCT. Secondary end points included morbidity and mortality from transplantation, temporal changes in exogenous insulin requirements, and serum levels of HbA1c. Results During a 7- to 58-month follow-up (mean, 29.8 months; median, 30 months), 20 patients without previous ketoacidosis and not receiving corticosteroids during the preparative regimen became insulin free. Twelve patients maintained this status for a mean 31 months (range, 14-52 months) and 8 patients relapsed and resumed insulin use at low dose (0.1-0.3 IU/kg). In the continuous insulin-independent group, HbA(1c) levels were less than 7.0% and mean (SE) area under the curve (AUC) of C-peptide levels increased significantly from 225.0 (75.2) ng/mL per 2 hours pretransplantation to 785.4 (90.3) ng/mL per 2 hours at 24 months posttransplantation (P<.001) and to 728.1 (144.4) ng/mL per 2 hours at 36 months (P=.001). In the transient insulin-independent group, mean (SE) AUC of C-peptide levels also increased from 148.9 (75.2) ng/mL per 2 hours pretransplantation to 546.8 (96.9) ng/mL per 2 hours at 36 months (P=.001), which was sustained at 48 months. In this group, 2 patients regained insulin independence after treatment with sitagliptin, which was associated with increase in C-peptide levels. Two patients developed bilateral nosocomial pneumonia, 3 patients developed late endocrine dysfunction, and 9 patients developed oligospermia. There was no mortality. Conclusion After a mean follow-up of 29.8 months following autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM, C-peptide levels increased significantly and the majority of patients achieved insulin independence with good glycemic control. Trial Registration clinicaltrials.gov Identifier: NCT00315133

Prevention of ""Risky"" drinking among students at a Brazilian University

Aim: The aim of this paper was to compare the quantity and frequency of alcohol use and its associated negative consequences between two groups of college students who were identified as being ""risky drinkers."" Subjects were randomly allocated in a clinical trial to intervention or control groups. Methods: Risky drinking use was defined as Alcohol Use Disorders Identification Test (AUDIT) >= 8 and/or Rutgers Alcohol Problem Index (RAPI) >= 5 problems in the previous year. Students who had undergone the Brief Alcohol Screening and Intervention for College Students (BASICS) (N = 145 at baseline; 142 at 12 months, and 103 at 24 months, loss of 29.7%) were compared with a control group (N = 121 at baseline; 121 at 12 months and 113 at 24 months, loss of 9.3%), the nonintervention group. Variables included drinking frequency, quantity and peak consumption, dependence assessment, and family and friends` abuse assessment. Results: Treated students at a 24-month follow-up decreased quantity of alcohol use per occasion and lowered AUDIT and RAPI scores. Conclusions: This is the first brief intervention work on risky drinking with college students in Brazil and the results are encouraging. However, it is difficult to conduct individual prevention strategies in a country where culture fosters heavy drinking through poor public policy on alcohol and lack of law enforcement.

Oral lesions and immune reconstitution syndrome in HIV+/AIDS patients receiving highly active antiretroviral therapy. Epidemiological evidence

Objective: To determine whether opportunistic oral infections associated to HIV infection (OOI-HIV) are found in HIV+/AIDS patients with immune reconstitution related to highly active antiretroviral therapy (HAART). Methods. From among 1100 HIV+/AIDS patients (Service of Internal Medicine, Carlos Haya Hospital, Malaga, Spain) subjected to review of the oral cavity between January 1996 and May 2007, we identified those examined in 1996 and which were again examined between 1997 and 2007, and were moreover receiving HAART. The following data were collected: age, gender, form of contagion, antiretroviral therapy at the time of review, number of CD4+ lymphocytes/ml, and viral load (from 1997 onwards). We identified those subjects with an increase in CD4+ lymphocytes/ ml associated to HAART, and classified them as subjects with quantitative evidence of immune reconstitution (QEIR). Among these individuals with QEIR we moreover identified those with undetectable viral loads (QEIR+VL), and differentiated those patients with an increase in CD4+ lymphocytes > 500/ml (QEIRm+VL). In each group we determined the prevalence of OOI-HIV, following the diagnostic recommendations of the EC-Clearinghouse (CDC-Atlanta, USA - WHO). In addition, we analyzed the prevalence of OOI-HIV in the different groups in relation to the duration of HAART. Results. A total of 86 subjects were included (44 females and 42 males; 19 heterosexuals, 34 male homosexuals, and 33 intravenous drug abusers). Forty-two patients showed QEIR: 21 belonged to the QEIR+VL group, and 17 conformed the QEIRm+VL group. The prevalence of OOI-HIV per group was as follows: QEIR = 54.8%; QEIR+VL = 33%; QEIRm+VL = 35%. The most prevalent lesion in all groups was erythematous candidiasis. OOI-HIV increased with the duration of HAART (p=0.008), and were seen to be dependent upon late appearance of the mycotic lesions ( after 24 months under HAART). Conclusions: It is suggested that opportunistic oral infections associated to HIV infection form part of the clinical picture of immune reconstitution inflammatory syndrome, though such infections are of late onset.

Bone crestal height and bone density after third-molar extraction and grafting: a long-term follow-up study

The objective of this study was to evaluate the long-term influence of xenogenic grafts on bone crestal height and radiographic density following extraction of teeth. The right and left third lower molars of 22 patients were surgically extracted, and one randomly chosen socket was filled with a xenogenic graft (Gent-Tech). The contralateral molar was left to heal naturally, serving as a paired control. Digital intraoral radiographies were taken at surgery and 2, 6, and 24 months after, to evaluate bone density (BD) and alveolar bone crest to cementoenamel junction distance. The data obtained were subjected to two-way analysis of variance and Tukey`s test (alpha = 0.05). The significant decrease in cementoenamel junction distance observed for both groups was limited to the first 6 months. BD values increased significantly in the first 6 months, with no alterations observed up to 24 months for both groups. BD was higher for the experimental group at all time points (p < 0.05). Socket grafting with the xenogenic materials tested did not changed bone crestal height and bone radiographic density in the long term.

An in vitro study of non-axial forces upon the retention of an O-ring attachment

Objective The purpose of this study was to evaluate the retention force of an O-ring attachment system in different inclinations to the ideal path of insertion, using devices to compensate angulations. Material and methods Two implants were inserted into an aluminum base, and ball attachments were screwed to implants. Cylinders with O-rings were placed on ball attachments and connected to the test device using positioners to compensate implant angulations (0 degrees, 7 degrees, and 14 degrees). Plexiglass bases were used to simulate implant angulations. The base and the test device were positioned in a testing apparatus, which simulated insertion/removal of an overdenture. A total of 2900 cycles, simulating 2 years of overdenture use, were performed and 36 O-rings were tested. The force required for each cycle was recorded with computer software. Longitudinal sections of ball attachment-positioner-cylinder with O-rings of each angulation were obtained to analyze the relationship among them, and O-ring sections tested in each angulation were compared with an unused counterpart. A mixed linear model was used to analyze the data, and the comparison was performed by orthogonal contrasts (alpha=0.05). Results At 0 degrees, the retention force decreased significantly over time, and the retention force was significantly different in all comparisons, except from 12 to 18 months. When the implants were positioned at 7 degrees, the retention force was statistically different at 0 and 24 months. At 14 degrees, significant differences were found from 6 and 12 to 24 months. Conclusions Within the limitations of this study, it was concluded that O-rings for implant/attachments perpendicular to the occlusal plane were adequately retentive over the first year and that the retentive capacity of O-ring was affected by implant inclinations despite the proposed positioners. To cite this article:Rodrigues RCS, Faria ACL, Macedo AP, Sartori IAM, de Mattos MGC, Ribeiro RF. An in vitro study of non-axial forces upon the retention of an O-ring attachment.Clin. Oral Impl. Res. 20, 2009; 1314-1319.doi: 10.1111/j.1600-0501.2009.01742.x.

Outcome analysis of immediately placed, immediately restored implants in the esthetic area: The clinical relevance of different interimplant distances

Background: The purpose of this study was to compare and evaluate bone and soft tissue levels between immediately placed, immediately restored implants positioned in the esthetic anterior region with different interimplant distances (IID). Methods: Forty-nine patients requiring multiple implant restorations in the anterior regions received 152 implants, which were restored immediately. Periapical radiographs and digital images of 99 interimplant sites were taken at the regular follow-up examinations at 0, 6, 12, and 24 months after surgery. They were digitally recorded and analyzed. The presence of the interproximal papilla was assessed and compared to the distances between the bone crest and the contact point between the natural teeth and the restoration crowns. Results: Implants with an IID <2 mm seemed to lose less bone laterally. When the IID was <2 mm, vertical crestal bone loss was significantly greater than in the group with IID >4 mm. The percentage of the interproximal papilla presence decreased when the distance between the bone crest and the contact point between the two restoration crowns was >6 mm and when two implants were placed at a distance >= 4 mm. Conclusions: To guarantee a better esthetic result in immediately placed, immediately restored implants, the contact point between the two prosthetic crowns should be placed at 3 to 4 mm, and never >6 mm, from the bone peak. Two adjacent implants should be placed at a distance >2 and <4 mm.