Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment.

PURPOSE: The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer. METHODS: Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3-4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints: SOM duration and grade 2-4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration. RESULTS: Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms. CONCLUSIONS: Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.

TLI in pediatric patients.

PURPOSE: Hematopoietic progenitor cell transplantation (HSCT) is a procedure used in different hematological diseases as part of the curative treatment, so the investigators propose a system of conditioning of reduced intensity based on total lymphoid irradiation (TLI) as an alternative to the classic total body irradiation (TBI) followed by haploidentical transplantation in patients compatible with a single HLA haplotype, as an alternative to patients who do not have an HLA compatible donor. MATERIALS AND METHODS: A cohort of 25 patients with hematological disease underwent haploidentical HSCT from February 2015 to May 2018, conditioned with TLI from day - 10 (2-4 days of treatment) followed by thiotepa (5 mg/kg/12 h) and melphalan (70 mg/m2/day) prior to HSCT and prophylaxis with ciclosporin (1.5 mg/kg/12 h). 2 Gy/fraction was administered to complete 8 Gy with IMRT and VMAT technique. RESULTS: 12% rejection of the transplant was obtained with acute GVHD < II (48%) and chronic GVHD 12%. No acute toxicity was recorded in irradiated patients and 56% survival of patients at the end of follow-up. CONCLUSION: Conditioning the haploidentical transplant with TLI, IMRT, and VMAT techniques compared with TBI and RT3D-C techniques is a feasible technique that helps inducing the necessary immunosuppression in patients with a high risk of graft rejection, minimal adverse effects, low incidence of GVHD, and high survival rate.

Infrastructure and equipment for radiation oncology in the Spanish National Health System: analysis of external beam radiotherapy 2015-2020.

PURPOSE: Planning for radiation oncology requires reliable estimates of both demand for radiotherapy and availability of technological resources. This study compares radiotherapy resources in the 17 regions of the decentralised Spanish National Health System (SNHS). MATERIALS AND METHODS: The Sociedad Española de Oncología Radioterápica (SEOR) performed a cross-sectional survey of all Spanish radiation oncology services (ROS) in 2015. We collected data on SNHS radiotherapy units, recording the year of installation, specific features of linear accelerators (LINACs) and other treatment units, and radiotherapeutic techniques implemented by region. Any machine over 10 years old or lacking a multileaf collimator or portal imaging system was considered obsolete. We performed a k-means clustering analysis using the Hartigan-Wong method to test associations between the gross domestic regional product (GDRP), the number of LINACs per million population and the percentage of LINACs over 10 years old. RESULTS: The SNHS controls 72 (61%) of the 118 Spanish ROS and has 180 LINACs, or 72.5% of the total public and private resources. The mean rate of LINACs per million population is 3.9 for public ROS, and 42% (n = 75) of the public accelerators were obsolete in 2015: 61 due to age and 14 due to technological capability. There was considerable regional variation in terms of the number and technological capacity of radiotherapy units; correlation between GRDP and resource availability was moderate. CONCLUSION: Despite improvements, new investments are still needed to replace obsolete units and increase access to modern radiotherapy. Regular analysis of ROS in each Spanish region is the only strategy for monitoring progress in radiotherapy capacity.

Anatomical redistribution of sweating after T2-T3 thoracoscopic sympathicolysis: a study of 210 patients.

BACKGROUND: The cutaneous influence areas of the different sympathetic ganglia have not been fully established to date. The aim of this study was to define the cutaneous influence area of sympathetic ganglia T2-T3. METHODS: A total of 210 patients with primary hyperhidrosis (PH) underwent 420 thoracoscopic sympathicolysis procedures of ganglia T2-T3 in a prospective study. All completed a preoperative questionnaire and a second questionnaire 12 months after the operation. The questionnaires evaluated perspiration in the different body areas. Only the zones of anhidrosis were considered in delimiting the cutaneous expression of sympathetic ganglia T2-T3. RESULTS: Redistribution of perspiration as reported by the patients comprised significant reduction in the palms, axillas, and soles, and an increase in the abdomen, back, and gluteal and popliteal regions. Regarding the incidence of anhidrosis by anatomical location, statistically significant changes were recorded in the head, hands, axillas, and soles (p < 0.001). CONCLUSIONS: Bilateral upper thoracic sympathicolysis is followed by redistribution of body perspiration, with a clear decrease in the zones regulated by mental or emotional stimuli, and an increase in the areas regulated by environmental stimuli, though we are unable to establish the etiology of this redistribution.

Thoracic sympathicolysis for primary hyperhidrosis: a review of 918 procedures.

BACKGROUND: Bilateral upper thoracic sympathectomy or sympathicolysis, currently the standard treatment for palmar or axillary hyperhidrosis, is regarded as a safe procedure. This study evaluates the quantitative and qualitative incidence of intraoperative and postoperative complications resulting from bilateral thoracic sympathicolysis. METHODS: From 1996 to 2004, 458 consecutive patients with primary hyperhidrosis underwent surgery. These patients comprised 143 men (31.2%) and 315 women (68.7%) with a mean age of 26 years (range, 14-52 years). In all but seven cases, the procedure was bilaterally synchronous. RESULTS: No mortality was recorded. The anhydrosis rate was 97.4%, with a hypohidrosis rate of 2.4% and a failure rate of 0.2%. The latter was resolved with reintervention. The mean hospital stay was 17 h. The rate of major perioperative complications with conversion to thoracotomy was 0.4%. The overall rate of postoperative complications was 3.6%. The complications and rates observed were as follows: pneumothorax (2.06%), subcutaneous emphysema (1.08%), pleural bleeding (0.2%), hemothorax (0.1%), and atelectasis (0.1%). Compensatory hyperhidrosis was observed in 48.4% of the patients, but the sensation of compensatory hyperhidrosis was reported in 85.6% of the cases. Excessive dryness of the hands was reported in 0.38%, Horner's syndrome in 0.32%, and gustatory hyperhidrosis in 1.1% of the cases. The overall satisfaction rate was 88.5%. CONCLUSIONS: The results suggest that endoscopic bilateral thoracic sympathicolysis is an effective method for managing primary hyperhidrosis, especially severe palmar hyperhidrosis, but it is necessary to inform patients fully concerning the undesirable effects.

[Results of high bilateral endoscopic thoracic sympathectomy and sympatholysis in the treatment of primary hyperhidrosis: a study of 1016 procedures]. / Resultados de la simpaticólisis y la simpatectomía torácica superior bilateral endoscópica en el tratamiento de la hiperhidrosis primaria. Estudio de 1.016 procedimientos.

OBJECTIVE: Thoracic sympatholysis and sympathectomy are the current standard treatments for primary hyperhidrosis. In this study, we evaluated the incidence of peri- and postoperative complications associated with these procedures. PATIENTS AND METHODS: From 1996 to 2004, 520 consecutive patients (364 women), with a mean age of 26.8 years, were treated for primary hyperhidrosis at our hospital. The procedure was bilateral in all but 24 cases. The 484 patients in the sympatholysis group underwent a single intervention while the 36 patients in the sympathectomy group underwent 2 separate interventions. RESULTS: No deaths occurred. Anhidrosis of the target area was achieved in 97.6% of patients while 2.2% experienced hypohidrosis. In 0.2% of the cases, the procedure was initially unsuccessful and a second intervention was required. The mean duration of hospital stay was 72 hours for patients in the sympathectomy group and 17 hours for the sympatholysis group. Serious intraoperative complications requiring conversion to thoracotomy were recorded in 0.2% of patients. Postoperative complications--of which pneumothorax was the most common--occurred in 5.2% of the cases (in 22.5% of the sympathectomy group and 3.55% of the sympatholysis group). Compensatory hyperhidrosis occurred in 48.4% of the patients, excessive dryness of the hands and palpebral ptosis in 0.38%, and gustatory sweating in 0.9%. The degree of patient satisfaction was quite high (88.5%) and only 2.3% were very unsatisfied. CONCLUSIONS: Given the results obtained, we can conclude that both sympatholysis and sympathectomy are appropriate treatments for hyperhidrosis. Nonetheless, because sympatholysis is both easier to perform and less aggressive, we consider it the treatment of choice for primary hyperhidrosis.

Oral butyrate for mildly to moderately active Crohn's disease.

BACKGROUND: Butyrate exerts anti-inflammatory effects in experimental colitis and on Crohn's disease lamina propria mononuclear cells in vitro. AIM: To explore the efficacy and safety of oral butyrate in Crohn's disease. METHODS: Thirteen patients with mild-moderate ileocolonic Crohn's disease received 4 g/day butyrate as enteric-coated tablets for 8 weeks. Full colonoscopy and ileoscopy were performed before and after treatment. Endoscopical and histological score, laboratory data, Crohn's disease activity index and mucosal interleukin (IL)-1beta, IL-6, IL-12, interferon-gamma, tumour necrosis factor-alpha and nuclear factor-kappa B (NF-kappaB) were assessed before and after treatment. RESULTS: One patient withdrew from the study, and three patients did not experience clinical improvement. Among the nine patients (69%) who responded to treatment, seven (53%) achieved remission and two had a partial response. Endoscopical and histological score significantly improved after treatment at ileocaecal level (P < 0.05). Leucocyte blood count, erythrocyte sedimentation rate and mucosal levels of NF-kappaB and IL-1beta significantly decreased after treatment (P < 0.05). CONCLUSIONS: Oral butyrate is safe and well tolerated, and may be effective in inducing clinical improvement/remission in Crohn's disease. These data indicate the need for a large investigation to extend the present findings, and suggest that butyrate may exert its action through downregulation of NF-kappaB and IL-1beta.

[Primary hyperhidrosis and anxiety: a prospective preoperative survey of 158 patients]. / Hiperhidrosis primaria y ansiedad: estudio prospectivo preoperatorio de 158 pacientes.

OBJECTIVE: To determine the location of hyperhidrosis, the accompanying signs and symptoms, and patient anxiety assessed on 2 scales and standardized psychometric instruments. PATIENTS AND METHODS: A prospective study of patients with hyperhidrosis was carried out between September 1, 2001 and June 30, 2003 with a self-administered preoperative questionnaire. The variables studied included the location of hyperhidrosis, the accompanying signs and symptoms, and the self-reported degree of anxiety and perception of its effect on daily life assessed by the State-Trait Anxiety Inventory (STAI) and a questionnaire designed in our department. RESULTS: Palmar hyperhidrosis was reported by 93.6% of patients, plantar by 70.2%, axillary by 66.4%, facial by 12.1%, groin by 8.2%, chest by 5%, and abdominal by 2%. While more than 50% of the patients reported facial blushing and palpitations as accompanying signs and symptoms, approximately 30% experienced epigastric pain, trembling, and headaches. Over half of the patients reported that their anxiety was incapacitating, and a mere 1.2% experienced none at all. STAI scores were similar to those of the general population whereas scores on our department's questionnaire reflected those of the self-reported anxiety ratings. CONCLUSIONS: Primary hyperhidrosis is a disorder in which excessive sweating occurs mainly, but not exclusively, on the palms. The condition is accompanied by signs and symptoms typical of autonomic nervous system hyperactivity and by a degree of anxiety that has an incapacitating effect on normal life, although that anxiety is not detected by the STAI questionnaire alone.

Points to consider when choosing a biopsy method in cases of pleurisy of unknown origin.

Blind pleural needle biopsy and diagnostic thoracoscopy are procedures sometimes used in the work-up of a patient with pleural effusion of unknown origin. We reviewed 203 diagnostic thoracoscopies in patients with malignant pleural effusion to show the different location of pleural metastasis, some out of the reach of blind needle biopsy. Based on these data, we find diagnostic thoracoscopy a superior procedure because of its higher reliability, faster diagnostic results, slight or no complications, and the possibility of carrying out pleurodesis in the same examination.

Immunoglobulin M memory B cell decrease in inflammatory bowel disease.

BACKGROUND & OBJECTIVES: Memory B cells represent 30-60% of the B cell pool and can be subdivided in IgM memory and switched memory. IgM memory B cells differ from switched because they express IgM and their frequency may vary from 20-50% of the total memory pool. Switched memory express IgG, IgA or IgE and lack surface expression of IgM and IgD. Switched memory B cells derive from the germinal centres, whereas IgM memory B cells, which require the spleen for their survival and/or generation, are involved in the immune response to encapsulated bacteria. Since infections are one of the most frequent comorbid conditions in inflammatory bowel disease, we aimed to verify whether IgM memory B cell pool was decreased in Crohn's disease and ulcerative colitis patients. PATIENTS & METHODS: Peripheral blood samples were obtained from 22 Crohn's disease patients, 20 ulcerative colitis patients, 22 healthy controls and 18 splenectomized patients. To analyse peripheral blood lymphocytes, flow cytometry was performed using anti-CD19, anti-CD22, anti-CD27, anti-IgM, anti-IgD and anti-CD38 monoclonal antibodies. RESULTS: Circulating IgM memory B cells were significantly lower in Crohn's disease (median 7.1%, range 1.8-20.7) and ulcerative colitis patients (median 8.1%, range 2.1-18.8) in comparison to control subjects (median 14.0%, range 6.8-31.1). As expected, there was a highly significant difference in the proportion of IgM memory B cells between splenectomized patients (median 2.4%, range 0.9-6.9) and healthy controls. Crohn's disease patients with abscesses showed the lowest frequency of IgM memory B cells. DISCUSSION: Our findings show that peripheral IgM memory B cells are reduced in inflammatory bowel disease patients. Further studies are necessary to answer the question of whether high risk of infection (abscess development) is promoted by the reduction/depletion of IgM memory B-cell pool in inflammatory bowel disease.

[Histopathological changes in sympathetic ganglia of patients treated surgically for palmar-axillary hyperhidrosis. A study of 55 biopsies]. / Cambios anatomopatológicos observados en los ganglios simpáticos de pacientes intervenidos de hiperhidrosis palmar-axilar. Estudio de 55 muestras.

INTRODUCTION: Primary palmar hyperhidrosis (PPH) mainly affects the sympathetic ganglia. This study aims to analyze the histopathological changes in the sympathetic ganglia of patients with PPH. MATERIAL AND METHOD: We studied 55 tissue samples from 35 patients with PPH who underwent T2-T3 gangliectomy for definitive treatment of their disease, analyzing the presence of inflammation, chromatolysis and lipofuscin accumulation. Findings were analyzed in relation to age, compensatory sweating and type of surgery: unilateral, synchronic bilateral or sequential bilateral. RESULTS: We found inflammation in 5.5%, chromatolysis in 61.8% and lipofuscin accumulation in 41.8% of the samples. Chromatolysis and lipofuscin were found without inflammation in 32.1%. Chromatolysis and lipofuscin accumulation were each found in 60% of the samples from synchronic bilateral sympathectomies. However, those percentages decreased between the first and second sympathectomies in sequential procedures, such that chromatolysis was found in 71.4% of first-procedure samples and 42.8% of second-procedure samples; the rates for lipofuscin accumulation changed from 64.2% to 14.2%. Although findings were unrelated to age, they did correlate with compensatory sweating, which was found in 79.7% of patients undergoing synchronic bilateral sympathectomy, 78.5% of sequential bilateral sympathectomy patients and only 56.25% of unilateral sympathectomy patients. CONCLUSIONS: Neuronal death and lipofuscin accumulation unrelated to inflammation are evident in sympathetic ganglia from patients with PPH. Such changes are atypical for a group of patients whose mean age is 29 years, unless such lesions are the result of functional hyperstimulation. Surgery performed sequentially does not lead to overloading of contralateral T2-T3 ganglia; on the contrary, decreased injury is evident.

[Compensatory sweating after upper thoracic sympathectomy. Prospective study of 123 cases]. / Sudación compensatoria secundaria a la simpaticólisis torácica superior. Estudio prospectivo de 123 casos.

OBJECTIVE: The most unpleasant consequence of upper thoracic sympathectomy is compensatory sweating (CS). De-pending on the series, the incidence of CS ranges from 24% to 85%. The aim of this study was to determine the relation between CS and the following factors: distribution of hyperhidrosis, procedure performed (unilateral, synchronic bilateral, or sequential bilateral), and number of sympathetic ganglia eliminated. In addition, the degree of patient satisfaction was recorded as objectively as possible. PATIENTS AND METHODS: Prospective study of 123 patients who underwent upper thoracic sympathectomy for palmar and/or axillary hyperhidrosis between 1 January, 1996 and 1 June, 2002 at our unit. All patients completed a questionnaire on symptoms 8 weeks before and after surgery to deter-mine postoperative changes in distribution of the hyperhidrosis and the overall degree of satisfaction on a scale of 0 to 4. RESULTS: The sensation of CS was reported by 86.1% of the patients. When asked to relate this sensation to changes in sweating intensity in specific parts of the body, 46.54% reported CS and 48.37% no change. The trunk was the only region where statistically significant increases in CS occurred; in the feet, a decrease in sweating was noted. No differences in CS were observed with respect to the type of surgery or the number of sympathetic ganglia eliminated. The overall results were considered very satisfactory or quite satisfactory by 84.55% of the patients, while 4.88% were very dissatisfied. CONCLUSIONS: Although CS is a side effect of upper thoracic sympathectomy, not all patients are affected by it. Significant CS occurs mainly in the back, chest, and abdomen. Neither the type of intervention nor the number of ganglia eliminated has an effect on CS. This side effect notwithstanding, overall satisfaction with the treatment is very satisfactory given that the palmar hyperhidrosis is eliminated.

[Effectiveness of omeprazole, clarithromycin and amoxycillin therapy to eradicate Helicobacter pylori in patients with active peptic ulcer. Preliminary results of GENPY study]. / Efectividad de la combinación de omeprazol, claritromicina y amoxicilina en la erradicación de Helicobacter pylori en pacientes con ulcus péptico activo: resultados preliminares del Estudio GEHPY. Grupo de Estudio de Helicobacter pylori.

BACKGROUND: To compare the effectiveness of two length of the same therapy to eradicate Helicobacter pylori in patients with non complicated active peptic ulcer. PATIENTS AND METHODS: 223 patients visited at primary health centres. A randomised controlled trial was carried out to compare the results of 6 or 7 days of treatment with clarithromycin 500 mg, amoxicillin 1 g and omeprazole 20 mg, b.i.d. All patients received omeprazole for other 14 days. RESULTS: 108 patients were randomised to the 6 days group and 115 to the 7 days one. Both groups were comparable with respect to basic characteristics except for sex: the proportion of men was higher in the 6 days group (p = 0.04). 91.4% of the patients received all the treatment correctly. By intention to treat analysis, eradication rates were 76.9% in the 6 days group and 77.4% in the seven days group (IC 95% of the difference from -10.5 to 11.6). There were not statistically significant differences in eradication rates in relation to age, sex, ulcer location, recurrence or tobacco consumption. CONCLUSIONS: Although eradication rates are lower than expected, in this study there are no differences between 6 or 7 days of therapy.

[Quality of life in arterial hypertension]. / Calidad de vida en la hipertensión arterial.

BACKGROUND: Quality of life is a key issue for the consideration of hypertension therapy. However, reliable and sensitive evaluation methods are not available in Spain. To this end, a quality of life questionnaire has been elaborated, its yield has been evaluated, and the influence of hypertension and several associated variables on the quality of life has been assessed. METHODS: A questionnaire on quality of life consisting of 62 items was elaborated. Its final evaluation was divided in an overall value and in four subindexes related with anxiety, depression, side effects, and somatic complaints. It was applied to two groups of hypertensive patients, one from hospital care (n = 90) and another from primary care (n = 89), and to a control group (n = 76). RESULTS: Although both populations with hypertension were significantly different regarding age, sex, use of therapies, organic impact and blood pressure, they were overall similar in quality of life. However, quality of life was different from that in control group, which showed better indices. In the hypertensive population, sex, severity of hypertension, type of therapy or duration of the disease did not have any influence on quality of life. CONCLUSIONS: The overall similar quality of life in both hypertensive groups (in spite of the many significant differences in their descriptive features) and the different quality of life between hypertensive and normotensive individuals (in spite of the similitude of their demographic parameters) suggest that the diagnosis of hypertension has by itself a greater influence on the quality of life than several hypertension-associated variables. It has also been found that the method used was sensitive and valid. Therefore, the use of the quality of life questionnaire can be a useful instrument for the monitorization of hypertensive patients.

[Asymptomatic polymyositis with pulmonary disease]. / Polimiositis asintomática con afectación pulmonar.

We present the case of a medium-aged patient with a alveolo-interstitial pulmonary affection after 5 months of evolution, characterized by cough and progressive dyspnea accompanied by sustained febricula, slight constitutional syndrome and dermatological and articular manifestations. It was finally concluded that the patient had a polymyositis, relating form of affection a secondary interstitial pneumopathy. The aim of this study has been to highlight a rare case of diffuse interstitial disease in the context of a polymyositis in which we obtained an excellent therapeutical response, as well as to make some considerations regarding its etiology and its clinical and pathological expression.