ILEOSTIM trial: a study protocol to evaluate the effectiveness of efferent loop stimulation before ileostomy reversal.

PURPOSE: A protective loop ileostomy is the most useful method to reduce sequelae in the event of an anastomotic leakage (AL) after rectal cancer surgery. However, it requires an additional stoma reversal surgery with its own potential complications. Postoperative ileus (POI) remains the most common complication after ileostomy reversal, which leads to an increase in morbidity, length of hospital stay (LOS) and overall healthcare costs. Several retrospective studies carried out in this field have concluded that there are insufficient evidence-based recommendations about the routine application of preoperative bowel stimulation in clinical practice. Here we discuss whether stimulation of the efferent limb before ileostomy reversal might reduce POI and improve postoperative outcomes. METHODS: This is a multicentre randomised controlled trial to determine whether mechanical stimulation of the efferent limb during the 2 weeks before the ileostomy reversal would help to reduce the development of POI after surgery. This study was registered on Clinicaltrials.gov (NCT05302557). Stimulation will consist of infusing a solution of 500 ml of saline chloride solution mixed with a thickening agent (Resource©, Nestlé Health Science; 6.4 g sachet) into the distal limb of the ileostomy loop. This will be performed within the 2 weeks before ileostomy reversal, in an outpatient clinic under the supervision of a trained stoma nurse. CONCLUSION: The results of this study could provide some insights into the preoperative management of these patients.

Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review.

BACKGROUND: Preoperative or neoadjuvant chemotherapy (NAC) has emerged as a novel alternative to treat locally advanced colon cancer (LACC), as in other gastrointestinal malignancies. However, evidence of its efficacy and safety has not yet been gathered in the literature. The aim of the present study was to perform an extensive review of the scientific evidence for NAC in patients with LACC. METHODS: PubMed, EMBASE, MEDLINE and Cochrane Library were searched for a systematic review of the literature from 2010 to 2019. Six eligible studies were included, with a total of 27,937 patients, 1232 of them (4.4%) treated with NAC. There were only one randomized controlled trial, three phase II non-randomized single arm studies and two retrospective studies. RESULTS: The baseline computed tomography scan showed that most of patients had a T3 tumor. The completion rate of the planned neoadjuvant treatment ranged from 52.5 to 93.8%. Between 97.2 and 100% of patients had the scheduled surgery. The median tumor volume reduction after NAC ranged from 62.5 to 63.7%. The anastomotic leak rate in the NAC group ranged from 0 to 7%, with no cases of postoperative mortality. There was major pathological tumor regression in 4-34.7% of cases. Between 84 and 100% of NAC patients had R0-surgery. Survival after NAC seems to be encouraging although significant improvement has only been proven in T4b tumours. CONCLUSIONS: According to our systematic review, the NAC may be a safe and effective emerging therapeutic alternative for treating LACC. This approach, which is still being tested, increases the reliance on accurate radiological staging.

Fluid intake of Latin American adults: results of four 2016 Liq.In7 national cross-sectional surveys.

PURPOSE: To report total fluid intake (TFI) and the intake of different fluid types in adults (≥ 18 years old) from Mexico, Argentina, Brazil and Uruguay. To compare intakes between countries and with recommended adequate intake (AI) of water from fluids. METHODS: Cross-sectional data were collected using a validated liquid intake 7-day record (Liq.In 7 ) in populations from Argentina (n = 1089), Brazil (n = 477), Mexico (n = 1677) and Uruguay (n = 554). Population characteristics, including age, gender, body mass index and socioeconomic level were recorded. Mean TFI was compared with the AI of water from fluids set by the USA Institute of Medicine. RESULTS: The lowest TFI was recorded in Mexican women (1748 mL/day) and the highest in Argentinean men (2318 mL/day). Median daily TFI was significantly different between countries; Uruguay and Argentina had higher values than Mexico and Brazil. In the former, plain water contributed to only 25% of TFI, the remainder being predominantly from hot beverages. Approximately, a third of adults did not drink enough fluid to meet the recommended AI. High SSB consumption was reported, which was significantly different between countries (p < 0.05), the highest being in Mexico (median 25-75th percentiles): 531 (300-895 mL/day. CONCLUSIONS: This survey highlights the need to increase water consumption and reduce SSB intake in this region to avoid potential associated health risks. These findings may be useful information in monitoring public health policy strategies.

Diversidad haplotípica del exón xii del gen dopamina p-hidroxilasa en tres razas bovinas / Haplothic diversity of exon xii of the dopamine p-hydroxylase gene in three cattle breeds

Los polimorfismos en el gen dopamina p-hidroxilasa (DBH) se asocian con el temperamento en los bovinos. En 16 animales de la raza criolla colombiana Blanco Orejinegro (BON), 20 Brahman (BRA) y 16 de Ganado de lidia (GLI), se evaluaron los polimorfismos del exón xii del gen DBH mediante secuenciación. Se encontraron 13 haplotipos, 6 en BON, 9 en BRA y 2 en GLI. El haplotipo H2 fue el más frecuente (0,615) y se encontró en las tres razas, mientras los haplotipos H6 y H9 fueron compartidos entre BON-BRA y BRA-GLI, respectivamente. La mayor diversidad genética (DG: 0,915 ± 0,04) y nucleotídica (DN: 0,011 ± 0,006) se encontró en la raza BRA, seguida por BON (DG: 0,700 ± 0,12; DN: 0,008 ± 0,004) y GLI (DG: 0,350 ± 0,14; DN: 0,0011 ± 0,001). Si bien el test de D-Tajima fue mayor que cero, no fue significativo (P > 0,05) en BON y BRA, pero en la raza GLI presentó un valor de -1,92 (P < 0,05). El análisis de varianza molecular mostró una variación entre las razas de 23,9% y una estructura poblacional (F^) de 0,23 (P < 0,001). Los mayores valores del coeficiente de coancestría se presentaron entre GLI y BRA (0,52) y entre GLI y BON (0,22). Se concluye que la raza GLI tiene baja diversidad en el gen DBH en comparación con las razas BON y BRA, que hay efectos de la selección natural en BON y BRA mientras que en la raza GLI se evidencia un barrido selectivo reciente y no a favor del temperamento.

Polymorphisms in the dopamine p-hydroxylase gene (DBH) have been associated with temperament in cattle. In 16 animals of Colombian creole breed Blanco Orejinegro (BON), 20 Brahman (BRA) and 16 fighting bulls (GLI), polymorphisms of exon xii of the DBH gene were evaluated by sequencing. 13 haplotypes were found, 6 in BON, 9 and 2 in BRA and GLI respectively. Haplotype H2 was the most frequent in the whole population (0,615) and it was found in all breeds. Haplotypes H6 and H9 were shared between BON-BRA and BRA-GLI, respectively. The greatest value of genetic (DG: 0.915 ± 0.04) and nucleotide (DN: 0.011 ± 0.006) diversity, was found in BRA, followed by BON (DG: 0.700 ± 0.12; DN: 0.008 ± 0.004) and GLI (DG: 0.350 ± 0.14; DN: 0.0011 ± 0.001). The D-Tajima test was greater than zero, but not significant (P > 0.05) in BON and BRA, GLI presented a value of -1.92 (P < 0.05). The analysis of molecular variance showed a variation between the breeds of 23.9% and a poblacional structure (F$t) of 0.23 (P < 0.001). The highest values of the coancestry coefficient were presented between GLI and BRA (0.52) and between GLI and BON (0.22). It is concluded that the GLI race has low diversity in the DBH gene compared to BON and BRA, that there are effects of neutral selection in BON and BRA breeds, whereas, in the GLI and not in favor of temperament.

Preparación y Caracterización de Nanocompositos Quitosano-Cobre con Actividad Antibacteriana para aplicaciones en Ingeniería de Tejidos / Preparation and characterization of Copper Chitosan Nanocomposites with Antibacterial Activity for Applications in Tissue Engineering

RESUMEN: El presente trabajo describe la preparación de nanocompositos formulados a partir de quitosano (QS)/nanopartículas de cobre (nCu) con características antibacterianas y aplicación potencial en ingeniería de tejidos. Para ello, se prepararon nanocompositos mediante mezclado en solución asistido con ultrasonido con el objetivo de incrementar la dispersión de la carga nanométrica en el biopolímero. El análisis de FTIR demostró que la presencia de nCu en la matriz de QS favorece la interacción del nCu con los grupos amino/hidroxilo de la molécula del QS. Se determinó mediante UV-Vis que los nanocompositos QS/nCu presentan absorción asociada con la presencia de nanopartículas y la posible liberación de iones Cu2+ en medio líquido. Mediante AFM se determinó que el QS hidratado forma una malla con microporos, que puede favorecer la penetración de bacterias en el nanocomposito y su interacción con las nCu. Finalmente, se determinó el efecto antibacteriano del material al contacto con la bacteria Staphylococcus aureus, en donde se presenta una actividad antibacteriana superior al 90% entre los 90 y 180 min de interacción. Dichos resultados sugieren que es posible obtener nanomateriales antibacterianos biocompatibles para su posible aplicación en ingeniería tisular.

ABSTRACT: The Present work describes the preparation of nanocomposites based on chitosan (QS)/copper nanoparticles (nCu) with antibacterial properties and potential application in tissue engineering. For this purpose, nanocomposites were prepared by solution blending with ultrasound assisted, aiming to increase the nanoparticles dispersion in the biopolymer. FTIR analyses demonstrates that nCu supported in QS increase their interaction of nanoparticles with amine/hydroxyl groups of QS molecule. UV-Vis analyses demonstrates that QS/nCu nanocomposites have an absorption signal associated with the presence of nanoparticles and the possible Cu2+ ions release in liquid media. AFM analyses shown that hydrated QS form a mesh with micro pores, improving the bacterial penetration and the direct contact with nCu. This behavior was corroborated by antibacterial assays, where QS/nCu nanocomposites shown an antibacterial activity higher than 90% between 90-180 minutes of interaction. Our results suggest that is possible to obtain combined antibacterial/biocompatible nanomaterials with potential application in tissue engineering.

Mid-term oncologic outcome of a novel approach for locally advanced colon cancer with neoadjuvant chemotherapy and surgery.

PURPOSE: Neoadjuvant chemotherapy is being actively tested as an emerging alternative for the treatment of locally advanced colon cancer (LACC) patients, resembling its use in other gastrointestinal tumors. This study assesses the mid-term oncologic outcome of LACC patients treated with oxaliplatin and fluoropyrimidines-based preoperative chemotherapy followed by surgery. METHODS AND PATIENTS: Patients with radiologically resectable LACC treated with neoadjuvant therapy between 2009 and 2014 were retrospectively analyzed. Radiological, metabolic, and pathological tumor response was assessed. Both postoperative complications, relapse-free survival (RFS), and overall survival (OS) were studied. RESULTS: Sixty-five LACC patients who received treatment were included. Planned treatment was completed by 93.8 % of patients. All patients underwent surgery without delay. The median time between the start of chemotherapy and surgery was 71 days (65-82). No progressive disease was observed during preoperative treatment. A statistically significant tumor volume reduction of 62.5 % was achieved by CT scan (39.8-79.8) (p < 0.001). It was also observed a median reduction of 40.5 % (24.2-63.7 %) (p < 0.005) of SUVmax (Standard Uptake Value) by PET-CT scan. Complete pathologic response was achieved in 4.6 % of patients. Postoperative complications were observed in 15.4 % of patients, with no cases of mortality. After a median follow-up of 40.1 months, (p 25-p 75: 27.3-57.8) 3-5 year actuarial RFS was 88.9-85.6 %, respectively. Five-year actuarial OS was 95.3 %. CONCLUSION: Preoperative chemotherapy in LACC patients is safe and able to induce major tumor regression. Survival times are encouraging, and further research seems warranted.

Clinical significance of cellular and acellular mucin pools in rectal carcinoma following preoperative chemoradiotherapy.

BACKGROUND AND OBJECTIVES: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Pathological findings remain the most significant prognostic factor. The presence of mucin pools and their prognostic significance is a controversial issue. The aim of this study was to analyze the incidence of cellular and acellular mucin pools and their clinical significance. METHODS: Four-hundred and forty-six consecutive prospectively collected specimens from patients with LARC treated with long-course preoperative CRT and surgery were analyzed. Kaplan-Meier analysis was performed. RESULTS: Mucin pools were present in 182 specimens (40.8 %); 66 (14.7 %) were acellular, and viable tumor cells were identified in 116 (26 %). The complete pathological response rate was 13.5 % (60 of 446). With a median follow-up of 79.0 months, the 5- and 10-year disease-free survivals for patients with acellular and cellular mucin pools were 81.5, 78.1, 63.7 and 61.2 %, respectively (p ≤ 0.026). The presence of cells in the colloid response to treatment was associated with a 17.8 and 16.9 % decrease in 5- and 10-year disease survival vs. acellular colloid response. CONCLUSIONS: Our results suggest that cellular mucin pools are an indicator of an aggressive phenotype and harbingers of a worse prognosis.

Patterns and management of distant failure in locally advanced rectal cancer: a cohort study.

PURPOSE: To determine the long-term outcomes of locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (CRT) and surgery, and to analyze the management and survival once distant failure has developed. METHODS: Data from LARC patients treated from 2000 to 2010 were retrospectively reviewed. CRT protocols were based on fluoropirimidines ± oxaliplatin. Follow-up consisted of physical examination, carcinoembryonic antigen levels, and chest-abdominal-pelvic CT scan. RESULTS: The study included 228 patients with a mean age of 59 years. Forty-eight (21.1 %) patients had distant recurrence and 6 patients (2.6 %) had local recurrence. Median follow-up was 49 months. The 5- and 10-year actuarial disease free survival was 75.3 and 65.0 %, respectively. The 5- and 10-year actuarial overall survival (OS) was 89.6 and 71.2 %, respectively. Patients were classified as having liver (14 patients) or lung (27 patients) relapse according to the organ firstly metastasized. The variables significantly associated by univariate Cox analysis to survival were the achievement of an R0 metastases resection and the Köhne risk index, while the metastatic site showed a statistical trend. By multivariate Cox analysis, the only variable associated with survival was a R0 resection (HR = 16.3, p < 0.001). Median OS for patients undergoing a R0 resection was 73 months (95 % CI 67.8-78.2) compared to 25 months (95 % CI 5.47-44.5) in those non-operated patients (p < 0.001). CONCLUSIONS: Combined treatment for LARC obtains a 5-year OS rounding 90 %. Follow-up based on thoracic-abdominal CT scan allows an early diagnosis of metastatic lesions. Surgical resection of metastases, regardless of their location, greatly increases the patient's survival rate.

[Small bowel intussusception in the adult caused by ileal submucous lipoma]. / Invaginación de intestino delgado en el adulto causada por lipoma submucoso de íleon.

We present the case of a 68 year-old male patient with secondary intestinal intussuspection due to a submucous li-poma of the ileum. This is a rare entity in adults and is usually due to an organic lesion. The clinical manifestation is characterized by vomiting, abdominal pain and melenas. In our case the patient, following a colonoscopy and an abdominal CT-scan, was subjected to an extended resection of caecum and terminal ilium. At present, the precision of the etiological diagnosis of intussuspections has increased thanks to the development of image tests, like CT-scan. Early surgical treatment is recommended, without intraoperative deintussuspection given the high risk of presenting a malign or ischemic lesion in the adult.

Impact of perineural and lymphovascular invasion on oncological outcomes in rectal cancer treated with neoadjuvant chemoradiotherapy and surgery.

BACKGROUND: The prognostic significance of perineural and/or lymphovascular invasion (PLVI) and its relationship with tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT) and surgery. METHODS: A total of 324 patients with LARC were treated with CRT and operated on between January 1992 and June 2007. Tumors were graded using a quantitative 5-grade TRG classification and the presence of PLVI was histologically studied. RESULTS: At a median follow-up of 79.0 months (range 3-250 months), a total of 80 patients (24.7%) relapsed. The observed 5- and 10-year overall survival (OS) was 83.2 and 74.9 %, respectively. The 5- and 10-year disease-free survival (DFS) was 75.1 and 71.4%, respectively. A significant correlation was found between the TRG and survival (log rank, p < 0.001). The 10-year OS was 32.7% for grade 1, 63.8% for grade 2, 75.0% for grade 3, 90.4% for grade 3+, and 96.0%,for grade 4. The 10-year DFS was 31.8% for grade 1, 58.6% for grade 2, 70.4% for grade 3, 88.4% for grade 3+, and 97.1% for grade 4. In patients with PLVI, the TRG had no impact on survival. When excluding patients with PLVI, the TRG was an independent prognostic factor for OS and DFS. CONCLUSIONS: The presence of PLVI is a more powerful prognostic factor than TRG in LARC patients treated with neoadjuvant CRT followed by surgery. PLVI denotes an aggressive phenotype, suggesting that these patients may benefit from adjuvant systemic therapy.

Is the cleft lift procedure for non-acute sacrococcygeal pilonidal disease a definitive treatment? Long-term outcomes in 74 patients.

PURPOSE: No definitive surgical treatment for non-acute pilonidal disease has been established thus far. We herein report the short-term and long-term outcomes of 74 consecutive patients who underwent the cleft lift procedure for non-acute pilonidal disease. METHODS: A total of 74 consecutive patients who underwent the cleft lift procedure for the treatment of non-acute pilonidal disease were evaluated. RESULTS: Complete healing was achieved in 54 patients (73%). Wound seroma was observed in 12 patients (15%) in the first week, and this persisted until the second week in 10 patients (13%). Partial dehiscence was found in eight patients (11%). One patient presented with complete wound dehiscence (1%), and another experienced early postoperative bleeding (1%). Wound infection was observed in one patient (1%). The median follow-up period was 51.5 months (range 15-88 months). Three cases of recurrences were observed, which occurred after 51, 42 and 12 months of follow-up. CONCLUSIONS: If longer-term follow-up is achieved, definitive conclusions may be obtained. However, the present results suggest that the cleft lift procedure may become the gold standard technique for the surgical management of non-acute pilonidal disease.

Exome sequencing detection of two untranslated GFPT1 mutations in a family with limb-girdle myasthenia.

The term 'limb-girdle myasthenia' (LGM) was first used to describe three siblings with proximal limb weakness without oculobulbar involvement, but with EMG decrement and responsiveness to anticholinesterase medication. We report here that exome sequencing in the proband of this family revealed several sequence variations in genes linked to proximal limb weakness. However, the only mutations that cosegregated with disease were an intronic IVS7-8A>G mutation and the previously reported 3'-UTR c.*22C>A mutation in GFPT1, a gene linked to LGM. A minigene assay showed that IVS7-8A>G activates an alternative splice acceptor that results in retention of the last seven nucleotides of intron 7 and a frameshift leading to a termination codon 13 nucleotides downstream from the new splice site. An anconeus muscle biopsy revealed mild reduction of the axon terminal size and postsynaptic fold simplification. The amplitudes of miniature endplate potentials and quantal release were also diminished. The DNA of the mildly affected father of the proband showed only the intronic mutation along with sequence variations in other genes potentially relevant to LGM. Thus, this study performed in the family originally described with LGM showed two GFPT1 untranslated mutations, which may cause disease by reducing GFPT1 expression and ultimately impairing protein glycosylation.

Presence of a radioactive gas in archaeological excavations, determination and mitigation.

During recent archaeological discovery and excavation of a tunnel build approximately 2000 years ago by the Teotihuacans under the feathered serpent temple, in Mexico, abnormal radon concentrations up to 700 Bq m(-3) were measured at several excavation stages. The tunnel is at 15m below the earth surface with a vertical rectangular entrance of 4×4 m(2), a semi cylindrical shape of 3m in diameter, with a probable length of 100 m. This study supports the assumption that at the opening of the tunnel radon concentration was around 5500 Bq m(-3); however, although natural convection in the tunnel atmosphere naturally pups radon out, it build up to a maximum concentration of 2000 Bq m(-3). This paper presents the identification of the radon problem in this archaeological site, dose determination, and the mitigation actions that reduced the radon concentration down to 40 Bq m(-3) that ensure a negligible radon risk for archaeologist.

[DIEP flap reconstruction after palliative curettage mastectomy in locally advanced breast cancer]. / Colgajo DIEP de cobertura tras mastectomía de limpieza paliativa en cáncer de mama localmente avanzado.

BACKGROUND: Curettage mastectomy is indicated as a palliative treatment in locally advanced breast cancer. We present our experience with the use of a DIEP flap reconstruction following extensive mastectomy. METHODS: We report the case of a patient with very advanced local breast cancer that was subsidiary to aggressive palliative surgery after chemotherapy. RESULTS: It was considered that the closure that could be performed with the latissimus dorsi muscle was unsuitable, therefore a DIEP flap was performed. The patient was discharged uneventfully. CONCLUSION: The DIEP reconstruction offers great cutaneous extension. It can be a resource in highly selected cases of locally advanced breast cancer in which surgery becomes the main treatment.

Preliminary outcome of a treatment strategy based on perioperative chemotherapy and surgery in patients with locally advanced colon cancer.

AIM: Preoperative chemotherapy followed by radical surgery is an attractive treatment for locally advanced colon cancer (LACC) given the promising results of this approach in other locally advanced tumours. The study evaluates the outcome and treatment-related complications of perioperative oxaliplatin- and capecitabine-based chemotherapy and surgery for clinical Stage III colon cancer. METHOD: Twenty-two consecutive patients with a CT-staged LACC were included. All were staged at baseline and before surgery. Surgery-related complications and oncological outcome were determined. RESULTS: Toxicity was manageable, with 19/22 patients completing the planned chemotherapy protocol. The median time from initial diagnosis to surgery was 65.5 days. The median time from the end of chemotherapy to surgery was 22 days. After neoadjuvant treatment, tumour reduction of 69.5% was observed by CT scan and a 59.9% decrease of SUVmax (standard uptake value) was achieved on positron emission tomography/CT. No progressive disease was reported during preoperative chemotherapy and surgery was performed in all 22 patients. Four patients developed postoperative complications. After a median postoperative follow-up of 14.4 months, the actuarial overall and disease-free survival rates were 100 and 90%. CONCLUSION: Neoadjuvant chemotherapy followed by surgery and chemotherapy for LACC is safe without apparent increase of early and medium-term complications.

Efficacy of laparoscopic approach in the management of early liver transplant complications.

The use of the laparoscopic approach in managing early liver transplant complications has been shown to be safe and feasible in various settings with the advantages of shorter recovery period, decreased postoperative pain, and rapid functional recovery. The laparoscopic approach has been used to resolve postoperative complications in kidney and pancreas recipients and less often in orthotopic liver transplantation (OLT) recipients, most of them in the late period (> 1 month posttransplantation). We herein describe our experience with the laparoscopic management of early complications after liver transplantation. From May 2009 to May 2011, we successfully treated three patients with early abdominal complications after OLT using a laparoscopic approach. Three patients-two with intraabdominal bleedings and one with a small bowel obstruction were treated successfully, thereby avoiding risks of a relaparotomy. In addition to these benefits, the laparoscopic approach causes less tissue injury and consequently evokes a minor innate immune response.