Collagen content and C-X-C motif chemokine ligand 12 expression in neoplastic breast stroma.

OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data. METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1-4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011-2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images. RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%). CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.

Collagen content and C-X-C motif chemokine ligand 12 expression in neoplastic breast stroma

SUMMARY OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data. METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1-4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011-2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images. RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%). CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.

The antitumoral activity of TLR7 ligands is corrupted by the microenvironment of pancreatic tumors.

Toll-like receptors (TLRs) are key players in the innate immune system. Recent studies have suggested that they may affect the growth of pancreatic cancer, a disease with no cure. Among them, TLR7 shows promise for therapy but may also promotes tumor growth. Thus, we aimed to clarify the therapeutic potential of TLR7 ligands in experimental pancreatic cancer models, to open the door for clinical applications. In vitro, we found that TLR7 ligands strongly inhibit the proliferation of both human and murine pancreatic cancer cells, compared with TLR2 agonists. Hence, TLR7 treatment alters cancer cells' cell cycle and induces cell death by apoptosis. In vivo, TLR7 agonist therapy significantly delays the growth of murine pancreatic tumors engrafted in immunodeficient mice. Remarkably, TLR7 ligands administration instead increases tumor growth and accelerates animal death when tumors are engrafted in immunocompetent models. Further investigations revealed that TLR7 agonists modulate the intratumoral content and phenotype of macrophages and that depleting such tumor-associated macrophages strongly hampers TLR7 agonist-induced tumor growth. Collectively, our findings shine a light on the duality of action of TLR7 agonists in experimental cancer models and call into question their use for pancreatic cancer therapy.

COVID-19 therapy: What weapons do we bring into battle?

Urgent treatments, in any modality, to fight SARS-CoV-2 infections are desired by society in general, by health professionals, by Estate-leaders and, mainly, by the scientific community, because one thing is certain amidst the numerous uncertainties regarding COVID-19: knowledge is the means to discover or to produce an effective treatment against this global disease. Scientists from several areas in the world are still committed to this mission, as shown by the accelerated scientific production in the first half of 2020 with over 25,000 published articles related to the new coronavirus. Three great lines of publications related to COVID-19 were identified for building this article: The first refers to knowledge production concerning the virus and pathophysiology of COVID-19; the second regards efforts to produce vaccines against SARS-CoV-2 at a speed without precedent in the history of science; the third comprehends the attempts to find a marketed drug that can be used to treat COVID-19 by drug repurposing. In this review, the drugs that have been repurposed so far are grouped according to their chemical class. Their structures will be presented to provide better understanding of their structural similarities and possible correlations with mechanisms of actions. This can help identifying anti-SARS-CoV-2 promising therapeutic agents.

Intestinal Malrotation and Volvulus in Neonates: Laparoscopy Versus Open Laparotomy.

BACKGROUND: Intestinal malrotations with midgut volvulus are surgical emergencies that can lead to life-threatening intestinal necrosis. This study evaluates the feasibility and the outcomes of laparoscopic treatment of midgut volvulus compared with classic open Ladd's procedure in neonates. MATERIALS AND METHODS: The medical records of all neonates with diagnosis of malrotation and volvulus, who underwent surgery between January 1993 and January 2014, were reviewed. We considered the group of neonates laparoscopically treated (Group A, n = 20) and we compared it with an equal number of neonates treated with the classical open Ladd's procedure (Group B, n = 20). RESULTS: The median age at surgery was 8.4 days and the mean weight was 3.340 kg. The suspicion of volvulus was documented by plain abdominal radiograph, upper gastrointestinal contrast study, and/or ultrasound scanning of the mesenteric vessels. All the patients were treated according to the Ladd's procedure. Conversion to an open procedure was necessary in 25% of the patients. The mean operative time was 80 minutes (28-190 minutes) in Group A and 61 minutes (40-130 minutes) in Group B (P = .04). The median time to full diet (P = .02) and hospital stay (P = .04) was better in Group A. Rehospitalization because of recurrence of occlusive symptoms occurred in 30% of patients in Group A (n = 6) and in 40% of patients in Group B (n = 8). Among these, all the 6 patients of Group A underwent redo surgery for additional division of Ladd's bands or debridement; instead in Group B, 4 of 8 patients underwent open redo surgery. CONCLUSIONS: Laparoscopic exploration is the procedure of choice in case of suspicion of intestinal malrotation and volvulus. Laparoscopic treatment is feasible and safe even in neonatal age without additional risks compared with classical open Ladd's procedure.

Twenty years' experience for reduction of ileocolic intussusceptions by saline enema under sonography control.

BACKGROUND: Ultrasonography is a well-established efficient diagnostic tool for ileocolic intussusceptions in children. It can also be used to control hydrostatic reduction by saline enemas. This reduction method presents the advantage of avoiding radiations. Parents can even stay with their children during the procedure, which is comforting for both. The purpose of this study was to present our 20 years' experience in intussusception reductions using saline enema under ultrasound control and to assess its efficiency and safety. MATERIAL AND METHODS: This retrospective single center study included patients with ileocolic intussusceptions diagnosed by ultrasound between June 1993 and July 2013. We excluded the data of patients with spontaneous reduction or who underwent primary surgery because of contraindications to hydrostatic reduction (peritonitis, medium or huge abdominal effusion, ischemia on Doppler, bowel perforation). A saline enema was infused into the colon until the reduction was sonographically confirmed. The procedure was repeated if not efficient. Light sedation was practiced in some children. RESULTS: Eighty-tree percent of the reductions were successful with a median of 1 attempt. Reduction success decreased with the number of attempts but was still by 16% after 4 attempts. The early recurrence rates were 14.5%, and 61.2% of those had a successful second complete reduction. Forty-six patients needed surgery (11 of them had a secondary intussusception). Sedation multiplies success by 10. In this period, only one complication is described. CONCLUSION: Ultrasound guided intussusception reduction by saline enema is an efficient and safe procedure. It prevents exposure of a young child to a significant amount of radiation, with similar success rate. We had very low complication rate (1/270 cases or 3‰). The success rate could be increased by standardized procedures including: systematic sedation, trained radiologists, accurate pressure measurement, and number and duration of attempts.

Laparoscopic modified Orr-Loygue mesh rectopexy for rectal prolapse in children.

AIM: We present an operating technique inspired from the Orr-Loygue mesh rectopexy adapted for laparoscopy, and detail the technical steps that differ from laparoscopic posterior suture rectopexy more commonly described in the paediatric literature. METHOD: We present a retrospective study of all children who underwent a modified Orr-Loygue procedure for recurrent complete rectal prolapse from 1999 to 2012 after failure of conservative treatment. Pathological conditions, technical details of the procedure (excision of the Douglas pouch, use of a prerectal non-absorbable mesh to suspend the rectum to the presacral fascia and promontory avoiding any tension on the rectal wall) and postoperative results were reviewed. RESULTS: Eight patients were included, median age 6.5 years (range, 2-17). Median symptoms duration before surgery was 14 months (range, 6-24). Four patients presented with associated pathological conditions: 1 neurological impairment (Williams-Beuren syndrome), 1 severe malnutrition (mental anorexia), 1 solitary rectal ulcer with frequent bleeding, 1 syringomyelic cavity in the spinal cord. All procedures were completed laparoscopically with a median operative time of 98 minutes (range, 80-125). Median hospital stay was 3.5 days (range, 2-5). No postoperative constipation or recurrence was reported during the median follow-up period of 6 years (range 2-13). CONCLUSION: The laparoscopic modified Orr-Loygue mesh rectopexy is a simple operating technique, reproducible and efficient as surgical treatment of nonresolving recurrent complete rectal prolapse in children. To avoid postoperative constipation, it is important to perform a tension-free rectopexy which can be achieved by the use of a mesh to simply suspend and not "fix" the redundant rectosigmoid. Nonetheless, a greater number of patients as well as colorectal electromyography or anorectal manometry would be necessary to prove the absence of postoperative deleterious functional disorder.

Staged gastroschisis closure using Alexis wound retractor: first experiences.

INTRODUCTION: The aim of this study is to analyze the effectiveness of an Alexis wound retractor (AWR) device for staged gastroschisis closures. PATIENTS AND METHODS: AWR device was used to cover unreduced viscera of a gastroschisis when primary abdominal wall closure was not convenient. The eviscerated organs were covered with one of the two spring-loaded rings of the AWR inserted underneath the abdominal wall. Gradual reduction was guaranteed through careful traction on the external ring. We retrospectively analyzed the prenatal, post-natal and operative data of the first patients treated with AWR and report their post-operative outcomes. RESULTS: The AWR device was used for staged closure in eight cases. Complete reduction and fascial closure were performed at a median of 3.5 ± 1.6 days. Ventilatory support was necessary for 4.0 ± 3 days and full parenteral feeds for 7.5 ± 6.1 days after fascial closure. Median full enteral feeding was observed at 18 ± 12.5 days after closure allowing discharge in a median period of 30.5 ± 15.6 days after closure. CONCLUSION: The AWR device is not only a safe and efficient silo for a progressive reduction of severe gastroschisis, but also an interesting tool for continuous stretching leading to an increase of the peritoneal cavity volume, enhancing the equalizing of the viscero-abdominal disproportion.

Thoracoscopic treatment of congenital diaphragmatic eventration in children: lessons learned after 15 years of experience.

INTRODUCTION: We present our experience with the thoracoscopic treatment of congenital diaphragmatic eventration (CDE) in children through 15 years to evaluate the efficiency of the procedure and the potential risk of recurrence. Materials and METHODS: We reviewed the medical files of patients treated for CDE through thoracoscopy from 2000 to 2011. Age at surgery, sex, side of the lesion, procedure's details, postoperative course, and complications were analyzed. Mean follow-up was 12 months. RESULTS: In this study, eight patients (five males and three females) aged from 6 months to 7 years underwent thoracoscopic plication for six right and two left eventrations; one conversion was necessary due to a too small operative field. Mean operative time was 60.5 minutes. A chest drainage was placed in six patients. We observed two recurrences from which the first one was treated thoracoscopically by endostapler resection/suturing and the other one by laparotomy. At follow-up, all patients were asymptomatic with a correct level of the diaphragm. CONCLUSIONS: Thoracoscopic plication is feasible and safe, and we consider this approach as the gold standard for the treatment of CDE. However, we still need to carefully consider the possibility of introducing certain modifications to reduce the potential risk of recurrence.

Congenital diaphragmatic hernia: an evaluation of risk factors for failure of thoracoscopic primary repair in neonates.

PURPOSE: Publications aiming to prove the feasibility and safety of thoracoscopic CDH-repair in neonates grow in numbers. Some teams use selection criteria, but none have proven statistical evidence. The aim of this study is to detect risk factors for failure of thoracoscopic primary closure of CDH in neonates. METHODS: In 8 centers performing minimal access surgery (MAS), complete prenatal, postnatal, and operative data were evaluated for a retrospective study concerning patients with thoracoscopic congenital diaphragmatic hernia (CDH) repair. Most of the selection criteria and risk factors mentioned in the literature were analyzed. Two groups were defined: Group A - neonates who tolerated thoracoscopic primary repair, and Group B - neonates who required conversion or presented with major complications after thoracoscopic repair. Univariate and multivariate logistic regressions were used to compare these two groups. RESULTS: From 2006 to 2010, thoracoscopy was performed in 40 neonates: Group A consisting of 28 neonates, and Group B 9 patients. Three patients were excluded because of insufficient data or major associated malformations. Significant statistical differences were found in Group B for postnatal PaCO2 >60 mmHg, need of iNO during postnatal stabilization, intrathoracic position of the stomach, pulmonary hypertension signs on the postnatal cardiac ultrasound, and preoperative OI >3.0. On multivariate analysis, only an OI >3.0 was significantly associated with conversion or major post-operative complication of thoracoscopic primary repair. CONCLUSION: CDH can be safely repaired in the neonatal period by thoracoscopy. The limiting factor for thoracoscopic CDH repair is PPHN. The best preoperative indicator for PPHN is OI. Prospective studies are nonetheless necessary to prove the effectiveness of using these risk factors as selection criteria to help design surgical management protocols for neonates presenting CDH.

Button cystostomy for bladder drainage: which children can benefit from this device?

AIM: The aim of this study is to define which children could benefit from a button cystostomy. We describe a safe way to perform the insertion of a button cystostomy for urinary diversion and provide more precise instructions concerning the best indications for this device. MATERIALS AND METHODS: We analyzed several criteria of the follow-up of all the patients who had a button cystostomy since 2007 including indications, age, urodynamic variables, and complications. RESULTS: Twenty-one patients underwent a button cystostomy. A group of young children was included in the study (mean age, 2 years), in which most of the failed procedures were observed, whereas we had better results with the second group of older children (mean age, 12 years). CONCLUSIONS: The analysis of indications and, more particularly, urodynamic variables regarding the quality of the results allows us to clearly define which children can benefit from this procedure with a good chance of success and low risk of complications.

Pectus excavatum repair according to Nuss: is it safe to place a retrosternal bar by a transpleural approach, under thoracoscopic vision?

We present a new case of cardiac perforation during retrosternal dissection beginning a Nuss procedure for pectus excavatum repair in an 18-year-old boy. The true incidence of life-threatening complications, such as heart injuries during Nuss bar placement for pectus excavatum repair, as well as cardiac lacerations during removal of the bar, remains unknown. Many papers suggest measures to prevent these complications: approaching the retrosternal space through an additional subxiphoid short incision, lifting the sternum during bar placement, or placing the bar extrapleuraly. Nuss procedure is gaining more and more popularity due to its apparent simplicity; however, its operational complications should be well known and discussed to be avoided later on.

Neonatal minimally invasive surgery for congenital diaphragmatic hernias: a multicenter study using thoracoscopy or laparoscopy.

BACKGROUND: Minimally invasive surgery (MIS) for late-presenting congenital diaphragmatic hernia (CDH) has been described previously, but few neonatal cases of CDH have been reported. This study aimed to report the multicenter experience of these rare cases and to compare the laparoscopic and thoracoscopic approaches. METHODS: Using MIS procedures, 30 patients (16 boys and 14 girls) from nine centers underwent surgery for CDH within the first month of life, 26 before day 5. Only one patient had associated malformations. There were 10 preterm patients (32-36 weeks of gestational age). Their weight at birth ranged from 1,800 to 3,800 g, with three patients weighing less than 2,600 g. Of the 30 patients, 18 were intubated at birth. RESULTS: The MIS procedures were performed in 18 cases by a thoracoscopic approach and in 12 cases by a laparoscopic approach. No severe complication was observed. For 20 patients, reduction of the intrathoracic contents was achieved easily with 15 thoracoscopies and 5 laparoscopies. In six cases, the reduction was difficult, proving to be impossible for the four remaining patients: one treated with thoracoscopy and three with laparoscopy. The reasons for the inability to reduce the thoracic contents were difficulty of liver mobilization (1 left CDH and 2 right CDH) and the presence of a dilated stomach in the thorax. Reductions were easier for cases of wide diaphragmatic defects using thoracoscopy. There were 10 conversions (5 laparoscopies and 5 thoracoscopies). The reported reasons for conversion were inability to reduce (n = 4), need for a patch (n = 5), lack of adequate vision (n = 4), narrow working space (n = 1), associated bowel malrotation (n = 1), and an anesthetic problem (n = 1). Five defects were too large for direct closure and had to be closed with a patch. Four required conversion, with one performed through video-assisted thoracic surgery. The recurrences were detected after two primer thoracoscopic closures, one of which was managed by successful reoperation using thoracoscopy. CONCLUSIONS: In the neonatal period, CDH can be safely closed using MIS procedures. The overall success rate in this study was 67%. The indication for MIS is not related to weeks of gestational age, to weight at birth (if >2,600 g), or to the extent of the immediate neonatal care. Patients with no associated anomaly who are hemodynamically stabilized can benefit from MIS procedures. Reduction of the herniated organs is easier using thoracoscopy. Right CDH, liver lobe herniation, and the need for a patch closure are the most frequent reasons for conversion.