Loss of RAS Mutations in Liquid Biopsies of Patients With Multi-Treated Metastatic Colorectal Cancer.

BACKGROUND: Liquid biopsy (LB) is a non-invasive tool to evaluate the heterogeneity of tumors. Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment. The main aim of this study was to evaluate the prognostic value of the loss of RAS-mut (NeoRAS-wt) in LB, during the treatment of metastatic colorectal cancer (mCRC). METHODS: A retrospective study was conducted on patients with mCRC between January 2018 and December 2021. RAS-mut were examined in tissue biopsy, at mCRC diagnosis, and with LB, during treatment. RESULTS: Thirty-nine patients with RAS-mut mCRC were studied. LB was performed after a median of 3 lines (0-7) of systemic treatment including anti-vascular endothelial growth factor (anti-VEGF) Mabs. NeoRAS-wt was detected in 13 patients (33.3%); 9 (69.2%) of them received further treatment with anti-EGFR Mabs with a disease control rate of 44.4%. Median overall survival (OS), from the date of LB testing, was 20 months in the NeoRAS-wt group and 9 months in the persistent RAS-mut group (log-rank 2.985; P = .08), with a 12-month OS of 84.6% and 57.7%, respectively. NeoRAS-wt was identified as a predictor of survival (HR = 0.29; P = .007), with an 11-month improvement in median OS and a 71% decrease in risk of death, in heavily pretreated patients. CONCLUSIONS: In conclusion, monitoring clonal evolution in mCRC by LB may provide an additional treatment line for patients with NeoRAS-wt in advanced disease.

Skene's Gland Cyst - Case Report of a 2-Year-Old Girl.

BACKGROUND: Skene's glands are the two largest paraurethral glands and the female homologue to the prostate glands. When their ducts become obstructed, cysts may be formed. This usually occurs in adult women. Most cases reported in pediatrics are neonatal, with a single report in a prepubertal girl. CASE REPORT: We present a 25-month-old girl with a 7 mm nontender, solid, oval, pink-orange paraurethral mass, with no change over a five-month period. Histopathology revealed the cyst to be lined with transitional epithelium consistent with a Skene's gland cyst. The child did well with no sequalae. CONCLUSION: We describe a Skene's gland cyst found in a prepubertal child.

Early results of a distance learning paediatric surgery programme in Mozambique.

Introduction: A pre-graduate training programme in paediatric surgery was applied to students in four medical schools of Mozambique. In this paper, we evaluate the early results of the programme. Materials and Methods: A pre-graduate training programme was developed and applied in two stages, theoretical education available at an online platform and a face-to-face session. To evaluate the programme, a diagnostic test was applied to all participants before the face-to-face session and, the same test, was applied again at the end of the session. Results: A total of 236 students participated in the programme. Forty-four per cent had a negative score on the diagnostic test. When the test was repeated, 91.9% had a positive score, and the difference between the scores in both tests reached statistical significance (P < 0.05). The participants who completed the first phase of the programme presented a higher median score in both tests (P < 0.05). Conclusions: : The diagnostic tests allowed us to verify there was an increase in knowledge before and after the face-to-face session. There was also a significant difference between those participants who completed the online phase of the programme and those who did only the face-to-face session, which allows us to conclude that the online teaching programme was effective.

Injury patterns in competitive and recreational surfing: a systematic review.

CONTEXT: Despite the growing evidence regarding surf-related injuries, investigation seems to overlook the differences between professional and recreational surfers' injuries and their specific risk factors. OBJECTIVE: This review aimed at identifying differences in injuries sustained by recreational and competitive surfers. It also presents research gaps and suggests recommendations for future injury research and prevention. METHODS: Study search was conducted on MEDLINE/PubMed, SportDiscus and Web of Science databases. To be included studies needed to report original data, clearly specify if recreational and/or competitive surfers were included, provide information regarding acute surfing injuries and/or analyse data concerning those injuries. RESULTS: 17 studies were included in the analysis. All included studies had at least Oxford Centre for Evidence-Based Medicine level of evidence 3. The percentage of recreational surfers sustaining at least one injury ranged from 31% to 35% in the 12 months prior to data collection and from 88% to 100% in lifetime while 42% to 49% and 81% to 100% of competitors were injured over the same periods. Competitive surfers appear to have a higher injury risk. Both recreational and competitive surfers appear to sustain more frequently skin, joint/ligament and muscle/tendon injuries affecting the lower limbs and caused by contact with their own equipment. CONCLUSIONS: Competitive status, less surfing experience, older age and prior surgical injuries are risk factors for sustaining injuries while surfing. The most common types, anatomical locations and mechanisms of injury seem to be similar between recreational and competitive surfers.

Characterization of technical skill progress in a standardized rabbit model for training in laparoscopic duodenal atresia repair.

BACKGROUND: Laboratory skills training is an essential step before conducting minimally invasive surgery in clinical practice. Our main aim was to develop an animal model for training in clinically highly challenging laparoscopic duodenal atresia repair that could be useful in establishing a minimum number of repetitions to indicate safe performance of similar interventions on humans. MATERIALS AND METHODS: A rabbit model of laparoscopic duodenum atresia surgery involving a diamond-shaped duodeno-duodenostomy was designed. This approach was tested in two groups of surgeons: in a beginner group without any previous clinical laparoscopic experience (but having undergone previous standardized dry-lab training, n = 8) and in an advanced group comprising pediatric surgery fellows with previous clinical experience of laparoscopy (n = 7). Each participant performed eight interventions. Surgical time, expert assessment using the Global Operative Assessment of Laparoscopic Skills (GOALS) score, anastomosis quality (leakage) and results from participant feedback questionnaires were analyzed. RESULTS: Participants in both groups successfully completed all eight surgeries. The surgical time gradually improved in both groups, but it was typically shorter in the advanced group than in the beginner group. The leakage rate was significantly lower in the advanced group in the first two interventions, and it reached its optimal level after five operations in both groups. The GOALS and participant feedback scores showed gradual increases, evident even after the fifth surgery. CONCLUSIONS: Our data confirm the feasibility of this advanced pediatric laparoscopic model. Surgical time, anastomosis quality, GOALS score and self-assessment parameters adequately quantify technical improvement among the participants. Anastomosis quality reaches its optimal value after the fifth operation even in novice, but uniformly trained surgeons. A minimum number of wet-lab operations can be determined before surgery can be safely conducted in a clinical setting, where the development of further non-technical skills is also required.

Febrile Neutropenia in Patients with Solid Tumors Undergoing Intravenous Chemotherapy.

INTRODUCTION: Febrile neutropenia (FN) is a potentially life-threatening complication of systemic chemotherapy (CT) that often requires hospital admission. Delay in diagnosis and treatment are associated with higher morbidity and mortality. OBJECTIVE: We aimed to determine the factors that influence FN episodes outcomes in the emergency room (ER). METHODS: This was a retrospective study of all FN episodes (with a collected blood culture [BC]) that occurred between 2012 and 2016 at our institution. FN was defined as a temperature ≥38°C and an absolute neutrophil count (ANC) <1,000/µL, expected to decrease to <500/µL in the following week. RESULTS: Between 2012 and 2016, there were 173 FN episodes in 153/1,947 patients treated with intravenous CT. Most of these episodes (n = 121, 70%) were diagnosed in the ER, 29 in the outpatient clinic, and 23 as inpatients. In the ER, the median time was 36 min from hospital nurse triage to medical observation, and 52 min from medical observation to complete blood count specimen collection. There was a positive BC in 33 FN episodes, 72% with Gram-negative bacteria. A total of 160 FN episodes led to hospital admission and 13 were treated as outpatients. Mortality associated with the FN episode was 15% and an ANC <100/µL was predictive of increased mortality. CONCLUSION: This study confirms that FN is a serious and common complication of IV CT which must be diagnosed and treated promptly. Profound neutropenia was the only predictive factor of mortality.

Fatal Clostridium septicum febrile neutropenia during adjuvant chemotherapy for early breast cancer.

We report the case of a 76-year-old female patient with early breast cancer (hormone receptor-positive erbb2 amplified) that had started adjuvant chemotherapy with docetaxel, carboplatin and trastuzumab (TCH). Eight days after the first cycle of TCH chemotherapy, the patient was diagnosed with grade 1 oral mucositis, treated conservatively. The next day she started with nausea, vomiting, chills and fever, followed by a generalised tonicoclonic seizure. She presented to the emergency department with fever, hypotension and mild abdominal tenderness. Grade 4 neutropenia (370 µL/mL) and severe metabolic acidosis were documented. An abdominal CT scan documented extensive ischaemic bowel changes, with gas in portal and mesenteric veins, and pneumoretroperitoneum. Despite broad spectrum antibiotics and fluid resuscitation, she died 4 hours after admitted to hospital. Blood cultures collected on hospital admission eventually grew Clostridium septicum bacteria, an extremely rare infection in patient with breast cancer.

ONKOTEV Score as a Predictive Tool for Thromboembolic Events in Pancreatic Cancer-A Retrospective Analysis.

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in patients with cancer and causes considerable morbidity and mortality. The risk of VTE is higher in patients with pancreatic cancer and is often associated with treatment delays or interruptions. Recently, the ONKOTEV score was proposed as a VTE risk predictor model for patients with cancer, but its validation is still ongoing. PATIENTS AND METHODS: We conducted a retrospective study to determine the incidence of VTE and to evaluate the ONKOTEV score as a VTE predictive tool in a population of patients with pancreatic cancer. RESULTS: Between February 2012 and May 2017, 165 patients were included in the study. The median age was 73 years, 45.5% of patients were female, and 55.8% had stage IV disease. Fifty-one patients had a VTE (30.9%); 23.5% had pulmonary embolism, 25.5% had deep venous thrombosis, and 51.0% had visceral VTE (VsT). At a median follow-up time of 6.3 months, cumulative incidence of VTE was less than 10% for ONKOTEV scores 0 or 1 and approximately 40% and 70% for scores 2 and ≥3, respectively. CONCLUSION: The high VTE incidence observed in this study is consistent with prior reports. Patients at high risk for VTE with no increase in hemorrhagic risk should be considered for primary thromboprophylaxis. The ONKOTEV score may stratify VTE risk in patients with pancreatic cancer, with ONKOTEV score ≥2 being associated with a higher VTE occurrence. IMPLICATIONS FOR PRACTICE: Venous thromboembolism (VTE) is a frequent complication of patients with pancreatic cancer and causes considerable morbidity, treatment delays or interruptions, and mortality. Thromboprophylaxis is not used routinely in ambulatory patients. Tools to stratify the risk of VTE are important to help select patients who may benefit from thromboprophylaxis. Recently, the ONKOTEV score was proposed as a VTE risk predictor model for patients with cancer, but its validation is still ongoing. In this patient series, ONKOTEV score ≥2 was associated with high VTE occurrence and may stratify VTE risk in patients with pancreatic cancer, suggesting that ONKOTEV can be considered to select patients with pancreatic cancer for primary thromboprophylaxis.

Preliminary Assessment of a Dry-Lab Model for Laparoscopic Percutaneous Inguinal Ring Suture Training.

INTRODUCTION: Laparoscopic percutaneous inguinal ring suturing (PIRS) is a valuable technique to repair indirect inguinal hernias in children. The aim of the study was to show the preliminary results of training in an easy-to-build dry-lab model for laparoscopic PIRS technique. MATERIALS AND METHODS: The dry-lab model consists of two surgical gloves (being the smaller inside the larger). The entry of the glove is tied with a rubber letting a 5-mm trocar within it (optic). Carbon dioxide is inflated through the trocar at 8 mmHg pressure. The four long fingers of the glove simulate four internal inguinal rings. Eighteen participants without significant laparoscopic experience were asked to visualize a video showing a laparoscopic PIRS performed in a 4-year-old girl with a right inguinal hernia followed by a video showing the same technique performed in our dry-lab model. They were then asked to repeat the procedure in each of the four fingers, and the procedures were recorded. Two surgeons using the task-specific checklists (TSCs), global rating scale of operative performance (GRS), and time for the whole procedure evaluated the performance blindly. RESULTS: We found significant improvement in median TSC (P < .05) and median GRS each time the procedure was repeated (P < .05). There was significant shortening each time the procedure was repeated (P < .05), except between the third and fourth finger (P = .068). CONCLUSION: Our dry-lab model might be a good option for starting laparoscopic PIRS training.

Endoscopic pilonidal sinus treatment versus total excision with primary closure for sacrococcygeal pilonidal sinus disease in the pediatric population.

PURPOSE: To evaluate the effectiveness and safety of Endoscopic Pilonidal Sinus Treatment (EPSiT) in the pediatric population and compare it with excision followed by primary closure (EPC) regarding intra- and postoperative outcomes. METHODS: A retrospective analysis of all patients with chronic sacrococcygeal pilonidal sinus submitted to EPSiT and EPC during a 12-month period in our institution was performed. Data concerning patients' demographics and surgical outcomes were collected and compared between the two groups. RESULTS: We analyzed a total of 21 cases that underwent EPSiT and 63 cases of EPC, both groups with similar demographic characteristics. Operative time was similar for both groups (30 vs. 38min; p>0.05). No major intraoperative complications were reported. Wound infection rate was lower for EPSiT ((5.2% [n=1] vs. 20.0% [n=12]); p>0.05). Healing time was similar for both groups (28 vs. 37.5days). Recurrence occurred in 18,9% (n=15), with 2 cases (10.5%) reported in the EPSiT group versus 13 (21.6%) in EPC. There were no differences between groups regarding postoperative complications, complete wound healing and recurrence rates or healing time (p>0.05). CONCLUSIONS: Our results suggest that EPSiT is as viable as excision followed by primary closure in the management of sacrococcygeal pilonidal sinus in the pediatric population. LEVEL OF EVIDENCE: Therapeutic study - level III.

Five-years' experience with outpatient thyroglossal duct cyst surgery.

OBJECTIVES: Many pediatric surgeons feel uncomfortable doing Sistrunk procedure without drain placement and in an outpatient setting. This study aimed to review our pediatric surgery department's experience in managing thyroglossal duct cyst surgery and to prove feasibility and safety of Sistrunk procedure without drain placement in an outpatient setting. METHODS: A retrospective review was performed of all patients who underwent Sistrunk procedure, between January 2011 and December 2015, in our department. RESULTS: A total of 36 patients were included, with age ranging from 1 to 14 years (mean 6.3 years). Sixteen patients underwent day surgery, and 20 stayed overnight (with less than 24 h postoperative discharge). The main reason to stay overnight was distance (greater than 60 km or 1 h driving) between the hospital and patient's residence. All patients had histopathological confirmation of the diagnosis. None of the patients had a drain placed intraoperatively. There was only one readmission at 48 h postoperative; a patient who underwent day surgery came back with cervical edema, which resolved with non-operative treatment. Short-term complications included post-operative local wound infection (8,5%) and hematoma (2,9%), none of which required surgical treatment. CONCLUSIONS: Sistrunk procedure without drain placement is safe and can be performed in an outpatient setting.

Acute Alithiasic Cholecystitis and Human Herpes Virus Type-6 Infection: First Case.

A three-year-old male child presented with erythematous maculopapular nonpruritic generalized rash, poor feeding, vomiting, and cramping generalized abdominal pain. He was previously healthy and there was no family history of immunologic or other diseases. On examination he was afebrile, hemodynamically stable, with painful palpation of the right upper quadrant and positive Murphy's sign. Laboratory tests revealed elevated inflammatory markers, elevated aminotransferase activity, and features of cholestasis. Abdominal ultrasound showed gallbladder wall thickening of 8 mm with a positive sonographic Murphy's sign, without gallstones or pericholecystic fluid. Acute Alithiasic Cholecystitis (AAC) was diagnosed. Tests for underlying infectious causes were negative except positive blood specimen for Human Herpes Virus Type-6 (HHV-6) by polymerase chain reaction. With supportive therapy the child became progressively less symptomatic with gradual improvement. The child was discharged on the sixth day, asymptomatic and with improved analytic values. Two months later he had IgM negative and IgG positive antibodies (1/160) for HHV-6, which confirmed the diagnosis of previous infection. In a six-month follow-up period he remains asymptomatic. To the best of our knowledge, this represents the first case of AAC associated with HHV-6 infection.

Hybrid endoscopic thymectomy: combined transesophageal and transthoracic approach in a survival porcine model with cadaver assessment.

BACKGROUND: Video-assisted thoracoscopic surgery thymectomy has been used in the treatment of Myastenia Gravis and thymomas (coexisting or not). In natural orifice transluminal endoscopic surgery, new approaches to the thorax are emerging as alternatives to the classic transthoracic endoscopic surgery. The aim of this study was to assess the feasibility and reliability of hybrid endoscopic thymectomy (HET) using a combined transthoracic and transesophageal approach. METHODS: Twelve consecutive in vivo experiments were undertaken in the porcine model (4 acute and 8 survival). The same procedure was assessed in a human cadaver afterward. For HET, an 11-mm trocar was inserted in the 2nd intercostal space in the left anterior axillary line. A 0° 10-mm thoracoscope with a 5-mm working channel was introduced. Transesophageal access was created through a submucosal tunnel using a flexible gastroscope with a single working channel introduced through the mouth. Using both flexible (gastroscope) and rigid (thoracoscope) instruments, the mediastinum was opened; the thymus was dissected, and the vessels were ligated using electrocautery alone. RESULTS: Submucosal tunnel creation and esophagotomy were performed safely without incidents in all animals. Complete thymectomy was achieved in all experiments. All animals in the survival group lived for 14 days. Thoracoscopic and postmortem examination revealed pleural adhesions on site of the surgical procedure with no signs of infection. Histological analysis of the proximal third of the esophagus revealed complete cicatrization of both mucosal defect and myotomy site. In the human cadaver, we were able to replicate all the procedure even though we were not able to identify the thymus. CONCLUSIONS: Hybrid endoscopic thymectomy is feasible and reliable. HET could be regarded as a possible alternative to classic thoracoscopic approach for patients requiring thymectomy.

Ureteroneocystostomy after failed dextranomer/hyaluronic acid copolymer injection for vesicoureteral reflux treatment.

PURPOSE: To report our experience of open ureteroneocystostomy after failed endoscopic treatment. MATERIAL AND METHODS: Clinical charts of 787 children who entered our dextranomer/hyaluronic acid copolymer (DxHA) endoscopic injection program for vesicoureteral reflux (VUR) treatment between May 2000 and December 2009 were reviewed. Fifty-one of these patients were submitted to open ureteroneocystostomy for complete resolution of VUR. RESULTS: Twenty-eight patients (55%) were female. Median age at surgery was 65 months (range: 26-182). Median time going from first endoscopic injection until open surgery was 13 months (range 1-58). Surgical ureteral reimplantation was bilateral in 62.7% of the cases. Of a total of 83 operated ureters, nine were duplex ureters, nine were megaureters, six were ectopic, and two had periureteral diverticulum. Mean operative time was 70 min (range 45-120 min). There were no intra-operative complications. Follow-up VCUG showed complete resolution of VUR in 98% of patients. There was only one right-sided grade III VUR that persisted after bilateral reimplantation. It resolved with a single subureteral DxHA injection. CONCLUSIONS: Ureteroneocystostomy after a failed endoscopic treatment can achieve successful results in a high percentage of patients with minimal complications.

Five really easy steps to build a homemade low-cost simulator.

AIM: The aim of this study was to evaluate how simple it is to build a homemade low-cost simulator using a simple 5-step scheme. METHODS: A scheme explaining how to build an endoscopic surgery simulator in 5 easy steps was presented to 26 surgeons. The simulator required a pair of scissors and easy-to-find materials. Its total cost was less than €35. The participants assessed the simulator using common endoscopic training toys or ex vivo tissue and completed an anonymous query comparing it with other commercial simulators that they had experienced before. RESULTS: In all, 84.6% found the simulator really easy to build. Every participant felt that he or she could do the same simulator themselves. Comparing with other commercial available box simulators, the majority of participants found the homemade simulator easier to (a) mount and dismount, (b) transport, (c) clean, and (d) use when practicing alone. CONCLUSIONS: Anyone can build its own simulator for a small amount of money.

Transthoracic single port with peroral assistance: an animal experiment to assess a less invasive technique for human esophageal atresia repair.

Thoracoscopic repair of esophageal atresia has becoming the gold standard in many centers because it allows a better cosmetic result and avoids the musculoskeletal sequelae of a thoracotomy. Natural orifice translumenal endocopic surgery (NOTES) is a new surgical paradigm, and its human application has already been started in some procedures. In the present study, we explore the feasibility of performing an esophagoesophageal anastomosis using a single transthoracic single port combined with a peroral access in a rabbit model to simulate repair of esophageal atresia by hybrid NOTES in a human newborn. Adult male rabbits (Oryctolagus cuniculus, n=28) were used to perform the surgical protocol. We used a transthoracic telescope with a 3-mm working channel and a flexible endoscope with a 2.2-mm working channel by peroral access. We performed total esophagotomy with peroral scissors followed by an esophagoesophageal anastomosis achieved with a rigid transthoracic scope helped by the peroral operator. Extracorporeal transthoracic knots were performed to complete the anastomosis. The anastomoses were examined in loco and ex loco, after animal sacrifice. We successfully accomplished a complete esophageal anastomosis in all rabbits using a combination of transthoracic and peroral 3-mm instruments. This study provides important insights for a possible translation of hybrid NOTES to human newborns with esophageal atresia. Forward studies to accomplish their feasibility in human newborns will still be necessary.

Dismembered pyeloplasty for ureteropelvic junction syndrome treatment in children.

BACKGROUND: Open dismembered pyeloplasty remains the preferred surgical technique for ureteropelvic junction syndrome (UPJS) in most paediatric urology units. The authors present their experience of 230 patients and describe their form of presentation, treatment and early and long-term results. MATERIALS AND METHODS: Retrospective analysis of clinical records of 230 patients submitted to dismembered pyeloplasty in an 8-year period, from 1999 until 2007. Pre-operative data, early and long-term complications were registered. Image studies included renopelvic ultrasonography, mercapto-acetyl triglycine (MAG3) renal scan with furosemide test and, in some cases, elimination urography and retrograde cystography. Pre-operative and post-operative results were compared. RESULTS: Median age of our patients at time of surgery was 14.9 months (range: 21 days until 16.6 years). The majority of patients were male (72%, n = 166) and 74% (n = 120) had pre-natal diagnosis. The majority of hydronephrosis were in the left side (61%, n = 141). There were only 3% of complications in early post-operative period: four had acute pyelonephritis, two had renocutaneous fistula and one died due to respiratory failure. Mean follow-up period was 5 years, ranging from 12 months to 9.7 years. There was only one case of recurrence with the need of reoperation. Comparing pre-operative and post-operative imaging results, we found that 89% had normal renal function, 7% diminished but better than before and 2% equal as before surgery. CONCLUSION: Open dismembered pyeloplasty is a safe and effective treatment in paediatric UPJS.

Natural orifice transesophageal endoscopic surgery: state of the art.

The main goal of Natural Orifice Transluminal Endoscopic Surgery (NOTES) is performing surgery avoiding skin incisions. Theoretical advantages of NOTES include decreased postoperative pain, reduction/elimination of general anesthesia, improved cosmetic outcomes, elimination of skin incision-related complications such as wound infections and hernias, and increased overall patient satisfaction. Although various forms of port creation to accomplish thoracic NOTES procedures have been proposed, transesophageal NOTES has been shown to be the most reliable one. The evolution of endoscopic submucosal transesophageal access resulted in the development of per-oral endoscopic myotomy (POEM), which had a fast transition to clinical practice. The authors present a review of the current state of the art concerning transesophageal NOTES, looking at its potential for diagnostic and therapeutic interventions as well as the hurdles yet to be overcome.