Dragan Kravarusic

Colorectal carcinoma in childhood: a retrospective multicenter study.

Objectives:Colorectal carcinoma, a common adult malignancy, has an estimated childhood incidence of 0.3 to 1.5/million in Western countries and 0.2/million in Israel. Diagnosis is difficult because adult screening measures are unfeasible in children. The tumor is frequently associated with predisposing genetic factors, aggressive biological behavior, and poor prognosis. The aim of this multicenter study was to document the clinical profile, treatment and prognosis of colorectal carcinoma in children in Israel. Patients and Methods:The clinical, laboratory, therapeutic, and prognostic parameters of all 7 children from 4 medical centers in Israel who were diagnosed with colorectal carcinoma over a 25-y period were reviewed. Results:Patients presented with rectal bleeding (4 of 7), abdominal pain (2 of 7), and abdominal distension (2 of 7). Average time to diagnosis was 6 months. Six patients underwent surgery (1 refused), and 5 received chemotherapy. Histopathological studies showed poorly differentiated mucinous adenocarcinoma, signet-ring type, in 4 cases, moderately differentiated adenocarcinoma in 2, and well-differentiated carcinoma in 1. Three patients died of the disease, 2 shortly after diagnosis. One patient with recurrent metastatic disease was lost to follow-up. Conclusion:Colorectal carcinoma in children is characterized by aggressive tumor behavior and delayed diagnosis, resulting in a worse prognosis than in adults. Heightened physician awareness of the possibility of this disease in children, with special attention to adolescents with predisposing factors and rectal bleeding, could help to improve outcome.

Cryopreservation of in vitro matured oocytes in addition to ovarian tissue freezing for fertility preservation in paediatric female cancer patients before and after cancer therapy

STUDY QUESTION Is a protocol that combines in vitro maturation of germinal vesicle-stage oocytes and their vitrification with freezing of cortical ovarian tissue feasible for use in fertility preservation for both chemotherapy-naive paediatric patients as well as patients after initiation of cancer therapy? SUMMARY ANSWER Follicle-containing ovarian tissue as well as oocytes that can undergo maturation in vitro can be obtained from paediatric patients (including prepubertal girls) both before and after cancer therapy. WHAT IS KNOWN ALREADY Anticancer therapy reduces the number of follicles/oocytes but this effect is less severe in young patients, particularly the paediatric age group. Autotransplantation of ovarian tissue has yielded to date 60 live births, including one from tissue that was cryostored in adolescence. However, it is assumed that autografting cryopreserved-thawed ovarian cortical tissue poses a risk of reseeding the malignancy. Immature oocytes can be collected from very young girls without hormonal stimulation and then matured in vitro and vitrified. We have previously shown that there is no difference in the number of ovarian cortical follicles between paediatric patients before and after chemotherapy. STUDY DESIGN, SIZE, DURATION A prospective study was conducted in a cohort of 42 paediatric females with cancer (before and after therapy initiation) who underwent fertility preservation procedures in 2007-2014 at a single tertiary medical centre. PARTICIPANTS/MATERIALS, SETTING, METHODS The study group included girls and adolescent females with cancer: 22 before and 20 after chemotherapy. Following partial or complete oophorectomy, immature oocytes were either aspirated manually ex vivo from visible small antral follicles or filtered from spent media. Oocytes were incubated in oocyte maturation medium, and those that matured at 24 or 48 h were vitrified. Ovarian cortical tissue was cut and prepared for slow-gradual cryopreservation. Anti-Mullerian hormone (AMH) levels were measured in serum before and after oophorectomy. MAIN RESULTS AND ROLE OF CHANCE Ovarian tissue was successfully collected from 78.7% of the 42 patients. Oocytes were obtained from 20 patients before chemotherapy and 13 after chemotherapy. The youngest patients from whom oocytes were retrieved were aged 2 years (two atretic follicles) and 3 years. Of the 395 oocytes collected, ∼30% were atretic (29.6% in the pre-chemotherapy group, 37% in the post-chemotherapy group). One hundred twenty-one oocytes (31%) were matured in vitro and vitrified: 67.8% from patients before chemotherapy, the rest after chemotherapy. Mature oocytes suitable for vitrification were obtained from 16/20 patients before chemotherapy and from 12/13 patients after chemotherapy (maturation rate, 32 and 26.4%, respectively). There were significant correlations of the number of vitrified oocytes with patient age (more matured oocytes with older age) (P = 0.001) and with pre-oophorectomy AMH levels (P = 0.038 pre-chemotherapy group, P = 0.029 post-chemotherapy group). Oocytes suitable for vitrification were obtained both by manual aspiration of antral follicles (45%) and from rinse solutions after dissection. There were significantly more matured oocytes in the pre-chemotherapy group from aspiration than in the post-chemotherapy group after both aspiration (P < 0.033) and retrieval from rinsing fluids (P < 0.044). The number of pre-antral follicles per histological section did not differ in the pre- versus post-chemotherapy. AMH levels dropped by approximately 50% after ovarian removal in both groups, with a significant correlation between pre- and post-oophorectomy levels (P = 0.002 pre-chemotherapy group, P = 0.001 post-chemotherapy group). LIMITATIONS, REASONS FOR CAUTION There were no patients between 5 years and 10 years old in the post-chemotherapy group, which might have affected some results and correlations. Oocytes from patients soon after chemotherapy might be damaged, and caution is advised when using them for fertility-restoration purposes. The viability, development capability and fertilization potential of oocytes from paediatric patients, especially prepubertal and after chemotherapy, are unknown, in particular oocytes recovered from the media after the tissue dissection step. WIDER IMPLICATIONS OF THE FINDINGS Although more oocytes were collected and matured from chemotherapy-naïve paediatric patients, ovarian tissue and immature oocytes were also retrieved from young girls in whom cancer therapy has already been initiated. Our centre has established a protocol for potential maximal fertility preservation in paediatric female patients with cancer. Vitrified-in vitro-matured oocytes may serve as an important gamete source in paediatric female patients with cancer because the risk of reseeding the disease is avoided. Further studies are needed on the fertility-restoring potential of oocytes from paediatric and prepubertal patients, especially after exposure to chemotherapy. STUDY FUNDING/COMPETING INTERESTS The study was conducted as part of the routine procedures for fertility preservation at our IVF unit. No funding outside of the IVF laboratory was received. Funding for the AMH measurements was obtained by a research grant from the Israel Science Foundation (to B.-A.I., ISF 13-1873). None of the authors have competing interests. TRIAL REGISTRATION NUMBER N/A.

Thoracoscopic Segmentectomy for Congenital and Acquired Pulmonary Disease: A Case for Lung-Sparing Surgery

PURPOSE Over the last 15 years thoracoscopic lobectomy for congenital and acquired lesions has become an accepted modality in pediatric thoracic surgery. There is still debate about the need to perform a complete lobectomy for some of these lesions, and some advocate observation rather than resection, despite possible long-term complications of untreated lesions. High-resolution computed tomography (CT) scans and physical findings at the time of surgery, along with new advanced techniques, now allow for discrete partial anatomic resections, which may preserve normal lung. This study evaluates the feasibility and early results using these techniques in selected cases. PATIENTS AND METHODS With institutional review board approval, the records of all patients undergoing thoracoscopic lung resection were reviewed. From January 2006 to December 2012, 23 patients, ranging from 1 month to 16 years of age and weighing 3.8-42 kg, underwent thoracoscopy for planned resection. Pathology was congenital cystic lung disease in 19 patients, bronchiectasis in 3 patients, and arteriovenous malformation in 1 patient. In each case findings on CT scan and at the time of surgery warranted consideration of lung-preserving surgery. Procedures were performed through three ports using single lung ventilation and CO2 insufflation to achieve lung collapse. The LigaSure™ device (Covidien, Norwalk, CT) was the primary instrument used to seal and divide the lung parenchyma and seal vessels. RESULTS All procedures were completed successfully thoracoscopically. An anatomic segmental resection was achieved in 22 of 23 cases. Operative time ranged from 30 to 300 minutes (mean, 120 minutes). Segmental resections included the left upper lobe apical/posterior (n=4), lingula (n=3), left lower lobe superior (n=5), medial or posterior basal (n=3), right middle lobe medial (n=1), right upper lobe apical (n=1), right lower lobe superior (n=4), and posterior basal (n=2). Two patients had more than one segment excised. Chest tubes were left in for 24 hours in 16 cases, 48 hours in 4 cases, and 5 days in 1 case. Hospital stay ranged from 1 to 6 days (mean, 2 days). Follow-up CT scans obtained at 1-6 years (mean, 28 months) show no residual disease in 20 of 21 patients. One patient underwent a nonanatomic resection and had evidence of recurrent congenital pulmonary airway malformation at the 4-year follow-up. This patient underwent a secondary thoracoscopic resection. CONCLUSIONS Thoracoscopic lung-conserving therapy is technically feasible and safe in infants and children. The magnification provided by a thoracoscopic approach makes identification of segmental anatomic planes easier, aiding in safe dissection and resection. Anatomic resection appears to be associated with a low morbidity. It may be appropriate in the case of bilateral or extensive disease or in cases where the diseased tissue is clearly limited to an anatomic segment. Continued long-term follow-up is needed.

Androgen insensitivity syndrome: Risk of malignancy and timing of surgery in a paediatric and adolescent population

BACKGROUND Management of female phenotype XY disorders poses a series of problems for the treating clinician. Even after a series of investigations and imaging modalities, there are lingering doubts about the exact nature of the disease and the correct management option. Optimal timing and necessity for removal of their testes have been a debated issue by physicians. There is a generally accepted opinion among physicians that the risk of malignancy in androgen insensitivity syndrome (AIS) is considerably lower than with other intersex disorders and occurs at a later age. OBJECTIVE The highlight of this presentation is to reinforce the value of laparoscopic gonadectomy in management of AIS in correlation with data suggesting higher risk of malignancy. PATIENTS AND METHODS A retrospective review of 11 phenotypic females with XY karyotype was carried out. The patients were evaluated by a diagnostic protocol which included clinical, hormonal, sonographic and cytogenetic examinations. Patients/parents were counselled by the team concerning the different treatment modalities and contrary to the assigned gender, laparoscopy was offered to them. Uneventful bilateral gonadectomy was performed in all the patients and gonads submitted for histopathological examination. RESULTS A total of 11 patients (mean age, 10.4 ± 4.1 years), including six with complete AIS and five with partial AIS (PAIS) were reviewed. In two patients with PAIS (18.1%), histopathology revealed malignancy (bilateral seminoma and gonadoblastoma) and in an additional patient, a benign hamartoma was found. Literature evidence suggests that AIS female phenotype patients retaining their testes through puberty have a 5% chance for developing malignant tumours. Reviewing our results in correlation with literature, we found that PAIS patients may harbour a higher risk of malignancy. CONCLUSIONS In complementation to hormonal tests and cytogenetic techniques, laparoscopic gonadectomy is required to complete the diagnostic work up for AIS as it also adds a final therapeutic approach with low risk and huge benefit. Since laparoscopy is now a well-tolerated and widely accepted gold standard, it should be included in routine management for patients with AIS. Risk of malignancy in PAIS should be investigated in larger cohort of these patients.

Thoracoscopic sympathectomy ganglia ablation in the management of palmer hyperhidrosis: A decade experience in a single institution

BACKGROUND Hyperhidrosis can cause significant professional and social handicaps. Surgery is the preferred treatment modality for hyperhidrosis. There has been evolution in the surgical management of hyperhidrosis. This study evaluated the place of minimally invasive surgical approach and its long-term outcome in the management of hyperhidrosis. PATIENTS AND METHODS A 10-year prospective study of all children and adolescents who underwent thorascopic sympathectomy at the Schneider Childrens Hospital of Israel. Data were validated for the procedure and analysed for outcome of procedure. RESULTS There were 148 patients, 66 were males and 82 were females, with a median age of 13.8 SD ± 4.0 years. Two hundred and ninety-six thoracopic sympathectomies were performed with no conversion to open procedure. The mean operation time was 18 min. Ninety-five per cent of the patients were discharged the next day with a mean hospital stay of 1.2 days. Postoperative complications included segmental atelectasis in seven (4.72%) patients, pneumothorax in two (1.35%) and transient unilateral Horners syndrome in one (0.67%). Seventy-one (38.8%) experienced some form of compensatory hyperhidrosis. Complete relief of palmer hyperdidrosis was achieved in all patients (mean follow-up = 5.03 ± 1.76 years). The outcome was very satisfactory in 91 (61.5%) and satisfactory in 48 (32.4%). Only nine (6.1%) were not satisfied with the outcome. CONCLUSION Thorascopic sympathectomy provides effective and satisfactory cure for palmer hyperhidrosis with acceptable complication rate and excellent satisfactory outcome. There is a possibility of compensatory sweating in some individuals.

The 16 golden hours for conservative treatment in children with postoperative small bowel obstruction

BACKGROUND Conservative treatment of postoperative small bowel obstruction in children is widely accepted, provided that there are no clinical signs of bowel strangulation. However, the length of time surgery can be safely deferred remains unclear. PURPOSE The aim of this study was to determine the time limit for observant management of postoperative small bowel obstruction. METHODS The medical records of 128 children with 174 episodes of postoperative small bowel obstruction were reviewed. RESULTS Spontaneous resolution occurred in 63% of cases, 85% within 48 hours of admission. Bowel compromise was noted in 31% of the operated cases, and about half of them underwent bowel resection, accounting for 6% of all admissions. None of the cases treated surgically within 16 hours of admission was associated with bowel strangulation or need for resection. CONCLUSIONS In children presenting with postoperative small bowel obstruction, prolonging observant treatment for more than 48 hours yields only a small benefit in terms of spontaneous resolution. Bowel strangulation can occur within 16 hours of admission. On the basis of these findings, we suggest raising the index of suspicion for compromised bowel after 16 hours and making the decision for surgery at around 48 hours.

Perineal hernias in children: Case report and review of the literature

Perineal hernias (pelvic floor hernias) are extremely rare occurring through defects in musculature of the pelvic floor. This report presents a successfully treated case of primary perineal hernia and takes a review of the existing literature. The case of a 14-month-old girl with a great perineal hernia is presented. Diagnosis was secured by barium enema. The pelvic defect was successfully treated by primary suture with prolene. The literature shows many different approaches for treatment of perineal hernia, such as open or laparoscopic mesh repair, and perineal, abdominal or combined access in the adult, but our case like others confirms that primary closure of the hernial orifice through a perineal approach is also feasible in children.

Dual versus Triple Antibiotics Regimen in Children with Perforated Acute Appendicitis

Introduction Acute appendicitis is the most common emergency condition in pediatric surgery. Historically, a triple‐antibiotic therapy consisted of ampicillin, gentamicin, and clindamycin has been used postoperatively for perforated appendicitis. According to recently published trials, dual therapy consists of ceftriaxone and metronidazole only, offers a more efficient and cost‐effective antibiotic management compared with triple therapy. Based on these results, our department applied dual antibiotic therapy for children with perforated appendicitis that underwent appendectomy from 2009 and forth. Aim The aim of our study was to compare postoperative outcomes between patients treated with triple therapy (ampicillin, gentamicin, and metronidazole) (group A) versus dual therapy (ceftriaxone and metronidazole) (group B). Methods Clinical and laboratory data were retrospectively collected by review of the medical records for all children who underwent appendectomy for the perforated appendix at the Schneider Childrens Medical Center of Israel, a tertiary pediatric care center between 2007 and 2011. Children with perforated appendicitis received antibiotic therapy in accordance with the hospitals guidelines that were valid at the time the surgery took place. In the first period (years 2007‐2009) (group A) a triad of ampicillin, gentamicin, and metronidazole and the second period (2009‐2011) (group B) dual therapy consists of ceftriaxone and metronidazole. The two groups were compared for outcome and complications, such as wound infections, changing of antibiotic therapy, and length of stay. Results During the study period 1,203 patients underwent an appendectomy. Of these, 175 patients were diagnosed with perforated appendix and were treated with postoperative antibiotics regimen. Group A and group B consisted of 89 and 86 patients, respectively. The two groups were not different significantly in terms of demographic data, length of stay, or readmission rates. However, more rates of wound infection and changing of antibiotic therapy were seen in group B, although not statistically significant (p = 0.064). Conclusion Dual antibiotic therapy for perforated appendicitis is a cost‐effective and efficient mode of therapy compared with triple‐antibiotics regimen. However, prospective studies are required to determine whether this policy is associated with higher rates of wound infections and change in antibiotic therapy.

Caudal Duplication Syndrome: the Vital Role of a Multidisciplinary Approach and Staged Correction.

Caudal duplication syndrome is a rare entity that describes the association between congenital anomalies involving caudal structures and may have a wide spectrum of clinical manifestations. A full-term male presented with combination of anomalies including anorectal malformation, duplication of the colon and lower urinary tract, split of the lower spine, and lipomyelomeningocele with tethering of the cord. We report this exceptional case of caudal duplication syndrome with special emphasis on surgical strategy and approach combining all disciplines involved. The purpose of this report is to present the pathology, assessment, and management strategy of this complex case.

Laparoscopic-Assisted Retrieval of Migrated Intra-Abdominal Pacemaker Generator

A 5-year-old boy born with a congenital heart defect had insertion of an epicardial pacemaker that was found on routine evaluation to have been displaced into the rectovesical pouch. He underwent transvenous insertion of another pacemaker, and the displaced pacemaker was successfully retrieved by laparoscopy without incident.