Primary anastomosis as a valid alternative for extremely low birth weight infants with spontaneous intestinal perforation.

The aim was to assess the results of primary anastomosis (PA) compared to enterostomy (ES) in infants with spontaneous intestinal perforation (SIP) and a weight below 1000 g. Between 2014 and 2016, enterostomy was routinely carried out on extremely low birth weight (ELBW) patients with SIP. From 2016 until 2019, all patients underwent anastomosis without stoma formation. We compared outcome and complications in both groups. Forty-two patients with a median gestational age of 24.3 weeks and a birth weight of 640 g with SIP were included. Thirty patients underwent PA; ES was performed in 12 patients. Overall in-hospital mortality was 11.9% (PA: 13.3%, ES: 8.3%). Reoperations due to complications became necessary in 10/30 patients with PA and 4/12 patients with ES. Length of stay was 110.5 days in the PA group and 124 days in the ES group. Median weight at discharge was higher in the PA group (PA: 2258 g, ES: 1880 g, p = .036).Conclusion: Primary anastomosis is a feasible treatment option for SIP in infants < 1000 g and may have a positive impact on weight gain and length of hospitalization. However, further studies on selection criteria for PA are necessary. What is Known: • Enterostomy (ES) and primary anastomosis (PA) are feasible treatment options in preterm infants with spontaneous intestinal perforation (SIP). • Stomal complications or failure to thrive due to poor food utilization can pose significant problems. What is New: • Primary anastomosis in case of SIP is equal to enterostomy in terms of mortality and revision rate; however, length of stay and weight gain can be presumably positively influenced. • Primary anastomosis is a valid treatment option even for patients weighing less than 1000 g.

[Flap Reconstruction as Alternative Anastomosis Technique for the Surgery of Oesophageal Atresia with Distal Oesophagotracheal Fistula]. / Die Lappenplastik als alternative Anastomosentechnik für die operative Korrektur der Ösophagusatresie mit distaler ösophagotrachealer Fistel.

AIM: The creation of a primary anastomosis in newborns with oesophageal atresia and distal oesophageotracheal fistula (EA-DF) is technically challenging, especially in small children. The goal is to approximate the fragile oesophageal ends without suture disruption and to minimize the mobilisation of the lower segment. We describe an alternative anastomosis technique aiming at reducing the tension on the first sutures at the posterior wall. INDICATIONS: EA-DF was corrected in 13 newborns either by open (n = 11) or thoracoscopic (n = 2) surgery using this technique. METHOD: The anastomosis technique is based on creation of a dorsal flap of the upper oesophageal pouch and insertion in the spatulated lower oesophageal segment after the fistula has been separated. Subsequently, the first sutures of the posterior wall can be accomplished with reduced tension. Upon completion of the anastomosis, a diagonally shaped anastomotic plane results. CONCLUSION: The method is a helpful alternative to approximate the oesophageal stumps of newborns with EA and distal oesophagotracheal fistula. By this technique, the first stabilising sutures of the posterior wall can be accomplished with reduced tension. This results in reduced tensile stress on the individual sutures and simplifies the anastomisation in comparison to the conventional end-to-end anastomosis.

Update on Transumbilical Single-Incision Laparoscopic Assisted Appendectomy (TULAA) - Which Children Benefit and What are the Complications?

BACKGROUND: Transumbilical laparoscopic-assisted appendectomy (TULAA) is fast and cost-effective since no endoloops, staplers or wound protection devices are used. We analyzed the effects of TULAA as first approach for perforated (PA) and non-perforated (NPA) appendicitis in children. PATIENTS: We performed a retrospective analysis of 181 children for whom TULAA was the first approach for appendicitis between October 2010 and March 2016. METHODS: Morbidity, additional laparoscopic instrument insertion (AI), conversions to open extraumbilical appendectomy (OC), and complications were evaluated. RESULTS: TULAA was initiated in 181 (87.4%) children (113 boys: 68 girls). Median age was 10.3 years (3.3-13.9 years) and BMI 16.8 kg/m2 (12.4-30.8). Appendicitis was non-perforated in 157 (86.7%) and perforated in 24 (13.3%) patients. TULAA was finalized in 142 (78.5%) patients, AI were inserted in 20 (11%) and OC were performed in 19 (10.5%) patients. Duration of surgery did not exceed 20 min for 12.8%, and 30 min for 43.6% of patients with TULAA and NPA. The rate of wound infections did not differ between procedures (TULAA 3/142 (2.1%), AI 0 (0%), OC 1/19 (5.3%), P=1.000). Further postoperative course was uneventful in 179 (98.9%) patients. CONCLUSION: TULAA can be used as first approach for appendicitis in all children with a low rate of complications. Extracorporeal appendix stump closure can be safely achieved in the majority of children without using laparoscopic disposable devices.

Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months.

BACKGROUND: Although several studies have been conducted on the role of surgery in localized neuroblastoma, the impact of surgical timing and extent of primary tumor resection on outcome in high-risk patients remains controversial. METHODS: Patients from the German neuroblastoma trial NB97 with localized neuroblastoma INSS stage 1-3 age > 18 months were included for retrospective analysis. Imaging reports were reviewed by two independent physicians for Image Defined Risk Factors (IDRF). Operation notes and corresponding imaging reports were analyzed for surgical radicality. The extent of tumor resection was classified as complete resection (95-100%), gross total resection (90-95%), incomplete resection (50-90%), and biopsy (<50%) and correlated with local control rate and outcome. Patients were stratified according to the International Neuroblastoma Risk Group (INRG) staging system. Survival curves were estimated according to the method of Kaplan and Meier and compared by the log-rank test. RESULTS: A total of 179 patients were included in this study. 77 patients underwent more than one primary tumor operation. After best surgery, 68.7% of patients achieved complete resection of the primary tumor, 16.8% gross total resection, 14.0% incomplete surgery, and 0.5% biopsy only. The cumulative complication rate was 20.3% and the surgery associated mortality rate was 1.1%. Image defined risk factors (IDRF) predicted the extent of resection. Patients with complete resection had a better local-progression-free survival (LPFS), event-free survival (EFS) and OS (overall survival) than the other groups. Subgroup analyses showed better EFS, LPFS and OS for patients with complete resection in INRG high-risk patients. Multivariable analyses revealed resection (complete vs. other), and MYCN (non-amplified vs. amplified) as independent prognostic factors for EFS, LPFS and OS. CONCLUSIONS: In patients with localized neuroblastoma age 18 months or older, especially in INRG high-risk patients harboring MYCN amplification, extended surgery of the primary tumor site improved local control rate and survival with an acceptable risk of complications.

Does metabolic alkalosis influence cerebral oxygenation in infantile hypertrophic pyloric stenosis?

BACKGROUND: This pilot study focuses on regional tissue oxygenation (rSO2) in patients with infantile hypertrophic pyloric stenosis in a perioperative setting. To investigate the influence of enhanced metabolic alkalosis (MA) on cerebral (c-rSO2) and renal (r-rSO2) tissue oxygenation, two-site near-infrared spectroscopy (NIRS) technology was applied. MATERIALS AND METHODS: Perioperative c-rSO2, r-rSO2, capillary blood gases, and electrolytes from 12 infants were retrospectively compared before and after correction of MA at admission (T1), before surgery (T2), and after surgery (T3). RESULTS: Correction of MA was associated with an alteration of cerebral oxygenation without affecting renal oxygenation. When compared to T1, 5-min mean (± standard deviation) c-rSO2 increased after correction of MA at T2 (72.74 ± 4.60% versus 77.89 ± 5.84%; P = 0.058), reaching significance at T3 (80.79 ± 5.29%; P = 0.003). Furthermore, relative 30-min c-rSO2 values at first 3 h of metabolic compensation were significantly lowered compared with postsurgical states at 16 and 24 h. Cerebral oxygenation was positively correlated with levels of sodium (r = 0.37; P = 0.03) and inversely correlated with levels of bicarbonate (r = -0.34; P = 0.05) and base excess (r = -0.36; P = 0.04). Analysis of preoperative and postoperative cerebral and renal hypoxic burden yielded no differences. However, a negative correlation (r = -0.40; P = 0.03) regarding hematocrite and mean r-rSO2, indirectly indicative of an increased renal blood flow under hemodilution, was obtained. CONCLUSIONS: NIRS seems suitable for the detection of a transiently impaired cerebral oxygenation under state of pronounced MA in infants with infantile hypertrophic pyloric stenosis. Correction of MA led to normalization of c-rSO2. NIRS technology constitutes a promising tool for optimizing perioperative management, especially in the context of a possible diminished neurodevelopmental outcome after pyloromyotomy.

An experimental study in six fresh human cadavers using a novel approach to avoid abdominal wall incisions in total colectomy: totally transanal laparoendoscopic single-site pull-through colectomy with J-pouch creation.

BACKGROUND: The use of transanal laparoscopic access to completely avoid abdominal wall incisions represents the most current evolution in minimally invasive surgery. The combination of single-site surgery and natural orifice transluminal endoscopic surgery (NOTES™) can be used for totally transanal laparoendoscopic pull-through colectomy with J-pouch creation (TLPC-J). The aim of the present study was to provide evidence for the feasibility of TLPC-J in adult human cadavers. METHODS: TLPC-J was performed in six fresh adult human cadavers. The procedure involved endorectal submucosal dissection from 1 cm above the dentate line to a point above the peritoneal reflection, where the rectal muscle was divided circumferentially. The edge of the mucosal cuff was closed distally in order to prevent fecal contamination and the endorectal tube was placed back into the abdomen. A Triport+™ or QuadPort+™ system was introduced transanally, and it served as a multiport device (MD). Resection of the entire colon, mobilization of the distal ileal segment, and extracorporeal suture of the ileal J-loop were performed via the transanal approach. The J-pouch was created using Endo GIA™. After removal of the MD, the J-pouch was sutured to the rectal wall. RESULTS: TLPC-J was performed in all cadavers, with a mean operation duration of 236 ± 22 min. Conversion to either transabdominal laparoscopy or laparotomy was not required in any of the cadavers. No bowel perforation or damage to other organs was observed. The use of a curved endoscope greatly facilitated visualization during transanal laparoscopic dissection for partial and total colectomy, making the procedure feasible. All specimens were retrieved through the anus, eliminating the need for additional transabdominal incisions. CONCLUSIONS: TLPC-J was technically feasible in adult human cadavers, and abdominal wall incisions were not required. However, clinical studies are needed to determine its feasibility in living adults.

Transumbilical cord access (TUCA) for laparoscopy in infants and children: simple, safe and fast.

PURPOSE: We herein report a case series evaluating the safety and complication rate of transumbilical cord access (TUCA) for pediatric laparoscopic surgery. METHODS: Data were collected for 556 infants and children. Access into the abdominal cavity was gained via a transverse infraumbilical stab incision passing the fibrotic umbilical cord remnant. Ninety-two infants underwent laparoscopic pyloromyotomy (LPM), 159 female infants underwent herniorrhaphy (LHR) and 309 infants underwent appendectomy (LAP). Of the total operations, 70 % were performed by board-certified surgeons and 30 % were performed by non-board-certified surgeons. The median time of follow-up was 24 months. RESULTS: No cases of acute severe bleeding or organ laceration were noted. TUCA-related complications were observed in nine patients (1.6 %). Omphalitis and persistent wound secretion were detected in eight children and foreign bodies consisting of cyanoacrylate were removed from three of these patients. Meanwhile, umbilical pain leading to surgical revision was observed in one child, and eight umbilical hernias were repaired during the TUCA procedures. No signs of postoperative incisional hernia were recorded. CONCLUSIONS: TUCA is a safe and comfortable access method for pediatric laparoscopic surgery in various age groups. This method is easy to learn and can be quickly and safely performed in the vast majority of children.

Tracheoscopic Findings and Their Impact on Respiratory Symptoms in Children with Esophageal Atresia.

INTRODUCTION: Esophageal atresia (EA) is often accompanied by tracheobronchial malformations leading to stridor, recurrent bronchitis, and occasionally to life-threatening obstructive apnea after surgical repair. The aim of this study was to identify the presence of tracheomalacia in patients with EA and tracheoesophageal fistula (TEF) pre- and postoperatively and to find endoscopic correlates leading to clinical airway symptoms. METHODS: In a cohort of 362 patients with EA-TEF who underwent 595 tracheoscopies at the Children's Hospital of Cologne between January 1983 and December 2002, impaired tracheal lumen, localization of TEF, tracheal pulsations, and corresponding clinical symptoms were retrospectively analyzed. RESULTS: The incidence of tracheomalacia was higher in patients with EA and TEF (Gross B-D) compared with patients with EA alone (Gross A) and average tracheal collapse does not significantly change before and after surgical repair of the esophagus in all types. Patients with cyanosis while eating and obstructive apnea presented with an average tracheal collapse of 89%. The presence of respiratory symptoms such as cough, stridor, or bronchitis was not associated with a higher grade of tracheal collapse compared with patients without any airway symptoms (average tracheal collapse of 37% in symptomatic patients vs. 33% in nonsymptomatic patients). CONCLUSION: Tracheomalacia tends to be present independently of surgical procedure. Tracheomalacia should be measured by tracheoscopy (in % of tracheal collapse). Patients with a tracheal collapse of >80%, a ventral pulsation, and obstructive apnea or cyanosis in combination, are at risk for life-threatening situations and further surgical treatment should be considered.

Retrospective analysis of relapsed abdominal high-risk neuroblastoma.

BACKGROUND/PURPOSE: The impact of abdominal topography and surgical technique on resectability and local relapse pattern of relapsed abdominal high-risk neuroblastoma (R-HR-NB) is not clearly defined. METHODS: A sample of thirty-nine patients with R-HR-NB enrolled in the German neuroblastoma trials between 2001 and 2010 was analyzed retrospectively using surgical and imaging reports. We evaluated resectability and local relapse pattern within 6 standardized abdominal regions, impact of extent of the first resective surgery on overall survival (OS), and of number of operations and a higher cumulative surgical assessment score (C-SAS) on OS after the first event. RESULTS: In the left upper abdomen, rates for tumor persistence and relapse were 45.9% and 13.5% and in the left lower abdomen 27.7% and 8.3%, respectively. OS in months did not differ between complete and incomplete first resections (median (interquartile range): 35 (45.6) vs. 40 (65.4), P=.649). Better OS after the first event was associated with repeated as compared to single surgery (47.7 (64.7) vs. 4.3 (12.5), P=.000), and with higher as compared to lower C-SAS (47.7 (64.3) vs. 7.6 (14.7), P=.002). CONCLUSIONS: OS after relapse/progression was not dependent on the extent of first resection. The number of operations was associated with better outcome after event. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: LEVEL III Retrospective comparative study.

Surgical Implications for Diagnosis and Treatment of Intestinal Aspergillosis in Pediatric Patients with ALL.

BACKGROUND: The incidence of invasive aspergillosis (IA) in children with hematooncological malignancies is increasing as a result of intensive treatment, immunosuppression, and extended use of broad-spectrum antibiotics. Infection of the GI tract by Aspergillus spp. is a rare and fatal complication, which often requires surgical diagnostic and therapeutic exploration. OBJECTIVE: The aim of this study was to determine the characteristics of symptomatic intestinal aspergillosis, diagnosis, treatment, and outcome of pediatric patients with an underlying hemato-oncologic disease. PATIENTS AND METHODS: We analyzed 2,307 German patients with acute lymphoblastic leukemia (ALL) from age 1 to 17 years registered in the AIEOP-BFM ALL 2000 study from 2000 to 2006. All reported adverse events were assessed for symptoms of IA and retrospectively reviewed for any sign or proof of intestinal involvement of IA. RESULTS: In this cohort, IA was reported in 30 of 2,307 patients while intestinal involvement was documented in five patients. Four of these patients had intestinal symptoms and three patients underwent explorative laparotomy. Among clinical cases with IA, gastrointestinal manifestation of IA mostly occurred in adolescent patients (10-16 years). Symptoms varied from abdominal tenderness and pain to constipation. Intestinal aspergillosis was proven by microbiological and histopathological examination and fungal infection was observed macroscopically in the jejunal lumen during surgery. Despite the extended surgery and antifungal therapy, outcome of disseminated IA with intestinal involvement remains poor. CONCLUSION: Surgeons should be aware of surgical complications of intestinal aspergillosis in children with hematooncological diseases requiring exploration and resection. IA is a rare event and still difficult to diagnose due to unspecific abdominal symptoms. Thus, biopsy sampling is of utmost importance to ensure diagnosis, and resection of necrotic or perforated tissue should be attempted early.

Lymphotoxin-beta receptor immune interaction promotes tumor growth by inducing angiogenesis.

Growth of solid fibrosarcoma tumors in mice was inhibited by the release of a solublelymphotoxin-beta receptor inhibitor (LTbetaR-immunoglobulin fusion protein) from the tumor cells. Tumor growth arrest in mice deficient in the ligand LTalpha1beta2 demonstrated the requirement for activation of the LTbetaR on the tumor cells by host cell-derived LTalpha1beta2. Activation of the LTbetaR resulted in enhanced release of macrophage inflammatory protein-2. Blocked angiogenesis was revealed in LTbetaR inhibitor-producing tumor nodules by immunohistochemistry and in vivo microscopy. The growth arrest of LTbetaR inhibitor-producing fibrosarcomas was overcome by forced MIP-2 expression in the tumor cells. Thus, LTbetaR activation on tumor cells by activated host lymphocytes can initiate a novel proangiogenic pathway leading to organized tumor tissue development.

Experiences with LESS-appendectomy in Children.

PURPOSE: To evaluate the outcome of laparoendoscopic single-site (LESS-A) through one transumbilical port vs. 3-port laparoscopic (3TA) appendectomy in children. METHODS: We reviewed the records of 309 children (65 LESS-A, 244 3TA) operated on between 2008 and 2012. One hundered forty-nine patients had acute catarrhalis (CA), 133 phlegmonous (PLA), and 27 perforated appendicitis (PA). We compared the duration of operation (DO) the incidence of abdominal abscesses (AA) and wound infections (WI), as well as the degree of appendiceal inflammation (DI) among surgeons with and without board certification. RESULTS: For all DI, LESS-A resulted in a shorter DO than 3TA (CA 57.9 ± 22.8 vs. 68.5 ± 23.2, P = 0.014; PLA 51.5±16.5 vs. 68.4±33.0, P = 0.006; PA 66.0 ± 29.0 vs. 97.3 ± 41.8, P = 0.039). LESS-A was not used for less complicated cases when compared to 3TA (CA 50.8% vs. 47.5%; PLA 33.8% vs. 45.5%; PA 15.4% vs. 7.0%; CA vs. PLA, P = 0.292; CA vs. PA, P = 0.142; PLA vs. PA, P = 0.031). Surgeons without board certification were assigned to a similar percentage to perform both techniques for any DI (CA 30.3% vs. 37.1%, P = 0.541; PLA 31.8% vs. 40.5%, P= 0.484; PA 40% vs. 35.3%, P = 1.0). We found no significant differences concerning AA (1.5% vs. 1.2%, P = 1.0) and WI (3.1% vs. 1.6%, P = 0.61). CONCLUSIONS: LESS-A can be done by surgeons with and without board certification for all DI, with shorter DO and similar complication rates as compared to 3TA.

Can a simplified algorithm prevent incomplete laparoscopic pyloromyotomy?

PURPOSE: The purpose of this study is to analyze an algorithm intended to prevent incomplete pyloromyotomy in 3-port laparoscopic (3TP) and laparoendoscopic single-site (LESS-P) procedures in a teaching hospital. METHODS: We defined the pyloroduodenal and pyloroantral junctions as anatomical margins prior pyloromyotomy by palpating and coagulating the serosa with the hook cautery instrument. Incomplete pyloromyotomies, mucosa perforations, serosa lacerations, and wound infections were recorded for pediatric surgical trainees (PST) and board-certified pediatric surgeons (BC). RESULTS: We reviewed the medical files of 233 infants, who underwent LESS-P (n=21), 3TP (n=71), and open pyloromyotomy (OP, n=141). No incomplete pyloromyotomies occurred. In contrast to OP, mucosa perforations did not occur in the laparoscopic procedures during the study period (6.38% vs. 0%, P=.013). OP had insignificantly more serosal lacerations (3.5% vs. 1.4%, P=.407). There was no difference in the rate of wound infections between OP and laparoscopic procedures (2.8% vs. 4.3%, P=.715). In the latter, all wound infections were associated with the use of skin adhesive. CONCLUSIONS: This algorithm helps avoiding incomplete laparoscopic pyloromyotomy during the learning curve and in a teaching setting. It is not risky to assist 3TP and LESS-P to PST as this led to a decreased rate of mucosa perforations without experiencing incomplete pyloromyotomies.

GFP-transfected tumor cells are useful in examining early metastasis in vivo, but immune reaction precludes long-term tumor development studies in immunocompetent mice.

To develop effective therapeutic strategies aimed at treating tumor metastasis, critical steps in this process must be better understood. For this purpose we have established a new model to visualize and quantify early metastasis. Murine CT-26 colon adenocarcinoma cells were stably transfected with green fluorescent protein (GFP). Tumor cells were intraportally delivered to the liver of Balb/c mice and subsequently tracked by intravital fluorescence microscopy. Coinjection of fluorescent beads and in vivo propidium iodide staining allowed examination of initial tumor cell arrest, extravasation, viability and proliferation. Results showed that GFP-transfection compared to conventional labeling procedures (Calcein, cytoplasmic microspheres) did not alter early metastatic properties. However, the long-term development of liver metastases expressing GFP was markedly reduced compared to wild type CT-26 tumor cells. An increase in the size and the number of liver metastases in T- and B-cell-deficient SCID mice suggested an immune response to the GFP transfected cells responsible for the reduced metastatic growth in wild-type mice. Based on our findings, this model can be used to examine the early steps of metastasis in vivo. However, in immunocompetent mice, the use of GFP-labeled tumor cells should be limited to tracking cell arrest and extravasation, whereas evaluations of long-term metastatic growth should be performed in immunodeficient mice.

Laparoscopic appendectomy for perforated appendicitis in children has complication rates comparable with those of open appendectomy.

PURPOSE: To evaluate the outcome of laparoscopic (LA) vs. open appendectomy (OA) in children with perforated appendicitis (PA). METHODS: We reviewed the medical files of 221 children who underwent LA (n=75), OA (n=122), and conversion (CO) (n=24), comparing duration of operation, re-admissions, re-operations, intra-abdominal abscesses (IAA), and wound infections. RESULTS: Compared to OA, LA resulted in fewer re-admissions (1.3% vs. 12.3%; P=.006), fewer re-operations (4% vs. 17.2%; P=.006), and fewer wound infections (0% vs. 11.5%; P=.001). No differences in the duration of operation (72.9 ± 23.0 min vs. 77.7 ± 48.0 min; P=.392) or IAA (4% vs. 11.5%; P=.114) were observed. Compared to LA, CO had more complications. CONCLUSIONS: We report that LA is superior to OA with regard to incidence of re-admission, re-operation, and wound infection.

Totally transanal LESS pull-through colectomy: a novel approach for avoiding abdominal wall incision in children with long-segment intestinal aganglionosis.

UNLABELLED: Abstract Introduction: Minimally invasive surgery in children with long-segment intestinal aganglionosis aims to reduce the number of abdominal wall incisions. Conventional laparoscopic and laparoendoscopic single-site (LESS) surgeries fulfill this goal. In children, natural orifice translumenal endoscopic surgery (NOTES™; American Society for Gastrointestinal Endoscopy [Oak Brook, IL] and Society for American Gastrointestinal and Endoscopic Surgeons [Los Angeles, CA]) has been limited because of fear of access site complications. We present a novel technique of totally transanal LESS pull-through colectomy (TLPC), avoiding abdominal wall incision, which combines LESS technology and the NOTES approach. SUBJECTS AND METHODS: Two boys and one girl (2.5 months, 6 months, and 5 years of age, respectively) with sigmoid and transverse colon aganglionosis underwent surgery. The TLPC procedure consisted of an endorectal technique with submucosal dissection starting 1 cm orally from the dentate line to above the peritoneal reflection, where the rectal muscle was divided circumferentially. After ligation of the rectal mucosa, the proximal bowel was replaced into the abdominal cavity, and a TriPort(®) (Olympus Surgical Technologies Europe, Hamburg, Germany) was introduced transanally. Mesenterial resection of the aganglionic bowel was accomplished via transanal LESS until the normoganglionic colon segment was reached and pulled down to the site of anastomosis. After removal of the port, a conventional pull-through procedure was performed. RESULTS: All children displayed normal bowel movements and were complication-free during the follow-up period of up to 7 months. CONCLUSIONS: TLPC combines the minimally invasive LESS surgery with the scarless concept of NOTES and allows resection of long-segment aganglionosis without abdominal incision. TLPC is a safe, effective, and feasible surgical procedure in children with long-segment intestinal aganglionosis.

Appendiceal carcinoid tumor with lymph node metastasis in a child: case report and review of the literature.

Most appendiceal carcinoids (ACs) in children present without lymph node metastasis. Lymph node metastasis is rarely present when primary tumor diameter exceeds 1 cm. We present the extraordinary case of an AC with a primary tumor diameter of 0.7 cm and infiltration of the mesentery, as well as 1 positive lymph node of the mesentery in a 14-year-old boy. Besides adding a rare case, we review the data published in the current literature on AC with lymph node metastasis in children and summarize up-to-date guidelines for diagnostic workup, therapy, and follow-up.

Stone-containing periampullary duodenal duplication cyst with aberrant pancreatic duct.

This case report describes a unique variant of a duodenal duplication cyst in an 8-year-old boy who had recurrent episodes of upper abdominal pain. Imaging revealed a stone-containing cyst near the biliaropancreatic ducts and concomitant hydrops of the gallbladder. Open transduodenal marsupialization of the cyst and resection of the inflamed gallbladder were performed. Further episodes of pancreatitis did not occur for a follow-up of 2 years.

All-trans retinoic acid arrests neuroblastoma cells in a dormant state. Subsequent nerve growth factor/brain-derived neurotrophic factor treatment adds modest benefit.

BACKGROUND: Therapies aiming at inducing differentiation or apoptosis of neuroblastoma (NB) are an important research topic. Although retinoic acid showed promising antitumoral results, its effects against refractory disease are limited. Putative candidates for combination therapies are nerve growth factor (NGF; Tebu-Bio/Peprotech, Offenbach, Germany) and brain-derived neurotrophic factor (BDNF; Tebu-Bio/Peprotech, Offenbach, Germany) because their receptors are of prognostic clinical value in clinical neuroblastoma. Another clinical prognostic factor is the number of Schwann cells. Substances secreted by Schwann cells proved antitumoral capacities in vitro. The aim of the study was to analyze whether retinoic acid may offer an additional line of attack acting independent from Schwann cells and whether additive treatment with the neurotrophin-receptor ligands NGF/BDNF confers additional benefit. METHODS: Human SHSY-5Y NB cells were cultured in vitro. After a 7-day all-trans retinoic acid (ATRA; Sigma-Aldrich Chemie, Taufkirchen, Germany) treatment (15 mumol/L of ATRA), NB proliferation was proportional to extinction in dimethyl-thiazol-diphenyltetrazoliumbromide (MTT) tests. Fluorescence-activated cell sorter (FACS) analysis for annexin and propidium iodide determined the degree of apoptosis and necrosis as well as the expression of the Schwann type cell marker S100. The S100 messenger RNA was assessed by reverse transcriptase polymerase chain reaction. In addition, the effect on NB proliferation was investigated when ATRA was combined with a 7-day treatment with NGF or BDNF (10, 50, 100 ng/mL) either before or after the 7-day ATRA treatment. RESULTS: All-trans retinoic acid reduced proliferation (0.116 +/- 0.006 SEM vs 0.359 +/- 0.010 SEM in the untreated control group; P < .001). After ATRA treatment, 95% +/- 1.82% SEM were still viable, with only 2.61% +/- 1.17% SEM apoptotic and 2.38% +/- 0.69% SEM necrotic cells. All-trans retinoic acid induced a remarkable decrease in S100 expression in FACS (16.91% +/- 1.72% SEM vs 32.33% +/- 2.54% SEM in controls; P = .009). The S100 messenger RNA levels were not increased by ATRA (DeltaDeltaT values: 1.73, 2.77, and 1.43; n = 3). Both NGF and BDNF had only a modest synergistic effect when given after ATRA treatment. No effect was seen when they were administered before ATRA treatment. CONCLUSIONS: All-trans retinoic proved to be a vigorous inhibitor of NB proliferation in vitro. However, because most NB cells remained viable combination therapies are required. Treatment with NGF and BDNF showed only a modest benefit and did not reflect the strong prognostic impact of tyrosine kinase receptors in clinical NB. The ATRA-induced proliferation arrest is not related to Schwann type subdifferentiation. This suggests that substances secreted by Schwann cells could be possible independent combination partners. We suggest studies using combinations of ATRA and substances secreted by Schwann cells.

TNP-470 fails to block the onset of angiogenesis and early tumor establishment in an intravital minimal disease model.

BACKGROUND AND AIMS: The angiogenesis inhibitor TNP-470 (AGM-1470) has shown encouraging results in animal models of established tumors. However, results of recent clinical trials using TNP-470 have been disappointing. Since little is known about the effects of TNP-470 at the minimal disease stage, we analyzed the effects of TNP-470 on the early stages of tumor establishment. METHODS: Twenty thousand green fluorescent protein (GFP)-transfected murine CT-26 (colonic carcinoma) or Panc-02-H0 (pancreatic adenocarcinoma) cells were inoculated in dorsal skin-fold chambers in BALB/c or C57BL6 mice. Tumor area and microvessel density (MVD) were quantified by intravital microscopy (IVM). Body weight was also monitored. Effects were compared with those in a conventional model involving subcutaneous (s.c.) inoculation of 10(6) tumor cells, followed by measurement of tumor volume, endogenous plasma VEGF/endostatin (ELISA) and proliferation/apoptosis/microvessel density (Ki-67/TUNEL/CD-34). TNP-470 was injected s.c. over the 10-day experimental period (30 mg/kg every 2 days [n=6] to 100 mg/kg/day [n=5 dorsal skin-fold chamber model, n=4 s.c. tumor model]). RESULTS: At 30 mg/kg/every second day neither CT-26 nor PANC-02-H0 tumors were inhibited in neither of the two models. TNP-470 dosage was escalated in CT-26-bearing animals until an antiangiogenic effect could be observed. In the IVM model, only TNP-470 100 mg/kg/day reduced MVD (P=0.006), but failed to block the onset of angiogenesis and tumor area increase. Body weight decreased by 25% (P<0.05). In the subcutaneous tumor model, tumor growth was reduced (P=0.045) but not blocked, while vascular endothelial growth factor (VEGF)/endostatin synthesis and Ki67/TUNEL/CD-34 were not significantly affected. CONCLUSION: While capable of reducing tumor growth in a conventional model, treatment with TNP-470 does not block the onset of angiogenesis and tumor establishment in a model of minimal disease. When used as a single agent TNP-470 does not control minimal tumor disease in experimental colonic carcinoma.