Does Massive Bowel Resection in Newborns Affect Further Immunity in Children?

BACKGROUND: The massive resection of the small intestine leading to short bowel syndrome (SBS) deprives an organism of many immunocompetent cells concentrated in gut-associated lymphoid tissue, the largest immune organ in humans. We have aimed to access the influence of bowel resection on adaptive immunity in children, based on peripheral lymphocyte subsets and serum immunoglobulins. METHODS: 15 children who underwent bowel resection in the first months of their life and required further home parenteral nutrition were enrolled into the study. Based on flow cytometry, the following subsets of lymphocytes were evaluated: T, B, NK, CD4+, C8+, and activated T cells. RESULTS: Statistically significant differences were found for the rates of lymphocytes B, T, CD8+, and NK cells. The absolute count of NK cells was lower in the SBS group than in the control group. Absolute counts of lymphocytes, lymphocytes B, T, CD4+, and percentages of lymphocytes CD4+, and activated T cells inversely correlated with age in SBS group. CONCLUSIONS: Children with SBS do not present with clinical signs of immunodeficiency as well as deficits in peripheral lymphocyte subsets and serum immunoglobulins. The tendency of the lymphocyte subpopulations to decrease over time points out the necessity for longer follow- up.

Laparoscopic nephron-sparing surgery and laparoscopic nephrectomy for Wilms' tumor.

Introduction: The place of laparoscopy in the resection of Wilms' tumors has remained debatable, but evidence that neoadjuvant chemotherapy causes tumor shrinkage has made laparoscopic nephrectomy (LN) a feasible option. Laparoscopic nephron-sparing surgery (NSS) is technically very demanding and seems to be feasible and effective only when performed by a very experienced surgeon. Aim: We report 7 cases of laparoscopic nephrectomy and 1 case of laparoscopic heminephrectomy for Wilms' tumor. Material and methods: Forty-two consecutive children with primary renal tumor underwent nephrectomy between 2013 and 2020; 11 had an LN. Among them there were 8 children with Wilms' tumor, with age between 13 months and 7 years. All patients received neoadjuvant chemotherapy according to the current SIOP protocol. The mean tumor volume before and after chemotherapy was 174.4 ml (range: 14.7-501) and 32.8 ml (range: 4.3-68) respectively. Results: Seven laparoscopic nephrectomies and one heminephrectomy were performed. No patient had an intraoperative tumor rupture. All children had an attempt of lymph node sampling (their number per pathology assessment was in the range 0-5). There were no intraoperative events. One complication after heminephrectomy occurred, which was urine leak. Five patients had stage I tumor and 3 had stage II. Seven patients had an intermediate-risk and one had a high-risk tumor. There were no local or distant relapses. All patients remained disease-free at a median follow-up of 71 months (range: 16-94). Conclusions: This report demonstrates the feasibility of LN in children with Wilms' tumors. The patients should be carefully selected and specific training in laparoscopy is necessary, particularly with regard to laparoscopic heminephrectomy.

Arterial constriction after resection of neuroblastic tumors in children: Two-center retrospective study.

BACKGROUND/PURPOSE: Neuroblastic tumors are the most common pediatric extracranial solid tumors in infants and very young children. Although, especially in newborns, there is an increasing number of situations in which observation alone is used, surgery remains an important step in the treatment of neuroblastoma but can be complicated by arterial vasospasm in the surgical field. The aim of this two-center retrospective study was to analyze the occurrence of arterial constriction as a complication of neuroblastic tumors resection. METHODS: Medical records of patients who were treated surgically for neuroblastic tumors in the years 2012-2019 were reviewed. RESULTS: For 8 years, 113 children were treated for neuroblastic tumors. The treatment included both primary and delayed surgery after initial chemotherapy carried out according to SIOPEN protocols. In 11 out of 113 cases (9.7%) local arterial constriction was observed. In 6 out of 11 cases an attempt was made to save the organ, however, two patients suffered from kidney atrophy, two other partial kidney infarctions, one child suffered from partial limb paresis, and another from brain ischemia and death. CONCLUSIONS: Local arterial constriction constitutes a relatively common (10% of cases) and severe complication of neuroblastic tumors resection. Efficacy of local application of papaverine based on our experience remains unproven hence further research is warranted.

Laparoscopic resection of liver tumors in children.

BACKGROUND: Laparoscopy for the resection of liver tumors in children has remained undeveloped in comparison to adults. Most of the indications for pediatric laparoscopic hepatic surgery have been limited to diagnostic laparoscopy (biopsy). Over the past ten years, however, laparoscopic liver resections for pediatric hepatic diseases have been performed successfully, and many case reports have been published. METHODS: The authors report 6 cases of laparoscopic hepatic resection of benign tumors in children. The most important aspects of surgical technique are presented. There were 3 boys and 3 girls, with age between 4 months and 16 years. The lesions were located in the following segments: II and III (4 patients), I (1), V (1). The maximum tumor size was 7 cm. RESULTS: One anatomical (left bisegmentectomy) and 5 nonanatomical resections were performed. Conversion to laparotomy was necessary in 1 patient owing to bleeding from the posterior branch of the right hepatic artery. There were no postoperative complications and patients were discharged on postoperative day 4, 5, 5, 5, 7 and 3 accordingly. The postoperative pathology of the specimens confirmed their benign nature: infantile hemangioendothelioma (1), nested stromal epithelial tumor (1), focal nodular hyperplasia (3), mixed benign tumor (hamartoma + vascular malformation) (1). CONCLUSIONS: This report demonstrates the feasibility of a laparoscopic hepatic resection in children. On the other hand, laparoscopic liver resection is challenging and teamwork and specific training are necessary.

Dysgerminoma with a Somatic Exon 17 KIT Mutation and SHH Pathway Activation in a Girl with Turner Syndrome.

This article reports a case of a 7-year-old girl with Turner syndrome, treated with growth hormone (GH), who developed ovarian dysgerminoma. The patient karyotype was mosaic for chromosome Xq deletion: 46,X,del(X)(q22)/45,X. No Y chromosome sequences were present. Molecular studies revealed the presence of a driving mutation in exon 17 of the KIT gene in the neoplastic tissue, as well as Sonic-hedgehog (SHH) pathway activation at the protein level. The patient responded well to chemotherapy and remained in complete remission. This is the first case of dysgerminoma in a Turner syndrome patient with such oncogenic pathway.

One, two or three port appendectomy - a rational approach.

INTRODUCTION: Laparoscopic appendectomy is a safe and feasible technique accepted by many surgeons as the gold standard approach for the treatment of acute appendicitis in children. Traditionally laparoscopic appendectomy requires the use of three ports. However, surgical techniques with fewer ports have been reported. AIM: To evaluate the efficacy of laparoscopic appendectomy in children according to the proposed 3-step protocol using one, two or three ports. MATERIAL AND METHODS: A total of 100 children with the diagnosis of acute appendicitis underwent laparoscopic appendectomy. Patients were treated according to the following protocol: transumbilical access with one 10 mm port using the laparoscope with working channel. The appendix was mobilized and delivered through the umbilical port and tied extracorporeally and removed. If the appendix was placed retrocecally or had adhesions, a second port was introduced. The appendix was mobilized and finally retrieved from the abdominal cavity through the camera port, and resected extracorporeally. In the cases of very short and gangrenous appendix and immobile colon, a third port was introduced and totally intra-abdominal appendectomy was performed. Patients were evaluated regarding the duration of the operation, and operative and postoperative complications. RESULTS: During the study period 100 children (58 males, 42 females) had laparoscopic appendectomy: 48 children by one-port technique (group I), 27 children by two-port technique (group II) and 25 children by three-port technique (group III). The mean operative time was 33 min (20-55 min) in group I, 39 min in group II (23-60 min), and 49 min (30-75 min) in group III. There were no intraoperative complications. Wound infections were recorded in 4 (8.3%) patients in group I, three (11.1%) in group II and four (16.0%) in group III. One patient in group III developed an abdominal abscess managed conservatively. CONCLUSIONS: One-port laparoscopic appendectomy is a feasible technique in children. It allows 48% of children to have the operation. The addition of a second port allows one to mobilize the appendix and perform extracorporeal resection in an additional 27% of cases. These approaches have shorter operative time compared to 3-port technique. Laparoscopic extracorporeal appendectomy, especially one-port, is found to be cost effective and have excellent cosmetic results.

Laparoscopic versus open upper pole heminephroureterectomy for the treatment of duplex kidneys in children.

AIM: To evaluate the safety and feasibility of laparoscopic upper pole heminephroureterectomy (HNU) in pediatric patients with duplex kidneys in comparison with open surgery. PATIENTS AND METHODS: From 2007 to 2011, 27 patients underwent HNU. A dimercaptosuccinic acid (DMSA) isotope scan revealed hypofunctioning of ipsilateral moieties in all cases. The patients were divided randomly into laparoscopic HNU (LHNU) and open surgery HNU (OHNU) groups. LHNU was performed by the transperitoneal approach in 10 girls and 5 boys with a mean age of 33 months (range, 9-108 months). All procedures were performed using three or four ports. Open surgery was performed in 10 girls and 2 boys with a mean age of 29 months (range, 7-174 months) by the retroperitoneal approach in all cases. Follow-up included ultrasound and DMSA. RESULTS: Mean operative time in the LHNU and OHNU groups was 148 minutes (range, 100-220 minutes; 95% confidence interval [CI] 129-167 minutes) and 124 minutes (range, 100-150 minutes; 95% CI 115-133 minutes), respectively. In the LHNU and OHNU groups, mean analgesic requirement was 2.8 days (range, 2-4 days; 95% CI 2.4-3.2 days) and 3.7 days (range, 3-5 days; 95% CI 3.3-4.1 days), and mean hospital stay was 4.0 days (range, 2-8 days; 95% CI 3.2-4.8 days) and 5.1 days (range, 3-8 days; 95% CI 4.3-5.9 days), respectively. No intraoperative or major postoperative complications occurred. No conversion to open surgery was necessary in the LHNU group. Statistical analysis showed no statistical significant difference (P>.05) in the operating time between groups, whereas differences in the mean hospital stay (P=.048) and analgesic requirements (P=.005) were significant. The function of the remnant pole was preserved in all patients. Follow-up ultrasound showed asymptomatic cystic structures in 1 patient. CONCLUSIONS: The laparoscopic upper pole HNU is a safe and feasible procedure, even in infants. It is associated with minimal morbidity, and the operative time is acceptable and not significantly longer in comparison with the open approach. LHNU reduces analgesic requirements and hospital stay. In our opinion it should be the preferred option for HNU in children.

Isolated caudate lobe (Spiegel lobe) resection for hepatoblastoma. Is it enough to achieve a sufficient resection margin? A case report.

BACKGROUND: Hepatoblastoma arising from and limited to the caudate lobe is an extremely rare clinical entity. The object of this case report is to present a case of isolated caudate lobe resection due to hepatoblastoma originating in the caudate lobe. METHODS: The patient was an 18-month-old male who was admitted with a huge tumor located in the left hepatic lobe. The histological diagnosis was fetal type of hepatoblastoma. The patient received 4 cycles of preoperative and 2 cycles of postoperative chemotherapy. RESULTS: During surgical exploration, a well-defined, exophytic tumor originating in the caudate lobe was found. Isolated caudate lobe (Spiegel lobe) resection was performed. The intra- and postoperative course was uneventful. Surgical margins were negative for tumor. The patient remains alive with no signs of recurrence 15 months after surgery. CONCLUSIONS: Isolated caudate lobe resection is one of the most challenging procedures in liver surgery. Despite the technical difficulties and high complications risk, isolated caudate lobectomy can be performed successfully in children. It needs to be noted that in the reported case, preoperative chemotherapy shrunk the tumor and largely facilitated its resection.

The Foker technique (FT) and Kimura advancement (KA) for the treatment of children with long-gap esophageal atresia (LGEA): lessons learned at two European centers.

INTRODUCTION: We present the experiences from two European centers performing the Foker technique (FT) of esophageal lengthening by axial traction and the Kimura advancement (KA) method of lengthening the upper pouch by extrathoracic resiting a spit fistula (SF) in children with long-gap esophageal atresia (LGEA, gap length > 5 cm). MATERIALS AND METHODS: A total of 15 children were treated (8 pure EA, 6 lower tracheoesophageal fistula [TEF], and 1 upper TEF). Gaps ranged from 5 to 14 cm. Nine children already had a SF. Patients were grouped according to the presence of a SF and the subsequent surgical strategy: Group A (no SF, n = 6) received FT on both pouches. Group B (with SF, n = 6) received KA of SF and FT of the lower pouch. Group C (with SF, n = 3) received closure of the SF and subsequent Foker traction (CSFT) on both pouches. RESULTS: Group A: Primary repairs for all six children (mean age 3 months, gap length 6.5 cm) after a mean traction time of 3 weeks and a mean of 2.1 thoracotomies (range 2 to 3). Dilations were required in three out of six for anastomotic strictures with one perforation during the second dilation. Group B: All six children (mean age 16.4 months, gap length 9.5 cm) had a primary anastomosis, although for two it was significantly delayed (48 and 143 weeks traction time) because of infections. The number of thoracotomies ranged from 2 to 8 (mean 3.6). Leaks occurred in five out of six anastomoses (responsive to conservative management). Two children developed severe strictures, which required the anastomosis to be redone. In group C (mean age 10.6 months, gap length 6.5 cm), several major complications occurred. The three SF closures leaked (one iatrogenic) causing severe mediastinitis. CSFT was successful in only one case and the other two children had an esophageal replacement (stomach, jejunum). No deaths occurred in the series. CONCLUSION: FT of both pouches (group A) resulted in primary repairs of all six LGEA patients. The combination of KA and FT (group B) resulted in an equivalent rate of primary repairs, but with an increased number of thoracotomies and rate of complications compared with group A. CSFT (group C) resulted in a high failure rate. More data are needed (we propose a multicenter registry) to elucidate the safety and efficacy of each elongation technique and to establish an algorithm with clearer inclusion and exclusion criteria.

Laparoscopic surgical technique to facilitate management of high anorectal malformations - report of seven cases.

Anorectal malformations (ARMs) occur in approximately 1 per 5000 live births. The most commonly used procedure for repair of high ARMs is posterior sagittal anorectoplasty (PSARP). This operation is performed entirely through a perineal approach. The first report of laparoscopically assisted anorectal pull-through (LAARP) for repair of ARMs was presented by Georgeson in 2000. The aim is presenting early experience with laparoscopically assisted anorectal pull-through technique in boys with high anorectal malformations. In the last 5 years 7 boys (9 months to 2 years old) with high ARMs were operated on using the LAARP technique. Laparoscopically the rectal pouch was exposed down to the urethral fistula, which was clipped and divided. Externally, the centre of the muscle complex was identified using an electrical stimulator. In the first 4 patients after a midline incision of 2 cm at the planned anoplasty site, a tunnel to the pelvis was created bluntly and dilated with Hegar probes under laparoscopic control. In the last 3 boys a minimal PSARP was done creating a channel into the pelvis. The separated rectum was pulled down and sutured to the perineum. Laparoscopic mobilization of the rectal pouch and fistula division was possible in all cases. There were no intraoperative complications except one ureteral injury. Patients were discharged home on post-operative day 5 to 7. The early results prove that LAARP, an alternative option to PSARP for treatment of imperforate anus, offers many advantages, including excellent visualization of the pelvic anatomical structures, accurate placement of the bowel into the muscle complex and a minimally invasive abdominal and perineal incision. It allows for shorter hospital stay and faster recovery. However, to compare the functional results against the standard procedure (PSARP), longer follow-up of all patients is necessary.

Using acetaminophen's toxicity mechanism to enhance cisplatin efficacy in hepatocarcinoma and hepatoblastoma cell lines.

BACKGROUND/AIMS: Acetaminophen overdose causes hepatotoxicity mediated by toxic metabolites generated through the cytochrome P450 enzyme. The objective of this study was to investigate whether acetaminophen (AAP) can enhance cisplatin (CDDP) cytotoxicity against human hepatocarcinoma and hepatoblastoma cells in vitro and whether this effect can be prevented by N-acetylcysteine (NAC). METHODS: In vitro studies (glutathione [GSH] level, cell viability, and immunoblot assays) were performed using human hepatocarcinoma and hepatoblastoma cells cultured in AAP, CDDP, and the combination of both with or without delayed NAC administration. The pharmacology and toxicology of high-dose AAP in rats were also examined. RESULTS: Acetaminophen decreased GSH levels in liver cancer cells in a dose- and time-dependent manner. Acetaminophen combined with CDDP had enhanced cytotoxicity over CDDP alone. The cytotoxicity caused by AAP plus CDDP was decreased by NAC, with the effectiveness being time-dependent. The GSH level was lowered in the liver but not in the blood or the brain in rats treated with a high dose of AAP (1000 mg/kg). The expression of CYP2E1 protein, a key cytochrome P450 enzyme, varies among species but is not correlated to AAP sensitivity in liver cancer cells. CONCLUSIONS: Our results suggest that a chemotherapeutic regimen containing both AAP and CDDP with delayed NAC rescue has the potential to enhance chemotherapeutic efficacy while decreasing adverse effects. This would be a promising approach particularly for hepatoblastomas regardless of cellular CYP2E1 protein level but could also be beneficial in other malignancies.