Larotrectinib as an Effective Therapy in Congenital Infantile Fibrosarcoma: Report of Two Cases.

Congenital infantile fibrosarcoma (CIF) is a rare tumor in children that occurs in the first years of life. It usually arises in the extremities but some cases affect the trunk, neck, abdomen, or retroperitoneum. Surgical resection has been traditionally the treatment of choice but the development of genomic analysis and targeted therapies has shed light on new therapeutic options. We present two patients with a congenital mass, one in the abdominal cavity (1-month-old) and the second in the left lower extremity respectively (2-months-old). In both cases, the clinical and radiological findings showed heterogeneous masses with rapidly progressive growth. MRI in the first patient exhibited an abdominal mass surrounding the aorta and inferior vena cava associated with a giant infrarenal aortic aneurysm. CT-guided biopsy was performed with pathological findings of fibrosarcoma and ETV6-NTRK3 gene fusion. The second patient underwent open biopsy also with histopathological diagnosis of fibrosarcoma and the same mutation in the TRK gene ( NTRK3 ). Targeted therapy with a specific TRK inhibitor, larotrectinib, was started in both patients. Periodical controls were made by ultrasound or MRI, and after a few weeks of treatment, both children showed significant decrease in the mass. By the second and third months after starting the treatment, both tumors disappeared. The first patient is now 15-months-old and the second one is 8-months-old. Larotrectinib is a novel targeted therapy with excellent results in CIF but long-term outcomes are limited to establish it as a gold standard treatment.

Ultrashort Bowel Syndrome Outcome in Children Treated in a Multidisciplinary Intestinal Rehabilitation Unit.

Aim Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in the pediatric population. Our aim was to review long-term outcome of ultrashort bowel syndrome (USBS) in an Intestinal Rehabilitation Unit (IRU). Patients and Methods Retrospective study of patients with USBS (defined as < 10 cm of remnant small bowel) treated between 2000 and 2015. Demographic data, clinical, and treatment variables including parenteral nutrition (PN), surgical techniques, and intestinal transplantation (IT) were analyzed. Results Out of 250 children, 30 referred to the IRU met inclusion criteria. Upon first assessment, patients had a median age of 3 (1-217) months and had undergone 3 (1-6) previous laparotomies that left 5 (0-9) cm of remnant small bowel. The main cause of USBS was neonatal midgut volvulus (50%). Follow-up was 28 (4-175) months. Advanced IF-associated liver disease (IFALD) was documented in 63%. None of the patients achieved digestive autonomy and was consequently considered for IT. One patient was excluded, five died before IT, and three are still on the waiting list. Six patients received an isolated IT, 6 a combined liver IT, and 18 a multivisceral graft. Digestive autonomy was achieved in 71% after 31 (14-715) days after IT and currently 62% are alive and off total PN. A significant drop in IFALD progression prior to IT was observed with the introduction of new lipid emulsions in 2010 (SMOF or Soy oil MCT (mid-chain triglycerides) Olive oil Fish oil). Conclusion A multidisciplinary IRU including an IT program offers a comprehensive approach for patients with IF and is crucial to improve survival rate of USBS. New PN lipid emulsions had an impact on IFALD progression and may eventually reduce overall mortality.

Surgical Rehabilitation Techniques in Children with Poor Prognosis Short Bowel Syndrome.

Intestinal failure (IF) requires a multidisciplinary management based on nutritional support, surgical and medical rehabilitation, and transplantation. The aim of this study is to review our experience with surgical rehabilitation techniques (SRTs: enteroplasty, Bianchi, Serial Transverse Enteroplasty Procedure [STEP]) in patients with short bowel syndrome (SBS) and poor prognosis due to complex abdominal pathology. We performed a single-center retrospective study of patients with IF evaluated for intestinal transplantation in the Intestinal Rehabilitation Unit who underwent an SRT. Nonparametric tests were used for statistical analysis.A total of 205 patients (107 males/98 females) with mean age of 25 ± 7 months were assessed for IF. A total of 433 laparotomies were performed on 130 patients including intestinal resection, enteroplasties, adhesiolysis, and transit reconstruction. SRT were performed in 22 patients: 12 enteroplasties, 8 STEPs, and 4 Bianchi procedures. All patients were parenteral nutrition (PN) dependent with different stages of liver disease: mild (13), moderate (5), and severe (4). The adaptation rate for patients who underwent enteroplasty, STEP, and Bianchi were 70, 63, and 25%, respectively, although the techniques are not comparable. Overall, intestinal adaptation was achieved in nine (41%) patients, and four (18%) patients showed significant reduction of PN needs. One child did not respond to SRT and did not meet transplantation criteria. The remaining eight (36%) patients were included on the waiting list for transplant: four were transplanted, two are still on the waiting list, and two died. Better outcomes were observed in milder cases of liver disease (mild 77%, moderate 40%, severe 25%) (p < 0.05). Conversely, a trend toward a poorer outcome was observed in cases with ultrashort bowel (p > 0.05). One patient required reoperation after a Bianchi procedure due to intestinal ischemia and six needed further re-STEP or adhesiolysis procedure several months later. The median follow-up was 62 (3-135) months. Overall mortality was 19%, and was due to end-stage liver disease and/or central venous catheter-related sepsis. SRT led to intestinal adaptation in a significant number of patients with poor prognosis SBS referred for intestinal transplantation. However, SRT requires a multidisciplinary evaluation and should be attempted only in suitable cases. Careful assessment and optimal surgical timing is crucial to obtain a favorable outcome.

Portal Cavernoma in the Era of Mesoportal Shunt (Rex) and Liver Transplant in Children.

OBJECTIVE: The mesoportal shunt (MPS) and liver transplantation (LT) have changed the scenario of extrahepatic portal vein obstruction (EHPVO) since the MPS, the only "curative" technique, can now be offered in asymptomatic patients and also thrombotic complications of LT have increased the incidence of EHPVO. MATERIAL AND METHODS: A retrospective study of patients undergoing surgery for EHPVO was conducted between 1990 and 2015. An analysis was done for the shunt permeability and clinical evolution over time. RESULTS: Of the 73 children with EHPVO, 39 were operated (12 posttransplant and 27 idiopathic). The median age at surgery was 9.36 years (range, 1.60-17.42 years). The MPS was the technique of choice; it was offered in 21 patients but eventually could be performed in only 18 (9 posttransplant and 9 idiopathic). The results of MPS were better in idiopathic (just one thrombosis successfully converted into mesocaval bypass). In the MPS after LT (n = 9), six shunts are permeable, two became thrombotic (one patient requiring retransplantation), and one late thrombosis occurred and the patient died eventually because of gastrointestinal bleeding. In the remaining patients (21 out of the 39), MPS was not performed because of intrahepatic cavernoma, portal vein hypoplasia, or insufficient length of vascular graft (especially in left lateral segment graft LT, since the portal vein is usually located in the right upper quadrant). They underwent 10 distal splenorenal shunts (DSRS) (1 posttransplant and 9 idiopathic), 5 proximal splenorenal shunts (PSRS) (1/4), 6 mesocaval shunts (1/5), and 1 modified Sugiura procedure. The results with DSRS have been favorable (one thrombosis, converted into mesocaval bypass). In the PSRS no thrombosis was identified and in the mesocaval shunt one early thrombosis occurred. Posttransplantation group had higher risk of shunt thrombosis, regardless of the surgical technique (chi-square, 0.021). The total increase of platelets after 6 months was not different in MPS as compared with other surgical techniques (analysis of variance, 0.110). CONCLUSIONS: The MPS is the technique of choice in EHPVO for idiopathic thrombosis as well as secondary to LT. Not all cases are favorable for MPS, so the surgeon must consider the possibility of alternative techniques for EHPVO. The results in terms of shunt patency are much better in idiopathic cavernoma that posttransplant patients.