Improved local control with an aggressive strategy of preoperative (with or without intraoperative) radiation therapy combined with radical surgical resection for retroperitoneal sarcoma.

BACKGROUND AND OBJECTIVES: We sought to examine our outcomes with advanced preoperative and intraoperative radiation therapy (XRT) combined with aggressive en bloc surgical resection of retroperitoneal sarcoma (RPS) as a strategy to minimize the risk of local recurrence (LR). METHODS: From 2003 to 2013, 46 patients with RPS received preoperative XRT followed by radical en bloc surgical resection, with or without intraoperative electron radiation therapy (IOERT). Clinical and pathologic variables predictive of LR and distant recurrence (DR) were evaluated. RESULTS: Thirty-seven patients had primary tumors and 80% were intermediate grade or higher. All patients received preoperative XRT to a median dose of 50.4 Gy and underwent complete (R0/R1) tumor resection, and 16 patients received IOERT. After a median follow-up of 53 months, 33 (72%) patients were disease-free, and there were 8 (17%) DRs, 2 (4%) abdominal recurrences outside of the XRT field, and 5 (10.9%) LRs. High tumor grade and recurrent disease at presentation were the only factors associated with higher rates of recurrence. CONCLUSIONS: Excellent local control can be achieved with a coordinated strategy of preoperative (±intraoperative) XRT combined with aggressive en bloc surgical resection of RPS, but systemic failure remains a problem for higher-grade tumors.

Preoperative radiation therapy combined with radical surgical resection is associated with a lower rate of local recurrence when treating unifocal, primary retroperitoneal liposarcoma.

BACKGROUND AND OBJECTIVES: Local recurrence (LR) is the primary cause of death in patients with retroperitoneal liposarcoma (RP-LPS). The purpose of this study was to evaluate if the addition of preoperative radiation therapy (XRT) to radical resection for RP-LPS at a single institution was associated with improved LR. METHODS: This retrospective analysis included patients with unifocal, primary RP-LPS who underwent complete R0/R1 resection at a single institution between 1991 and 2013. Multiple patient, tumor, and surgeon characteristics were tested to evaluate their association to LR (recurrence in the retroperitoneal space). We used competing risk hazards regression to evaluate the effect of preoperative XRT on the probability of LR. RESULTS: There were 41 patients with liposarcoma histology whose tumors included entirely well-differentiated (N = 13), de-differentiated components (n = 26), myxoid (n = 1), and NOS (n = 1). Preoperative XRT was significantly associated with a lower probability of LR (HR 0.11, 95%CI 0.01-0.91, P = 0.04) and a higher 5-year local recurrence-free survival (95.6%, 95%CI 72.4-99.4%, vs. 75.0%, 95%CI 40.8-91.2%; P = 0.0213), but not with 5-year distant recurrence-free survival or disease-specific survival. CONCLUSIONS: Preoperative XRT combined with complete R0/R1 resection for unifocal, primary RP-LPS was associated with improved LR and it should be considered in the multimodality treatment of RP-LPS. J. Surg. Oncol. 2016;114:814-820. © 2016 2016 Wiley Periodicals, Inc.

Post-operative renal function following nephrectomy as part of en bloc resection of retroperitoneal sarcoma (RPS).

BACKGROUND AND OBJECTIVES: Although resection of RPS with en bloc nephrectomy confers the potential benefit of improved locoregional tumor control, little has been published about the long-term post-operative renal function of these patients. METHODS: Retrospective review of 54 patients undergoing nephrectomy for RPS was performed. Clinicopathologic and treatment characteristics, pre- and post-operative creatinine (Cr) values, and estimated glomerular filtration rates (eGFR) were recorded. The primary outcome measure was progression of chronic kidney disease (CKD) stage. RESULTS: Median preoperative eGFR was 85 ml/min. Post-nephrectomy, median nadir eGFR was 44 ml/min, rebounding to 62 ml/min at median follow-up of 50 months. Of 49 patients with preoperative eGFR ≥60 ml/min (CKD stage 1,2), 51% preserved eGFR ≥60 postoperatively, whereas 49% progressed to CKD stage 3 (eGFR 30-59). Independent risk factors for progression of CKD stage were age and preoperative eGFR. Eleven patients died of recurrent disease, whereas no patient died of end stage renal disease (ESRD) or required dialysis. CONCLUSIONS: Although progression of CKD stage occurs in nearly one-half of patients followed for more than 4 years after nephrectomy for RPS, no patient progressed to ESRD or had a limitation in systemic therapy options, even with progression to CKD stage 3.

Mortality associated with laparotomy-confirmed neonatal spontaneous intestinal perforation: a prospective 5-year multicenter analysis.

BACKGROUND: Spontaneous intestinal perforation (SIP) has been recognized as a distinct disease entity. This study sought to quantify mortality associated with laparotomy-confirmed SIP and to compare it to mortality of laparotomy-confirmed necrotizing enterocolitis (NEC). METHODS: Data were prospectively collected on 177,618 very-low-birth-weight (VLBW, 401-1500g) neonates born between January 2006 and December 2010 admitted to US hospitals participating in the Vermont Oxford Network (VON). SIP was defined at laparotomy as a focal perforation of the intestine without features suggestive of NEC or other intestinal abnormalities. The primary outcome was in-hospital mortality. RESULTS: At laparotomy, 2036 (1.1%) neonates were diagnosed with SIP and 4076 (2.3%) with NEC. Neonates with laparotomy-confirmed SIP had higher mortality (19%) than infants without NEC or SIP (5%, P=0.003). However, laparotomy-confirmed SIP patients had significantly lower mortality than those with confirmed NEC (38%, P<0.0001). Mortality in both NEC and SIP groups decreased with increasing birth weight and mortality was significantly higher for NEC than SIP in each birth weight category. Indomethacin and steroid exposure were more frequent in the SIP cohort than the other two groups (P<0.001). CONCLUSIONS: In VLBW infants, the presence of laparotomy-confirmed SIP increases mortality significantly. However, laparotomy-confirmed NEC mortality was double that of SIP. This relationship is evident regardless of birth weight. The variant mortality of laparotomy-confirmed SIP versus laparotomy-confirmed NEC highlights the importance of differentiating between these two diseases both for clinical and research purposes.

Citrulline levels following proximal versus distal small bowel resection.

PURPOSE: Citrulline, a nonprotein amino acid synthesized by enterocytes, is a biomarker of bowel length and the capacity to wean from parenteral nutrition. However, the potentially variant effect of jejunal versus ileal excision on plasma citrulline concentration [CIT] has not been studied. This investigation compared serial serum [CIT] and mucosal adaptive potential after proximal versus distal small bowel resection. METHODS: Enterally fed Sprague-Dawley rats underwent sham operation or 50% small bowel resection, either proximal (PR) or distal (DR). [CIT] was measured at operation and weekly for 8 weeks. At necropsy, histologic features reflecting bowel adaptation were evaluated. RESULTS: By weeks 6-7, [CIT] in both resection groups significantly decreased from baseline (P<0.05) and was significantly lower than the concentration in sham animals (P<0.05). There was no difference in [CIT] between PR and DR at any point. Villus height and crypt density were higher in the PR than in the DR group (P≤0.02). CONCLUSION: [CIT] effectively differentiates animals undergoing major bowel resection from those with preserved intestinal length. The region of intestinal resection was not a determinant of [CIT]. The remaining bowel in the PR group demonstrated greater adaptive potential histologically. [CIT] is a robust biomarker for intestinal length, irrespective of location of small intestine lost.

Mortality and management of surgical necrotizing enterocolitis in very low birth weight neonates: a prospective cohort study.

BACKGROUND: Necrotizing enterocolitis (NEC) is a leading cause of death in very low birth weight (VLBW) neonates. The overall mortality of NEC is well documented. However, those requiring surgery appear to have increased mortality compared with those managed medically. The objective of this study was to establish national birth-weight-based benchmarks for the mortality of surgical NEC and describe the use and mortality of laparotomy vs peritoneal drainage. STUDY DESIGN: There were 655 US centers that prospectively evaluated 188,703 VLBW neonates (401 to 1,500 g) between 2006 and 2010. Survival was defined as living in-hospital at 1-year or hospital discharge. RESULTS: There were 17,159 (9%) patients who had NEC, with mortality of 28%; 8,224 patients did not receive operations (medical NEC, mortality 21%) and 8,935 were operated on (mortality 35%). On multivariable regression, lower birth weight, laparotomy, and peritoneal drainage were independent predictors of mortality (p < 0.0001). In surgical NEC, a plateau mortality of around 30% persisted despite birth weights >750 g; medical NEC mortality fell consistently with increasing birth weight. For example, in neonates weighing 1,251 to 1,500 g, mortality was 27% in surgical vs 6% in medical NEC (odds ratio [OR] 6.10, 95% CI 4.58 to 8.12). Of those treated surgically, 6,131 (69%) underwent laparotomy only (mortality 31%), 1,283 received peritoneal drainage and a laparotomy (mortality 34%), and 1,521 had peritoneal drainage alone (mortality 50%). CONCLUSIONS: Fifty-two percent of VLBW neonates with NEC underwent surgery, which was accompanied by a substantial increase in mortality. Regardless of birth weight, surgical NEC showed a plateau in mortality at approximately 30%. Laparotomy was the more frequent method of treatment (69%) and of those managed by drainage, 46% also had a laparotomy. The laparotomy alone and drainage with laparotomy groups had similar mortalities, while the drainage alone treatment cohort was associated with the highest mortality.

Report of 111 consecutive patients enrolled in the International Serial Transverse Enteroplasty (STEP) Data Registry: a retrospective observational study.

BACKGROUND: The International Serial Transverse Enteroplasty (STEP) Data Registry is a voluntary online database created in 2004 to collect information on patients undergoing the STEP procedure. The aim of this study was to identify preoperative factors that are significantly associated with transplantation or death or attainment of enteral autonomy after STEP. STUDY DESIGN: Data were collected from September 2004 to January 2010. Univariate and multivariate logistic regression analyses were applied to determine the predictors of transplantation or death or enteral autonomy post-STEP. Time to reach full enteral nutrition was estimated using a Kaplan-Meier curve. RESULTS: Fourteen of the 111 patients in the Registry were excluded due to inadequate follow-up. Of the remaining 97 patients, 11 patients died and 5 progressed to intestinal transplantation. On multivariate analysis, higher direct bilirubin and shorter pre-STEP bowel length were independently predictive of progression to transplantation or death (p = 0.05 and p < 0.001, respectively). Of the 78 patients who were 7 days of age or older and required parenteral nutrition at the time of STEP, 37 (47%) achieved enteral autonomy after the first STEP. Longer pre-STEP bowel length was also independently associated with enteral autonomy (p = 0.002). Median time to reach enteral autonomy based on Kaplan-Meier analysis was 21 months (95% CI, 12-30). CONCLUSIONS: Overall mortality post-STEP was 11%. Pre-STEP risk factors for progressing to transplantation or death were higher direct bilirubin and shorter bowel length. Among patients who underwent STEP for short bowel syndrome, 47% attained full enteral nutrition post-STEP. Patients with longer pre-STEP bowel length were significantly more likely to achieve enteral autonomy.

Low serum citrulline concentration correlates with catheter-related bloodstream infections in children with intestinal failure.

BACKGROUND: Serum citrulline concentration is used as a biomarker of enterocyte mass and enteral tolerance, and low serum concentrations are correlated with bacteremia in immunosuppressed adults undergoing hematopoietic stem cell transplant. The authors sought to determine if citrulline was associated with the development of catheter-related bloodstream infections (CRBSIs) in children with intestinal failure. METHODS: Data were reviewed from 66 children treated in a multidisciplinary intestinal rehabilitation program, who had serum concentration citrulline measured between January 2007 and August 2009. All patients had a diagnosis of intestinal failure requiring parenteral nutrition (PN) support. Exclusion criteria included central venous catheter in situ <30 days, creatinine clearance <20 mL/minute, or a history of organ transplant/immunosuppression. RESULTS: A total of 15 patients were excluded because of the above criteria. In this cohort of 51 patients, 26 (51%) developed CRBSIs. Both groups were similar in terms of gestational age, diagnosis, nutrition status, and biochemical liver function tests. The mean (± standard deviation [SD]) minimum serum citrulline concentration was significantly lower in patients who developed CRBSIs (6.7 ± 4.6 µmol/L) than in those who did not (11.3 ± 6.4 µmol/L, P = .004). Multivariate logistic regression analysis identified lower minimum serum citrulline concentration and longer central venous catheter duration as independently associated with CRBSI (P = .003 and P = .038, respectively). CONCLUSIONS: Low serum citrulline concentration and longer central venous catheter time are independently associated with CRBSI in children with intestinal failure. Serum citrulline concentration may be a useful biomarker to identify patients with intestinal failure who are at high risk of developing a CRBSI.

Combined en bloc liver-double kidney transplantation in an infant with IVC thrombosis.

We report a case of a pediatric en bloc liver-double kidney transplant in a patient with IVC thrombosis below the renal veins. The patient is an 11-month-old girl diagnosed with congenital nephrotic syndrome at two months of age. Multifocal liver masses were identified on routine ultrasound at eight months of age. Alpha fetoprotein level was 55 319. Biopsy confirmed hepatoblastoma. CT scan confirmed multiple lesions in both lobes, which would require liver transplantation for resection. She was also found to have thrombosis of her infrarenal IVC secondary to multiple central lines. She was listed for combined liver-kidney transplant and began chemotherapy. After four cycles of chemotherapy, she underwent bilateral nephrectomies followed by a combined en bloc liver-double kidney transplant from a size matched donor. In order to provide adequate venous outflow from the kidneys in the absence of a recipient infrarenal IVC, the donor liver and kidneys were procured en bloc with a common arterial inflow via the infrarenal aorta and common outflow via the suprahepatic IVC. Kidney transplantation in the absence of adequate recipient venous drainage may require unusual vascular reconstruction techniques. This case demonstrates a novel approach in patients who may require combined liver-kidney transplantation.

Efficacy of ethanol locks in reducing central venous catheter infections in pediatric patients with intestinal failure.

PURPOSE: We sought to determine whether a regimen of 70% ethanol locks could reduce the rate of central venous catheter (CVC) infections in parenteral nutrition-dependent children with intestinal failure. METHODS: We performed a retrospective review of 23 parenteral nutrition-dependent children in our multidisciplinary intestinal rehabilitation clinic who started ethanol lock therapy between September 2007 and June 2009. The treatment regimen consisted of a 70% ethanol lock instilled 3 times per week in each catheter lumen. The rate of CVC infections before and after initiation of ethanol lock therapy was compared using the Wilcoxon signed ranks test with significance set at P < .05. RESULTS: The most common diagnoses leading to intestinal failure were necrotizing enterocolitis (26.1%), gastroschisis (21.7%), and intestinal atresia (14.3%). Ethanol locks were well tolerated with no reported adverse side effects. The infection rate decreased from 9.9 per 1000 catheter days prior to initiation of ethanol locks to 2.1 per 1000 catheter days during therapy (P = .03). CONCLUSIONS: A regimen of ethanol lock therapy administered three days per week appears to be a safe and effective means of reducing the rate of CVC infections in parenteral nutrition-dependent children with intestinal failure.

Autologous intestinal reconstruction surgery for intestinal failure management.

PURPOSE OF REVIEW: Multidisciplinary management of intestinal failure has progressed over the past 30 years, facilitating the transition to enteral autonomy in many pediatric patients. However, there remains a select group of patients who reach a plateau in advancement of their enteral nutrition. Numerous surgical options have been pursued to attempt to slow intestinal transit, taper dilated bowel, and promote intestinal adaptation. This review highlights the current literature on autologous intestinal reconstruction surgery, focusing on the two most commonly performed procedures, the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP). RECENT FINDINGS: LILT and STEP remain viable options to treat medically refractory short bowel syndrome. There is over 20 years of experience with the LILT procedure in the literature, with one large series showing that 67% of patients eventually transitioned to full enteral nutrition. The International STEP Data Registry reported a weaning rate of 34% after median follow-up of 12.6 months. Repeat STEP has been described as a possible treatment for the redilation that occurs after both LILT and STEP. SUMMARY: LILT and STEP may facilitate enteral feeding advancement in patients with medically refractory short bowel syndrome.

Autologous intestinal reconstruction surgery.

Multidisciplinary management of intestinal failure has progressed over the last 30 years, facilitating the transition to enteral autonomy in many pediatric patients. However, there remains a select group of patients who reach a plateau in advancement of their enteral nutrition. Numerous surgical options have been pursued to attempt to slow intestinal transit, taper dilated bowel, and promote intestinal adaptation. The purpose of this chapter is to review the current literature on autologous intestinal reconstruction surgery, including a brief historical perspective, descriptions of procedures, and reported surgical outcomes.

Relationship between biopsy-proven parenteralnutrition-associated liver fibrosis and biochemical cholestasis in children with short bowel syndrome.

PURPOSE: The aim of the study was to determine the frequency of biochemical cholestasis (direct bilirubin [DB] > or =2 mg/dL) in children with short bowel syndrome and biopsy-proven parenteral nutrition (PN)-associated liver disease and to define predictive factors for the occurrence and degree of hepatic fibrosis. METHODS: After institutional review board approval, a retrospective review was conducted of patients followed by 2 multidisciplinary intestinal rehabilitation programs between January 1, 2000, and September 30, 2008. Inclusion criteria were exposure to PN (>30 days) and having undergone a liver biopsy. Liver biopsy specimens were graded from 0 to 3 based upon degree of fibrosis in the pathology report. The most recent DB within 10 days before biopsy was recorded. RESULTS: A total of 66 children underwent 83 liver biopsy procedures. The most common diagnoses included necrotizing enterocolitis (NEC) (36.4%), gastroschisis (22.7%), and intestinal atresia (15.1%). Median age at biopsy was 6.1 months with a median duration of PN of 4.7 months. Of the patients, 70.3% had a history of exposure to parenteral omega-3 lipid emulsion. Of the liver biopsy specimens, 89% (74/83) demonstrated some degree of fibrosis (fibrosis scale 1-3), including 9.6% (8/83) with evidence of cirrhosis. 83% of biopsies without fibrosis and 55% of biopsies with fibrosis were obtained in patients without evidence of biochemical cholestasis (P = .20). Three (37%) of the 8 patients with cirrhosis on liver biopsy had no evidence of biochemical cholestasis. Univariate analysis identified only gestational age (GA) at birth as significantly associated with the degree of liver fibrosis (P = .03). A multivariate logistic regression model accounting for multiple biopsy procedures in patients revealed that GA was a predictor of fibrosis only in patients with a diagnosis other than NEC (P < .01). CONCLUSIONS: In children with short bowel syndrome, biochemical cholestasis does not reflect the presence or degree of histologically confirmed PN-associated liver fibrosis. Careful follow-up, combined with further refinement of diagnostic and hepatoprotective strategies, may be warranted in this patient population.

Persistent alanine aminotransferase elevations in children with parenteral nutrition-associated liver disease.

BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) is a serious condition affecting many children with short bowel syndrome. The aim of this study was to longitudinally assess serum alanine aminotransferase (ALT), a marker for hepatocyte injury, in enterally fed children with PNALD. METHODS: Retrospective chart review of 31 patients treated from 1999 to 2006 by the Center for Advanced Intestinal Rehabilitation at Children's Hospital Boston (Mass). Inclusion criteria included PN duration of greater than 3 months with subsequent tolerance of full enteral nutrition and evidence of PN-associated liver injury. Time to normalize ALT and direct bilirubin were estimated using Kaplan-Meier and Cox proportional hazards methods. RESULTS: Mean age PN cessation was 6 months (range, 2-14 months). Median PN duration was 18 weeks (interquartile range [IQR], 13-33 weeks), and median follow-up was 24 weeks (IQR, 14-48 weeks). After transition to full enteral nutrition, 74% of children normalized direct bilirubin, whereas only 50% normalized ALT. Kaplan-Meier median time to direct bilirubin and ALT normalization were 13 weeks and 35 weeks, respectively (P = .001). CONCLUSION: Children with PNALD who have achieved PN independence have persistent ALT elevation despite normal direct bilirubin levels. This implies that hepatic injury may be ongoing beyond the time of bilirubin normalization in this cohort of patients.