Publications by authors named "Richard S Whitlock"

11 Publications

  • Page 1 of 1

Characteristics of benign neuroblastic tumors: Is surgery always necessary?

J Pediatr Surg 2021 Jul 7. Epub 2021 Jul 7.

Division of Pediatric Surgery, Texas Children's Surgical Oncology Program, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, BCM 185, One Baylor Plaza, Houston, TX 77030, USA; Department of Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA. Electronic address:

Purpose: Ganglioneuroma (GN) and ganglioneuroblastoma-intermixed (GNB-I) represent benign variants of neuroblastic tumors in children; however, differentiating from more aggressive histological variants of GNB including the nodular subtype (GNB-N) prior to resection can be challenging, even with biopsy. Currently, no standard treatment guidelines exist. The purpose of this study was to identify pre-operative characteristics of benign neuroblastic tumors and evaluate outcomes for patients who underwent surgical resection or observation.

Methods: Retrospective chart review of children treated at a single institution between 2009 and 2019 for non-metastatic tumor with a tissue diagnosis of GN, GNB-N or GNB-I. Demographics, imaging, labs, operative details and outcomes were recorded and analyzed.

Results: Of 53 patients, 45% were male. The most common tumor location was abdomen (49%), followed by thorax (34%). Forty-five percent had at least one image defined risk factor. Biopsy was performed in 32% (17/53) and upfront surgery in 68% (36/53). Three patients (3/53, 5.6%) with biopsy demonstrating GN tumors were observed due to high surgical risk. Pathology of resected specimens demonstrated GN in 52% (26/50) and GNB-I or GNB-N in 48% (24/50). The majority of GNB tumors (75% (18/24) were GNB-I and 25% (6/24) were GNB-N. Therefore, 88% of the resected tumors were benign spectrum neuroblastic tumors (GN & GNB-I). Seven (7/50, 14%) patients experienced perioperative complication (temporary paralysis, Horner's syndrome, chylothorax, vocal cord paralysis). Recurrence was noted in 1 patient with GN (1/50, 2%) and 3 with GNB-N (3/50, 6%). There were no tumor-related deaths. Patients with GN were older than those with GNB (8.8 years (IQR 6-11.25) vs 5.6 years for GN (IQR 3-7); p = 0.01). GNB tumors were also more likely to have calcifications on imaging (63% vs. 38%, p = .01) and more commonly had MIBG avidity (88% vs 66%, p = .04). There were no significant differences in tumor size or symptoms at presentation.

Conclusions: In children with neuroblastic tumors, older age, CT without tumor calcifications, lack of MIBG avidity, and/or normal urine catecholamines may indicate benign GN. Close observation could be considered for asymptomatic patients meeting these criteria with biopsy-proven GN, with resection reserved for progressive growth or symptom development. However, larger, multicenter studies are needed for further validation.

Level Of Evidence: IV.
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http://dx.doi.org/10.1016/j.jpedsurg.2021.07.002DOI Listing
July 2021

Angiosarcoma of the Pancreas in a Pediatric Patient With an Activating KDR-Internal Tandem Duplication: A Case Report and Review of the Literature.

J Pediatr Hematol Oncol 2021 Jul 1. Epub 2021 Jul 1.

Michael E. DeBakey Department of Surgery, Division of Pediatric Surgery, Texas Children's Surgical Oncology Program Texas Children's Department of Surgery, Dan L. Duncan Cancer Center, Baylor College of Medicine Department of Pathology and Immunology Division of Pediatric Gastroenterology Singleton Department of Radiology Department of Hematology Oncology Michael E. DeBakey Department of Surgery, Division of Vascular Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.

Pancreatic angiosarcoma is an exceedingly rare malignancy accounting for <1% of pancreatic neoplasms. A very limited number of pancreatic angiosarcomas have been reported in the literature without any cases described in children. We present the case of a 17-year-old female diagnosed with angiosarcoma of the pancreas following pancreaticoduodenectomy for a pancreatic mass, initially presumed to be a solid pseudopapillary neoplasm of the pancreas. The angiosarcoma was found to have a novel activating internal tandem duplication in the KDR gene (KDR-internal tandem duplication). We discuss the current literature on this disease process. This is the first reported case of pancreatic angiosarcoma in a pediatric patient and the first with an activating KDR-internal tandem duplication.
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http://dx.doi.org/10.1097/MPH.0000000000002248DOI Listing
July 2021

Pathologic correlation with near infrared-indocyanine green guided surgery for pediatric liver cancer.

J Pediatr Surg 2021 Apr 25. Epub 2021 Apr 25.

Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX USA. Electronic address:

Purpose: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the most common primary malignant tumors of childhood. Intraoperative indocyanine green (ICG) administration with near-infrared imaging (NIR) has emerged as a surgical technology that can be used to assist with localization of pulmonary metastases secondary to HB; however, there has been limited application as an adjunct for resection of the primary liver tumor and assessment of extrahepatic disease.

Methods: We present 14 patients treated for HB, HCC, and malignant rhabdoid tumor at our institution with the use of intraoperative NIR-ICG guidance. All patients were treated with 0.2-0.75 mg/kg IV ICG, 48-96 h prior to surgery. Intraoperative NIR-ICG guided imaging was performed with several commercial devices.

Results: Intraoperative NIR-ICG guidance allowed pulmonary metastasectomy in five patients using thoracoscopy or thoracotomy allowing for visualization of multiple nodules not seen on preoperative imaging most of which were positive for malignancy. NIR-ICG guidance allowed for assessment of extrahepatic extension in three patients; an HCC patient with extrahepatic lymph node extension of disease, an HB patient with extrapulmonary thoracic recurrence in the diaphragm and chest wall, and a patient with tumor rupture at diagnosis with peritoneal nodules at the time of surgery. This technique was used to guide partial hepatectomy in 11 patients for which the technique enabled successful identification of tumor and tumor margins. Three patients had nonspecific staining of the liver secondary to decreased timing from ICG injection to surgery or biliary obstruction. NIR-ICG enabled resection of satellite HB lesions in three multifocal patients and confirmed a benign satellite lesion in two additional patients.

Conclusions: Intraoperative use of NIR-ICG imaging during partial hepatectomy enabled enhanced identification and guidance for surgical resection of extrahepatic disease and multifocal liver tumors for the treatment of children with primary liver cancer.
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http://dx.doi.org/10.1016/j.jpedsurg.2021.04.019DOI Listing
April 2021

Transarterial Radioembolization Treatment as a Bridge to Surgical Resection in Pediatric Hepatocellular Carcinoma.

J Pediatr Hematol Oncol 2021 Mar 23. Epub 2021 Mar 23.

Michael E. DeBakey Department of Surgery, Division of Pediatric Surgery, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine Department of Pathology and Immunology, Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine E. DeBakey Department of Surgery, Division of Abdominal Transplantation, Michael Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine Department of Pediatrics, Texas Children's Cancer Center, Center for Cell and Gene Therapy, Texas Children's Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine Singleton Department of Pediatric Radiology, Texas Children's Hospital Liver Tumor Program, Baylor College of Medicine Department of Interventional Radiology, MD Anderson Cancer Center Singleton Department of Pediatric Radiology, Division of Interventional Radiology, Texas Children's Hospital Liver Tumor Program, Baylor College of Medicine, Houston Department of Pediatrics, Texas Tech University Health Sciences Center, El Paso, TX Division of Hematology and Oncology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

Background: Children with unresectable hepatocellular carcinoma (HCC) have a poor prognosis and limited treatment options. Transarterial radioembolization (TARE) using Yttrium-90 (Y90) has emerged as a potential bridge therapy to hepatic resection or transplantation for HCC with very limited studies in children.

Observations: Here we present the clinical course of 2 children successfully treated with TARE Y90 for initially unresectable fibrolamellar HCC (FL-HCC) and bridged to partial hemihepatectomy with >1-year overall survival post-TARE.

Conclusion: Although there have been prior published reports of pediatric patients with HCC being treated with TARE Y90 and some being able to undergo subsequent orthotopic liver transplantation, this is the first report of pediatric HCC patients treated with TARE Y90 as a bridge to nontransplant resections and going on to have >1-year overall survival.
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http://dx.doi.org/10.1097/MPH.0000000000002089DOI Listing
March 2021

MDM4 inhibition: a novel therapeutic strategy to reactivate p53 in hepatoblastoma.

Sci Rep 2021 Feb 3;11(1):2967. Epub 2021 Feb 3.

Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Texas Children's Hospital, 1102 Bates Ave., Suite 460G, Houston, TX, 77030-2399, USA.

Hepatoblastoma (HB) is the most common pediatric liver malignancy. High-risk patients have poor survival, and current chemotherapies are associated with significant toxicities. Targeted therapies are needed to improve outcomes and patient quality of life. Most HB cases are TP53 wild-type; therefore, we hypothesized that targeting the p53 regulator Murine double minute 4 (MDM4) to reactivate p53 signaling may show efficacy. MDM4 expression was elevated in HB patient samples, and increased expression was strongly correlated with decreased expression of p53 target genes. Treatment with NSC207895 (XI-006), which inhibits MDM4 expression, or ATSP-7041, a stapled peptide dual inhibitor of MDM2 and MDM4, showed significant cytotoxic and antiproliferative effects in HB cells. Similar phenotypes were seen with short hairpin RNA (shRNA)-mediated inhibition of MDM4. Both NSC207895 and ATSP-7041 caused significant upregulation of p53 targets in HB cells. Knocking-down TP53 with shRNA or overexpressing MDM4 led to resistance to NSC207895-mediated cytotoxicity, suggesting that this phenotype is dependent on the MDM4-p53 axis. MDM4 inhibition also showed efficacy in a murine model of HB with significantly decreased tumor weight and increased apoptosis observed in the treatment group. This study demonstrates that inhibition of MDM4 is efficacious in HB by upregulating p53 tumor suppressor signaling.
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http://dx.doi.org/10.1038/s41598-021-82542-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859402PMC
February 2021

Necrotizing Enterocolitis-like Pneumatosis Intestinalis in an Infant With COVID-19.

Pediatr Infect Dis J 2021 02;40(2):e85-e86

Department of Surgery, Division of Pediatric Surgery, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.

We report an infant with COVID-19 who presented with bloody stools, lethargy and imaging findings significant for pneumatosis intestinalis. The infant was treated with conservative therapy, including resuscitation, bowel rest and intravenous antibiotics, successfully avoiding surgical intervention.
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http://dx.doi.org/10.1097/INF.0000000000002968DOI Listing
February 2021

Sclerosing Encapsulating Peritonitis in a Pediatric Patient Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

J Pediatr Hematol Oncol 2021 Jul;43(5):e685-e688

Michael E. DeBakey Department of Surgery, Divisions of Pediatric Surgery and Surgical Research, Texas Children's Hospital Surgical Oncology Program, Dan L. Duncan Cancer Center.

Background: Sclerosing encapsulating peritonitis (SEP) is a rare chronic inflammatory condition characterized by small bowel encapsulation by a thick fibrocollagenous membrane. Patients with SEP often present with nonspecific symptoms, such as abdominal pain and distension, however some patients may present with symptoms suggestive of intestinal obstruction. Secondary SEP has been reported in patients undergoing peritoneal dialysis and has been recently described in adults following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Observations: We report a clinical case of a 13-year-old female who presented with worsening abdominal pain and distension and persistent emesis who was found to have SEP 13 months following CRS and HIPEC for management of desmoplastic small round cell tumor and subsequently required operative intervention.

Conclusion: Although there have been published reports of adult patients experiencing cases of SEP following CRS/HIPEC, this is the first published case of secondary SEP occurring in a pediatric oncology patient.
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http://dx.doi.org/10.1097/MPH.0000000000001899DOI Listing
July 2021

Animal Modeling of Pediatric Liver Cancer.

Cancers (Basel) 2020 Jan 22;12(2). Epub 2020 Jan 22.

Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.

Hepatoblastoma (HB) is the most common pediatric liver malignancy. Management of HB requires multidisciplinary efforts. The 5-year overall survival of this disease is about 80% in developed countries. Despite advances in the care of these patients, survival in recurrent or treatment-refractory disease is lower than 50%. This is due to more complex tumor biology, including hepatocellular carcinoma (HCC)-like mutations and expression of aggressive gene signatures leading to chemoresistance, vascular invasion, and metastatic spread. The current treatment protocols for pediatric liver cancer do not incorporate targeted therapies, and the ability to test these therapies is limited due to the inaccessibility of cell lines and mouse models. In this review, we discuss the current status of preclinical animal modeling in pediatric liver cancer, primarily HB. Although HB is a rare cancer, the research community has worked together to develop a range of interesting and relevant mouse models for diverse preclinical studies.
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http://dx.doi.org/10.3390/cancers12020273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072332PMC
January 2020

Surgical Management of Hepatoblastoma and Recent Advances.

Cancers (Basel) 2019 Dec 4;11(12). Epub 2019 Dec 4.

Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.

Hepatoblastoma is the most common childhood liver malignancy. The management of hepatoblastoma requires multidisciplinary efforts. The five-year overall survival is approximately 80% in developed countries. Surgery remains the mainstay of treatment for hepatoblastoma, and meticulous techniques must be employed to ensure safe and effective local control surgeries. Additionally, there have been several advances from both pediatric and adult literature in the way liver tumor surgery is performed. In this review, we highlight important aspects of liver surgery for hepatoblastoma, the management of metastatic disease, and the most current technical advances in performing these procedures in a safe and effective manner.
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http://dx.doi.org/10.3390/cancers11121944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966548PMC
December 2019

Review: perspectives on renal and visceral protection during thoracoabdominal aortic aneurysm repair.

Indian J Thorac Cardiovasc Surg 2019 Jun 14;35(Suppl 2):179-185. Epub 2018 Dec 14.

Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, BCM 390, Houston, TX USA.

Open repair of a thoracoabdominal aortic aneurysm (TAAA) is an extensive operation and associated with significant perioperative morbidities and mortality, in large part due to distal aortic ischemia secondary to aortic cross-clamping that is necessitated during repair. Distal aortic ischemia may manifest as complications of the kidneys and viscera. Postoperative renal complications range from temporarily elevated levels of creatinine resulting from impaired kidney function to acute renal failure necessitating dialysis that may persist after hospital discharge. Continued advances in the management and adjuncts associated with TAAA repair since the groundbreaking era of E.S. Crawford have led to improved postoperative outcomes following surgery, but the dramatic improvements seen in reducing rates of spinal cord deficits, mesenteric ischemia and other serious postoperative complications have not been seen in contemporary rates of postoperative renal failure. We provide an overview of the various surgical techniques and adjuncts as they relate to the management of visceral and renal ischemia.
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http://dx.doi.org/10.1007/s12055-018-0757-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525488PMC
June 2019

Socioeconomic Factors Associated with Readmission after Deceased Donor Renal Transplantation.

Am Surg 2017 Jul;83(7):755-760

Early hospital readmissions after kidney transplantation pose a significant financial burden and hardship for patients and health-care institutions alike. We sought to identify the risk factors associated with increased likelihood of readmission after transplantation, and examined to determine whether patient socioeconomic demographics impacted the likelihood of perioperative readmissions. We evaluated all deceased donor renal transplants performed at our institution between August 2011 and December 2015. In a cohort of 325 transplant operations that met our inclusion criteria, 117 (36%) were readmitted to the hospital within 90 days of discharge. In univariable analyses, length of stay and pretransplant disabled status were associated with increased likelihood of readmission within 90 days of transplant. When placed into multivariable models, there was a suggestion association with length of stay and disability status. Kidney donor profile index, estimated posttransplant survival, employment, race, age, and payor status were not associated with readmission. In conclusion, the factors associated with posttransplant readmission are not necessarily influenced by socioeconomic factors in our study population. The data collected in this single center study indicate that the factors associated with increased rates of readmission are likely clinical in nature.
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July 2017
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