Cecilia G. Ethun

Fetal MRI lung volumes are predictive of perinatal outcomes in fetuses with congenital lung masses.

PURPOSE The purpose of this study was to evaluate fetal magnetic resonance imaging (MRI) as a modality for predicting perinatal outcomes and lung-related morbidity in fetuses with congenital lung masses (CLM). METHODS The records of all patients treated for CLM from 2002 to 2012 were reviewed retrospectively. Fetal MRI-derived lung mass volume ratio (LMVR), observed/expected normal fetal lung volume (O/E-NFLV), and lesion-to-lung volume ratio (LLV) were calculated. Multivariate regression and receiver operating characteristic analyses were applied to determine the predictive accuracy of prenatal imaging. RESULTS Of 128 fetuses with CLM, 93% (n=118) survived. MRI data were available for 113 fetuses. In early gestation (<26weeks), MRI measurements of LMVR and LLV correlated with risk of fetal hydrops, mortality, and/or need for fetal intervention. In later gestation (>26weeks), LMVR, LLV, and O/E-NFLV correlated with neonatal respiratory distress, intubation, NICU admission and need for neonatal surgery. On multivariate regression, LMVR was the strongest predictor for development of fetal hydrops (OR: 6.97, 1.58-30.84; p=0.01) and neonatal respiratory distress (OR: 12.38, 3.52-43.61; p≤0.001). An LMVR >2.0 predicted worse perinatal outcome with 83% sensitivity and 99% specificity (AUC=0.94; p<0.001). CONCLUSION Fetal MRI volumetric measurements of lung masses and residual normal lung are predictive of perinatal outcomes in fetuses with CLM. These data may assist in perinatal risk stratification, counseling, and resource utilization.

Maternal morbidity and reproductive outcomes related to fetal surgery

PURPOSE The purpose of this manuscript was to examine the maternal morbidity and reproductive outcomes following maternal-fetal surgery with an emphasis on the EXIT procedure. METHODS The medical records of all women who underwent an ex-utero intrapartum treatment (EXIT) procedure or mid-gestation open maternal fetal surgery (OMFS) at our center from December 2001 to December 2011 were reviewed retrospectively. Future reproductive outcomes were obtained via telephone questionnaire. RESULTS Thirty-three women underwent maternal-fetal surgery. Twenty-six had EXIT, and seven had OMFS. The questionnaire response was 82% (27/33). Eighty-one percent (17/21) of the EXIT cohort desired future pregnancy. All who attempted (13/13) were successful. The majority (85%) conceived spontaneously and within 2.5 years on average. In the OMFS group, 40% experienced complications. One had uterine dehiscence, and another had uterine rupture requiring urgent delivery at 36 weeks. In subsequent pregnancies, 20% of OMFS cases were complicated by uterine rupture, and 8% of EXIT patients had uterine dehiscence. All had good maternal-fetal outcome. CONCLUSION Future reproductive capacity and complication rates in subsequent pregnancies following EXIT procedure are similar to those seen in the general population. In contrast, mid-gestation OMFS remains associated with relatively morbid complications. This evidence can help guide in counseling expectant mothers who are faced with the challenge of considering fetal surgery.

Association of Preoperative Risk Factors With Malignancy in Pancreatic Mucinous Cystic Neoplasms: A Multicenter Study

Importance Pancreatic mucinous cystic neoplasms (MCNs) harbor malignant potential, and current guidelines recommend resection. However, data are limited on preoperative risk factors for malignancy (adenocarcinoma or high-grade dysplasia) occurring in the setting of an MCN. Objectives To examine the preoperative risk factors for malignancy in resected MCNs and to assess outcomes of MCN-associated adenocarcinoma. Design, Setting, and Participants Patients who underwent pancreatic resection of MCNs at the 8 academic centers of the Central Pancreas Consortium from January 1, 2000, through December 31, 2014, were retrospectively identified. Preoperative factors of patients with and without malignant tumors were compared. Survival analyses were conducted for patients with adenocarcinoma. Main Outcomes and Measures Binary logistic regression models were used to determine the association of preoperative factors with the presence of MCN-associated malignancy. Results A total of 1667 patients underwent resection of pancreatic cystic lesions, and 349 (20.9%) had an MCN (310 women [88.8%]; mean (SD) age, 53.3 [14.7] years). Male sex (odds ratio [OR], 3.72; 95% CI, 1.21-11.44; P = .02), pancreatic head and neck location (OR, 3.93; 95% CI, 1.43-10.81; P = .01), increased radiographic size of the MCN (OR, 1.17; 95% CI, 1.08-1.27; P < .001), presence of a solid component or mural nodule (OR, 4.54; 95% CI, 1.95-10.57; P < .001), and duct dilation (OR, 4.17; 95% CI, 1.63-10.64; P = .003) were independently associated with malignancy. Malignancy was not associated with presence of radiographic septations or preoperative cyst fluid analysis (carcinoembryonic antigen, amylase, or mucin presence). The median serum CA19-9 level for patients with malignant neoplasms was 210 vs 15 U/mL for those without (P = .001). In the 44 patients with adenocarcinoma, 41 (93.2%) had lymph nodes harvested, with nodal metastases in only 14 (34.1%). Median follow-up for patients with adenocarcinoma was 27 months. Adenocarcinoma recurred in 11 patients (25%), with a 64% recurrence-free survival and 59% overall survival at 3 years. Conclusions and Relevance Adenocarcinoma or high-grade dysplasia is present in 14.9% of resected pancreatic MCNs for which risks include male sex, pancreatic head and neck location, larger MCN, solid component or mural nodule, and duct dilation. Mucinous cystic neoplasm–associated adenocarcinoma appears to have decreased nodal involvement at the time of resection and increased survival compared with typical pancreatic ductal adenocarcinoma. Indications for resection of MCNs should be revisited.

Low Abdominal NIRS Values and Elevated Plasma Intestinal Fatty Acid-Binding Protein in a Premature Piglet Model of Necrotizing Enterocolitis

To identify early markers of necrotizing enterocolitis (NEC), we hypothesized that continuous abdominal near-infrared spectroscopy (A-NIRS) measurement of splanchnic tissue oxygen saturation and intermittent plasma intestinal fatty-acid binding protein (pI-FABP) measured every 6 hours can detect NEC prior to onset of clinical symptoms. Premature piglets received parenteral nutrition for 48-hours after delivery, followed by enteral feeds every three hours until death or euthanasia at 96-hours. Continuous A-NIRS, systemic oxygen saturation (SpO2), and heart rate were measured while monitoring for clinical signs of NEC. Blood samples obtained at 6-hour intervals were used to determine pI-FABP levels by ELISA. Piglets were classified as fulminant-NEC (f-NEC), non-fulminant-NEC (nf-NEC) and No-NEC according to severity of clinical and histologic features. Of 38 piglets, 37% (n=14) developed nf-NEC, 18% (n=7) developed f-NEC and 45% (n=17) had No-NEC. There were significant differences in baseline heart rate (p=0.008), SpO2 (p<0.001) and A-NIRS (p<0.001) among the three groups. A-NIRS values of NEC piglets remained lower throughout the study with mean for f-NEC of 69±3.8%, 71.9±4.04% for nf-NEC, and 78.4±1.8% for No-NEC piglets (p<0.001). A-NIRS <75% predicted NEC with 97% sensitivity and 97% specificity. NEC piglets demonstrated greater variability from baseline in A-NIRS than healthy piglets (10.1% vs. 6.3%; p=0.04). Mean pI-FABP levels were higher in animals that developed NEC compared to No-NEC piglets (0.66 vs. 0.09 ng/mL;p<0.001). In f-NEC piglets, pI-FABP increased precipitously after feeds (0.04 to 1.87 ng/mL;p<0.001). pI-FABP levels increased in parallel with disease progression and a value >0.25ng/mL identified animals with NEC (68% sensitivity and 90% specificity). NIRS is a real-time, non-invasive tool that can serve as a diagnostic modality for NEC. In premature piglets, low A-NIRS in the early neonatal period and increased variability during initial feeds are highly predictive of NEC, which is then confirmed by rising plasma I-FABP levels. These modalities may help identify neonates with NEC prior to clinical manifestations of disease.

Frailty and cancer: Implications for oncology surgery, medical oncology, and radiation oncology

Answer questions and earn CME/CNE

The importance of surgical margins in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with a grim prognosis. Surgical resection offers the best chance for long‐term survival, yet recurrence rates are high and outcomes are poor. The influence of margin status in PDAC is controversial, as conflicting data have been plagued by a lack of standardization in margin definitions, pathologic analysis, and reporting. Despite recent efforts, international consensus is still needed for this disease. J. Surg. Oncol. 2016;113:283–288.

Fetal MRI improves diagnostic accuracy in patients referred to a fetal center for suspected esophageal atresia

PURPOSE The purpose of this study was to describe prenatal imaging characteristics and outcomes of fetuses with suspected esophageal atresia (EA) in order to improve prenatal diagnosis, counseling, and management. METHODS The medical records of all patients referred to our multidisciplinary fetal center for suspected EA from January 2003 to April 2013 were reviewed retrospectively. RESULTS Thirty-three patients were referred with a prenatal diagnosis of possible EA. Following fetal center evaluation with MRI, EA was deemed unlikely in 6 (18%) fetuses. Of 27 fetuses in whom EA could not be excluded, EA was confirmed postnatally in 15 (56%), excluded in 7 (26%), and unconfirmed in 5 (3 fetal losses; 2 lost to follow-up). Imaging characteristics on fetal MRI associated with the highest positive predictive values (PPV) were an esophageal pouch (100%) and a small stomach (75%). The finding of polyhydramnios had high sensitivity (93%) but low specificity (31%) and PPV (61%) for a diagnosis of EA. CONCLUSION Prenatal imaging and fetal center evaluation correctly identify the presence or absence of esophageal atresia in 78% of patients referred on suspicion of this condition. The presence of an esophageal pouch on fetal MRI has significant predictive value for EA. These data may assist with evidence-based prenatal family counseling.

Outcomes of fetuses with lower urinary tract obstruction treated with vesicoamniotic shunt: A single-institution experience

PURPOSE The purpose of this manuscript was to examine the outcomes of patients with lower urinary tract obstruction (LUTO) treated with vesicoamniotic shunt (VAS) to improve the quality of prenatal consultation and therapy. METHODS The medical records of all patients diagnosed with LUTO at our center between January 2004 and March 2012 were reviewed retrospectively. RESULTS Of 14 male fetuses with LUTO, all with characteristic ultrasound findings, 11 underwent intervention. One patient received vesicocentesis alone, while 10 had VAS. Two fetuses additionally underwent cystoscopy (one with attempted valve ablation), and two had peritoneoamniotic shunts. Of 16 total VAS, 13 were placed successfully, 8 dislodged (median 7 days), and 1 obstructed (84 days). Two fetuses suffered in utero demise, and two have unknown outcomes. LUTO was confirmed in six of eight live-born fetuses. One patient died in the neonatal period, while seven survived. All six available at follow-up (median 3.7 years), had significant genitourinary morbidity. Five patients had chronic kidney disease, but only one has required dialysis and transplant. Three had respiratory insufficiency, and one required a tracheostomy. CONCLUSION Despite significant perinatal and long-term morbidity, VAS offers patients faced with a poor prognosis an improved chance of survival. Our results underscore the need for further research into the diagnosis and treatment of LUTO.

The importance of surgical margins in melanoma

Optimization of margins to minimize morbidity and maximize local control is critical to the success of surgical management of primary melanomas. This article synthesizes the historical perspectives and key clinical trials that have contributed to the evolution of resection margins for melanoma, focusing on the importance of surgical margins in the context of an era of improvements in systemic therapy and greater use of minimally invasive techniques. J. Surg. Oncol. 2016;113:339–345.

Elevated NLR in gallbladder cancer and cholangiocarcinoma – making bad cancers even worse: results from the US Extrahepatic Biliary Malignancy Consortium

BACKGROUND Gallbladder and extrahepatic biliary malignancies are aggressive tumors with high risk of recurrence and death. We hypothesize that elevated preoperative Neutrophil-Lymphocyte Ratios (NLR) are associated with poor prognosis among patients undergoing resection of gallbladder or extrahepatic biliary cancers. METHODS Patients who underwent complete surgical resection between 2000-2014 were identified from 10 academic centers (n=525). Overall (OS) and recurrence-free survival (RFS) were analyzed by stratifying patients with normal (<5) versus elevated (>5) NLR. RESULTS Overall, 375 patients had NLR <5 while 150 patients had NLR >5. Median OS was 24.5 months among patients with NLR<5 versus 17.0 months among patients with NLR>5 (p<0.001). NLR was also associated with OS in subgroup analysis of patients with gallbladder cancer. In fact, on multivariable analysis, NLR>5, dyspnea and preoperative peak bilirubin were independently associated with OS in patients with gallbladder cancer. Median RFS was 26.8 months in patients with NLR<5 versus 22.7 months among patients with NLR>5 (p=0.030). NLR>5 was independently associated with worse RFS for patients with gallbladder cancer. CONCLUSIONS Elevated NLR was associated with worse outcomes in patients with gallbladder and extrahepatic biliary cancers after curative-intent resection. NLR is easily measured and may provide important prognostic information.