Does CD10 Expression Predict Lymph Node Metastasis in Colorectal Cancer?

BACKGROUND: Accurate preoperative prediction of lymph node status would be a revolutionary adjunct in treating colorectal cancer. The immunohistochemical marker CD10 has been suggested recently to have a predictive capacity for lymph node involvement in colorectal cancer. OBJECTIVE: The aim of our study was to evaluate the relationship between the presence of the CD10 molecular marker and lymph node metastasis in a US patient population using previously banked colorectal cancer specimens. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at a single academic institution. PATIENTS: Included were specimens from 191 patients, with cancer stages ranging from T1N0 to T3N2. MAIN OUTCOME MEASURES: The relationship between CD10 and different clinicopathologic parameters was assessed, as well as the ability to predict lymph node metastasis by itself and in conjunction with lymphovascular invasion. RESULTS: CD10 was significantly correlated with left-sided colon cancers (p = 0.01) and the presence of mucinous histology and had a relatively high specificity (75.7%) for lymph node metastasis. CD10 did not correlate with lymph node status (p = 0.33) or enhance the ability of lymphovascular invasion to predict lymphatic metastasis in our patient population. Sensitivity and specificity of lymphovascular invasion alone for lymph node metastasis were 62.8% and 93.6%, whereas adding CD10 status resulted in a sensitivity of 70.6% and specificity of 69.3%. Multivariate analysis revealed only lymphovascular invasion as a predictor of lymph node metastasis in our patient population. LIMITATIONS: This study was primarily limited by its small sample size and retrospective nature. CONCLUSIONS: In our patient population, CD10 status was not significantly associated with lymph node metastasis, and it was no better than lymphovascular invasion alone when predicting lymph node status.

Fulminant pH1N1-09 influenza-associated myocarditis in pediatric patients.

OBJECTIVE: To report an atypical presentation of pH1N1-09 influenza infection in children as fulminant myocarditis and tamponade and the successful treatment with extracorporeal membrane oxygenation. DESIGN: Case report. SETTING: Pediatric cardiac intensive care unit in a quarternary care children's hospital. PATIENTS: Two girls, 5 and 7 yrs of age, infected with pH1N1-09 influenza virus who presented in cardiogenic shock with a pericardial effusion and echocardiographic evidence of tamponade from fulminant myocarditis. INTERVENTIONS: Both patients received a pericardiocentesis. One was managed with multiple, high-dose inotropic agents, whereas the other required institution of extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Acute respiratory distress syndrome is the major reported clinical manifestation of pH1N1-09 influenza virus infection in hospitalized pediatric patients. In this report we describe two children with confirmed pH1N1-09 influenza infection that required intensive care for fulminant myocarditis. Neither patient had the typical symptoms of influenza-like illness, respiratory compromise, or evidence of pulmonary involvement. One child required extracorporeal membrane oxygenation. Both children survived to hospital discharge. CONCLUSIONS: pH1N1-09 influenza infection can cause fulminant myocarditis in the healthy pediatric population. The clinical presentation may be nonspecific, and the lack of pulmonary symptoms may make diagnosis difficult. Extracorporeal membrane oxygenation support may offer an effective bridge to the recovery of heart function.

The role of fiberoptic endoscopy in the evaluation and management of long gap isolated esophageal atresia.

Accurate measurement of gap length is useful for operative planning in cases of esophageal atresia (EA) without distal fistula. This paper demonstrates how fiberoptic endoscopy of the distal esophagus enables measurement of the gap in the case of isolated EA, and compares other commonly practiced techniques.

Gastrointestinal Histoplasmosis as an Obstructing Ileocecal Mass.

Histoplasmosis is a self-limiting and asymptomatic disease in immunocompetent individuals. Patients in an immunocompromised state are susceptible to disseminated disease. We present a case of a 60-year-old male with a history of psoriatic and rheumatoid arthritis treated with a tumor necrosis factor inhibitor (adalimumab), who presented with abdominal pain and was found to have gastrointestinal histoplasmosis as an obstructing ileocecal mass. Although gastrointestinal involvement is common in disseminating disease, symptomatic involvement is rare. This case presentation has implications in rheumatological patients on biologic medications.

Surgeon Perspectives Regarding Death and Dying.

BACKGROUND: Surgical patients most commonly receive palliative care services within 24-48 hours of death, and reasons for this delay are poorly understood. Research with nonsurgeons suggests that physician characteristics and beliefs about death and dying may contribute to late referral. OBJECTIVE: To describe surgeon perspectives related to death and dying, and their relationship with delayed referrals to palliative care. DESIGN: Using a previously validated survey instrument supplemented by open-ended questions, deductive content analysis was used to describe surgeon preferences for end-of-life care. SETTINGS: Participants were all current nonretired members of the American Society of Colon and Rectal Surgeons. MAIN OUTCOME MEASURES: Surgeon descriptions of a "good death" and how personal experiences influence care provided. RESULTS: Among 131 survey respondents (response rate 16.5%), 117 (89.3%) completed all or part of the qualitative portion of the survey. Respondents consistently reported their personal preferences for end-of-life care, and four central themes emerged: (1) pain and symptom management, (2) clear decision making, (3) avoidance of medical care, and (4) completion. Surgeons also reflected on both good and bad experiences with patients and family members dying, and how these experiences impact practice. LIMITATIONS: The small sample size inherent to Internet surveys may limit generalizability and contribute to selection bias. CONCLUSION: This study reveals surgeon preferences for end-of-life care, which may inform initiatives aimed at surgeons who may underuse or delay palliative care services. Future studies are needed to better understand how surgeon preferences may directly impact treatment recommendations for their patients.

Characterizing the Role of U.S. Surgeons in the Provision of Palliative Care: A Systematic Review and Mixed-Methods Meta-Synthesis.

CONTEXT: The provision of palliative care varies appropriately by clinical factors such as patient age and severity of disease and also varies by provider practice and specialty. Surgical patients are persistently less likely to receive palliative care than their medical counterparts for reasons that are not clear. OBJECTIVES: We sought to characterize surgeon-specific determinants of palliative care in seriously ill and dying patients. METHODS: We performed a systematic review of the literature focused on surgery and palliative care within PubMed, CINAHL, EMBASE, Scopus, and Ovid Medline databases from January 1, 2000 through December 31, 2016 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Quantitative and qualitative studies with primary data evaluating surgeons' attitudes, knowledge, and behaviors or experiences in care for seriously ill and dying patients were selected for full review by at least two study team members based on predefined inclusion criteria. Data were extracted based on a predetermined instrument and compared across studies using thematic analysis in a meta-synthesis of qualitative and quantitative findings. RESULTS: A total of 2589 abstracts were identified and screened, and 35 articles (26 quantitative and nine qualitative) fulfilled criteria for full review. Among these, 17 articles explored practice and attitudes of surgeons regarding palliative and end-of-life care, 11 articles assessed training in palliative care, five characterized surgical decision making, one described behaviors of surgeons caring for seriously ill and dying patients, and one explicitly identified barriers to use of palliative care. Four major themes across studies affected receipt of palliative care for surgical patients: 1) surgeons' experience and knowledge, 2) surgeons' attitudes, 3) surgeons' preferences and decision making for treatment, and 4) perceived barriers. CONCLUSIONS: Among the articles reviewed, surgeons overall demonstrated insight into the benefits of palliative care but reported limited knowledge and comfort as well as a multitude of challenges to introducing palliative care to their patients. These findings indicate a need for wider implementation of strategies that allow optimal integration of palliative care with surgical decision making.

Surgeons' Perceived Barriers to Palliative and End-of-Life Care: A Mixed Methods Study of a Surgical Society.

BACKGROUND: Nearly 20% of colorectal cancer (CRC) patients present with potentially incurable (Stage IV) disease, yet their physicians do not integrate cancer treatment with palliative care. Compared with patients treated by primary providers, surgical patients with terminal diseases are significantly less likely to receive palliative or end-of-life care. OBJECTIVE: To describe surgeon perspectives on palliative and end-of-life care for patients with Stage IV CRCs. DESIGN: This is a convergent mixed methods study using a validated survey instrument from the Critical Care Peer Workgroup of the Robert Wood Johnson Foundation's Promoting Excellence in End-of-Life Care Project with additional qualitative questions. SETTINGS: Participants were all current, nonretired members of the American Society of Colon and Rectal Surgeons. MAIN OUTCOME MEASURES: Surgeon-perceived barriers to palliative and end-of-life care for patients with Stage IV CRCs were identified. RESULTS: Among 131 Internet survey respondents (response rate 16.5%), 76.1% reported no formal education in palliative care, and specifically noted inadequate training in techniques to forgo life-sustaining measures (37.9%) and communication (42.7%). Over half (61.8%) of surgeons cited unrealistic expectations among patients and families as a barrier to care, which also limited discussion of palliation. At the system level, absence of documentation, appropriate processes, and culture hindered the initiation of palliative care. Thematic analysis of open-ended questions confirmed and extended these findings through the following major barriers to palliative and end-of-life care: (1) surgeon knowledge and training; (2) communication challenges; (3) difficulty with prognostication; (4) patient and family factors encompassing unrealistic expectations and discordant preferences; and (5) systemic issues including culture and lack of documentation and appropriate resources. LIMITATIONS: Generalizability is limited by the small sample size inherent to Internet surveys, which may contribute to selection bias. CONCLUSIONS: Surgeons valued palliative and end-of-life care but reported multilevel barriers to its provision. These data will inform strategies to reduce these perceived barriers.

Contrast ultrasound imaging for identification of early responder tumor models to anti-angiogenic therapy.

Agents targeting vascular endothelial growth factor (VEGF) have been validated as cancer therapeutics, yet efficacy can differ widely between tumor types and individual patients. In addition, such agents are costly and can have significant toxicities. Rapid noninvasive determination of response could provide significant benefits. We tested if response to the anti-VEGF antibody bevacizumab (BV) could be detected using contrast-enhanced ultrasound imaging (CEUS). We used two xenograft model systems with previously well-characterized responses to VEGF inhibition, a responder (SK-NEP-1) and a non-responder (NGP), and examined perfusion-related parameters. CEUS demonstrated that BV treatment arrested the increase in blood volume in the SK-NEP-1 tumor group only. Molecular imaging of α(V)ß(3) with targeted microbubbles was a more sensitive prognostic indicator of BV efficacy. CEUS using RGD-labeled microbubbles showed a robust decrease in α(V)ß(3) vasculature following BV treatment in SK-NEP-1 tumors. Paralleling these findings, lectin perfusion assays detected a disproportionate pruning of smaller, branch vessels. Therefore, we conclude that the response to BV can be identified soon after initiation of treatment, often within 3 days, by use of CEUS molecular imaging techniques. The use of a noninvasive ultrasound approach may allow for earlier and more effective determination of efficacy of antiangiogenic therapy.

Monitoring early tumor response to drug therapy with diffuse optical tomography.

Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy-thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

The use of recombinant tissue-type plasminogen activator in a newborn with an intracardiac thrombus developed during extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) support is often used to support infants and children with hemodynamic or respiratory failure. One of the major obstacles of safely treating a child with ECMO is balancing the risk of hemorrhage with the potential for thrombus development. Managing thrombosis in the setting of ECMO is challenging and has no defined algorithm. The use of recombinant tissue-type plasminogen activator (tPA) for thrombolysis has been previously described in cases where thrombi have developed despite adequate anticoagulation. In such situations, the risk of hemorrhage must be carefully balanced with the benefit of dissolving the clot and reestablishing flow. We present a case of an infant who required ECMO because of severe primary pulmonary hypertension and subsequently developed a right atrial thrombus adjacent to the ECMO cannula. The patient was treated with tPA with immediate improvement but had fatal intracranial hemorrhage almost 3 days after the tPA was administered. In this report, we review the current literature on tPA use during ECMO support and suggest a rational approach.

Early recurrence of congenital diaphragmatic hernia is higher after thoracoscopic than open repair: a single institutional study.

INTRODUCTION: Experience in thoracoscopic congenital diaphragmatic hernia (CDH) repair has expanded, yet efficacy equal to that of open repair has not been demonstrated. In spite of reports suggesting higher recurrent hernia rates after thoracoscopic repair, this approach has widely been adopted into practice. We report a large, single institutional experience with thoracoscopic CDH repair with special attention to recurrent hernia rates. METHODS: We reviewed the records of neonates with unilateral CDH repaired between January 2006 and February 2010 at Morgan Stanley Children's Hospital. Completely thoracoscopic repairs were compared to open repairs of the same period. In addition, successful thoracoscopic repairs were compared with thoracoscopic repairs that developed recurrence. Data were analyzed by Mann-Whitney U and Fisher exact tests. RESULTS: Thirty-five neonates underwent attempted thoracoscopic repair, with 26 completed. Concurrently, 19 initially open CDH repairs were performed. Preoperatively, patients in the open repair group required more ventilatory support than the thoracoscopic group. Recurrence was higher after thoracoscopic repair (23% vs 0%; P = .032). In comparing successful thoracoscopic repairs to those with recurrence, none of the factors analyzed were predictive of recurrence. CONCLUSIONS: Early recurrence of hernia is higher in thoracoscopic CDH repairs than in open repairs. Technical factors and a steep learning curve for thoracoscopy may account for the higher recurrence rates, but not patient severity of illness. In an already-tenuous patient population, performing the repair thoracoscopically with a higher risk of recurrence may not be advantageous.

Limb ischemia after common femoral artery cannulation for venoarterial extracorporeal membrane oxygenation: an unresolved problem.

PURPOSE: Extracorporeal Life Support Organization Registry data confirm that the number of pediatric patients being supported by extracorporeal membrane oxygenation (ECMO) is increasing. To minimize the potential neurologic effects of carotid artery ligation, the common femoral artery (CFA) is frequently being used for arterial cannulation. The cannula has the potential for obstructing flow to the lower limb, thus increasing ischemia and possible limb loss. We present a single institution's experience with CFA cannulation for venoarterial (VA) ECMO and ask whether any precannulation variables correlate with the development of significant limb ischemia. METHODS: We reviewed all pediatric patients who were supported by VA ECMO via CFA cannulation from January 2000 to February 2010. Limb ischemia was the primary variable. The ischemia group was defined as the patients requiring an intervention because of the development of lower extremity ischemia. The patients in the no-ischemia group did not develop significant ischemia. Continuous variables were reported as medians with interquartile ranges and compared using Mann-Whitney U tests. Differences in categorical variables were assessed using χ² testing (Fisher's Exact). Statistical significance was assumed at P < .05. RESULTS: Twenty-one patients (age, 2-22 years) were cannulated via the CFA for VA ECMO. Significant ischemia requiring intervention (ischemia group) occurred in 11 (52%) of 21. In comparing the 2 groups (ischemia vs no ischemia), no clinical variables predicted the development of ischemia (Table 1). In the ischemia group, 9 (81%) of 11 had a distal perfusion catheter (DPC) placed. Complications of DPC placement included one case of compartment syndrome requiring a fasciotomy and one patient requiring interval toe amputation. Of the 2 patients in the ischemia group who did not have a DPC placed, 1 required a vascular reconstruction of an injured superficial femoral artery and 1 underwent a below-the-knee amputation. Mortality was lower in the ischemia group (27% vs 60%). CONCLUSIONS: Limb ischemia remains a significant problem, as more than half of our patients developed it. The true incidence may not be known as a 60% mortality in the no-ischemia group could mask subsequent ischemia. Although children are at risk for developing limb ischemia/loss, no variable was predictive of the development of significant limb ischemia in our series. Because of the inability to predict who will develop limb ischemia, early routine placement of a DPC at the time of cannulation may be warranted. However, DPCs do not completely resolve issues around tissue loss and morbidity. Prevention of limb ischemia/loss because of CFA cannulation for VA ECMO continues to be a problem that could benefit from new strategies.

Laparoscopic excision of choledochal cysts with total intracorporeal reconstruction.

PURPOSE: There are numerous published reports of laparoscopic resection of choledochal cysts (CDCs), but almost all involve extracorporeal reconstruction of a biliary drainage system. We describe and evaluate the technique of laparoscopic CDC resection with total intracorporeal reconstruction. METHODS: We reviewed all patients who underwent a laparoscopic CDC resection from March 2005 to January 2010 at Rocky Mountain Children's Hospital and Children's Hospital of New York-Presbyterian. We obtained data on operative time, characteristics of reconstruction, time to initiation of diet, length of stay, complications, and outcome. RESULTS: Thirteen patients (median age 5 years, range 1-16) underwent a laparoscopic CDC excision with total intracorporeal reconstruction. Four ports were used in all cases and no patients required conversion to an open procedure. Operative time ranged from 130 to 325 minutes (median 240 minutes). Median time to initiation of diet was 1 day (range 1-4 days). Median length of stay was 5 days (range 4-8 days). There were no cases of cholangitis; however, 1 patient developed a small bowel obstruction requiring re-operation. CONCLUSION: Laparoscopic resection of CDCs with total intracorporeal reconstruction is a safe and effective technique. The minimal handling of the bowel appears to minimize postoperative ileus, allows for early postoperative feeding and discharge.