The RPL/RPS gene signature of melanoma CTCs associates with brain metastasis.

Melanoma brain metastasis (MBM) is linked to poor prognosis and low overall survival. We hypothesized that melanoma circulating tumor cells (CTCs) possess a gene signature significantly expressed and associated with MBM. Employing a multi-pronged approach, we provide first-time evidence identifying a common CTC gene signature for ribosomal protein large/small subunits (RPL/RPS) which associate with MBM onset and progression. Experimental strategies involved capturing, transcriptional profiling and interrogating CTCs, either directly isolated from blood of melanoma patients at distinct stages of MBM progression or from CTC-driven MBM in experimental animals. Second, we developed the first Magnetic Resonance Imaging (MRI) CTC-derived MBM xenograft model (MRI-MBM CDX) to discriminate MBM spatial and temporal growth, recreating MBM clinical presentation and progression. Third, we performed the comprehensive transcriptional profiling of MRI-MBM CDXs, along with longitudinal monitoring of CTCs from CDXs possessing/not possessing MBM. Our findings suggest that enhanced ribosomal protein content/ribogenesis may contribute to MBM onset. Since ribosome modifications drive tumor progression and metastatic development by remodeling CTC translational events, overexpression of the CTC RPL/RPS gene signature could be implicated in MBM development. Collectively, this study provides important insights for relevance of the CTC RPL/RPS gene signature in MBM, and identify potential targets for therapeutic intervention to improve patient care for melanoma patients diagnosed with or at high-risk of developing MBM.

Adherence to surveillance colonoscopy guidelines in patients following curative-intent colorectal cancer resection.

BACKGROUND: Current guidelines recommend that patients who have undergone curative-intent resection for colorectal cancer (CRC) should undergo colonoscopy one year following their surgery or at six months post-operatively if a pre-operative colonoscopy was not performed due to an obstructing lesion. We sought to determine adherence to postoperative surveillance colonoscopy guidelines in our National Cancer Institute designated comprehensive cancer center and potentially identify factors associated with non-adherence. MATERIALS AND METHODS: A retrospective review of 100 patients who underwent curative-intent CRC resection was performed between 2013 and 2019. Patients were divided into two groups based upon adherence to surveillance colonoscopy guidelines. Demographic, tumor, and postoperative variables were analyzed. RESULTS: The median age of all patients was 62. Fifty-seven percent of patients were male. Thirty-eight patients underwent surveillance colonoscopy in accordance with current guidelines. Sixty-two patients did not undergo surveillance colonoscopy postoperatively or did so outside of the National Comprehensive Cancer Network guidelines. Factors associated with non-adherence to surveillance colonoscopy included presence of comorbidities, albumin less than 3.5, and performance of a pre-operative colonoscopy. CONCLUSIONS: Adherence to surveillance colonoscopy guidelines was low among our patients. Efforts should be directed toward patients at increased risk for non-adherence to surveillance colonoscopy guidelines.

Current Guidelines for Integration of Palliative Care in Oncology.

Multiple cancer societies and professional medical organizations recommend integration of palliative care into routine oncology care. A growing body of literature supports the benefits of palliative care in patients with cancer. Palliative care improves pain and other symptoms, enhances quality of life, and reduces depression. The best method and timing for integration of palliative care is unclear. Multiple barriers exist that prevent optimal palliative care integration; these barriers will require additional education and research to overcome.

Artificial Nutrition in Patients with Advanced Malignancy.

Cancer is a progressive disease that can lead to malnutrition and cachexia. Artificial nutrition is a medical therapy used to combat malnutrition in these patients. In this article, the authors discuss factors affecting the decision to use artificial nutrition, including the patient's mental and physical health, technical factors of the procedures used to deliver artificial nutrition, and the oncologic factors affecting treatment. Through this review, the authors provide guidelines on who is and is not likely to benefit from therapy, available routes of administration, and necessary factors to consider for appropriate decision-making for palliative patients and those with advanced cancers."

A Multicenter, Randomized Controlled Trial of Perioperative Palliative Care Surrounding Cancer Surgery for Patients and Their Family Members (PERIOP-PC).

Background: Despite positive outcomes associated with specialist palliative care (PC) in diverse medical populations, little research has investigated specialist PC in surgical ones. Although cancer surgery is predominantly safe, operations can be extensive and unpredictable perioperative morbidity and mortality persist, particularly for patients with upper gastrointestinal (GI) cancers. Objectives and Hypotheses: Our objective is to complete a multicenter, randomized controlled trial comparing surgeon-PC co-management with surgeon-alone management among patients pursuing curative-intent surgery for upper GI cancers. We hypothesize that perioperative PC will improve patient postsurgical quality of life. This study and design are based on >8 years of engagement and research with patients, family members, and clinicians surrounding major cancer surgery and advance care planning/PC for surgical patients. Methods: Randomized controlled superiority trial with two study arms (surgeon-PC team co-management and surgeon-alone management) and five data collection points over six months. The principal investigator and analysts are blinded to randomization. Setting: Four, geographically diverse, academic tertiary care hospitals. Data collection began December 20, 2018 and continues to December 2020. Participants: Patients recruited from surgical oncology clinics who are undergoing curative-intent surgery for an upper GI cancer. Interventions: In the intervention arm, patients receive care from both their surgical team and a specialist PC team; the PC is provided before surgery, immediately after surgery, and at least monthly until three months postsurgery. Patients randomized to the usual care arm receive care from only the surgical team. Main Outcomes and Measures: Primary outcome: patient quality of life. Secondary outcomes: patient: symptom experience, spiritual distress, prognostic awareness, health care utilization, and mortality. Caregiver: quality of life, caregiver burden, spiritual distress, and prognostic awareness. Intent-to-treat analysis will be used. Ethics and Dissemination: This study has been approved by the institutional review boards of all study sites and is registered on clinicaltrials.gov (NCT03611309, First received: August 2, 2018).

Prognostication in oncology.

Prognostication involves formulation and communication about the expected course of the disease and is unique in surgical oncology because of the need to incorporate patient, procedural, and cancer-related factors. Several tools and techniques are available to assist physicians in formulating prognosis on the basis of these factors. Use of established communication techniques are effective in discussing prognosis. In situations with prognostic uncertainty, use of the best case/worst case/most likely case or time-limited trial of therapy can be helpful.

Introduction: Role of palliative care for the surgical patient.

Palliative care (PC) seeks to improve the quality of life for patients facing serious illness. Several oncology organizations have guidelines about PC, reflecting the need to integrate PC into standard oncology care. Many surgical patients do not receive PC despite the need for these services and established surgical PC competencies. Recent educational and research efforts reveal increased appreciation of the need and benefit of integrating PC services with cancer care in general, and surgical care, specifically.

Estimation of Risk in Cancer Patients Undergoing Palliative Procedures by the American College of Surgeons Risk Calculator.

BACKGROUND: Surgical palliation is defined as the use of a procedure to relieve symptoms. The American College of Surgeons Risk Calculator (ACSRC) was created based on data from the National Surgical Quality Improvement Program to predict the risk of surgical complications on a patient-specific level. Whether the ACSRC can accurately predict the risk of postoperative complications following palliative procedures in cancer patients is unknown. The purpose of this study was to determine if the ACSRC accurately predicted postoperative complication rates in this setting. STUDY DESIGN: A prospectively maintained, surgical oncology database of patient outcomes from 2011 to 2013 was queried. Data extracted included the following: demographics, comorbidities, site and stage of cancer, type of procedure, and post-operative complication rate and type. Risk assessment was performed for each patient using the ACSRC. Predicted outcomes were compared to actual outcomes for length of stay (LOS), complications, and death. Main outcome measures were differences in actual versus predicted outcomes. RESULTS: Thirty-two patients were included. Occurrence of any complication was significantly lower than predicted (31% vs. 59%, p < 0.05). The predicted LOS, however, was 2.9 days; significantly lower than 5.4 days (p < 0.05). CONCLUSION: The ACSRC is a powerful tool for aid in surgical decision-making; however, in the case of palliative procedures for cancer patients, it overestimated the risk of postoperative complications and underestimated the LOS. Overestimation of post-operative complications could result in fewer patients being offered potentially beneficial palliative procedures.

Utilization of palliative care consultation service by surgical services.

BACKGROUND: Palliative medicine was recognized as a unique medical specialty in 2006. Since that time, the number of hospital-based palliative care services has increased dramatically. It is unclear how palliative care consultation services (PCCS) are utilized by surgical services. The purpose of this study was to examine utilization of PCCS by surgical services compared to medical services at the University of New Mexico. METHODS: A database of palliative care consultations performed at University of New Mexico Hospital between 2009 and 2013 was queried to identify consultations requested by surgical vs. medical services. Demographic, clinical, and outcome variables were compared. RESULTS: A total of 521 consultations were analyzed: 441 (85%) consultations from medical and 80 (15%) consultations from surgical services. Surgical patients were older than medical patients and more likely to be in an intensive care unit (ICU) at the time of consultation. There was no difference between referring services in indication for palliative care consultation or time from hospital admission to consultation. Surgical patients were more likely to die in the hospital compared to medical patients. Among patients discharged from the hospital alive, there was no difference between the groups in discharge disposition. More patients in both groups had a change from full code to do-not-resuscitate (DNR) status following palliative care consultation. CONCLUSIONS: Referrals for palliative care consultations are much less common from surgical than medical services. Characteristics of surgical patients suggest that palliative care consultations are reserved for older patients, critically ill patients, and those more likely to be at end-of-life. Our findings suggest the possible need for increased palliative care consultations among less critically ill patients and/or those with an improved prospect of recovery.

Challenges in deactivating a total artificial heart for a patient with capacity.

The use of mechanical circulatory support (MCS) devices has increased sixfold since 2006. Although there is an established legal and ethical consensus that patients have the right to withdraw and withhold life-sustaining interventions when burdens exceed benefits, this consensus arose prior to the widespread use of MCS technology and is not uniformly accepted in these cases. There are unique ethical and clinical considerations regarding MCS deactivation. Our center recently encountered the challenge of an awake and functionally improving patient with a total artificial heart (TAH) who requested its deactivation. We present a narrative description of this case with discussion of the following questions: (1) Is it ethically permissible to deactivate this particular device, the TAH? (2) Are there any particular factors in this case that are ethical contraindications to proceeding with deactivation? (3) What are the specific processes necessary to ensure a compassionate and respectful deactivation? (4) What proactive practices could have been implemented to lessen the intensity of this case's challenges? We close with a list of recommendations for managing similar cases.

Follow-up after curative resection of colorectal cancer.

Of the 13.7 million cancer survivors living in the United States as of January 2012, 1.2 million, or 9 %, were colorectal cancer (CRC) survivors. Determining an optimal surveillance for CRC survivors is necessary because of the significant burden follow-up poses to patients, physicians, and the health care system. Currently, there is no consensus regarding optimal follow-up in CRC patients. Current literature and published guidelines related to CRC follow-up were reviewed to examine the evidence for the surveillance strategies and specific tools demonstrated to improve outcome after curative CRC resection. An intensive surveillance strategy results in increased identification of recurrences amenable to curative resection but does not result in reduced overall or CRC-specific mortality. Patients most likely to benefit from surveillance include younger patients, those with earlier tumors, locoregional recurrences, longer time to recurrence, lower carcinoembryonic antigen (CEA) levels before reoperation, and those with isolated recurrence. Complete resection of recurrence is the only factor consistently associated with improved survival. CEA, colonoscopy, and liver-focused imaging surveillance appear to have the greatest impact on mortality after curative CRC resection. A CRC surveillance strategy is recommended that includes tumor risk stratification, that provides a focus on identifying recurrences amenable to complete resection, and that utilizes those modalities demonstrated to be most effective at improving outcome after CRC resection.

Synchronous resection of colorectal primary and hepatic metastasis.

Up to 50% of the over 140,000 new colorectal cancer patients will present with synchronous colorectal cancer and liver metastasis. Surgical management of patients with resectable synchronous colorectal hepatic metastasis is complex and must consider multiple factors, including the presence of symptoms, location of primary tumor and liver metastases, extent of tumor (both primary and metastatic), patient performance status, and underlying comorbidities. Possible approaches to this select group of patients have included a synchronous resection of the colorectal primary and the hepatic metastases or a staged resection approach. The available literature regarding the safety of synchronous versus staged approaches confirms that a simultaneous resection may be performed in selected patients with acceptable morbidity and mortality. Perioperative mortality when minor hepatectomies are combined with colorectal resection is consistently ≤5%. Perioperative morbidity varies considerably following both synchronous and staged resections. However, the bulk of the existing literature confirms that simultaneous resections are both feasible and safe when hepatic resections are limited to <3 segments. Data regarding the oncologic outcomes following synchronous versus staged resections for Stage IV colorectal cancer are more limited than those available regarding postoperative morbidity and mortality. The available data suggest equivalent overall and disease-free survival regardless of timing of resection. Experience with minimally invasive combined colorectal and hepatic resections is extremely limited to date and consists exclusively of small single center series. The potential benefits of a minimally invasive approach will await the results of larger studies.

Impact of hepatic malignancy on CYP3A4 gene expression.

BACKGROUND: The aim of this study was to examine differences in a major enzyme system for hepatic metabolism of drugs, CYP3A4, by measuring RNA levels in the liver tissue of subjects with and without hepatic malignancy and with primary versus metastatic liver tumors. MATERIALS AND METHODS: We identified liver specimens from a hospital-wide tissue repository of patients having liver resection for a clinical indication. Total RNA isolation, complementary DNA synthesis, and real-time quantitative polymerase chain reaction were performed according to the standards. Demographic, clinical, and laboratory data were obtained from medical records. Standard statistical analyses were performed with significance set to α=0.05. RESULTS: Liver tissue from 27 subjects was available for analysis: 13 were without malignancy and 14 had either primary liver malignancies (n=7) or metastatic disease (n=7). Median age was 57 y, and half of the subjects were men. More than 80% of subjects were overweight or obese without differentiation between benign or malignant tumors. Fewer than 20% of subjects had diabetes or hypercholesterolemia. No preresection laboratory differences were noted between the groups (benign versus malignant or primary versus metastatic disease). Subjects with malignant liver tumors had significantly lower relative-fold CYP3A4 RNA content than those with benign liver tumors (P=0.009), but no difference in the CYP3A4 RNA content between primary and metastatic disease was seen. CONCLUSIONS: This study demonstrates differences in the expression of CYP3A4 in benign and malignant human liver tumors and contributes to understanding the possible impact of malignancy on hepatic metabolism.

Portal application of human unrestricted somatic stem cells to support hepatic regeneration after portal embolization and tumor surgery.

Insufficient liver remnant volume still precludes patients with potentially resectable tumors from curative surgery. Clinically, it has been demonstrated that transplanted adult stem cells promote liver regeneration. However, the mechanisms of the observed functional improvements are unknown. The aim of our study was to evaluate the impact of transplanted human multipotent cord blood-derived unrestricted somatic stem cells (USSC) on liver regeneration and identify the underlying mechanisms in an ovine model. We performed partial embolization of the right liver lobe and grafted USSC in the portal venous system of the left liver lobe. After 4 weeks, livers were explanted and analyzed for differentiation of USSC into hepatocytes by histopathologic examination and for fusion of USSC with recipient hepatocytes by single-cell polymerase chain reaction. The studies revealed that transplanted USSC differentiate into hepatocytes and produce human albumin. No ovine DNA was found in the hepatocytes with a human phenotype. Transplantation of USSC enhances the number of viable hepatocytes in liver disease by differentiation and opens new therapeutic perspectives.

Surgical intern survival skills curriculum as an intern: does it help?

BACKGROUND: The transition from medical student to surgical intern is fraught with anxiety. We implemented a surgical intern survival skills curriculum to alleviate this through a series of lectures and interactive sessions. The purpose of this pilot study was to evaluate its effectiveness. METHODS: This was a prospective observational pilot study of our surgical intern survival skills curriculum, the components of which included professionalism, medical documentation, pharmacy highlights, radiographic interpretations, nutrition, and mock clinical pages. The participants completed pre-course and post-course surveys to assess their confidence levels in the elements addressed using a 5-point Likert scale (1 = unsatisfactory, 5 = excellent). A P value of less than .05 was considered significant. RESULTS: In 2009, 8 interns participated in the surgical intern survival skills curriculum. Fifty percent were female and their mean age was 27.5 ± 1.5 years. Of 33 elements assessed, interns rated themselves as more confident in 27 upon completion of the course. CONCLUSIONS: The implementation of a surgical intern survival skills curriculum significantly improved the confidence levels of general surgery interns and seemed to ease the transition from medical student to surgical intern.

Availability of acute care surgeons improves outcomes in patients requiring emergent colon surgery.

BACKGROUND: The need for emergent colon surgery is a common cause of severe sepsis/septic shock and mortality among surgical patients. We wanted to benchmark our outcomes against those of the National Surgical Quality Improvement Program (NSQIP). We hypothesized that having acute care surgeons to provide comprehensive perioperative care and rapid source control surgery would improve outcome. METHODS: We queried the 2005 to 2007 NSQIP dataset and our prospective database for patients with severe sepsis/septic shock requiring emergency colon surgery. Demographics, Acute Physiology and Chronic Health Evaluation II score, sepsis source, and hospital mortality data were obtained for all patients. RESULTS: Both cohorts were similar with regard to age and sex. The overall mortality rate for patients in our dataset was 28.3% compared with 40.1% in the NSQIP dataset (P = .06). The average Acute Physiology and Chronic Health Evaluation II score for our patients was 31 ± 8.2 with a predicted mortality rate of 73% (P < .0001 when compared with actual mortality rate of 28.3%). CONCLUSIONS: Patients with severe sepsis/septic shock requiring emergent colon surgery have a high mortality rate. Delivery of comprehensive emergency surgical care by acute care surgeons appears to improve survival.

How accurate is the Accreditation Council for Graduate Medical Education (ACGME) Resident survey? Comparison between ACGME and in-house GME survey.

PURPOSE: Increasing importance is being assigned to the annual Accreditation Council for Graduate Medical Education (ACGME) Resident/Fellow survey. In certain circumstances, the survey has prompted site visits for programs with significant areas of noncompliance. However, the dichotomous "yes/no" responses available for most questions on the ACGME survey limit the range of resident responses. Our Graduate Medical Education (GME) department administers an annual survey similar in content to the ACGME survey but with answers using a 5-point Likert scale. The purpose of the current study was to compare the responses obtained on the ACGME survey with our in-house GME survey. METHODS: Responses to the 2009 ACGME and GME surveys were compared among 26 general surgery residents from a single institution. Fifteen questions assessed similar information on both surveys; these questions related to faculty support, rotation/program evaluation, work and educational environment, and duty-hour compliance. RESULTS: Of the 15 questions compared on the 2 surveys, significant differences were found in the following areas: faculty time spent teaching, interference of other trainees, and rotation emphasis of education over other concerns. In each instance, resident responses on the ACGME survey were less favorable compared with the responses elicited on the GME survey. CONCLUSIONS: The results of the current study suggest that responses obtained on the ACGME survey may inaccurately reflect the magnitude of noncompliance found in certain areas. We propose that this discrepancy may be a result of the limited range of responses available on the ACGME survey.