Defining enhanced recovery after resection of peri-hilar cholangiocarcinoma.

INTRODUCTION: Enhanced recovery after surgery (ERAS) for peri-hilar cholangiocarcinoma (pCCA) has not been described in the literature. This study examined patients undergoing pCCA resection within a standard post hepatectomy ERAS pathway to define achievable targets suitable for these patients. METHODS: Patients undergoing pCCA resection at University Hospital Aintree (January 2009-October 2017) were identified. Achievement of key ERAS outcomes was assessed. Patients were stratified on incidence of major complications and pre-operative cardiopulmonary exercise testing. Chi Square and Mann Whitney analyses were undertaken as appropriate. Achievable ERAS targets were derived from patients who did not develop a major complication. RESULTS: 46 patients underwent resection with enhanced recovery. Median age 65 (24 male: 22 female). Key ERAS outcomes in patients who did not experience major complications are described as medians (interquartile range): length of stay 8 days (6-13), duration critical care 2 days (2-4), inotropes 6 h (0-24), epidural 3 days (3-4), early mobilization day 1 (1-2), full mobilization day 3 (3-4), urinary catheter removal day 4 (3-5), NGT removal day 1 (1-2) and restoration oral nutrition day 2 (2-4). Patients deemed high risk pre-operatively or those who developed major complications post-operatively required significantly longer critical care (p = 0.008 and p = 0.002 respectively). Other ERAS targets remained achievable in similar timeframes. CONCLUSIONS: ERAS for pCCA is achievable. Applicable ERAS standards are defined which take into account minor complications. High risk patients and those with major complications can be appropriately managed in an ERAS pathway, though there is increased need for critical care support.

Adherence to early mobilisation: Key for successful enhanced recovery after liver resection.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) has been proven effective in liver surgery. Adherence to the ERAS pathway is variable. This study seeks to evaluate adherence to key components of an ERAS protocol in liver resection, and identify the components associated with successful clinical outcomes. METHOD: All patients undergoing liver resections for two consecutive years were included in our ERAS pathway. Six key components of ERAS included preoperative assessment, nutrition and gastrointestinal function, postoperative analgesia, mobilisation and discharges. Successful accomplishment of ERAS was defined as hospital discharge by postop day (POD) 6. Adherences of these elements were compared between the successful and un-successful groups. RESULTS: During the studied period, 223 patients underwent liver resections, among which 103 had major hepatectomies. N = 147 patients (66%) were discharged within our ERAS protocol target (6 days). On multivariable analysis, sitting out of bed by POD 1 (p < 0.03), walking by POD 3 (p = 0.03), removal of urinary catheter by POD 3 (p < 0.01), and avoiding major complications (p < 0.01) were factors associated with successful completion to our ERAS protocol; whereas advanced age (p = 0.34) and discontinuation of PCA/epidural by POD 3 (p = 0.50) were not significant parameters. There was a significant difference in the length of stay (p < 0.01) following major and minor liver resection, of which the indications for surgery also varied significantly. There was no difference in hospital re-admission rate, and morbidity and mortality between major and minor liver resection. CONCLUSIONS: Facilitating early mobilisation and reducing postoperative complications are keys to successful outcomes of ERAS in liver resection.

Randomized clinical trial of prehabilitation before planned liver resection.

BACKGROUND: Patients with low fitness as assessed by cardiopulmonary exercise testing (CPET) have higher mortality and morbidity after surgery. Preoperative exercise intervention, or prehabilitation, has been suggested as a method to improve CPET values and outcomes. This trial sought to assess the capacity of a 4-week supervised exercise programme to improve fitness before liver resection for colorectal liver metastasis. METHODS: This was a randomized clinical trial assessing the effect of a 4-week (12 sessions) high-intensity cycle, interval training programme in patients undergoing elective liver resection for colorectal liver metastases. The primary endpoint was oxygen uptake at the anaerobic threshold. Secondary endpoints included other CPET values and preoperative quality of life (QoL) assessed using the SF-36®. RESULTS: Thirty-eight patients were randomized (20 to prehabilitation, 18 to standard care), and 35 (25 men and 10 women) completed both preoperative assessments and were analysed. The median age was 62 (i.q.r. 54-69) years, and there were no differences in baseline characteristics between the two groups. Prehabilitation led to improvements in preoperative oxygen uptake at anaerobic threshold (+1·5 (95 per cent c.i. 0·2 to 2·9) ml per kg per min) and peak exercise (+2·0 (0·0 to 4·0) ml per kg per min). The oxygen pulse (oxygen uptake per heart beat) at the anaerobic threshold improved (+0·9 (0·0 to 1·8) ml/beat), and a higher peak work rate (+13 (4 to 22) W) was achieved. This was associated with improved preoperative QoL, with the overall SF-36® score increasing by 11 (95 per cent c.i. 1 to 21) (P = 0·028) and the overall SF-36® mental health score by 11 (1 to 22) (P = 0·037). CONCLUSION: A 4-week prehabilitation programme can deliver improvements in CPET scores and QoL before liver resection. This may impact on perioperative outcome. REGISTRATION NUMBER: NCT01523353 (https://clinicaltrials.gov).

Blood cultures in acute surgical admissions.

INTRODUCTION: Obtaining blood cultures prior to the administration of antimicrobial therapy was a key recommendation of the 2012 UK Surviving Sepsis Campaign. Few studies have examined the effect blood cultures have on clinical management and there have been none on acute surgical admissions. This retrospective study sought to evaluate the effect of blood cultures on clinical management in acute surgical admissions. METHODS: Data on acute surgical patients admitted between 1 January and 31 December 2012 were extracted from hospital records. Patients given intravenous antibiotics within 24 hours of admission were identified. Data collected included antibiotics administered, blood culture results, admission observations and white blood cell count. Case notes were reviewed for patients with positive cultures to establish whether the result led to a change in management. RESULTS: Of 5,887 acute surgical admissions, 1,346 received intravenous antibiotics within 24 hours and 978 sets of blood cultures were taken in 690 patients. The recommended two sets of cultures were obtained in 246 patients (18%). Patients who had blood cultures taken had the same in-hospital mortality as those who had none taken (3.6% vs 3.5%, p=0.97). Blood cultures were positive in 80 cases (11.6%). The presence of systemic inflammatory response syndrome did not increase positivity rates (12.9% vs 10.3%, p=0.28). Overall, cultures altered management in two patients (0.3%). CONCLUSIONS: Blood cultures rarely affect clinical management. In order to assess the additional value that blood cultures bring to sepsis management in acute surgical admissions, a prospective randomised trial focusing on outcome is needed.

A systematic review of the role of hepatectomy in the management of metastatic renal cell carcinoma.

AIM: This review sought to systematically appraise the literature to establish the role of hepatectomy in treating renal cell carcinoma hepatic metastases. METHOD: Medline and EMBASE were systematically searched for papers reporting survival of patients who underwent hepatectomy for metastatic renal cell carcinoma. RESULTS: Six studies containing 140 patients were included. There were no randomised controlled trials. Perioperative mortality was 4.3%, with reported morbidity between 13 and 30%. Patients with metachronous presentation, and a greater time interval between resection of primary tumour and development of metachronous metastases, appeared to have better survival. There was no difference in survival between patients with solitary and multiple metastases. CONCLUSION: Few patients with hepatic metastases from renal cell carcinoma are suitable for hepatectomy as metastatic disease is usually widespread. Selected patients may experience a survival benefit, but identifying these patients remains difficult.

Controversies in the oncosurgical management of liver limited stage IV colorectal cancer.

Colorectal cancer is the fourth most common cancer diagnosis in the world (around 1.2 million diagnoses each year), and accounts for the second highest number of deaths. Over half of patients with colorectal cancer will develop liver metastases, with one quarter presenting in stage IV. There is growing evidence that patients with liver-limited disease represent a distinct biological cohort who will benefit from aggressive management. Only a minority of patients are technically resectable, but around 40% of patients with resected liver limited disease are alive 5 years after diagnosis compared with less than 1% for those with disseminated disease. Novel surgical techniques have been developed to allow more patients to undergo resection and there is also growing recognition that the chemotherapeutic manipulation of irresectable disease may bring some patients to resection with good long-term outcome. Perioperative chemotherapy can also improve long-term outcome through improved biological selection and destruction of occult micrometastases. This review outlines current oncosurgical treatment strategies for liver-limited stage IV colorectal cancer, and discusses some of the controversies surround the management of these complex patients.

Radiological assessment of response to neoadjuvant transcatheter hepatic therapy with irinotecan-eluting beads (DEBIRI(®)) for colorectal liver metastases does not predict tumour destruction or long-term outcome.

INTRODUCTION: Transcatheter hepatic therapy with irinotecan-eluting beads (DEBIRI(®)) allows targeted delivery of irinotecan direct to liver tissue and colorectal liver metastases (CRLM). Accurate assessment of tumour response to therapy is vital to guide optimal treatment. Preliminary work has suggested existing criteria for radiological response may not reflect pathological response after neoadjuvant DEBIRI. This study assessed the relationship between existing and novel radiological response criteria and pathological tumour response as well as long-term outcome. METHODS: Patients with easily resectable CRLM were treated with DEBIRI 4 weeks prior to resection and pathological tumour response graded using a validated system. Radiological response was assessed using RECIST and novel morphological response criteria. RESULTS: Twenty-two patients with 37 lesions were treated with DEBIRI. Median residual tumour was 20% (range 0-80), median necrosis 45% (10-100) and median fibrosis 10% (10-70). Twenty patients (91%) demonstrated stable disease by RECIST, with 11 (50%) demonstrating partial morphological response. Neither radiological response criteria correlated with pathological response. Overall median disease free survival (DFS) was 13.6 months (95% CI 4.7-22.5). Radiological response was not associated with DFS. CONCLUSION: Existing criteria reporting short-term radiological response to DEBIRI do not accurately predict pathological tumour response or long-term outcome. Further work is necessary to define the optimum timing and method of assessing response to DEBIRI.

Routine staging laparoscopy has no place in the management of colorectal liver metastases.

AIMS: Staging laparoscopy has been recommended in the management of patients with colorectal liver metastases prior to hepatectomy in order to reduce the incidence and associated morbidity of futile laparotomies. The utility of staging laparoscopy has not been assessed in patients undergoing CT, PET-CT and MRI as standard preoperative staging. METHODS: All patients undergoing attempted open hepatectomy for colorectal liver metastases between 1/4/2008 and 31/3/2012 were identified from a prospectively maintained research database. All patients who underwent futile laparotomy were identified, with demographics and operative notes subsequently analysed. RESULTS: A total of 274 patients underwent attempted open hepatectomy during the study period. At laparotomy 12 (4.4%) patients were found to have irresectable disease. There were no unifying demographic factors within the patients undergoing futile laparotomy. CONCLUSIONS: With modern imaging, the potential yield of staging laparoscopy is low. Staging laparoscopy should not be used routinely, but may have a role in the case of specific clinical concerns.

Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases.

BACKGROUND: The evidence surrounding optimal follow-up after liver resection for colorectal metastases remains unclear. A significant proportion of recurrences occur in the early postoperative period, and some groups advocate more intensive review at this time. METHODS: A systematic review of literature published between January 2003 and May 2010 was performed. Studies that described potentially curative primary resection of colorectal liver metastases that involved a defined follow-up protocol and long-term survival data were included. For meta-analysis, studies were grouped into intensive (more frequent review in the first 5 years after resection) and uniform (same throughout) follow-up. RESULTS: Thirty-five studies were identified that met the inclusion criteria, involving 7330 patients. Only five specifically addressed follow-up. Patients undergoing intensive early follow-up had a median survival of 39·8 (95 per cent confidence interval 34·3 to 45·3) months with a 5-year overall survival rate of 41·9 (34·4 to 49·4) per cent. Patients undergoing routine follow-up had a median survival of 40·2 (33·4 to 47·0) months, with a 5-year overall survival rate of 38·4 (32·6 to 44·3) months. CONCLUSION: Evidence regarding follow-up after liver resection is poor. Meta-analysis failed to identify a survival advantage for intensive early follow-up.

Oncologists' opinions on genetic testing for breast and ovarian cancer.

PURPOSE: To determine oncologists' practices and beliefs about genetic testing for hereditary breast and ovarian cancer and the extent to which oncologists are utilizing clinical genetics services. METHODS: A survey was mailed to oncologists who treat adult patients in Washington, Oregon, Idaho, or Alaska. RESULTS: Most oncologists (79%) had discussed genetic tests with their patients, and 76% indicated they would like patients considering genetic testing to consult with a genetic counselor. Yet few (19%) indicated their medical practice had the necessary services and staff to offer genetic testing, and only 11% had made referrals to medical genetics or genetic counselors. CONCLUSION: Most respondents support the use of genetic services, but few have made referrals to genetic counselors. Increased communication between oncologists and genetic counselors may enhance collaboration between these two disciplines.

Is the 15-in situ clone protocol necessary to detect amniotic fluid mosaicism?

OBJECTIVE: Our purpose was to evaluate the 15-clone analysis for detecting amniotic fluid mosaicism by the in situ method. STUDY DESIGN: A 10-year review was performed of all amniotic fluid mosaicism cases at two institutions using the in situ method exclusively, with sequential clonal analysis to determine the first and second clone in which the abnormal cell line occurred. RESULTS: Of the 28,497 amniotic fluid samples, 73 met criteria for amniotic fluid mosaicism by in situ method (0.26%). There were 54 cases (0.19%) with potential clinical significance (23 autosome and 31 sex chromosome mosaicism); 49 of the 54 cases (89%) were detected in the first six clones, including 22 of 23 involving autosomes and 27 of 31 involving sex chromosomes. In one of the six cases detected after clone 6 (46,XX/47,XX,+21) the mosaic cell line was present in 20% of the clones analyzed and was followed by a voluntary termination of the pregnancy. In the other five cases amniotic fluid mosaicism was present in < 20% of the clones; these included one case of 46,XX/47,XX+mar (15% amniotic fluid mosaicism, voluntary termination of pregnancy), two cases of 45,X/46,XY (10% to 12% amniotic fluid mosaicism, both normal at birth), and two cases of 45,X/46,XX (8% amniotic fluid mosaicism, lost to follow-up; 12% amniotic fluid mosaicism, voluntary termination of pregnancy). By limiting the analysis to six clones, approximately 20% of analysis time could be saved per case, but one autosomal amniotic fluid mosaicism case per 10,000 samples could potentially be missed. CONCLUSION: Reducing the number of clones analyzed by in situ method could result in increased efficiency, decreased costs, and minimal loss of sensitivity.