Observation versus intervention for incidental common bile duct stones at intraoperative cholangiogram: a systematic review.

BACKGROUND: The natural history of incidental common bile duct stones (CBDS) is poorly understood. Current evidence is conflicting, with several studies suggesting the majority may pass spontaneously. Despite this, guidelines recommend routine removal even if asymptomatic. This study aimed to systematically review the outcomes of expectant management for CBDS detected on operative cholangiography during cholecystectomy. METHODS: MEDLINE, Embase and CINAHL databases were systematically searched. Participants were adult patients with CBDS identified by intraoperative cholangiography. Intervention was regarded as any perioperative effort to remove common bile duct stones, including endoscopic retrograde cholangiopancreatography (ERCP), laparoscopic and open bile duct exploration. This was compared to observation. Outcomes of interest included rates of spontaneous stone passage, success of duct clearance and complications. Risk of bias was assessed using the ROBINS-I tool. RESULTS: Eight studies were included. All studies were non-randomized, heterogeneous and at serious risk of bias. In patients observed after a positive IOC, 20.9% went on to have symptomatic retained stones. In patients directed to ERCP for positive IOC, persistent CBDS were found in 50.6%. Spontaneous passage was not associated with stone size. Meta-analysis is dominated by the results from one large database, which recommends intervention for incidental stones, despite low rates of persistent stones seen at postoperative ERCP. CONCLUSIONS: Further evidence is required before a definitive recommendation on observation can be made. There is some evidence that asymptomatic stones may be safely observed. In clinical scenarios where the risks of biliary intervention are considered high, a conservative strategy could be more widely considered.

Propensity score-matched outcomes analysis of the liver-first approach for synchronous colorectal liver metastases.

BACKGROUND: Liver resection before primary cancer resection is a novel strategy advocated for selected patients with synchronous colorectal liver metastases (sCRLM). This study measured outcomes in patients with sCRLM following a liver-first or classical approach, and used a validated propensity score. METHODS: Clinical, pathological and follow-up data were collected prospectively from consecutive patients undergoing hepatic resection for sCRLM at a single centre (2004-2014). Cumulative disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were calculated by means of Kaplan-Meier analysis. Survival differences were analysed in the whole cohort and in subgroups matched according to Basingstoke Predictive Index (BPI). RESULTS: Of 582 patients, 98 had a liver-first and 467 a classical approach to treatment; 17 patients undergoing simultaneous bowel and liver resection were excluded. The median (i.q.r.) BPI was significantly higher in the liver-first compared with the classical group: 8·5 (5-10) versus 8 (4-9) (P = 0·030). Median follow-up was 34 months. The 5-year DFS rate was lower in the liver-first group than in the classical group (23 versus 45·6 per cent; P = 0·001), but there was no difference in 5-year CSS (51 versus 53·8 per cent; P = 0·379) or OS (44 versus 49·6 per cent; P = 0·305). After matching for preoperative BPI, there was no difference in 5-year DFS (37 versus 41·2 per cent for liver-first versus classical approach; P = 0·083), CSS (51 versus 53·2 per cent; P = 0·616) or OS (47 versus 49·1 per cent; P = 0·846) rates. CONCLUSION: Patients with sCRLM selected for a liver-first approach had more oncologically advanced disease and a poorer prognosis. They had inferior cumulative DFS than those undergoing a classical approach, a difference negated by matching preoperative BPI.

Patient-reported outcomes in long-term survivors of metastatic colorectal cancer needing liver resection.

BACKGROUND: Five-year survival after hepatic resection for colorectal cancer (CRC) liver metastases is good, but data on patient-reported outcomes are lacking. This study describes the long-term impact of liver surgery for CRC metastases on patient-reported outcomes. METHODS: The study used the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the disease-specific module, EORTC QLQ-LMC21. For functional scales, mean scores out of 100 with 95 per cent c.i. were calculated; differences of 10 points or more were considered clinically significant. Responses to symptom scales and items were categorized as 'minimal' or 'severe'. Proportions and 95 per cent c.i. for symptoms were calculated. RESULTS: A total of 241 patients were recruited; nine (3·7 per cent) had unresectable disease and were excluded. Some 68 (42 men) of 80 long-term survivors participated; their mean age was 69·5 years and median follow-up was 8·0 (range 6·9-9·2) years. Values for baseline and 1-year patient-reported outcome data were similar. Scores for functional scales were excellent (emotional function: 92, 95 per cent c.i. 87 to 96; social function: 94, 89 to 99; role function: 94, 90 to 98), reflecting clinically significant improvements from baseline values of 17 (10 to 24), 12 (3 to 21) and 12 (3 to 20) respectively. Severe symptoms were uncommon (affected less than 5 per cent of patients) for most patient-reported outcome scales or items, but persistent severe symptoms were noted for sexual function (2 per cent increase from baseline), peripheral neuropathy (2 per cent increase), constipation (10 per cent increase) and diarrhoea (5 per cent increase). CONCLUSION: Long-term survivors of metastatic colorectal cancer who have undergone liver surgery have excellent global quality of life, high levels of function and few symptoms.

Fatty liver disease as a predictor of local recurrence following resection of colorectal liver metastases.

BACKGROUND: Obesity and tissue adiposity constitute a risk factor for several cancers. Whether tissue adiposity increases the risk of cancer recurrence after curative resection is not clear. The present study analysed the influence of hepatic steatosis on recurrence following resection of colorectal liver metastases. METHODS: A prospective cohort of patients who had primary resection of colorectal liver metastases in two major hepatobiliary units between 1987 and 2010 was studied. Hepatic steatosis was assessed in non-cancerous resected liver tissue. Patients were divided into two groups based on the presence of hepatic steatosis. The association between hepatic steatosis and local recurrence was analysed, adjusting for relevant patient, pathological and surgical factors using Cox regression and propensity score case-match analysis. RESULTS: A total of 2715 patients were included. The cumulative local (liver) disease-free survival rate was significantly better in the group without steatosis (hazard ratio (HR) 1·32, 95 per cent confidence interval 1·16 to 1·51; P < 0·001). On multivariable analysis, hepatic steatosis was an independent risk factor for local liver recurrence (HR 1·28, 1·11 to 1·47; P = 0·005). After one-to-one matching of cases (steatotic, 902) with controls (non-steatotic, 902), local (liver) disease-free survival remained significantly better in the group without steatosis (HR 1·27, 1·09 to 1·48; P = 0·002). Patients with steatosis had a greater risk of developing postoperative liver failure (P = 0·001). CONCLUSION: Hepatic steatosis was an independent predictor of local hepatic recurrence following resection with curative intent of colorectal liver metastases.

Resection of colorectal liver metastases in the elderly: does age matter?

AIM: Despite the incidence of colorectal cancer increasing with age the proportion of patients undergoing surgery for colorectal liver metastases decreases dramatically in the elderly. Is this referral or selection bias justified? METHOD: A prospective database of resection for colorectal liver metastases at a single centre was retrospectively analysed to compare the outcome in patients aged ≥75 years (group E) with those aged <75 years (group Y). Data were analysed using the Kaplan-Meier method with Cox regression modelling. RESULTS: Of 1443 resections, 151 (10.5%) in group E were compared with 1292 (89.5%) in group Y. The two groups were matched apart from higher American Society of Anesthesiology scores (P=0.001) and less use of chemotherapy (P=0.01) in the elderly. Perioperative morbidity and 90-day mortality were higher in the elderly compared with the younger group (32.5%vs 21.2%, P=0.02, and 7.3%vs 1.3%, P=0.001). In the last 5 years, mortality in the elderly improved and was no longer significantly different from that of the younger patients [n=2/76 (2.6%) vs n=9/559 (1.6%); P=0.063]. The 5-year survival was similar in groups E and Y for cancer-specific (41.4%vs 41.6%, P=0.917), overall (37.0%vs 38.2%) and median (44.1 months vs 43.6 months, P=0.697) survival respectively. CONCLUSION: In the elderly liver resection for metastatic disease can be performed with acceptable mortality and morbidity with as good a prospect of survival as for younger patients.

The incidence and outcome of brain metastases after liver resection for colorectal cancer metastases.

AIM: Brain metastases from colorectal cancer are rare, with an incidence of 0.6-4%. The risk and outcome of brain metastases after hepatic and pulmonary metastasectomy have not been previously described. This study aimed to determine the incidence, predictive factors, treatment and survival of patients developing colorectal brain metastases, who had previously undergone resection of hepatic metastases. METHOD: A retrospective review was carried out of a prospectively maintained database of patients undergoing liver resection for colorectal metastases. RESULTS: Fifty-two (4.0%) of 1304 patients were diagnosed with brain metastases. The annual incidence rate was 1.03% per person-year. In the majority of cases brain metastases were found as part of multifocal disease. Median survival was 3.2 months (95% CI: 2.3-4.1), but was best for six patients treated with potentially curative resection [median survival = 13.2 (range, 4.9-32.1) months]. Multivariate analysis showed that a lymph node-positive primary tumour [hazard ratio (HR) = 2.7, 95% CI: 1.8-6.19; P = 0.019], large liver metastases (> 6 cm) [HR = 2.23, 95% CI: 1.19-2.33; P = 0.012] and recurrent intrahepatic and extrahepatic disease [HR = 2.11, 95% CI: 1.2-4.62; P = 0.013] were independent predictors for the development of brain metastases. CONCLUSION: The annual risk of developing brain metastases following liver resection for colorectal metastases is low, but highest for patients presenting with a Dukes' C primary tumour, large liver metastases or who subsequently develop disseminated disease. The overall survival from colorectal brain metastases is poor, but resection with curative intent offers patients their best chance of medium-term survival.

Long-term survival following delayed presentation and resection of colorectal liver metastases.

BACKGROUND: Long-term survival from metastatic colorectal cancer is partly dependent on favourable tumour biology. Large case series have shown improved survival following hepatectomy for colorectal liver metastases (CRLM) in patients diagnosed with metastases more than 12 months after index colorectal surgery (metachronous), compared with those with synchronous metastases. This study investigated whether delayed hepatic resection for CRLM affects long-term survival. METHODS: Consecutive patients undergoing hepatic resection for CRLM in a single centre (1987-2007) were grouped according to the timing of hepatectomy relative to index bowel surgery: less than 12 months (synchronous; group 1), 12-36 months (group 2) and more than 36 months (group 3). Cancer-specific survival was calculated using Kaplan-Meier analysis. RESULTS: There were 577 patients (48·0 per cent) in group 1, 467 (38·9 per cent) in group 2 and 158 (13·1 per cent) in group 3. The overall 5-year cancer-specific survival rate after liver surgery was 42·3 per cent, with no difference between groups. However, when measured from the time of primary colorectal surgery, group 3 showed a survival advantage at both 5 and 10 years (94·1 and 47·6 per cent respectively) compared with groups 1 (46·3 and 24·9 per cent) and 2 (57·1 and 35·0 per cent) (P = 0·003). Survival graphs showed a steeper negative gradient from 5 to 10 years for group 3 compared with groups 1 and 2 (-0·80 versus - 0·34 and - 0·37), indicating an accelerated mortality rate. CONCLUSION: Patients undergoing delayed liver resection for CRLM have a survival advantage that is lost during long-term follow-up.

Accuracy of liver-specific magnetic resonance imaging as a predictor of chemotherapy-associated hepatic cellular injury prior to liver resection.

BACKGROUND/AIMS: To evaluate the diagnostic precision of chemical-shift imaging MRI and ferucarbotran-enhanced MRI for hepatic parenchymal injury prior to hepatic resection for colorectal metastases. METHODS: Preoperative MRI criteria were used to score 37 patients with colorectal liver metastases by two independent radiologists, blinded to outcomes, for signal drop-out on chemical-shift imaging MRI and ferucarbotran uptake and compared to blinded standardized histopathological endpoints of steatosis, steatohepatitis and sinusoidal dilatation. Sensitivity, specificity, predictive values and the area under the receiver operating characteristic curve (AUC) were calculated for the MRI sequences. RESULTS: On histology, severe steatosis, steatohepatitis and sinusoidal dilation were evident in 6 (16.2%), 4 (10.8%) and 9 (24.3%) patients respectively. Chemical-shift imaging MRI had a positive predictive value (PPV) of 100% for severe steatosis, 80% for steatohepatitis and zero for sinusoidal dilatation, with an AUC of 1.0, 0.99 and 0.36 respectively. Ferucarbotran-enhanced MRI had a 100% PPV for the detection of severe sinusoidal dilatation, with an AUC of 0.61. CONCLUSIONS: This study demonstrates that liver-specific MRI can accurately predict the severity of pre-existing hepatic injury. Moreover, it may play a key role in planning the timing and extent of chemotherapy and hepatic resection for colorectal metastases.

Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens.

A large 1.29 x 10(11) antibody fragment library, based upon variable (V) genes isolated from human B-cells from 160 donors has been constructed and its performance measured against a panel of 28 different clinically relevant antigens. Over 5000 different target-specific antibodies were isolated to the 28 antigens with 3340 identified as modulating the biological function (e.g. antagonism, agonism) of the target antigen. This represents an average of approximately 120 different functionally active antibodies per target. Analysis of a sample of >800 antibodies from the unselected library indicates V gene usage is representative of the human immune system with no strong bias towards any particular V(H)-V(L) pairing. Germline diversity is broad with 45/49 functional V(H) germlines and 28/30 V(lambda) and 30/35 V(kappa) light-chain germlines represented in the sample. The number of functional V(H) germlines and V(kappa) light-chain germlines present is increased to 48/49 and 31/35, respectively, when selected V gene usage is included in the analysis. However, following selection on the antigen panel, V(H)1-V(lambda)1 germline family pairings are preferentially enriched and represent a remarkable 25% of the antigen-specific selected repertoire.

Elective intra-aortic balloon counterpulsation during a high risk liver resection.

SUMMARY: We present the case of a 65-year-old male with severe coronary artery disease and a single colorectal liver metastasis. An elective intra-aortic balloon pump (IABP) was inserted following induction of anaesthesia to reduce left ventricular workload during his liver resection. After an uneventful recovery he was discharged on day 5. We review the literature on the elective use of these devices in cardiac surgery in which it is becoming routine practice in high risk patients. However in non-cardiac surgery there have been only 15 published cases all in very high risk patients, with favourable outcomes. To our knowledge this is the first published case of the use of elective IABP during liver surgery.

Safe liver resection following chemotherapy for colorectal metastases is a matter of timing.

Neoadjuvant chemotherapy (NC) can improve the resectability of hepatic colorectal metastases (CRM). However, there is concern regarding its impact on operative risk. We reviewed 750 consecutive liver resections performed for CRM in a single unit (1996-2005) to evaluate whether NC affected morbidity and mortality. Redo hepatic resections or patients receiving adjuvant chemotherapy following primary resection were excluded. A total of 245 resections were performed in patients not requiring NC (control group) (mean age 63, 67% male) and 252 in patients who had NC (mean age 62, 67% male). The mean (s.d.) duration of surgery was less in the control group (241(64) vs 255(64)min, P=0.014) as was the mean blood loss (390(264) vs 449(424)ml, P=0.069). Postoperative mortality (2 vs 2%) and morbidity (27 vs 29%, P=0.34) was similar between groups. More NC patients developed septic (2.4%) or respiratory (10.3%) complications compared to controls (0 and 5.3%, P<0.03), with significantly more surgical complications if the interval between stopping NC and undergoing surgery was

A two-center experience with the exclusive use of laparoscopic transperitoneal nephrectomy for benign renal disease in children.

BACKGROUND: This study aimed to evaluate a two-center experience with pediatric transperitoneal laparoscopic nephrectomy, specifically focusing on the outcome parameters of operative time, complication, analgesic requirement, and postoperative stay. METHODS: This ambispective study was conducted over a 4-year period between May 2001 and May 2005 in two tertiary pediatric surgical centers. Data were prospectively recorded from an in-house expanded medical audit system (EMAS) and a Microsoft Excel database. Information on patient demographics, operative time, complications, analgesic requirement, and length of hospital stay were retrieved and analyzed. RESULTS: A total of 30 consecutive patients with a mean age of 4.43 years (range, 3 months to 15 years) underwent laparoscopic nephrectomy. All the patients underwent unilateral nephrectomy/nephroureterectomy for multidysplastic kidney (n = 12), reflux nephropathy (n = 13), pelvicoureteric junction obstruction (n = 4), or cystic disease of indeterminate cause (n = 1). The mean operative time was 93 +/- 30 min. The principal hemostatic devices used were the Harmonic Scalpel (20 cases), liga clips (5 cases), and hook diathermy and endoshears exclusively (4 cases). There were no conversions, but the intraoperative complications of bleeding (n = 2), difficult location (n = 1), difficult extraction (n = 1), and requirement for a liver retractor (n = 2) were encountered. An additional five patients had problems in the immediate postoperative period, two of whom went on to have long term difficulties with recurrent urinary tract infections resulting from a residual ureteric stump, which required surgery. Nearly one-third of the patients required morphine for analgesia in the immediate postoperative period, with the figure falling to 20% by day 1. The median postoperative hospital stay was 1 day (range, 0-16 days). At this writing, all the patients remain under surveillance with a mean follow-up period of 2.88 years, and no patients have experienced complications secondary to intraabdominal adhesions. CONCLUSION: Transperitoneal laparoscopic nephrectomy is technically feasible in most cases of benign renal disease. The intraoperative complications are minimal, and recovery for most is robust. Two-thirds of the patients are discharged within 24 h. In this study, narcotic analgesics were prescribed in about a one-third of all the cases for a limited period. Further problems may be seen when refluxing ureters are incompletely excised. However, the transperitoneal approach does not mitigate against complete excision because the exposure to the pelvis is adequate. At the midterm follow-up assessment, adhesive obstruction was not encountered, confirming this approach as a tenable alternative to other laparoscopic approaches for nephrectomy.

Repeat hepatic resection for recurrent colorectal liver metastases is associated with favourable long-term survival.

BACKGROUND: The management of patients with recurrent colorectal liver metastases (RCLM) remains controversial. This study aimed to determine whether repeat liver resection for RCLM could be performed with acceptable morbidity, mortality and long-term survival. METHODS: Of 1121 consecutive liver resections performed and prospectively analysed between 1987 and 2005, 852 'curative' resections were performed on patients with colorectal liver metastases. Single liver resection was performed in 718 patients, and 71 repeat hepatic resections for RCLM were performed in 66 patients. RESULTS: There were no postoperative deaths following repeat hepatic resection compared with a postoperative mortality rate of 1.4 per cent after single hepatic resection. Postoperative morbidity was comparable following single and repeat hepatectomy (26.1 versus 18 per cent; P = 0.172), although median blood loss was greater during repeat resection (450 versus 350 ml; P = 0.006). Actuarial 1-, 3- and 5-year survival rates were 94, 68 and 44 per cent after repeat hepatic resection for RCLM, compared with 89.3, 51.7 and 29.5 per cent respectively following single hepatectomy. CONCLUSION: The beneficial outcomes observed after repeat liver resection in selected patients with RCLM confirm the experience of others and support its status as the preferred choice of treatment for such patients.

Refining the role of laparoscopy and laparoscopic ultrasound in the staging of presumed pancreatic head and ampullary tumours.

Laparoscopy and laparoscopic ultrasound have been validated previously as staging tools for pancreatic cancer. The aim of this study was to identify if assessment of vascular involvement with abdominal computed tomography (CT) would allow refinement of the selection criteria for laparoscopy and laparoscopic ultrasound (LUS). The details of patients staged with LUS and abdominal CT were obtained from the unit's pancreatic cancer database. A CT grade (O, A-F) of vascular involvement was recorded by a single radiologist. Of 152 patients, who underwent a LUS, 56 (37%) had unresectable disease. Three of 26 (12%) patients with CT grade O, 27 of 88 (31%) patients with CT grade A to D, 17 of 29 (59%) patients with CT grade E and all nine patients with CT grade F were found to have unresectable disease. In all, 24% of patients with tumours <3 cm were found to have unresectable disease. In those patients with tumours considered unresectable, local vascular involvement was found in 56% of patients and vascular involvement with metastatic disease in 17%, while 20% of patients had liver metastases alone and 5% had isolated peritoneal metastases. The remaining patient was deemed unfit for resection. Selective use of laparoscopic ultrasound is indicated in the staging of periampullary tumours with CT grades A to D.

Avulsion of the gallbladder following trivial injury.

Traumatic cholecystectomy is a rare condition that has always been described in the context of major trauma and associated liver or biliary injuries. We present a case of isolated traumatic cholecystectomy following a trivial injury which resulted in both a delayed presentation and a difficult diagnosis.

Pre-operative short-course radiotherapy is associated with faecal incontinence after anterior resection.

OBJECTIVE: To determine the contribution of total mesorectal excision (TME), short-course pre-operative radiotherapy (SCRT), the level of the anastomosis and other putative contributory factors to the incidence and degree of faecal incontinence after anterior resection of the rectum. PATIENTS AND METHODS: Survivors of anterior resection of the rectum performed between February 1996 and February 2001, with a functioning anastomosis, were asked to complete a telephone questionnaire regarding their current bowel habit. Faecal incontinence was scored using the St. Mark's Incontinence Score. RESULTS: The median age of 124 patients who completed the questionnaire was 76 years. Of these, 104 patients had neoplastic disease, 66 (53%) patients exhibited some degree of incontinence, median St. Marks' Score 6, interquartile range 3-10. There was a significant association between the anastomotic level, and the St. Mark's Score (P < 0.0001, linear regression). Male sex (P = 0.047), SCRT (P = 0.0014) and an anastomotic leak (P = 0.038) were associated with significantly higher incontinence scores. Age, splenic flexure mobilization, TME, anastomotic configuration or use of a temporary stoma had no detectable independent effect on incontinence scores. CONCLUSIONS: Poor functional outcome following anterior resection was associated with a low anastomosis, SCRT or an anastomotic leak. The finding that SCRT was a predictor of postoperative incontinence emphasizes the need for stringent patient selection for this treatment modality.