Outcomes of multicystic peritoneal mesothelioma treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Multicystic peritoneal mesothelioma (MCPM) is a rare neoplasm, generally considered a borderline malignancy, best treated by cytoreductive surgery (CRS) to remove macroscopic disease, combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Owing to its rarity, little has been published on clinical presentation, clinical behaviour over time, or an optimal treatment approach. METHODS: A prospectively developed peritoneal malignancy database was interrogated for the years 2001-2018. Details on all patients with MCPM as a definitive diagnosis after CRS and HIPEC were analysed, including previous interventions, mode of presentation, surgical treatment, postoperative outcomes, and late follow-up information from abdominal CT and tumour markers. RESULTS: Some 40 patients with MCPM underwent CRS and HIPEC between 2001 and 2018. Of these, 32 presented with abdominal pain, distension or bloating, six patients presented with recurrence following previous surgery at the referring hospitals, and two had coincidental diagnoses during a surgical procedure. CRS involved peritonectomy in all 40 patients. Bowel resection was required in 18 patients, and seven had a temporary stoma. Thirty-eight patients were considered to have undergone a complete macroscopic tumour removal (completeness of cytoreduction CC0), and two had residual tumour nodules less than 2.5 mm in size, classified as CC1. Median duration of follow-up was 65 (range 48-79) months. There were no deaths during follow-up. The Kaplan-Meier-predicted recurrence-free interval was 115.4 months. CONCLUSION: MCPM is a rare peritoneal neoplasm with a heterogeneous pattern of presentation. CRS and HIPEC is an effective management option for this group of patients, with favourable long-term survival.

Not all abdominal masses after colorectal cancer surgery are malignant: intra-abdominal fibromatosis masquerading as recurrence.

AIM: Intra-abdominal fibromatosis is an unusual mesenchymal tumour that can be locally aggressive without any metastatic potential. Fibromatosis may simulate cancer recurrence on imaging surveillance for colorectal cancer follow-up. The optimal treatment of recurrent peritoneal malignancy is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Confirmatory biopsy of lesions suspicious for colorectal cancer recurrence may not be feasible, thereby rendering surgery the safest option. Our aim was to determine the incidence of fibromatosis in a cohort of patients undergoing CRS and HIPEC for suspected colorectal cancer recurrence. METHODS: One hundred and seventy-one CRS and HIPEC cases were performed at our Peritoneal Malignancy Institute between February 2007 and October 2018 for colorectal peritoneal metastases and were included in a prospectively maintained database. RESULTS: A total of 49 (29%) of 171 cases were performed for primary colorectal cancer with peritoneal metastases, whereas 122 (71%) of 171 cases were performed for suspected colorectal cancer recurrence detected on surveillance imaging after primary colorectal cancer resection. On histological analysis of the resected specimen, five (4.1%) of 122 cases undergoing CRS and HIPEC for colorectal recurrence had fibromatosis. CONCLUSION: Fibromatosis can masquerade as colorectal cancer recurrence. In this series it occurred with an incidence of 4.1% among a cohort of patients undergoing CRS and HIPEC for probable recurrence. Surgical resection may be the only option to confirm the diagnosis and rule out malignancy.

The clinical significance of a pathologically positive lymph node at the circumferential resection margin in rectal cancer.

BACKGROUND: This study aimed to determine if the nature of circumferential resection margin (CRM) involvement, either by tumour or lymph nodes, had an impact upon local recurrence and survival in rectal cancer. METHODS: A retrospective analysis of a prospectively collected database was performed. Consecutive patients with stage I-III rectal cancer having curative surgery were included. All specimens were analysed by a single histopathologist. Statistical analysis was performed using chi-squared test and Kaplan-Meier. RESULTS: Of 265 patients, 29 (11%) had a positive CRM. Compared to patients with a negative CRM, a positive margin due to tumour was associated with a higher 5-year cumulative incidence of local recurrence (43.7% versus 8.8%, p = 0.001) and distant metastases (62% versus 13.6%, p = 0.001) with poorer 5-year cancer-specific survival (32% versus 87.8%, p = 0.001). Although patients with margin positivity due to lymph nodes had a higher rate of distant metastases (41.3% versus 13.6%, p = 0.004) and poorer 5-year cancer-specific survival (59.3% versus 87.8%, p = 0.038), the rate of local recurrence was comparable to that of patients with negative margins (8.3% versus 8.8%, p = 0.694). CONCLUSIONS: Our findings suggest that the nature of CRM involvement may be important in determining prognosis in rectal cancer. Local recurrence is higher only when there is tumour present at the margin. Lymph node involvement of the margin confers similar risk of local recurrence to patients with CRM-negative, node-positive disease. These results need further evaluation in multicentre, prospective studies.

Single centre guidelines for radiological follow-up based on 775 patients treated by cytoreductive surgery and HIPEC for appendiceal pseudomyxoma peritonei.

AIM: Pseudomyxoma peritonei (PMP) is an uncommon malignancy, generally originating from a ruptured epithelial tumour of the appendix. Despite successful cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), some patients recur. Currently there are no guidelines on the methods, frequency and intensity of follow-up. METHODS: Between 1994 and 2016, 1070 patients underwent surgery for a perforated epithelial tumour of the appendix, predominantly with PMP. Overall (OS) and Disease Free Survival (DFS) were documented by annual CT scanning and evaluated according to the Kaplan-Meier method. The influence of histological differentiation was investigated. RESULTS: Overall, 775/1070 (72%) had complete cytoreductive surgery (CCRS) and HIPEC. Histological classification was low grade PMP in 615 (79.4%), high grade PMP in 134 (17.3%) and adenocarcinoma in 26 (3.4%). DFS and OS were significantly worse for high grade disease, with the steepest decline for both in the first three years. DFS curves, for low as well as high grade PMP, levelled off at year 6 at approximately 60% and 20% respectively. Thereafter there were few recurrences in either group. CONCLUSION: Annual CT of the abdomen and pelvis in the first six years appears to be adequate follow-up for low grade PMP. In high grade PMP, additional imaging of the chest and more frequent surveillance, during the first three years postoperatively, may detect recurrent disease earlier. From year 6 on, reduced frequency of follow-up is proposed, independent of the histology. This long-term follow-up in a large number of patients gives insight into tumour behavior after CCRS and HIPEC for PMP and guides intensity of surveillance.

Impact of ovarian metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancy originating from appendiceal and colorectal cancer.

AIM: Ovarian metastases from gastrointestinal tract malignancies have been considered an ominous finding with poor prognosis. The aim of this project was to determine the impact on survival, and potential cure, when cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are combined to treat peritoneal malignancy in women with Krukenberg tumours. METHOD: A retrospective analysis of prospectively collected data between January 2010 and July 2015. Female patients undergoing complete CRS (macroscopic tumour removal) and HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin, or colorectal peritoneal metastases (CPM) were included. Survival was estimated using the Kaplan-Meier method and survival rates compared using the log-rank test. RESULTS: In total, 889 patients underwent surgery for peritoneal malignancy, of whom 551 were female. Of these, 504/551 (91%) underwent complete CRS and HIPEC. Overall, 405/504 (80%) had at least one involved ovary removed either during CRS and HIPEC or at their index prereferral operation. Three hundred and fifty-two patients (87%) had an appendiceal tumour and 53 (13%) had CPM. At a median follow up of 40 months, overall survival (OS) did not differ significantly between patients with or without ovarian involvement in women with a primary low-grade appendiceal tumour or CPM. In women with high-grade primary appendiceal pathology, OS was significantly lower in patients with ovarian metastases compared with those without ovarian involvement. CONCLUSION: Women with ovarian metastases from low-grade appendiceal tumours or colorectal cancer treated with CRS and HIPEC have similar survival rates to patients without ovarian metastases. Long-term survival and cure is feasible in patients amenable to complete tumour removal.

The modified Glasgow prognosis score predicts for overall and disease-free survival following cytoreductive surgery and HIPEC in patients with pseudomyxoma peritonei of appendiceal origin.

BACKGROUND: The modified Glasgow prognostic score (incorporating C-reactive protein and albumin) predicts survival in patients with gastro-intestinal tract cancer but has not been evaluated in patients with peritoneal malignancy. The aim was to evaluate the modified Glasgow score preoperatively in patients undergoing complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) of appendiceal origin. METHODS: Prospectively collected data from patients with PMP of appendiceal origin following CCRS and HIPEC between January 2007 and December 2011 were analysed. The mGPS was calculated from preoperative C-reactive protein and albumin. Predicted overall survival (OS) and disease-free survival (DFS) for each mGPS score were calculated using the Kaplan-Meier model. In a separate analysis, a comparison was made between mGPS and Tumour Markers (TM). RESULTS: 260 patients were included in the study. The mGPS of 0, 1, and 2 were found in 111, 130, and 19 patients respectively. The median follow-up was 48 months. For mGPS-0, -1, and -2, the predicted OS was 82.2, 73.7, and 69.2 months and the DFS was 73.5, 62.9, and 54.4 months respectively. As mGPS increases, there is a reduction in long-term survival. There was no difference between mGPS and TM. CONCLUSION: Preoperative mGPS may be a cost effective prognostic tool for predicting OS and DFS in patients following complete CRS-HIPEC, and performs well compared to TM for predicting patients at high risk of recurrence.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1000 patients with perforated appendiceal epithelial tumours.

PURPOSE: To report early and long term outcomes following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in 1000 patients with perforated appendiceal epithelial tumours, predominantly with pseudomyxoma peritonei (PMP). METHODS: Retrospective analysis of a prospective database of 1000 consecutive patients undergoing CRS and HIPEC for perforated appendiceal tumours between 1994 and 2014 in a UK National Peritoneal Malignancy unit. RESULTS: Overall 1000/1444 (69.2%) patients treated for peritoneal malignancy had appendiceal primary tumours. Of these 738/1000 (73.8%) underwent complete cytoreductive surgery (CCRS), 242 (24.2%) had maximal tumour debulking (MTD) and 20 (2%) had laparotomy and biopsies only. Treatment related 30-day mortality was 0.8% in CCRS and 1.7% in MTD group with major postoperative morbidity rates of 15.2% (CCRS) and 14.5% (MTD). Five- and 10-year overall survival was 87.4% and 70.3% in the 738 patients who had CCRS compared with 39.2% and 8.1% respectively in the MTD group. On multivariate analysis, significant predictors of reduced overall survival were male gender (p = 0.022), elevated CEA (p = 0.001), elevated CA125 (p = 0.001) and high tumour grade or adenocarcinoma (p = 0.001). CONCLUSIONS: Perforated epithelial appendiceal tumours are rare, though may be increasing in incidence and can present unexpectedly at elective or emergency abdominal surgery, often with PMP. CRS and HIPEC results in good long term outcomes in most patients.

A protocol for management of blood loss in surgical treatment of peritoneal malignancy by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND AIMS: The treatment of peritoneal malignancies with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be associated with massive surgical blood loss. Maintaining high fibrinogen levels throughout surgery may reduce blood loss in these patients. The primary aim of the study was to see if Tranexamic Acid (TXA) and cryoprecipitate reduced surgical blood loss and hence red cell transfusions. A comparison was made with a cohort of patients treated with fresh frozen plasma (FFP) alone. The secondary aim was to measure the effect of both protocols on coagulation parameters and the incidence of arterial or venous thrombosis. METHOD: We used prospectively collected data from 201 patients who had complete CRS with HIPEC for peritoneal malignancy using different protocols during two discrete 12-month time periods. RESULTS: The new transfusion protocol led to a higher average fibrinogen level intra-operatively and post-operatively, with a significant reduction in average RBC, FFP and platelet transfusion intra-operatively per patient from 4·2 to 1·8 units, 6·2 to 0·2 units and 0·1 to 0 units, respectively. No significant difference in PT or APTT was seen between patients treated with the standard and new protocols. Venous thrombosis occurred in seven patients treated with the standard protocol and five with the new protocol. A single case of arterial thrombosis was seen in both groups. CONCLUSION: Patients treated with upfront TXA and cryoprecipitate during CRS required less RBC transfusion than those treated with the standard protocol of early FFP.

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.

The results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1200 patients with peritoneal malignancy.

AIM: The study determined the outcome of 1200 consecutive patients treated for peritoneal malignancy in one surgical unit over a 20-year period. METHOD: A retrospective analysis was conducted of a custom designed prospective database of patients undergoing surgery for peritoneal malignancy since 1994. Patient demographics, tumour type, extent of surgery and outcome were recorded. RESULTS: Between 1994 and January 2014 (when the 1200th case had undergone surgery) 2956 patients were referred with a diagnosis of peritoneal malignancy. Pseudomyxoma peritonei of appendiceal origin was the pathology in 956/1200 (79.7%) patients. Other aetiologies included colorectal peritoneal metastases [89/1200 (7.4%)], abdominal mesothelioma [65/1200 (5.4%)] and miscellaneous [90/1200 (7.5%)]. Overall 863/1200 (71.9%) had complete cytoreduction, 294 (24.5%) had maximal tumour debulking and 43 (3.6%) had laparotomy only. The proportion undergoing complete cytoreduction per quartile of 300 patients was 60.7%, 65.0%, 77.0% and 80.3%. Laparotomy and biopsy fell from 6.4% in the first quartile to 2.7%, 1.7% and 1.3% in subsequent quartiles. The 30-day mortality in the four quartiles was 3.0%, 1.0%, 0.7% and 0.7%. The 5-year survival was 84% in the 636 patients with appendix tumours who had complete cytoreduction, 76% in the 38 with abdominal mesothelioma and 44% in the 60 with colorectal peritoneal metastases. CONCLUSION: A centralized approach facilitated high volume experience in a single centre with an increase in the completeness of surgical excision rates and a reduction in mortality and morbidity over time.

Elevated tumour markers are normalized in most patients with pseudomyxoma peritonei 7 days after complete tumour removal.

AIM: Elevation of the preoperative tumour markers in pseudomyxoma peritonei (PMP) is common and is a risk factor for recurrence. There has, however, been no documentation of the effect of complete tumour removal on tumour markers levels after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of the study was to compare the tumour markers 7 days after surgery in patients with elevated preoperative levels. METHOD: This was an observational prospective study of patients with PMP of appendiceal origin treated in one of the UK National Referral Centres for this condition. Thirty patients [median age = 61 (range: 31-74) years; six men] with an elevated preoperative level of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA-125) and/or carbohydrate antigen 19-9 (CA19-9) underwent repeated estimation, 7 days after CRS and HIPEC for PMP. RESULTS: The median preoperative CEA level of 12 µg/l fell to 0.75 µg/l postoperatively (P < 0.0001), CA-125 fell from 45 to 31 kU/l (P = 0.183) and CA19-9 fell from 134 to 37 kU/l (P = 0.003). The CEA was raised in 22 (73%) of 30 patients preoperatively and in two (7%) of 30 patients 7 days after surgery (P < 0.0001). The corresponding data for CA-125 were 18 (60%) and 13 (43%) (P = 0.196) and for CA19-9 they were 24 (80%) and 16 (53%) (P = 0.028). CONCLUSION: This is the first documentation of a reduction or normalization of CEA 7 days after CRS, but not for CA19-9 or CA-125. This may indicate completeness of surgical resection and could aid selection for adjuvant therapy and predict prognosis. Long-term follow-up is, however, necessary to determine the significance of this observation.

Risk of definitive stoma after surgery for peritoneal malignancy in 958 patients: comparative study between complete cytoreductive surgery and maximal tumor debulking.

INTRODUCTION: Complete cytoreductive surgery (CRS) can achieve cure or long-term survival in selected patients with peritoneal malignancy. In selected patients, due to extensive disease, complete tumour removal is impossible and optimal strategy may be maximal tumour debulking (MTD). We analysed the stoma related outcome in a series of patients undergoing surgery in a National Peritoneal Malignancy Referral Centre. METHODS: All patients who underwent CRS, with or without, intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) between 1994 and 2012 were included. Data was collected prospectively in an institutional database and analysed retrospectively. RESULTS: CRS was performed in 958 patients (female: 595, male: 363) of whom 781 (81.5%) had a primary appendix tumour, 63 (6.6%) had a colorectal primary, 47 (4.9%) peritoneal mesothelioma, 38 (4%) an ovarian tumour and 29 patients (3%) other tumours. Complete CRS was achieved in 72% (693/958). Overall 352/958 (37%) had a stoma, which was permanent in 165/958 (17.2%). The median time interval from CRS to reversal of stoma was 4.4 months (range: 1.4-13.8). Stomas were created in 113/265 (42.6%) at MTD (permanent: n = 105 (93%), temporary: n = 8 (7%)), and 239/693 (34.5%) at complete CRS (permanent: n = 60 (25%), temporary: n = 179 (75%)) (p = 0.020). All temporary stomas in the 168/693 (24.4%) of patients who had complete CRS were subsequently reversed. CONCLUSION: To achieve complete CRS for peritoneal malignancy a stoma is often required and in a proportion this will be permanent. Overall over one third had a stoma at surgery with almost half subsequently reversed.

Recurrence and outcome after complete tumour removal and hyperthermic intraperitoneal chemotherapy in 512 patients with pseudomyxoma peritonei from perforated appendiceal mucinous tumours.

BACKGROUND: Pseudomyxoma peritonei (PMP) usually originates from perforated mucinous appendiceal tumours and may present unexpectedly at surgery, or be suspected at cross sectional imaging. The optimal treatment involves macroscopic tumour removal by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The 10-year Kaplan-Meier predicted disease-free survival is 61%. Some patients with recurrence are amenable to further CRS and HIPEC. AIM: To evaluate the outcomes of re-do surgery in a large single centre series of reoperation for recurrence of peritoneal surface malignancy. METHOD: Retrospective analysis of prospective database of 752 patients undergoing CRS for perforated appendiceal tumours analysed. Routine follow up involved annual CT scans and serum tumour marker measurement. The survival and recurrence in the 512/752 (68.1%) who had complete cytoreduction between March 1994 and January 2012 was calculated by Kaplan-Meier univariate analysis. RESULTS: Overall 137/512 (26.4%) developed recurrence and of those 35/137 (25.5%) underwent repeat surgery. Complete tumour removal was again achieved in 20/35 (57.1%). There were no postoperative deaths and no significant difference in early postoperative complications and length of stay compared to primary CRS surgery. The 5-year survival in the 375 without recurrence, the 35 who had re-do surgery and the 102 who had recurrence with no surgery was 90.9%, 79.0% and 64.5% respectively. CONCLUSION: Approximately one in four patients develops recurrence after complete CRS and HIPEC for PMP of appendiceal origin. Selected patients can undergo salvage surgery with good outcomes.

Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy improves survival in patients with colorectal peritoneal metastases compared with systemic chemotherapy alone.

BACKGROUND: Colorectal cancer peritoneal metastasis (CPM) confers an exceptionally poor prognosis, and traditional treatment involving systemic chemotherapy (SC) is largely ineffective. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly advocated for selected patients with CPM; however, opinions are divided because of the perceived lack of evidence, high morbidity, mortality, and associated costs for this approach. As there is no clear consensus, the aim of this study was to compare outcomes following CRS+HIPEC vs SC alone for CPM using meta-analytical methodology, focusing on survival outcomes. Secondary outcomes assessed included morbidity, mortality, quality of life (QOL), and health economics (HE). METHODS: An electronic literature search was conducted to identify studies comparing survival following CRS+HIPEC vs SC for CPM. The odds ratio (OR) was calculated using the Mantel-Haenszel method with corresponding 95% confidence intervals (CI) and P-values. Heterogeneity was examined using the Q-statistic and quantified with I(2). The fixed-effect model (FEM) was used in the absence of significant heterogeneity. For included studies, 2- and 5-year survival was compared for CRS+HIPEC vs SC alone. RESULTS: Four studies (three case-control, one RCT) provided comparative survival data for patients undergoing CRS+HIPEC (n=187) vs SC (n=155) for CPM. Pooled analysis demonstrated superior 2-year (OR 2.78; 95% CI 1.72-4.51; P=0.001) and 5-year (OR 4.07; 95% CI 2.17-7.64; P=0.001) survival with CRS+HIPEC compared with SC. Mortality ranged from 0 to 8%. No data were available for the assessment of QOL or HE. CONCLUSIONS: Although limited by between-study heterogeneity, the data support the assertion that in carefully selected patients, multimodal treatment of CPM with CRS+HIPEC has a highly positive prognostic impact on medium- and long-term survival compared with SC alone. There is a paucity of comparative data available on morbidity, QOL, and HE.

Pre-operative tumour marker status predicts recurrence and survival after complete cytoreduction and hyperthermic intraperitoneal chemotherapy for appendiceal Pseudomyxoma Peritonei: Analysis of 519 patients.

BACKGROUND: Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the optimal treatment for Pseudomyxoma Peritonei (PMP). Despite treatment, disease often recurs and may not be amenable to further CRS. Clinical experience suggests a spectrum of disease which may correlate with tumour marker levels. The aim of this study was to analyse the influence of markers on recurrence and survival. METHODS: The details of all patients undergoing surgery for PMP of appendiceal origin at a national centre for peritoneal malignancy were recorded in a dedicated prospective database. The data on all patients who had CRS and HIPEC between March 1994 and January 2012 was analysed and recurrence and survival correlated with pre-operative levels of CEA, CA-125 and CA19-9. RESULTS: Overall, 519 (69%) of 752 consecutive patients, underwent complete CRS and HIPEC. The median (range) age was 56 (20-82) years with 342/519 (66%) females. The mean overall (OS) and disease free survival (DFS) in the 131/519 patients who had normal preoperative tumour markers was 168 (128-207) and 125 (114-136) months respectively, significantly higher when compared with the 109/519 (21%) who had all three tumour markers elevated (OS of 65 (42-88) and DFS of 55 (41-70) months respectively) (P = 0.002). CONCLUSIONS: Elevated tumour markers predict an increased risk of recurrence and reduced survival after complete CRS. This may reflect cell biology in low grade tumours and is an independent prognostic feature. Further analysis may help to select patients for post-operative chemotherapy, second look procedures or stratification of follow up.

Comparative quality of life in patients following abdominoperineal excision and low anterior resection for low rectal cancer.

BACKGROUND: It is widely believed that quality of life is worse after abdominoperineal excision then after low anterior resection. However, this view is not supported unequivocally. OBJECTIVE: The aim of this study was to compare quality of life in patients 1 year following low anterior resection and abdominoperineal excision for low rectal cancer. DESIGN: Data were collected prospectively on 62 patients undergoing low anterior resection (32) and abdominoperineal excision (30) for low rectal adenocarcinoma within 6 cm of the anal verge. Patients with metastatic disease were excluded. Quality of life was assessed by the use of the European Organization for Research and Treatment of Cancer's QLQ-C30 and QLQ-CR38 modules and Coloplast stoma quality-of-life questionnaire. Bowel function was assessed by using the St Mark's bowel function questionnaire. Quality of life in patients who had low anterior resection was compared with those who had abdominoperineal excision both preoperatively and 1 year after surgery. SETTINGS: This study was conducted at 3 centers in the United Kingdom and 1 center in Europe. PATIENTS: Included were consecutive patients with rectal cancer within 6 cm of the anal verge, all of whom provided written consent for participation. MAIN OUTCOME MEASURES: Mann-Whitney U test comparisons of QLQ-C30 and QLQ-CR38 module scores for patients undergoing low anterior resection and abdominoperineal excision were the main outcomes measured. RESULTS: Patients undergoing low anterior resection were younger (median age, 59.5 vs 67, p = 0.03) with higher tumors (4 vs 3, p < 0.001) and less likely to receive neoadjuvant therapy (p = 0.02). At 1 year postoperatively, global quality-of-life ratings were comparable, but patients undergoing abdominoperineal excision reported better cognitive (100 vs 83, p = 0.018) and social (100 vs 67, p = 0.012) function, and less symptomatology with respect to pain (0 vs 17, p = 0.027), sleep disturbance (0 vs 33, p = 0.013), diarrhea (0 vs 33, p = 0.017), and constipation (p = 0.021). Patients undergoing low anterior resection reported better sexual function (33 vs 0, p = 0.006), but 72% experienced a degree of fecal incontinence. LIMITATIONS: This study was limited by its relatively small sample size. CONCLUSION: Abdominoperineal excision should not be regarded as an operation that is inferior to low anterior resection in the management of low rectal cancer on the basis of quality of life alone.

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.