Significance of R1 resection margin in colon cancer resections in the modern era.

AIM: Circumferential resection margin involvement (R1) in rectal cancer is a predictive factor for poor prognosis. The aim of this study was to confirm the prognostic significance of R1 in colon cancer resection and to establish whether the introduction of laparoscopic colorectal surgery influenced this. METHOD: Prospectively collected data on a patient pathway data manager for sequential patients with colon cancer treated at our specialist unit from January 2005 to December 2010 were analysed. There were 1110 colonic resections (elective 865; emergency 245). A circumferential resection margin involvement of < 1 mm was considered positive. RESULTS: The total R1 rate was 13.3% (elective 10.4%; emergency 23.6%; P < 0.001). Other statistically significant risk factors for an R1 resection included tumour perforation (P < 0.001), poorly differentiated carcinoma (P < 0.001), T4 tumour (P < 0.001), vascular invasion (P < 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and palliative resection (P < 0.001). Over half of the elective resections were undertaken laparoscopically (486/865; 56.2%). When compared with elective open resection (379/865; 43.8%), the R1 rate was similar (P = 0.491) with similar disease-free survival (DFS) and overall survival (OS). The overall relapse rate was 18.9% in R0 and 55.5% in R1 resections (P < 0.001). Kaplan-Meier survival analysis showed significant improvements in DFS and OS in R0 over R1 patients. CONCLUSION: The R1 margin in colon cancer resection is an important marker for advanced disease and a prognostic factor for DFS and OS. The introduction of laparoscopic surgery has not influenced the outcome in our unit despite a complex case mix.

An algorithm for the management of bile leak following laparoscopic cholecystectomy.

INTRODUCTION: The management of bile leaks following laparoscopic cholecystectomy has evolved with increased experience of ERCP and laparoscopy. The purpose of this study was to determine the impact of a minimally invasive management protocol. PATIENTS AND METHODS: Twenty-four patients with a bile leak following laparoscopic cholecystectomy were recorded consecutively between 1993 and 2003. Between 1993-1998, 10 patients were managed on a case-by-case basis. Between 1998-2003, 14 patients were managed according to a minimally invasive protocol utilising ERC/biliary stenting and re-laparoscopy if indicated. RESULTS: Bile leaks presented as bile in a drain left in situ post laparoscopic cholecystectomy (8/10 versus 10/14) or biliary peritonitis (2/10 versus 4/14). Prior to 1998, neither ERC nor laparoscopy were utilised routinely. During this period, 4/10 patients recovered with conservative management and 6/10 (60%) underwent laparotomy. There was one postoperative death and median hospital stay post laparoscopic cholecystectomy was 10 days (range, 5-30 days). In the protocol era, ERC +/- stenting was performed in 11/14 (P = 0.01 versus pre-protocol) with the main indication being a persistent bile leak. Re-laparoscopy was necessary in 5/14 (P = 0.05 versus preprotocol). No laparotomies were performed (P < 0.01 versus pre-protocol) and there were no postoperative deaths. Median hospital stay was 11 days (range, 5-55 days). CONCLUSIONS: The introduction of a minimally invasive protocol utilising ERC and re-laparoscopy offers an effective modern algorithm for the management of bile leaks after laparoscopic cholecystectomy.

Four gland parathyroidectomy without reimplantation in patients with chronic renal failure.

BACKGROUND: The optimal surgical management of patients in end stage chronic renal failure with secondary hyperparathyroidism is controversial. One approach advocated is four gland parathyroidectomy without reimplantation. The aim of this study was to review the medium term results of this procedure. METHODS: Fifty four consecutive patients with end stage chronic renal failure and secondary hyperparathyroidism who had a four gland parathyroidectomy without reimplantation were studied. The procedure was performed by a single surgeon with a median (range) follow up of 29 (0-70) months. RESULTS: Most patients (76%) developed postoperative hypocalcaemia but this was easily treated and doses of long term drugs necessary to prevent this were low. Pre-operative bone symptoms, hypercalcaemia, hyperphosphataemia, and an increased alkaline phosphatase were improved or resolved in most patients. Thirteen (24%) patients had an undetectable postoperative parathyroid hormone (PTH), (6 of 12 (50%) with a functioning renal transplant and 7 of 42 (17%) who required dialysis, p = 0.02). Median (range) postoperative PTH values in these groups were 0.1 (0.1-31) compared with 1.0 (0.1-24) pmol/l (p = 0.085) respectively. The remaining 41 of 54 (76%) patients had residual PTH secretion and postoperative hyperparathyroidism was identified in eight (15%) patients with only two requiring neck re-exploration. CONCLUSION: Four gland parathyroidectomy without reimplantation produced good medium term biochemical and clinical results. Most patients had minor residual PTH secretion that may contribute to this and mitigate concerns regarding adynamic bone disease. Endogenous PTH secretion is only completely lost in a few patients but occurs more often in those with a functioning renal transplant. Bone densitometry is required to investigate the long term impact of this procedure.

Heavy rectal bleeding secondary to the passage of a rectal leiomyoma per anus.

Leiomyoma of the rectum is rare and this is the first case reported where such a tumour has passed per rectum, resulting in heavy bleeding. The management of the acute surgical problem as well as rectal leiomyoma per se is discussed.

The impact of cyclosporine dose reduction with or without the addition of rapamycin on functional, molecular, and histological markers of chronic allograft nephropathy.

BACKGROUND: Overexposure to cyclosporine is a risk factor for chronic allograft nephropathy (CAN) and dose reduction has been advocated. The purpose of this study was to determine the impact of adding the non-nephrotoxic immunosuppressant, rapamycin, after cyclosporine dose reduction in renal-allograft recipients with CAN. METHODS: Thirty-one patients with biopsy-confirmed CAN were prospectively randomized to receive a 40% cyclosporine dose reduction with (rapamycin, n=16) or without (control, n=15) the addition of rapamycin 2 mg/day. Renal function and side-effect parameters were assessed. Patients had renal allograft biopsies taken at recruitment and after 6 months. Glomeruli were isolated from these and underwent total mRNA extraction followed by RT-PCR-ELISA to assess transforming growth factor-beta1, collagen III, TIMP-1, TIMP-2, and matrix metalloproteinase-2 expression. Samples were also stained with Sirius red and the percentage interstitial volume fraction quantified by computerized histomorphometric analysis. Data are presented as mean (+/-SD). RESULTS: Patient characteristics and cyclosporine trough levels after dose reduction (rapamycin 68 [+/-21] vs. control 56 [+/-19] ng/mL, P=NS) were similar in both groups. Rapamycin patients had a significant fall in Cr-51 radioisotope glomerular filtration rate (31.6 [+/-8.9] to 27.3 [+/-8.6] mL/min, P<0.01) that was not significant in controls (29.5 [+/-10.4] to 27.0 [+/-8.0] mL/min, P=NS). Transforming growth factor-beta1 expression fell over time in control but remained constant in rapamycin patients. Conversely collagen III expression increased over the 6-month follow-up in rapamycin patients but not in controls. Both had comparable increases in TIMP-1 and matrix metalloproteinase-2 but only rapamycin patients developed a significant increase in TIMP-2. Sirius red-stained interstitial volume fraction fell over the study in controls (15.3-11.2%, P=0.06) but not in rapamycin patients (16.2-16.3%, P=NS). CONCLUSION: Rapamycin (2 mg/day) did not improve functional, molecular, or histological outcome in patients with CAN after cyclosporine dose reduction. Further studies involving larger numbers of patients are necessary to confirm these findings.

A case-control comparison of the results of renal transplantation from heart-beating and non-heart-beating donors.

INTRODUCTION: The decline in heart-beating brainstem dead organ donors has necessitated the search for other organ sources. In the field of renal transplantation one alternative source currently available, but little used, is that of kidneys from non-heart-beating donors (NHBD). Reticence to use NHBD kidneys is in part due to concerns over the effect that warm ischemic may have subsequent graft function. Presented here are the results of the NHBD renal transplants at the Leicester transplant unit, and compared with matched heart-beating donor transplants as a case control analysis. METHODS: In order to analyze any differences in graft performance between the two organ sources, the confounding effect of other variables known to influence the outcome of renal transplantation was minimized by matching NHBD and HBD transplants for the following criteria: donor age and sex, first or re-transplant, anastomosis and cold times, tissue match and PRA sensitisation. Transplant performance was assessed primarily by graft survival, the statistical evaluation of which was by log rank analysis of Kaplan-Meier curves. RESULTS: 72 NHBD and 192 HBD transplants were performed over an eight year period. Of the 192 HBD transplants, 105 matched one or more of the NHBD by the criteria outlined above, and thus constituted the control group for comparison. There was no significant difference in overall graft survival between the two groups. The 5 year survival for the NHBD was 73% compared with 65% for HBD kidneys. When death with a functioning graft is treated as censored data, then these figures become 75% and 81% respectively, again without statistical significance. CONCLUSION: NHBD kidneys are a valuable additional source of organs for transplantation, with long-term survival, comparable to transplants from HBD.

Bilateral absence of the superior vena cava.

Congenital anomalies of the superior vena cava are rare and often coexist with other cardiac abnormalities. In this report, we present a case of absent bilateral superior vena cava with no associated cardiac anomaly. Blood from the arms, head, and upper torso returned to the right atrium through the azygos vein and the inferior vena cava, mimicking chronic superior vena cava obstruction.

Rapamycin in transplantation: a review of the evidence.

Rapamycin in transplantation: A review of the evidence. The calcineurin inhibitors have been the mainstays of immunosuppression for solid organ transplantation over the last two decades, but nephrotoxicity limits their therapeutic benefit. Rapamycin is a new drug with both immunosuppressant and antiproliferative properties that has a unique mechanism of action distinct from that of the calcineurin inhibitors. It has a role as a maintenance immunosuppressant either alone or in combination with a calcineurin inhibitor and can also be used to treat refractory acute rejection. Theoretical evidence suggests that it may limit the development and progression of chronic rejection in transplant recipients, but this has yet to be confirmed. This review examines the current in vitro animal and human work underlying the use of rapamycin and, in addition, comments on the pharmacokinetics and side-effect profile of this promising new agent.

Workload generated by a living donor programme for renal transplantation.

BACKGROUND: The ethical and medical implications of live kidney donation result in a comprehensive work-up process. The aim of this study was to determine the magnitude of the workload and the yield of renal transplants generated by a live donor programme. METHODS: Referrals to the Leicester live donor programme over the five-year period 1994-1998 were retrospectively assessed. These were initiated by nephrology referral and subsequently investigated in a stepwise manner. Patients were counselled and baseline tests performed prior to consultant surgeon review and assessment of donor renal function/anatomy. RESULTS: One hundred and fifty referrals consisting of 150 recipients with 269 potential donors were originally made. This resulted in 32/120 (27%) related and 3/30 (10%) unrelated recipients (P=0.06) and 32/220 (15%) related and 3/49 (6%) unrelated donors proceeding to live donor transplantation, with a mean work-up time (+/-SD) of 9 (+/-7) months. One hundred and fifteen recipients (77%) and 234 (87%) donors failed to proceed at various stages of assessment, for a variety of immunological, medical and social reasons. A large number of expensive immunological investigations were required for potential donors, the majority of which did not proceed to transplantation. However as a result of performing these in the early stages of assessment the number of more invasive tests is kept to a minimum. CONCLUSIONS: There is a relatively low yield of transplants from live donor referrals, particularly those between unrelated individuals. The vast majority of referrals fail to proceed for legitimate reasons, but as a result, create a significant workload with notable staffing and financial implications.