Surgical techniques in the management of rectal cancer: a modified Delphi method by colorectal surgeons in Australia and New Zealand.

BACKGROUND: Technological developments have allowed advances in minimally invasive techniques for total mesorectal excision such as laparoscopy, robotics, and transanal surgery. There remains an ongoing debate about the safety, benefits, and appropriate clinical scenarios for which each technique is employed. The aim of this study was to provide a panel of expert opinion on the role of each surgical technique currently available in the management of rectal cancer using a modified Delphi method. METHODS: Surveys were designed to explore the key patient- and tumor-related factors including clinical scenarios for determining a surgeon's choice of surgical technique. RESULTS: Open surgery was favoured in obese patients with an extra-peritoneal tumor and a positive circumferential resection margin (CRM) or T4 tumor when a restorative resection was planned. Laparoscopy was favoured in non-obese males and females, in both intra- and extra-peritoneal tumors with a clear CRM. Robotic surgery was most commonly offered to obese patients when the CRM was clear and if an abdominoperineal resection was planned. Transanal total mesorectal excision (taTME) was preferred in male patients with a mid or low rectal cancer, particularly when obese. Transanal endoscopic microsurgery/transanal minimally invasive surgery local excision was only offered to frail patients with small, early stage tumors. CONCLUSIONS: All surgical techniques for rectal cancer dissection have a role and may be considered appropriate. Some techniques have advantages over others in certain clinical situations, and the best outcomes may be achieved by considering all options before applying an individualised approach to each clinical situation.

The allogeneic T and B cell response is strongly dependent on complement components C3 and C4.

BACKGROUND: The mechanisms controlling the production of antibodies against histocompatibility antigens are of prime importance in organ transplantation. METHODS: We investigated the role of complement in the response to allogeneic stimulation, using mice deficient in C3, C4, or C5 to dissect the role of the alternative, classical, and terminal complement pathways. RESULTS: After fully major histocompatibility complex disparate skin grafts, the allospecific immunoglobulin (Ig)G response was markedly impaired in C3- and C4-, but not in C5-deficient mice. This defect was most pronounced for second set responses. C3-deficient mice also demonstrated a decreased range of IgG isotypes. In contrast, there was no impairment of the allospecific IgM response. In functional T cell assays, the proliferative response and interferon-gamma secretion of recipient lymphocytes restimulated in vitro with donor antigen was decreased two- to threefold in C3-deficient mice. CONCLUSIONS: These data show impairment of allogeneic T cell and B cell function in mice with defective complement activation and suggest a predominant role for the classical pathway in stimulating alloimmunity. The terminal pathway seems unimportant in this regard. This extends the results reported for soluble protein antigens and demonstrates a surprisingly marked effect on the alloresponse despite the presence of a stringent antigenic stimulus. These results have implications for the prevention of sensitization in naïve transplant recipients.

Hypotensive ischemic optic neuropathy and peritoneal dialysis.

PURPOSE: To report anterior ischemic optic neuropathy associated with systemic hypotension in a patient undergoing continuous ambulatory peritoneal dialysis. METHODS: Case report. A 58-year-old man undergoing continuous ambulatory peritoneal dialysis developed painless blurred vision in both eyes and bilateral optic disk swelling with an altitudinal field defect in the left eye. Twenty-four-hour ambulatory blood pressure monitoring was requested in addition to other routine investigations. RESULTS: Routine blood pressure measurement in the clinic was 130/86 mm Hg, but ambulatory blood pressure monitoring demonstrated pronounced early morning hypotension with individual readings as low as 91/41 mm Hg. CONCLUSIONS: Renal dialysis can render patients hypotensive, and this may be associated with anterior ischemic optic neuropathy. The overnight drop in blood pressure may not be appreciated with routine blood pressure measurement. Therefore, 24-hour ambulatory blood pressure monitoring should be considered when investigating patients with suspected anterior ischemic optic neuropathy who are undergoing renal replacement.

Maintenance of adequate dialysis in a patient with peritoneal calcification using tidal peritoneal dialysis.

A case report of a 50-year-old woman who has been treated with peritoneal dialysis for 9 years, with a short period off dialysis following transplantation. The patient had long-standing secondary hyperparathyroidism and had declined parathyroidectomy, she had had two episodes of peritonitis in the preceding eight years. She presented with blood-stained dialysate effluent and intermittent abdominal pain. Investigation revealed widespread peritoneal calcification with large plaques of calcium on the visceral peritoneum. She was treated with tidal automated peritoneal dialysis; adequate creatinine clearances have been maintained and the patient has had little further abdominal pain and bleeding. In this report we have illustrated an unusual complication of peritoneal dialysis, peritoneal calcification, and suggest that tidal peritoneal dialysis is a useful therapeutic tool in such cases.

Symptomatic cytomegalovirus infection complicating treatment of acute systemic vasculitis.

Cytomegalovirus (CMV) is usually a complication of renal/solid organ or bone marrow transplantation. We describe three cases of severe CMV in the context of vasculitis immunosuppression.

Assessing the prevalence, monitoring and management of chronic kidney disease in patients with diabetes compared with those without diabetes in general practice.

AIMS: To compare rates of chronic kidney disease (CKD) in patients with diabetes and management of risk factors compared with people without diabetes using general practice computer records, and to assess the utility of serum creatinine and albuminuria as markers of impaired renal function. METHODS: The simplified Modification of Diet in Renal Disease (MDRD) equation was used to estimate glomerular filtration rate (eGFR) and stage of CKD. Further data were extracted to assess how effectively impaired renal function was being identified and how well potentially modifiable risk factors were being managed. The setting was 17 practices in Surrey, Kent and Greater Manchester (2003-2004). Participants were all patients with serum creatinine (SCr) recorded. RESULTS: Of the total population of 162 113, 5072 were recorded as having a diagnosis of diabetes, giving a prevalence of 3.1%. Of patients with diabetes, 31% had clinically significant CKD (defined as eGFR < 60 ml/min per 1.73 m(2); CKD stages 3-5) compared with 6.9% of those without diabetes. Only 33% of patients with diabetes at CKD stage 3 had serum creatinine > 120 micromol/l. Of patients with diabetes with eGFR < 60 ml/min per 1.73 m(2), 63% had normoalbuminuria. Considering those with eGFR 30-60 ml/min per 1.73 m(2), 42% of people with diabetes were on an ACE inhibitor compared with 25% of those without diabetes; 32% of patients with diabetes who had any record of micro- or macroalbuminuria at CKD stage 3 were taking an ACE inhibitor. Of people with diabetes and hypertension (BP > 140/80 mmHg), 26% were not prescribed any hypertensive medication, regardless of level of CKD. CONCLUSIONS: CKD is common in people with diabetes living in the community in the UK. The study found a similar rate of stage 3-5 CKD to that found previously in the USA. Currently used measures of renal function fail to identify CKD as effectively as eGFR. Risk factors for CKD and its progression are suboptimally managed.

Chronic kidney disease management in the United Kingdom: NEOERICA project results.

Early identification of patients with chronic kidney disease (CKD) may allow health-care systems to implement interventions aimed at decreasing disease progression and eventual morbidity and mortality. Primary care in the United Kingdom is computerized suggesting a separate screening program for CKD may not be necessary because identifying data already populates primary care databases. Our study utilized a data set of 163 demographic, laboratory, diagnosis, and prescription variables from 130 226 adults in the regions of Kent, Manchester, and Surrey. The patients were 18 years of age and older in a 5-year study period culminating in November 2003. Estimated glomerular filtration rate was calculated from the four-variable Modification of Diet in Renal Disease equation using calibrated creatinine levels. A valid creatinine value was recorded in almost 30% of this cohort. The age-standardized prevalence of stage 3-5 CKD was 10.6% for females and 5.8% for males. In these patients, the odds ratio for hypertension was 2.1, for diabetes 1.33, and for cardiovascular disease 1.69. Only 20% of the diabetic people with stage 3-5 CKD had a blood pressure less than or equal to 130/80 mm Hg. The proportion of patients with anemia significantly rose as renal function declined. We suggest that stage 3-5 CKD is easily detected in existing computerized records. The associated comorbidity and management is readily available enabling intervention and targeting of specialist resources.

Late low-dose steroid withdrawal in renal transplant recipients increases bone formation and bone mineral density.

Corticosteroids have been the most widely used immunosuppressive agents since the first clinical transplantation in the 1950s. There are few studies of late steroid withdrawal in renal transplantation and none have prospectively assessed bone mineral density (BMD). The study aim was to assess the impact of corticosteroid withdrawal, in stable renal transplant recipients, on BMD and bone turnover. BMD, osteocalcin (OC) and cross-linked telopeptide of type I collagen (CTx) were measured in 92 patients randomized into a trial of steroid withdrawal. Patients with functioning renal transplants for more than 1 year with a serum creatinine below 200 micromol/L entered the trial. All patients were on triple immunosuppression (Cyclosporin microemulsion, Azathioprine and prednisolone), corticosteroids were withdrawn at 1 mg/month. BMD was measured twice annually with serum CTx and OC. One year following withdrawal of glucocorticoids there was no significant difference in creatinine. BMD increased in the withdrawal group (2.54% per year L1-L4, p < 0.01), there was a slight reduction in the control group. Mean OC increased from 5.3 to 12.2 ng/mL (p < 0.05) in the withdrawal group, but was unchanged in the controls. No change was seen in CTx. Corticosteroid withdrawal in renal transplant recipients results in an increase in BMD with a corresponding increase in serum OC.

Nephrotic syndrome and mesenteric infarction secondary to metastatic mesothelioma.

Malignant mesothelioma can present insidiously with progressive breathlessness and chest pain. Paraneoplastic, or non-chest related, presentations are very rare. The case of an elderly man with occupational exposure to asbestos who presented with nephrotic syndrome due to minimal change nephropathy in the context of advanced pleural mesothelial malignancy is reported.

Individual kidney function in atherosclerotic nephropathy is not related to the presence of renal artery stenosis.

BACKGROUND: Atherosclerotic renovascular disease is increasingly recognized as an important cause of renal failure in patients over 60 years of age but the processes leading to renal dysfunction have not been defined. We have examined the relationship between renal artery stenosis and individual renal function in patients with atherosclerotic renal artery stenosis. METHODS: In this prospective descriptive study over a 25-month period, we examined the relationship between the presence of renal artery stenosis and single kidney glomerular filtration rate (SKGFR). SKGFR was measured using a novel method of synchronous (51)Chromium ethylenediamine tetraacetic acid glomerular filtration rate ((51)CrEDTA-GFR) and (99m)Technetium dimercaptosuccinic acid ((99m)TcDMSA) scintigraphy. We studied 79 patients with a mean age of 68.9 years (25.2-88.2), 44 males and 35 females. The mean age of the males was 70 years (60-80) and females 67 years (25.2-88.2). RESULTS: We found that the precision of the SKGFR was 2 ml/min. For paired kidneys we found: (i) no significant difference between kidneys with stenosis (17.3 ml/min) compared to those without stenosis (13.6 ml/min) (P=0.22); (ii) kidneys with occluded renal arteries had significantly less function (2.6 ml/min) than those without occlusion (24.5 ml/min) (P<0.05). When degree of renal arteries stenosis was correlated with SKGFR there was a reduction with an increasing degree of stenosis (<30% 27 ml/min, 30-60% 17.7 ml/min, >60% stenosis 15 ml/min, P=0. 016). CONCLUSIONS: These data demonstrate that SKGFR provides a reproducible measure of individual kidney function. There was a similar impairment of function in paired kidneys with and without renal artery stenosis, but occlusion was associated with significant reduction in function compared to the contralateral kidney. This suggests that there is a process causing renal dysfunction in patients with atherosclerotic disease independent of renal artery narrowing.

An investigation of the effect of advancing uraemia, renal replacement therapy and renal transplantation on blood pressure diurnal variability.

BACKGROUND: Ambulatory blood pressure recordings have been shown to correlate better with target organ damage than have isolated clinic blood pressure readings. There have been some small studies demonstrating that abnormal blood pressure diurnal rhythm is common in uraemia and in patients on renal replacement therapy. Abnormal blood pressure diurnal rhythm itself may be a risk factor for accelerated target organ damage. METHODS: We retrospectively studied 480 ambulatory blood pressure recordings in 380 patients with essential hypertension, secondary hypertension, and on renal replacement therapy. We examined diurnal blood pressure rhythm in each group. RESULTS: Abnormal blood pressure diurnal rhythm (non-dipping) is significantly more prevalent in patients with underlying renal disease, even with normal excretory renal function (53%) than in age-, sex-, and race-matched controls with essential hypertension ((30%), P < 0.01). In patients with renal disease the prevalence of non-dipping rose with worsening renal function, reaching statistical significance once plasma creatinine was greater than 400 mumol/l. There was a direct correlation between plasma creatinine and percent decline in blood pressure at night for both systolic (r = 0.23) and diastolic (r = 0.24) blood pressure in patients with underlying renal disease and impaired excretory renal function. High prevalences of abnormal diurnal BP rhythm are seen in patients on haemodialysis (82%), peritoneal dialysis (78%), patients with plasma creatinine > 600 mumol/l (75%), and in renal transplant recipients (74%). CONCLUSIONS: Abnormal blood pressure diurnal rhythm ('non-dipping') is significantly more common in secondary than in primary hypertension, even with normal renal function. Abnormal blood pressure diurnal rhythm becomes increasingly common with advancing uraemia. Once the plasma creatinine is greater than 600 mumol/l the prevalence of non-dipping is the same as that seen with renal replacement therapy. This phenomenon is not modulated by successful renal transplantation.

Variability of different methods for measurement of ECG intervals and ECG interval temporal variation.

We found significant variation within each computer and cardiologist method for measurement of the ECG waveform intervals. Comparison between methods revealed that the HP system had a smaller variability than the MAC or the cardiologist, and that the MAC had a smaller variability than the cardiologist. No variability was found when a cardiologist used different paper trace speeds. Using HP measurements, we found a significant difference in ECG intervals over time, which was greater than the variability found within the method at baseline. The delineation of variability within and between ECG interval measurement methods may allow more reliable application of ECG interval changes in the therapeutic medical management of patients and prevention of side effects from drugs that affect ECG intervals. Computerized ECG waveform analysis is a widely available technology whose full role in therapeutic medical management may not be appreciated.

Progression of diabetic nephropathy--is diurnal blood pressure rhythm as important as absolute blood pressure level?

BACKGROUND: Hypertensive non-diabetic patients who lack the normal nocturnal decline in blood pressure ('non-dippers') have an increased incidence of cardiovascular complications. Poor blood pressure control is known to exacerbate the decline in glomerular filtration rate in patients with diabetic nephropathy. METHODS: The aim of this study was to assess the contribution of abnormal blood pressure diurnal rhythm to the progression of diabetic nephropathy. We retrospectively studied 26 diabetic patients with hypertension, proteinuria and relentless progressive impairment of renal function due to diabetic nephropathy between 1990 and 1996. Patients underwent ambulatory blood pressure monitoring and were classified as either 'dippers' or 'non-dippers' according to their blood pressure diurnal rhythm. Dippers were patients whose mean sleeping blood pressure (both systolic and diastolic) was 10% less than blood pressure whilst awake. Weight, glycated haemoglobin, serum creatinine (micromol/l) and blood pressure (mmHg) were recorded on a 3-monthly basis. Twenty four hour urine protein excretion and creatinine clearance were recorded annually. The rate of decline of creatinine clearance was derived from serum creatinine estimation. RESULTS: In the 'dipper' group, the rate of decline of creatinine clearance was -2.9 ml/min/year and in those with abnormal blood pressure diurnal rhythm it was -7.9 ml/min/year (P<0.05). There was no significant difference in day-time mean blood pressures, glycated haemoglobin, age and numbers with insulin-dependent diabetes mellitus. CONCLUSION: We found that there was a profound effect of non-dipping upon the rate of decline of renal function in patients with diabetic nephropathy.

How reproducible is diurnal blood pressure rhythm in patients with secondary (renal) hypertension?

Abnormalities (reduction in/absence of) in diurnal bp rhythm are much more commonly seen in patients with chronic uremia than in patients with primary hypertension or in normal subjects. Target-organ damage is greater in these patients. However, the extent to which these diurnal bp rhythm changes are consistent or variable is untested. We retrospectively examined 223 ambulatory blood pressure monitoring (ABPM) traces in 92 patients with chronic uremia who had undergone ABPM at least twice (mean 2.3 ABPM traces/patient) over the period 1991-1997. ABPM technique and analysis were constant over this period. We found that for patients with chronic declining renal function but not yet on dialysis therapy, 67% retained the same diurnal rhythm from one ABPM recording to the next; if the known tendency for declining renal function to accompanied by a greater prevalence of "non-dipping" is taken into account, 82% of all patients had a "predictable" diurnal pattern. 79% of transplant patients, 87% of haemodialysis patients and 100% of CAPD patients retained the diurnal rhythmicity from one ABPM session to the next. Non-dipping was much more frequent than dipping (67% vs 33%). We conclude that abnormalities of diurnal BP rhythm are reasonably consistent in patients with renal hypertension, especially as renal function declines and patients enter the renal replacement therapy programme.