Non-operative management of the primary tumour in patients with incurable stage IV colorectal cancer

BACKGROUND: Excision of primary colorectal cancer associated with irresectable synchronous metastases confers high morbidity and mortality with uncertain benefit. METHODS: For patients with incurable stage IV colorectal cancer, minimally symptomatic primary tumours were left in situ and 5-fluorouracil-based chemotherapy was administered systemically. Primary tumour-specific complications and survival were monitored. RESULTS: There were 13 men and 11 women with primary tumours in the right colon (eight), transverse colon (one), sigmoid colon (eight) or rectum (seven). Eleven patients had metastases limited to the liver (liver replacement less than 25 per cent in one, 25-50 per cent in four and more than 50 per cent in six) and 13 patients had extrahepatic disease (lung or peritoneum). Four patients with sigmoid colon tumours developed bowel obstruction, which required an uncomplicated operation in two and deployment of colonic stents in two patients, at 1, 3, 12 and 20 months from diagnosis. Three further patients underwent right hemicolectomy for abdominal pain of uncertain aetiology, with poor symptomatic relief, and another had a potentially curative operation following disease downstaging. The overall median survival was 10.3 months with a 1-year actuarial survival rate of 44 per cent. CONCLUSION: A policy to defer resection of minimally symptomatic primary colorectal cancer is associated with a low risk of complications before death from progressive systemic disease.     

Red cell membrane stiffness in iron deficiency

The purpose of this study was to characterize red blood cell (RBC) deformability by iron deficiency. We measured RBC deformability to ektacytometry, a laser diffraction method for determining the elongation of suspended red cells subjected to shear stress. Isotonic deformability of RBC from iron-deficient human subjects was consistently and significantly lower than that of normal controls. In groups of rats with severe and moderate dietary iron deficiency, RBC deformability was also reduced in proportion to the severity of iron deficiency. At any given shear stress value, deformability of resealed RBC ghosts from both iron-deficient humans and rats was lower than that of control ghosts. However, increase of applied shear stress resulted in progressive increase in ghost deformation, indicating that ghost deformability was primarily limited by membrane stiffness rather than by reduced surface area-to-volume ratio. This was consistent with the finding that iron-deficient cells had a normal membrane surface area. In addition, the reduced mean corpuscular hemoglobin concentration (MCHC) and buoyant density of the iron-deficient rat cells indicated that a high hemoglobin concentration was not responsible for impaired whole cell deformability. Biochemical studies of rat RBC showed increased membrane lipid and protein crosslinking and reduced intracellular cation content, findings that are consistent with in vivo peroxidative damage. RBC from iron-deficient rats incubated in vitro with hydrogen peroxide showed increased generation of malonyldialdehyde, an end-product of lipid peroxidation, compared to control RBC. Taken together, these findings suggest that peroxidation could contribute in part to increased membrane stiffness in iron- deficient RBC. This reduced membrane deformability may in turn contribute to impaired red cell survival in iron deficiency.     

Subungual squamous cell carcinoma presenting with minimal nail changes: A factor in delayed diagnosis?

Squamous cell carcinoma of the nail bed is a relatively uncommon tumour that may be diagnosed only after considerable delay. The first case presented is a 79-year-old man with a history of discomfort and discoloration affecting the right thumbnail of 3 years duration. The second case is a 70-year-old man who presented with a recurrent, offensive discharge from beneath the left thumbnail of 40 years duration. Clinical examination of the affected digits revealed minor nail abnormalities. The presence of tumour was fully apparent only after removal of the nail plate and inspection and biopsy of the nail bed. The cases demonstrate that subungual squamous cell carcinoma may present with prolonged symptoms and a deceptively benign appearance. The importance of consideration of the possibility of malignancy, removal of the nail plate for inspection of the nail bed and appropriate biopsy is emphasized.     

Canagliflozin and cardiovascular and renal events in type 2 diabetes

Review of: Neal B, Perkovic V, Mahaffey K, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644–657.

The report combines the data from two trials, CANVAS and CANVAS-Renal, which were designed to evaluate the safety and effect of canagliflozin, an SGLT-2 inhibitor, on the appearance of cardiovascular and renal events in patients with type 2 diabetes. Enrollees were patients with type 2 diabetes of at least 30 years of age, with a glycated hemoglobin of > or equal to 7.0% and < or equal to 10.5%. Patients either had to have preexisting cardiovascular disease or to be at elevated risk for cardiovascular disease, and to have an estimated glomerular filtration rate (eGFR) of >30 ml/min. Patients were randomized to canagliflozin at doses of either 100 mg or 300 mg or matching placebo in CANVAS, and to canagliflozin 100 mg with a possible increase to 300 mg, or placebo, in CANVAS-Renal. Physicians were instructed to continue appropriate diabetic management and other therapies in accordance with the best practices in their community. There was a significant 14% reduction in the combined endpoint of cardiovascular events of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in the canagliflozin treated patients. There was also a pattern of improvement in markers of renal disease, including the change in the level and nature of albuminuria, a 40% decrease in the glomerular filtration rate, the need for renal replacement therapy, or death from renal causes. This study expands the scope of SGLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study, raising the question as to whether SGLT-2 inhibitor therapy should be considered appropriate for most, if not all, type 2 diabetes patients, not only to control hyperglycemia but also to reduce cardiovascular and renal events.     

Measurements of pulmonary mechanics prior to the elective extubation of neonates

We measured total respiratory system compliance (CRS) and resistance (RRS) by the passive expiratory flow technique prior to the elective extubation of 61 neonates with a history of respiratory distress syndrome. Successful trials of extubation were characterized by a higher mean value of CRS when compared to trials that led to reintubation (1.52 vs. 1.10 mL/cm H2O, P = 0.004). Low values of CRS (0.9 mL/cm H2O or less) were invariably associated with extubation failure, whereas high values of CRS (1.3 mL/cm H2O or greater) were associated with extubation success in 94% of patients. A higher mean value of RRS was recorded in the group of infants who failed extubation when compared to those who were successful (0.22 vs. 0.17 cm H2O/mL/s, P = 0.042). We propose that measurements of pulmonary mechanics, particularly CRS, may be useful in identifying infants who will be at risk for extubation failure.     

Prevalence of Hypertension in Patients with Type II Diabetes in Referral versus Primary Care Clinics

We compared the prevalence of hypertension in patients with non–insulin-dependent diabetes mellitus (NIDDM) in referral and primary care practices using definitions of The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V), while controlling for other risk factors such as hypertension, obesity, smoking, and age. Patients (n = 1443) were enrolled consecutively from a large referral practice at the Jackson Diabetes Center and four primary care clinics in the vicinity. Blood pressures were measured at three clinic visits after a 5-min rest in a sitting position using a standard clinical sphygmomanometer. Charts were reviewed to determine diabetes duration, insulin usage, height, weight, smoking history, use of antihypertensive and oral hypoglycemic medications, socioeconomic status, and race. Patients were classified as hypertensive based on JNC-V definitions or if they were on antihypertensive medication. Hypertension was termed uncontrolled if blood pressure was JNC-V Stage 2 or higher while on antihypertensive medication.

Seventy-eight percent of referral clinic and 55% of primary care clinic patients had either JNC-V State 1 or higher hypertension or were on antihypertensive medication. Actual blood pressures indicated that more patients had JNC-V Stage 1 (mild) or higher hypertension in referral compared to primary care clinics (62% versus 48% p = 0.01) but fewer had JNC-V Stage 2 or higher (moderate-severe) hypertension (12% versus 19% p = 0.002). Patients seen in the referral clinic were significantly more likely to have greater age, greater duration of diabetes, higher insulin dosage, longer smoking history, antihypertensive medication, and live outside the metropolitan area. By logistic regression, the odds of hypertension were significantly increased with age (OR 1.51/decade), BMI greater than 27 (OR 2.17), diabetes duration (OR 1.04/year), and insulin dosage (OR 1.74/U/kg). Current smoking and attending a referral clinic were not significantly related. The odds of moderate-severe hypertension were significantly increased with age (OR 1.23/decade), decreased by attending a referral clinic (OR 0.45), and not significantly related to other confounders in the model.

The prevalence of hypertension among patients with NIDDM was higher in referral than primary care clinics. The higher prevalence in the referral practice can be accounted for by the greater severity of associated risk factors in the referral practice patients; however, most patients will be diagnosed and treated for hypertension prior to referral. More patients in the referral practice were on hypertensive medication, which lowered the stage or severity of hypertension but still not to the normal range. The results suggest that the primary detection of hypertension in patients with type II diabetes resides with the primary care physician. Management of hypertension will require both a delineation and acceptance of responsibilities between the primary care physician and diabetes specialists.