Author Archives: Hannah

The Carotid Revascularization Endarterectomy vs Stenting Trial (CREST)

Posted on by
1

One discussion this week involved the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST).

Reference: Brott TG, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. New England Journal of Medicine. 2010 Jul 1;363(1):11-23. doi:10.1056/NEJMoa0912321.

Summary:  CREST is an RCT with blinded end-point adjudication whose aim was “to compare the outcomes of carotid-artery stenting with those of carotid endarterectomy among patients with symptomatic or asymptomatic extracranial carotid stenosis” (p.12).

Between December 2000 through July 2008, 2522 patients were enrolled in 108 centers in the US and 9 in Canada. Of those, 1271 patients were randomly assigned to undergo carotid-artery stenting.

Primary findings include (p.18):

  • Carotid revascularization performed by highly qualified surgeons and interventionists is effective and safe.
  • Stroke was more likely after carotid-artery stenting.
  • Myocardial infarction was more likely after carotid endarterectomy, but the effect on the quality of life was less than the effect of stroke.
  • Younger patients had slightly fewer events after carotid-artery stenting than after carotid endarterectomy.
  • Older patients had few events after carotid endarterectomy.
  • Low absolute risk of recurrent stroke suggests that both carotid-artery stenting and carotid endarterectomy are clinically durable and reflect advances in medical therapy.

The Asymptomatic Carotid Atherosclerosis Study (ACAS)

Posted on by
Reply

One discussion this week included the Asymptomatic Carotid  Atherosclerosis Study (ACAS).

Reference: Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995 May 10;273(18):1421-1428.

Summary: ACAS was a prospective, randomized trial conducted at 39 sites in the US and Canada between December 1987 and December 1993. Its purpose was to “determine whether the addition of carotid endarterectomy to aggressive medical management can reduce the incidence of cerebral infarction in patients with asymptomatic carotid artery stenosis” (p.1421).

The primary finding was that the risk of ipsilateral stroke and any periopoerative stroke or death over 5 years was 5.1% for surgical patients and 11.0% for medically treated patients (p.1425). Furthermore, those who are good candidates for elective surgery and have carotid artery stenosis of 60% or greater reduction in diameter will have a significantly reduced 5-year risk of ipsilateral stroke “if carotid endarterecomy performed with less than 3% perioperative morbidity and mortality is added to aggressive management of modifiable risk factors” (p.1421).

Additionally, ACAS concluded that CEA reduces the relative stroke risk 66% for men and 17% for women. This difference is perhaps due to higher rates of perioperative complications in women.When arteriographic and perioperative complications are excluded, the risk reduction was 79% for men and 56% for women (p.1427).

The North American Symptomatic Carotid Endarterectomy Trial (NASCET)

Posted on by
Reply

One discussion this week involved the North American Symptomatic Carotid Endarterectomy Trial (NASCET).

Reference: Barnett HJM, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. New England Journal of Medicine. 1998 Nov 12;339(20):1415-1425.

Summary: NASCET involved 2226 patients with stenosis of less than 70 percent. They were randomly assigned to treatment groups: 1118 to medical therapy, 1108 to surgical therapy (p.1417).

Four patient characteristics are associated with greater benefit from surgery: male sex, recent stroke, recent hemispheric symptoms, and taking 650 mg or more of aspirin per day (p.1419).

NASCET authors explain that the lack of significant benefit for women may be due to their low risk of stroke. Among participants with 50-69% stenosis, the risk of any ipsilateral stroke at 5 years in the medically treated group was 15% for women, and 25% for men. Endarterectomy reduced the risk to 14% for women and 17% for men (p. 1421).

The table below shows the rate of events at 5-year followup:

table5

Mortality risk reduction associated with PTH reduction for Secondary Hyperparathyroidism

Posted on by
Reply

One discussion this week included parathyroid hormone (PTH) levels.

Reference: Komaba H, et al. Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney International. 2015 Aug;88(2):350-359. doi: 10.1038/ki.2015.72

Summary: In a nationwide study of 114,064 hemodialysis patients, Komaba et al asked if PTx for severe SHPT improves survival of dialysis patients.  They compared patient outcomes by PTH levels, and by those with a history of parathyroidectomy (PTx) (6,6280) and those without PTx (107,436).

fig2

(p.353)

Excess PTH is shown to increase cardiac fibrosis; elevations in serum calcium, phophorus, and PTH levels are associated with death and cardiovascular events primarily due to vascular calcification (p.350).

fig4

(p.355)

For cardiovascular death, there was a significant increase in the multivariate-adjusted HR for patients with intact PTH levels < 60 pg/ml (HR, 1.11; 95% CI, 1.02–1.20) and those with intact PTH levels >500 pg/ml (HR, 1.41; 95% CI, 1.20–1.64). In contrast, such an increased risk of mortality was not observed in patients with a history of PTx, despite the fact that these patients had severe SHPT preoperatively.

 

Metabolic effects of octreotide

Posted on by
Reply

One discussion this week involved the effects of octreotide.

Reference: Octreotide: a drug often used in the critical care setting but not well understood. Chest. 2013 Dec;144(6):1937-1945. doi:10.1378/chest.13-0382.

Summary: While a majority of octreotide is metabolized by the liver, 30-35% of octreotide acetate is excreted in the urine. Thus, octreotide accumulates in patients with moderate to severe renal or hepatic insufficiency.

Compared with SST-14, it exhibits 45-fold more potent inhibition of growth hormone, 11-fold more of glucagon, and 1.3-fold more insulin secretion.

octreotide

(p.1940)

Octreotide inhibits insulin secretion in the following ways (p.1943):

  • Binds to SSTR-5 present on pancreatic B islet cells, inhibiting the formation of cAMP and reducing influx of calcium into the cytoplasm, thus preventing insulin secretion.
  • Inhibition of direct phosphorylation of specific proteins required for secretion of insulin-containing vesicles.

Additional reading:  Adabala M, et al. Severe hyperkalaemia resulting from octreotide use in a haemodioalysis patient. Nephrology, Dialysis, Transplantation. 2010 Oct;25(10):3439-3442. doi:10.1093/ndt/gfq381.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer

Posted on by
Reply

One discussion this week involved the PCI cutoff for CRS/HIPEC for colorectal cancers.

References: Faron M, et al. Linear relationship of Peritoneal Cancer Index and survival in patients with peritoneal metastases from colorectal cancer. Annals of Surgical Oncology. 2016 Jan;23(1):114-119. doi:10.1245/s10434-015-4627-8.

Klaver CEL, et al. Recommendations and consensus on the treatment of peritoneal metastases of colorectal origin: a systematic review of national and international guidelines. Colorectal Disease. 2017 Mar;19(3):224-236. doi:10.1111/codi.13593

Summary: A diagnosis of peritoneal metastases (PM) is generally poor, approximately 5 months if untreated; however, CRS/HIPEC has been shown to increase median survival up to 22 months (Klaver et al, 2017).

Faron et al (2016) explored the relationship between the peritoneal cancer index (PCI) and overall survival in the setting of complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). In reviewing the literature, they found that CCRS/HIPEC is indicated for a PCI <12 and not appropriate for a PCI >17. There is an area of indecision in PCIs 12-17.

To bridge this PCI indecision gap, Faron et al (2016) recommend considering the following parameters (p.118):

  1. Presence of other site of metastases besides peritoneum
  2. General performance status and patient age, linked to morbidity and mortality
  3. Response to neoadjuvant chemotherapy, because progression of disease while receiving systemic chemotherapy reflects aggressive tumor behavior

In a systematic review of 21 guidelines, Klaver et al (2017) found a 71% consensus that CRS/HIPEC is the recommended treatment for PM. There is a need not only for additional evidence, but also an international platform for more trials on CRS/HIPEC and the overall treatment of PM (Klaver et al, 2017).

To drain or not to drain…the GRECCAR 5 randomized trial

Posted on by
Reply

One discussion this week focused on pelvic drains.

Reference: Denost Q, et al. To drain or not to drain infraperitoneal anastomosis after rectal excision for Cancer: The GRECCAR 5 randomized trial. Annals of Surgery. 2017 Mar;265(3):474-480. doi:10.1097/SLA.0000000000001991.

Summary: The GRECCAR 5 randomized trial sought to explore the benefit of a drain for postoperative pelvic sepsis, overall morbidity and mortality, rate of re-operation, length of stay, and rate of stoma closure at 6 months (p.474). It involved 469 patients (236 with drains, 233 without) between 2011 and 2014.

Ultimately, the trial did not find any benefit of the pelvic drain after low anterior resection for rectal cancer. Thus, the authors “recommend not using pelvic drain after rectal excision for cancer, except in case of operative bleeding or beyond TME surgery” (p.480).

The drain did not contribute to an efficient diagnosis of sepsis, for the time to diagnosis of pelvic sepsis was an average of 7.8 days, yet the drain was removed at 5.5 days postop (see figure below; p.1478).

pelvic sepsis

There was no significant difference between the two groups for any of the noted measurements. Pelvic sepsis occurred in 16.1% of those with the drain and 18.0% of those without drain. Re-operation for pelvic sepsis was done in 10.2% of those with drain and 12.0% of those without drain.

Additional reading: Placer C. To drain or not to drain infraperitoneal anastomosis after rectal excision for cancer: an unclosed debate [Letter to the Editor]. Annals of Surgery. 2018. doi:10.1097/SLA.0000000000003005. [Epub ahead of print]