Use of DOTATATE in the surgical management of small bowel neuroendocrine tumors

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A discussion this week included the use of DOTATATE in the surgical management of small bowel neuroendocrine tumors.

Reference: Howe JR et al. The surgical management of small bowel neuroendocrine tumors: consensus guidelines of the North American Neuroendocrine Tumor Society (NANTES). Pancreas. 2017 Jul;46(6):715-731. doi:10.1097/MPA.0000000000000846

Summary: The three most commonly used 68Ga-labeled somatostatin receptor PET imaging agents are 68Ga-DOTATATE, 68Ga-DOTATOC and 68Ga-DOTANOC. Despite the slight variation of the somatostatin receptor affinity of these agents, all of them have shown excellent sensitivity in detection of NETs. At this time, there is no evidence of significant diagnostic superiority of one agent over the others.

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Quick review: Receptors effecting the bladder

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A discussion this week involved a review of receptors effecting the bladder.

Reference: University of Washington. Urination. No date. Retrieved from https://courses.washington.edu/conj/bess/urination/urination.html, 25 January 2019.

Summary: The image below illustrates the innervation of the different bladder muscles. It was presented for the benefit of the residents.

receptors and bladder

(https://courses.washington.edu/conj/bess/urination/urination.html)

Symptomatic hyperthyroidism following parathyroidectomy

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A discussion in January included postoperative hyperthyroidism following parathyroidectomy.

Reference: Patel SG, et al. Hyperthyroidism after parathyroid surgery: A prospective analysis of potential contributing factors. (unpublished)

Summary:

In a prospective study of 101 patients between 2014 and 2015, Patel et al examined surgical extent, anatomic findings, thyroid manipulation, anesthetic medication, and outcomes in order to identify potential intraoperative contributing factors for hyperthyroidism after parathyroidectomy.

Unilateral exploration was found to be significantly less often associated with postoperative hyperthyroidism than bilateral exploration. Additionally, incidence was lower with intraoperative ephedrine and four-fold higher with bilateral exploration. The authors recommend that “postoperative TSH screening for those who require bilateral exploration and/or symptoms of hyperthyroidism should be strongly considered.”

It is stated that this prospective study is the first “to evaluate the type and extent of thyroid manipulation during parathyroid exploration as a cause of hyperthyroidism.”

Due to the fact that the data/manuscript is currently unpublished, minimal information is shared here. We will post a notification when it is published. Our deepest thanks to Dr. Patel for his generosity in sharing this information.

Additional reading: Madill EM, Cooray SD, Bach LA. Palpation thyroiditis following subtotal parathyroidectomy for hyperparathyroidism. Endocrinology, Diabetes & Metabolism Case Reports. 2016 July; pii: 16-0049. doi: 10.1530/EDM-16-0049

Mai VQ et al. Palpation thyroiditis causing new-onset atrial fibrillation. Thyroid. 2008;18(5):571-573. doi:10.1089/thy.2007.0246

Stang MT, et al. Hyperthyroidism after parathyroid exploration. Surgery. 2005 Dec;138(6):1058-1064.

 

Thymus carcinoid in multiple endocrine neoplasia syndrome type 1 (MEN-1)

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A discussion this week included thymus carcinoid in MEN-1.

References: Sadacharan D, et al. Rapid development of thymic neuroendocrine carcinoma despite transcervical thymectomy in a patient with multiple endocrine neoplasia type 1. Indian Journal of Endocrinology and Metabolism. 2013 Jul-Aug;17(4):743-746. doi:10.4103/2230-8210.113774.

Teh BT, et al. Thymic carcinoids in multiple endocrine neoplasia type 1. Annals of Surgery. 1998 Jul;228(1):99-105.

Summary: Thymic carcinoid is a rare malignancy, associated with MEN-1 and has no effective treatment (Teh et al, 1998). This is an insidious tumor not associated with Cushing’s or carcinoid syndrome. Local invasion, recurrence, and distant metastasis are common.

Teh et al (1998) recommended the following:

  • In asymptomatic gene carriers with biochemical evidence of hyperparathyroidism, parathyroidectomy with concurrent thymectomy should be considered as soon as possible.
  • In young gene carriers without evidence of hyperparathyroidsim, careful and regular follow-up should be done, including a CT scan or MRI of the chest as well as an octreoscan.

(p.104)

A case report by Sadacharan et al (2013) estimate that thymic neuroendocrine (NE) tumors are reported in only 1-8% of cases and are a major cause of mortality in MEN-1 and gastroentero pancreatic tumors, and are detected approximately 7-29 years after surgical treatment of primary hyperparathyroidism (PHPT). They found a complete surgical excision through a trans-sternal route is the only curative treatmet for thymic NE tumors. Aggressive enbloc resection of involved structures is recommended. Some have advocated routine postop radiotherapy to prevent loco-regional recurrence (Teh et al, 2013).

They further claim that MEN-1 patients need to be screened for thymic NE tumors by routine annual CT or MRI of the thorax even after transcervical thymetcomy (TCT) at the time of parathyroid surgery.

 

 

Surgical management of Crohn’s Disease

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One discussion this week involved the surgical management of Crohn’s Disease.

Reference: Strong S, et al. Clinical practice guideline for the surgical management of Crohn’s Disease. Diseases of the Colon and Rectum. 2015 Nov;58(11):1021-1036. doi:10.1097/DCR.0000000000000450

Summary: The authors state “these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient” (p.1021).

OPERATIVE INDICATIONS

Failed Medical Therapy

  1. Patients who demonstrate an inadequate response to, develop complications from, or are noncompliant with medical therapy should be considered for surgery. Grade of Recommendation: Strong  based on low-or very low-quality evidence, 1C.
  2. Patients receiving therapy with anti-TNFs, high-dose glucocorticoids and/or cyclosporine may warrant staged procedures because of concerns about postoperative complications; however, decisions should be individualized based on the patient’s risk stratification, overall clinical status, and surgeon judgment. Grady of Recommendation: Weak based on low- or very low-quality evidence, 2C.

Inflammation

  1. Patient with acute colitis who have symptoms or signs of impending or actual perforation should typically undergo surgery. Grade of Recommendation: Strong based on low- or very low-quality evidence, 1C.

Stricture

  1. Endoscopic dilation may be considered for patients with symptomatic small-bowel or anastomotic strictures that are not amenable to medical therapy. Grade of Recommendation: Strong based on low- or very low-quality evidence, 1C.
  2. Surgery is indicated for patients with symptomatic small-bowel or anastomotic strictures that are not amenable to medical therapy and/or dilation. Grade of Recommendation: Strong based on low- or very low-quality evidence, 1C.
  3. Patients with strictures of the colon that cannot be adequately surveyed endoscopically should be considered for resection. Grade of Recommendation: Strong based on low- or very-low quality evidence, 1C.

Penetrating Disease

  1. Patients with a free perforation should undergo surgery. Grade of Recommendation: Strong based on moderate-quality evidence, 1B.
  2. Patients with enteroparietal, interloop, intramesenteric, or retroperitoneal abscesses may be managed by antibiotics with or without percutaneous drainage. Surgical drainage with or without resection should be considered when this is not successful. Grade of Recommendation: Weak based on moderate-quality evidence, 2B.
  3. Patients with enteric fistulas and symptoms or signs of localized or systemic sepsis that persist despite appropriate medical therapy should be considered for surgery. Grade of Recommendation: Strong based on low- or very low-quality evidence, 1C.

Hemorrhage

  1. Stable patients with significant GI heomrrhage may be evaluated and treated by endoscopic and/or interventional radiological techniques. Unstable patients should typically undergo operative exploration. Grade of Recommendation: STrong based on low- or very low-quality evidence, 1C.

Growth Retardation

  1. Prepubertal patients with significant growth retardation despite appropriate medical therapy should be considered for surgery. Grade of Recommendation: STrong based on moderate-quality evidence, 1B.

Neoplasia

  1. Patients with long-standing Crohn’s disease of the ileocolic region or colon should have endoscopic surveillance of the large bowel. Grade of Recommendation: Strong based on moderate-quality evidence, 1B.
  2. Total proctocolectomy should be considered for patients with carcinoma, a nonadenoma-like dysplasi-associated lesion or mass (DALM), high-grade dysplasia, or multifocal low-grade dysplasia of the colon or rectum. Grade of Recommendation: Strong based on moderate-quality evidence, 1B.
  3. Suspicious lesions (mass, ulcer) identified in patients with Crohn’s should typically be biopsied, especially when considering a small-bowel strictureplasty. Grade of Recommendation: Strong based on low- or very low-quality evidence.

For complete guidelines (site-specific operations, technical considerations), methodologies, and definition of GRADE system-grading recommendations, see full text article.

Endovascular repair vs open repair for ruptured abdominal aortic aneurysm

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One discussion this week included open vs endovascular repair for ruptured AAA.

Reference: IMPROVE trial investigators. Comparative clinical effectiveness and cost effectiveness of endovascular strategy v open repair for ruptured abdominal aortic aneurysm: three year results of the IMPROVE randomised trial. BMJ. 2017 Nov 14;359:j4859. doi: 10.1136/bmj.j4859

Trial registration: Current controlled trials ISRCTN48334791; ClinicalTrials NCT00746122.

Summary: Involving 30 vascular centers – 29 in UK, one in Canada – and 613 patients between 2009 and 2016, the IMPROVE trial is the first RCT comparing keyhole endovascular aneurysm repair to the traditional open surgery with comprehensive mid-term outcomes. The primary outcome was mortality; secondary outcomes included reinterentions, quality of life, resource use, consts, quality adjusted life year (QALYs), and cost effectiveness.

The data analyses showed endovascular repair “offers no significant reduction in operative mortality at 30 or 90 days, but there is an interim midterm survival advantage (3 months to 3 years), that when taken together with the early gains in QoL, leads to a mid-term gain in QALYs after 3 years.

  • Mortality: 179 deaths in endovascular group, 183 in open repair, with similar results for mortality related to aneurysm
    • Of the 502 patients treated for confirmed rupture, mortality at 3 years: 109/259 (42%) in endovascular, 131/243 (54%) in open repair
  • Reinterventions related to aneurysm: occured at similar rate in both groups, especially those for life threatening conditions.
  • Cost differences at 30 days: “not erorded by an increased burden of reinterventions in later follow-up and therefore the endovascular strategy is cost effective” (p.7).

The authors conclude that at three years, the endovascular repair “offers an increase in QALYs, without an excess of reinterventions, and is cost effective” (p.9). The IMPROVE trial mid-term follow-up supports the benefits of endvascular vs open repair to treat ruptured AAA.

Table 5 (p.8) compares the mid-term outcomes from multiple RCTs of endovascular vs open repair for AAA, including the IMPROVE trial.

improve table 5

Additional reading: Bjorck M. Endovascular or open repair for ruptured abdominal aortic aneurysm? BMJ. 2017;359:j5170. doi:10.1136/bmj.j5170.

Laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss: Two RCTs

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A discussion in December included gastric bypass versus sleeve gastrectomy.

References: Peterli R, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss patients with morbid obesity: the SM-BOSS randomized clinical trial. JAMA. 2018 Jan 16;319(3):255-265. doi:10.1001/jama.2017.20897

Salminen P, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss at 5 years among patients with morbid obesity: the SLEEVEPASS randomized clinical trial. JAMA. 2018 Jan 16;319(3):241-254. doi:10.1001/jama.2017.20313

Summary: Published in the same issue of JAMA, these two trials – one in Switzerland, one in Finland – provide thorough insight into comparing the sleeve and gastric bypass for weight loss in morbidly obese patients. To be consice, the study designs, results, and conclusions are quoted below.

SM-BOSS trial – clinicaltrials.gov Identifier: NCT00356213

DESIGN, SETTING, AND PARTICIPANTS: The Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period.

RESULTS: Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205 (94.5%) completed the trial. Excess BMI loss was not significantly different at 5 years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3% (absolute difference, −7.18%; 95% CI, −14.30% to −0.06%; P = .22 after adjustment for multiple comparisons). Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%). Gastric reflux worsened (more symptoms or increase in therapy) more often after sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number of patients with reoperations or interventions was 16/101 (15.8%) after sleeve gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass.

CONCLUSIONS AND RELEVANCE: Among patients with morbid obesity, there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery.

SLEEVEPASS trial – clinicaltrials.gov Identifier: NCT00793143

DESIGN, SETTING, AND PARTICIPANTS: The Sleeve vs Bypass (SLEEVEPASS) multicenter, multisurgeon, open-label, randomized clinical equivalence trial was conducted from March 2008 until June 2010 in Finland. The trial enrolled 240 morbidly obese patients aged 18 to 60 years, who were randomly assigned to sleeve gastrectomy or gastric bypass with a 5-year follow-up period (last follow-up, October 14, 2015).

RESULTS: Among 240 patients randomized (mean age, 48 [SD, 9] years; mean baseline body mass index, 45.9, [SD, 6.0]; 69.6% women), 80.4% completed the 5-year follow-up. At baseline, 42.1% had type 2 diabetes, 34.6% dyslipidemia, and 70.8% hypertension. The estimated mean percentage excess weight loss at 5 years was 49% (95% CI, 45%-52%) after sleeve gastrectomy and 57% (95% CI, 53%-61%) after gastric bypass (difference, 8.2 percentage units [95% CI, 3.2%-13.2%], higher in the gastric bypass group) and did not meet criteria for equivalence. Complete or partial remission of type 2 diabetes was seen in 37% (n = 15/41) after sleeve gastrectomy and in 45% (n = 18/40) after gastric bypass (P > .99). Medication for dyslipidemia was discontinued in 47% (n = 14/30) after sleeve gastrectomy and 60% (n = 24/40) after gastric bypass (P = .15) and for hypertension in 29% (n = 20/68) and 51% (n = 37/73) (P = .02), respectively. There was no statistically significant difference in QOL between groups (P = .85) and no treatment-related mortality. At 5 years the overall morbidity rate was 19% (n = 23) for sleeve gastrectomy and 26% (n = 31) for gastric bypass (P = .19).

CONCLUSIONS AND RELEVANCE: Among patients with morbid obesity, use of laparoscopic sleeve gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not meet criteria for equivalence in terms of percentage excess weight loss at 5 years. Although gastric bypass compared with sleeve gastrectomy was associated with greater percentage excess weight loss at 5 years, the difference was not statistically significant, based on the prespecified equivalence margins.