Category Archives: Oncology

Perioperative fluid management: restrictive vs liberal regimens

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One discussion this week included restrictive vs liberal perioperative fluid management on the development of perioperative acute kidney injury.

References: Brandstrup B, et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Annals of Surgery. 2003 Nov;238(5):641-648.

Myles PS, et al. Restrictive versus liberal fluid therapy for major abdominal surgery. NEJM. 2018 Jun 14;378:2263-2274. doi:10.1056/NEJMoa1801601

Summary: Traditional intravenous-fluid regimens administered during abdominal surgery deliver up to 7 liters of fluid on the day of surgery. Some small trials have shown that a more restrictive fluid regimen led to fewer complications and a shorter hospital stay. However, the evidence for fluid restriction during and immediately after abdominal surgery is inconclusive. Fluid restriction could increase the risk of hypotension and decrease perfusion in the kidney and other vital organs, leading to organ dysfunction, but excessive intravenous-fluid infusion may increase the risk of pulmonary complications, acute kidney injury, sepsis, and poor wound healing (Myles 2018).

Each of the RCTs below compare restrictive vs liberal fluid management, with conflicting conclusions.

BRANDSTRUB ET AL (2003)

This multicenter RCT involved 172 patients allocated to either a restricted or a standard intraoperative and postoperative intravenous fluid regimen. The restricted regimen aimed at maintaining preoperative body weight; the standard regimen resembled everyday practice. The primary outcome measures were complications; the secondary measures were death and adverse effects.

Results: The restricted intravenous fluid regimen significantly reduced postoperative complications both by intention-to-treat (33% versus 51%, P = 0.013) and per-protocol (30% versus 56%, P = 0.003) analyses. The numbers of both cardiopulmonary (7% versus 24%, P = 0.007) and tissue-healing complications (16% versus 31%, P = 0.04) were significantly reduced. No patients died in the restricted group compared with 4 deaths in the standard group (0% versus 4.7%, P = 0.12). No harmful adverse effects were observed.

Conclusion: The restricted perioperative intravenous fluid regimen aiming at unchanged body weight reduces complications after elective colorectal resection.

MYLES ET AL (2018)

This international trial randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death.

Results: Up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters, as compared with 6.1 liters in 1493 patients in the liberal fluid group. The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group. The rate of AKI was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group. The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group; rates of surgical-site infection (16.5% vs. 13.6%) and renal-replacement therapy (0.9% vs. 0.3%) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing.

Conclusion: Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury.

Additional Reading: Romagnoli S, Ricci Z, Ronco C. Perioperative acute kidney injury: prevention, early recognition, and supportive measures. Nephron. 2018;140(2):105-110.

Salmasi V, et al. Relationship between intraoperative hypotension, defined by either reduction from baseline or absolute thresholds, and acute kidney and myocardial injury after noncardiac surgery: a retrospective cohort analysis. Anesthesiology. 2017;126:47-65. doi:10.1097/ALN.0000000000001432

OpenAnesthesia. Encyclopedia: Fluid Management. OpenAnesthesia. 2019. International Anesthesia Research Society. Retrieved from: http://www.openanesthesia.org/fluid-management/

EAST guidelines on the use of antibiotics in thoracostomy

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One discussion this week involved the use of antibiotics in thoracostomy.

Reference: Moore FO et al. Presumptive antibiotic use in tube thoracostomy for traumatic hemopneumothorax: An Eastern Association for the Surgery of Trauma practice management guideline. 2012. Retrieved from: https://www.east.org/education/practice-management-guidelines/tube-thoracostomy-presumptive-antibiotics-in

Summary:  A systematic review was done by 10 acute care surgeons and one statistician to update the 1998 guidelines for EAST. Routine presumptive antibiotic use to reduce the incidence of empyema and pneumonia in tube thoracostomy (TT) for traumatic hemopneumothorax is controversial. Moore et al (2012) conclude that there is insufficient published evidence to support any recommendation either for or against this practice. The authors further state that “until a large and likely multicenter, randomized, controlled trial can be performed, the routine practice of presumptive antibiotics in TT for chest trauma will remain controversial.”

Additionally, the authors are unable to recommend an optimal duration of antibiotic prophylaxis when antibiotics are administered for traumatic hemopneumothorax because there are insufficient published data to support the routine use of antibiotics.

Additional Reading: Department of Surgical Education, Orlando Regional Medical Center. Chest Tube Management. 2016 Sept 8. Retrieved from http://www.surgicalcriticalcare.net/Guidelines/Chest%20tube%20management%202016.pdf

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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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.

 

 

Simultaneous vs staged colorectal and hepatic resections

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One discussion this week involved the comparison of simultaneous and staged resections of colorectal cancer and synchronous colorectal liver metastases (SCRLM).

Reference: Reddy SK, et al. Simultaneous resections of colorectal cancer and synchronous liver metastases: a multi-institutional analysis. Annals of Surgical Oncology. 2007 Dec;14(12):3481-3491. doi:10.1245/s10434-007-9522-5

Summary: In a retrospective study of 610 patients at three institutions between 1985 and 2006, the authors compared postoperative morbidity and mortality after simultaneous and staged resections of colorectal cancer and SCRLM.

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Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma

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One discussion this week included using chemotherapy to enable initially unresectable intrahepatic cholangiocarcinoma (ICC) to be resectable.

Reference: Le Roy B, et al. Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma. The British Journal of Surgery. 2018 Jun;105(7):839-847. doi: 10.1002/bjs.10641

Summary: Surgical resection is the standard treatment for ICC, with a 5-year survival rate of 25-35% for those presenting with potentially resectable disease. Those with initially unresectable ICC are treated with chemotherapy alone and have a poor prognosis (p.839). The strategy of conversion to secondary resectability through chemotherapy regimens has resulted in good long-term survival for other tumors (colorectal liver and neuroendocrine liver metastases).  The authors state there is no published data on the use of neoadjuvant chemotherapy to achieve secondary resectability in locally advanced ICC.

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

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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).