No Additional Morbidity Associated with Adding Neck Dissection to a Thyroidectomy: A NSQIP Analysis of 44,887 Patients

Review article

No Additional Morbidity Associated with Adding Neck Dissection to a Thyroidectomy: A NSQIP Analysis of 44,887 Patients

Corresponding authorDr. Jon P. Ver Halen, Division of Plastic, Reconstructive and Hand Surgery, Baptist Cancer Center Research Faculty, Vanderbilt Ingram Cancer Center Adjunct Clinical Member, St Jude Children’s Research Hospital, United States, Tel: (901)227-9820; Fax: (901) 227 9825; Email: jpverhalen@gmail.com

Abstract

Background:

The potential oncologic benefit of adding neck dissection to thyroidectomy procedures is balanced with a presumed increased morbidity from more extensive surgery. Although there has been some literature documenting the risks of adverse events (AE) from neck dissection in single institutions, there has not been a large volume analysis to investigate this issue.

Methods
The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) 2005–2012 registry was queried to identify all patients undergoing thyroidectomy, with or without associated neck dissection. Patients were propensity- score matched 1:1 for preoperative factors. Outcomes of interest included surgical wound and medical complications, reoperation, and mortality. Univariate and multivariate analyses were utilized to identify predictors of these events. Odds ratios were calculated for adverse events between cohorts.

Results
A total of 44,887 patients were identified for analysis. Of these, 38,449 (85.4%) underwent an isolated thyroidectomy (IT) procedure without neck dissection, and 6,438 (14.6%) underwent a thyroidectomy with neck dissection (TND). After matching, there were 4,814 patients found to have similar pre-operative comorbidities, demographics and operative factors. There was a higher rate of overall complications in the IT group (4.25%) than the TND group (3.00%, p<0.001). There was no statistically significant difference in surgical complications. There was, however, a statistically significant increase in medical complications in the IT group (3.83%) over the TND group (2.68%, p=0.005). There was no difference in post-operative mortality between both groups. There was a higher rate of return to the operating room for the IT group (2.54%) compared to the TND group (1.54%, p=0.004).

Conclusions
The morbidity and mortality of thyroid surgery is relatively low overall. In this analysis there was no measurable increase in the complications conferred by the addition of a neck dissection. These data are important for patient informed consent, risk stratification, and surgical planning.

Keywords: Thyroidectomy; NSQIP; Neck Dissection; Outcomes; Mortality; Complications   

Introduction


The rate of thyroid cancer is increasing, but it is unknown whether this represents a true increase in incidence, or an increased detection rate of cancer in smaller nodules. The rate for new diagnoses of thyroid cancer has increased an average of 6.4% per year over the last 10 years, and mortality of thyroid cancer has increased 0.9% per year over the same period [1].

It has long been suggested that the presence of cervical metastasis of differentiated thyroid cancer does not affect survival. This was reflected in the various prognostic scoring systems of AMES, AGES, and MACIS [2-4]. One study challenged this dogma, noting there was increased survival with prophylactic removal of lymph nodes [5], however there is ongoing debate regarding the need for prophylactic neck dissection.

The potential oncologic benefit of adding neck dissection to thyroidectomy procedures is balanced, however, with a presumed increased morbidity from more extensive surgery. Although there has been some literature documenting the risks of hypoparathyroidism [6] and recurrent laryngeal nerve injury from neck dissection in single institutions, there has not been a large volume analysis to investigate potential increased risks of overall medical and surgical complications with the addition of neck dissection to a thyroidectomy procedure [7].

The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) is a multi-institutional collaborative effort that collects data from more than 500 hospitals. The data include 135 variables including preoperative status, intraoperative variables, and postoperative outcomes, including 30-day postoperative morbidity and mortality. The NSQIP database is an excellent resource for population-based analyses of critical health care issues, including registry-based trials, risk adjustment, surgical outcomes and cost [8].

The purpose of this study was to use the ACS-NSQIP database to evaluate a high volume of patients to assess whether adding a neck dissection to a thyroidectomy conferred more risk of complications. Although most reports on thyroidectomy outcomes focus on technical complications such as recurrent laryngeal nerve injury and hypoparathyroidism, we sought to understand nontechnical complications that occurred with the addition of neck dissection to thyroid surgery.

Methods

Data Acquisition and Patient Population

Data collection methods for the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) registry have been previously described [9,10]. All study aspects were approved by the respective Institutional Review Boards. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) 2005 – 2012 registry was queried. The ACS-NSQIP is a prospectively validated multi-institutional database which began in 2004 and provides comprehensive preoperative, perioperative, and 30-day postoperative data for 2.3 million de-identified patients from over 460 participating institutions across the United States. Patients with only primary current procedural terminology (CPT) codes 60220, 60225, and 60240 were stratified to the isolated thyroidectomy (IT) group. The thyroidectomy with neck dissection (TND) group consisted of patients with only primary CPT code 60252 or 60254. The CPT codes used are shown in Table 1.

Table 1. Pre- and post-match patient cohort totals, versus American Medical Association’s Current Procedural Terminology codes.

Peri-operative Variables

Preoperative variables defined in NSQIP included demographic variables age, sex, race, and BMI, medical comorbidities including diabetes, dyspnea, COPD, previous cardiac surgery, pervious stroke, hypertension, disseminated cancer, wound infection, steroid use, bleeding disorders, chemotherapy, radiotherapy, sepsis, wound class, and ASA class, and intraoperative characteristics including inpatient status and total RVU.

The primary outcomes of interest were 30-day complication rates, categorized as surgical wound complications, medical complications, and overall complications. Surgical wound complications included superficial, deep, or organ-space surgical site infection (SSI), wound dehiscence. Medical complications examined included pneumonia, unplanned reintubation, pulmonary embolism, ventilator dependence >48 hours, urinary tract infection, stroke, peripheral nerve injury, cardiac arrest, myocardial infarction, blood transfusions, deep vein thrombosis (DVT), sepsis, and septic shock. Return to the operating room and death were also included in this analysis as separate entities.

Statistical Analysis

Patients were propensity score matched to balance out differences between the patient populations. For each patient, the variables in Table 2 were used to model their probability for undergoing an outpatient procedure. Using these values, IT patients were paired with the nearest TND procedure without replacement in a 1:1 ratio. When a close match was not available, the case was eliminated. Specific variables included for matching included: age; BMI; current smoking status; current alcohol abuse; diabetes mellitus; dyspnea; COPD; previous cardiac surgery; previous TIA or stroke; hypertension; disseminated cancer; current steroid or immunosuppressant use; history of bleeding disorder; history of chemotherapy; history of radiotherapy; current sepsis; wound class; and hospital setting. Propensity score matching was carried out in SPSS (IBM Corp., Armonk, NY), and has been previously described in detail [11-13].

Comparison of the descriptive statistics and outcomes for the matched cohorts was performed using chi-square tests for categorical variables and Student’s t test for continuous variables, with significance defined as p <0.05. Statistical evaluation of outcomes were not evaluated for unmatched cohorts. Multiple logistic regression models with adjusted odds ratios for complications, return to OR, and death were constructed. Perioperative variables with n ≥ 10 and p <0.2 as identified in a bivariate screen were included in the regression models. Again, p <0.05 was considered significant. C-statistics were calculated to assess model discriminatory capability. All analyses were performed using SPSS version 22 (IBM Corp., Armonk, NY).

Results

A total of 44,887 patients were identified for analysis, of which 38,449 (85.4%) underwent an isolated thyroidectomy (IT) procedure without neck dissection, and 6,438 (14.6%) underwent a thyroidectomy with neck dissection (TND).

The mean age was 51.48 years in the IT group compared to 48.72 in the TND group (p<0.001). Males made up 18.2% of the IT group compared to 26.3% in the TND group (p<0.001). BMI was slightly higher in the IT group 29.77 (SEM 7.5) compared to the TND group (SEM 7.02, p<0.001). American Society of Anesthesiologists (ASA) classification 1 or 2 was assigned to 74.7% of those undergoing isolated thyroidectomy compared to 70.9% in those undergoing thyroidectomy with neck dissection (p<0.001).

Preoperative characteristics are described in Table 2. Within the isolated thyroidectomy group there was a significantly higher incidence of patient smoking (15.8% vs 12%, p<0.001), diabetes mellitus, dyspnea (11.4% vs 9%, p<0.001), chronic obstructive pulmonary disease (1.9% vs 1.4%, p=0.004), stroke (2.9% vs 2.2%, p=0.004), and hypertension (38% vs 31.1%, p<0.001). The thyroidectomy with neck dissection group had significantly higher rates of disseminated cancer (2.3% vs 0.5%, p<0.001), as well as history of radiotherapy (0.3% vs 0.1%, p=0.004). Wound classification was more likely to be clean in the isolated thyroidectomy group (98% vs 96.9%, p<0.001). Operative times were longer (180.5 vs 111.3 minutes, p<0.001) and total relative value units (RVUs) were higher (28.96 vs 15.72, p<0.001) in the thyroidectomy with neck dissection group.

Table 2. Preoperative and Operative Characteristics of Pre-Match Cohorts.

Matching of preoperative characteristics outlined in the methods section was performed to have homogenous groups for analysis. After matching, there were 4,814 patients found to have similar pre-operative comorbidities and demographics, as seen in Table 3.

Complications for the IT and TND groups, in the matched cohort, are reported in Table 4. There was a higher rate of overall complications in the IT group (4.25%) than the TND group (3.00%, p<0.001). There was no statistically significant difference in surgical wound complications among the IT cohort (0.65%) and the TND cohort (0.47%, p=0.284). However, a statistically significant increase in medical complications in the IT group (3.83%) over the TND group (2.68%, p=.005) was noted. With regard to the IT cohort, there were trends for higher rates of unplanned reintubation, pulmonary embolism, prolonged post-operative ventilation, urinary tract infection, myocardial infarction, blood transfusion, deep venous thromlarynbosis, and sepsis, but none of these were statistically significant. The only individual complication that reached statistical significance was post-operative stroke (0.16% for IT vs 0.00% for TND, p=0.014). There was no difference in post-operative mortality between each cohort. There was a higher rate of return to the operating room for the IT group compared to the TND group (2.54% vs1.54%, p=0.004).

Odds ratio analysis was performed between the IT and TND groups for the matched cohort, as seen in Table 5. With reference to the isolated thyroidectomy group, the thyroidectomy with neck dissection group had a significant adjusted odds ratio <1 for overall complications, medical complications, and return to the operating room.

Table 5. 30-day Complications Odds Ratio of TND vs IT.

Discussion

Differentiated thyroid cancer (comprised of papillary thyroid cancer and follicular thyroid cancer) makes up approximately 90% of all thyroid cancers overall [14]. Nodal metastases are known to significantly correlate with persistence and recurrence of disease, and micrometastases are found in up to 90% of prophylactically dissected neck compartments [15-18]. Although it was traditionally held that the presence of cervical metastases did not affect survival in thyroid cancer, this dogma has recently been challenged by a large population-based study demonstrating decreased survival in patients with cervical metastases [19-23]. However, little is known about the attendant surgical morbidity associated with neck dissection after thyroidectomy.

The NSQIP database is a unique and robust database with large volumes that can support critical analyses of risk factors with small confidence intervals. NSQIP collects data from both major academic tertiary-care medical centers as well as community hospitals, thereby capturing a broad snapshot of procedures and patients with their preoperative risks and postoperative outcomes. Because the data is prospectively collected and validated by a highly-trained and dedicated surgical clinical nurse reviewer (SCNR), the NSQIP has a large advantage over other registry and Medicare-based analyses that are primarily administrative discharge datasets without emphasis on accuracy.

A major weakness of the NSQIP database is that it was designed to capture data for all surgeries with general complications as the assessment goal; therefore, some procedure-specific information is not collected. For example, data on thyroidectomy does not include information on injury to the recurrent laryn geal nerve nor on the rate of hypocalcemia. Information on post-operative hematoma is not tracked, but some authors have used the information on “bleeding requiring transfusion” or “reoperation” as a surrogate for the development of neck hematoma [24, 25]. Another weakness is that NSQIP does not allow comparisons between high volume and low volume surgeons, nor between high volume and low volume institutions; therefore, conclusions cannot be made regarding surgical outcomes among these groups.

A 2014 NSQIP study assessed how various preoperative comorbidities and intraoperative variables were tied to thyroidectomy outcomes [26]. In an analysis of 38,577 cases they found that risk factors independently associated with morbidity after thyroidectomy included hypertension, diabetes, advanced age greater than 70 years, COPD, and dialysis. Interestingly they found that the surgical approach was related to the rate of return to the operating room. As compared with a partial thyroidectomy, patients undergoing a total thyroidectomy  were 73% less likely to return to the operating room and those undergoing substernal thyroidectomy were 37% less likely to return to the operating room.

In our study the 30 day mortality was 0.18% for isolated thyroidectomy and 0.08% for thyroidectomy with neck dissection. These mortality rates compare favorably with mortality rates of other procedures such as pancreatectomy (8.3%), coronary artery bypass graft (3.5%), craniotomy (10.7%), and repair of aortic aneurysm (3.9%) [27]. The overall complication rates found in our study were also low; 4.25% for isolated thyroidectomy and 3.0% for thyroidectomy with neck dissection. This underscores the relative safety profile of thyroidectomy procedures. Thyroidectomy surgeons and hospitals should use these data as a benchmark to compare their own rate of complications and improve their own quality control.

Rates of reoperation were significantly decreased in the TND group, compared to IT (OR 0.689, p =0.006). It seems reasonable that the increase in reoperation among the IT cohort may be accounted for by the need for completion thyroidectomy after a diagnostic lobectomy within the IT cohort. In fact, Qin et al. found that thyroid lobectomy had a higher rate of return to the operating room than total thyroidectomy [28]. Naturally, it would be expected that there would be an increased rate of hematoma with increased extent of surgery in the TND group compared to the IT group; but it appears that using rate of reoperation as a surrogate for development of hematoma is a dangerous assumption, and we would recommend against it for future NSQIP analyses.

It could easily be reasoned that the increased surgery of TND would confer more risk of complication than IT. Interestingly however, surgical wound complications were no different between cohorts on multivariable analysis, and surprisingly, postoperative medical complications were higher in the isolated thyroidectomy group. What is the driver behind the significantly increased medical (and thus, total) complications in theIT cohort?

On close examination, a number of hypotheses to explain these differences between IT and TND cohorts emerge. Case volume has been shown to correlate with outcomes after thyroidectomy, but is not tracked in NSQIP. Perhaps hospital setting could be used as a surrogate for case volume, as academic centers arguably are referred more advanced cases of thyroid carcinoma requiring neck dissection. Pre-match, the TND group had a higher percentage of academic medical centers (28.5% vs 25.3%, p< 0.05). Post-match, this difference was reversed, thus eliminating hospital setting as a possible reason for the differences seen in outcomes (5.9% vs 6.9%, p< 0.05). It is possible that case volume does indeed correlate with outcomes in these cohorts, but that “academic versus community” setting is not an accurate surrogate for this variable. It could also be reasoned that academic teaching hospitals may have different post-operative admitting protocols after thyroidectomy than their community hospital cohorts; and if the rates of post-operative admission differed in each group, then certainly this could affect the number of complications recorded by the NSQIP’s surgical clinical nurse reviewer.

In the analysis of matched cohorts (Table 4), overall complications were increased in the IT cohort compared to the TND cohort. This difference was not due to the surgical complications (no significant difference), but rather due to the increased post-operative medical complications in the IT cohort. Examination of the medical complications shows that, other than stroke, there was no single adverse event that was significantly higher in the IT group, but rather only in aggregate were the medical complications statistically higher in the IT group. This difference was identified despite the increased operative time and work RVU in the TND cohort (both p< 0.001). Given that there is no conceivable direct mechanism by which IT could increase the risk of stroke or other medical complication, we are limited to conjecture to explain this constellation of findings. It is conceivable that patients undergoing TND receive a more extensive preoperative workup, and more invasive postoperative monitoring, and that these factors help to minimize rates of postoperative medical adverse events.

In summary, this NSQIP analysis illustrates little to no objective morbidity conferred to patients by the addition of neck dissection to their thyroidectomy procedure in the matched cohort. No difference occurred regarding surgical wound complications or mortality. Medical complications, overall complications, and return to OR were significantly elevated in the IT group. However, the difference in medical complications was minimal (3.83% vs 2.68%), and should not be considered clinically significant.

Conclusion

The general morbidity and mortality of thyroid surgery is relatively low. In this analysis there was no measurable increase in general complications conferred by the addition of a neck dissection. This conclusion is guarded given the limitations of this study. Preoperative comorbidities should be considered when weighing the risks of thyroid surgery and its accompanying complications.

References

1.Howlader N, Noone AM, Krapcho M. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. Accessed June 1, 2014.

2.Cady B, Sedgwick CE, Meissner WA, Wool MS, Salzman FA et al. Risk factor analysis in differentiated thyroid cancer. Cancer. 1979, 43(3): 810-820.

3.Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery. 1987, 102(6): 1088- 1095.

4.Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS. Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery. 1993, 114(6): 1050-1057.

5.Lundgren CI, Hall P, Dickman PW, Zedenius J. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer. 2006, 106(6): 524-531.

6.Viola D, Materazzi G, Valerio L, Molinaro E, Agate L et al. Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J Clin Endocrinol Metab. 2015, 100(4):1316-1324.

7.Giordano D, Valcavi R, Thompson GB, Pedroni C, Renna L et al. Complications of central neck dissection in patients with papillary thyroid carcinoma: results of a study on 1087 patients and review of the literature. Thyroid. 2012, 22(9): 911-917.

8.Lauer MS, D’Agostino RB. The randomized registry trial – The next disruptive technology in clinical research? New Engl J Med. 2013, 369(17): 1579 – 1581.

9.ACS NSQIP Participant Use Data File.

10.Shiloach M1, Frencher SK Jr, Steeger JE, Rowell KS, Bartzokis K et al. Toward robust information: data quality and inter-rater reliability in the American College of Surgeons National Surgical Quality Improvement Program. J Am Coll Surg. 2010, 210(1): 6–16.

11.Austin PC. Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations. Biom J. 2009, 51(1): 171-184.

12.Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 2011, 10(2):150-161.

13.Thoemmes F. Propensity score matching in SPSS 2012 [December 12, 2013].

14.Sherman SI. Thyroid carcinoma. Lancet. 2003, 361(9356): 501-511.

15.Machens A Hinze R, Thomusch O, Dralle H. Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg. 2002, 26(1): 22-28.

16.Arturi F, Russo D, Giuffrida D, Ippolito A, Perrotti N et al. Early diagnosis by genetic analysis of differentiated thyroid cancer metastases in small lymph nodes. J Clin Endocrinol Metab. 1997, 82(5): 1638-1641.

17.Tisell LE, Hansson G, Jansson S, Salander H. Reoperation in the treatment of asymptomatic metastasizing medullary thyroid carcinoma. Surgery. 1986, 99(1): 60-66.

18.Moley JF, Wells SA. Compartment-mediated dissection for papillary thyroid cancer. Langenbecks Arch Surg. 1999, 384(1): 9-15.

19.Rossi RL, Cady B, Silverman ML, Wool MS, Horner TA. Current results of conservative surgery for differentiated thyroid carcinoma. World J Surg. 1986, 10(4): 612-622.

20.Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994, 97(5): 418-428.

21.Lundgren CI, Hall P, Dickman PW, Zedenius J. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer. 2006, 106(3): 524-531.

22.Hamming JF, Roukema JA. Management of regional lymph nodes in papillary, follicular, and medullary thyroid cancer. In: Clark OH, Duh Q-Y, Kebebew E, editors. Textbook of endocrine surgery, 2nd ed. Philadelphia, Saunders, 2005, pp195-206.

23.Kouvaraki MA, Lee JE, Shapiro SE, Sherman SI, Evans DB.Preventable reoperations for persistent and recurrent papillary thyroid carcinoma. Surgery. 2004, 136(6): 1183-1191.

24.Gupta PK, Smith RB, Gupta H, Forse RA, Fang X et al. Outcomes after thyroidectomy and parathyroidectomy. Head Neck. 2012, 34(4): 477-484.

25.Khavanin N, Mlodinow A, Kim JY, Ver Halen JP, Antony AK et al. Assessing safety and outcomes in outpatient versus inpatient thyroidectomy using the NSQIP: A propensity score matched analysis of 16,370 patients. Ann Surg Oncol. 2014, 22(2): 429-436.

26.Abraham CR, Ata A, Carsello CB, Chan TL, Stain SC et al. A NSQIP risk assessment for thyroid surgery based on comorbidities. J Am Coll Surg. 2014, 218(6): 1231-1238.

27.Dimick JB, Welch HG, Birkmeyer JD. Surgical mortality as an indicator of hospital quality: the problem with small sample size. J Am Med Assoc. 2004, 292(7): 847-851.

28.Qin CD, Saha S, Meacham R, Sandeep Samant, Jon P Ver Halen et al. Surgical risk after unilateral lobectomy versus total thyroidectomy: A review of 47,434 patients. Surgery Curr Res. 2014, 4: 208.

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