Unplanned reoperation after radical surgery for oral cancer: an analysis of risk factors and outcomes

Abstract

Background

Oral cancer (OC) ranks as the sixth most common carcinoma, and it’s a matter of global concern [1]. The higher prevalence and mortality of oral cancer have been reported in developing countries, and China has been perceived as a high incidence of oral cancer [1, 2]. Rapid diagnosis can better control the transformation of precancerous lesions to oral cancer, and improve the overall survival rate of patients [3]. Along with technological developments, tissue fluorescence imaging and molecular biomarkers are used extensively in the cancer clinic [3, 4]. While these technologies have attractive advantages, they all have disadvantages. For example, the characteristics of false-positive, insufficient diagnostic ability, and the clinical diagnostic ability have not been recognized internationally. Therefore, histopathological examination currently remains the diagnostic gold standard. Surgery is considered to be the most effective modalities for the treatment of oral cancer patients [5]. Despite continuing improvements in surgical methods, reducing the complications and improving long-term survival remains a concern. Due to the intricacy of the surgery, postoperative 30-day complication rates for oral cancer can be as high as 20.3% [6]. Approximately 10% of patients with these complications require reoperation [6].

In the perioperative period, patients with surgical complications may undergo unplanned reoperation. Unplanned reoperations have been extensively researched in a variety of surgical fields [7–10]. Previous studies have established that unplanned reoperation or readmission may be associated with colorectal cancer and brain tumor recurrence and mortality [11, 12]. Unplanned reoperations are not expected by surgeons and patients, which will bring physical and psychological pressure to patients, increase hospitalization costs, and put pressure on social resources [13]. Unplanned reoperations account for between 2 and 10% of all surgeries in most surgical areas [14–17]. Several studies examined the risk factors of unplanned reoperation for head and neck cancer surgery complications. Choi et al. showed that long operation time, previous treatment, and higher N (N2) classification were considered key risk factors for unplanned reoperation [18]. According to Zhao et al.’s study, the leading cause of UR were postoperative bleeding, vascular crisis, and diagnostic issues, and patients with microvascular flaps or malignant tumors [19]. Up to now, far too little attention has been paid to assessing the incidence and risk factors associated with UR for oral cancer. To our knowledge, no previous study has given sufficient consideration to the impact of UR on long-term survival after radical oral cancer surgery. Thus, there is a great need to understand the relationship between UR and cancer prognosis.

The aim of the study was to identify the incidence of and risk factors for unplanned reoperation following oral cancer radical surgery, and to explore a potential role for long-term survival. The result from the study may increase the attention of UR among clinicians and reduce the incidences of postoperative complications after surgery.

Methods

Materials and methods

A retrospective analysis was done on oral cancer patients treated with radical oral cancer surgery in the Department of Oral and Maxillofacial Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University. 506 patients undergoing radical surgery for OC between February 2014 and November 2019 were included. The exclusion criteria were as follows: (1) maxillofacial salivary cancer patients, leaving oral cavity cancer patients (n = 30); (2) patients who did not receive neck dissection (n = 27); (3) patients who received radiotherapy and chemotherapy before surgery (n = 28). Together, 421 patients were enrolled for further analysis. According to postoperative assessment, 66 patients were assigned to the UR group, and 355 patients were termed the non-UR group (Fig. 1). All patients were followed for up to 2 years. We strictly followed 1975 Declaration of Helsinki ethical guidelines. This study was approved by the ethical review board of The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University.

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Fig. 1

Flowchart of patient selection. UR, unplanned reoperation

Results

UR as a prognostic factor for long-term survival

In the survival analysis of OC patient prognosis, the mean follow-up time was 53 months. According to the univariate survival analyses, unplanned reoperation, type of reconstruction, age, diabetes, preoperative anemia, tumor size, and cervical nodal metastasis may be predictive factors for recurrence-free survival (Table ​(Table5).5). Furthermore, the results of multivariate logistic regression analysis showed that age (HR = 3.077, 95%CI 1.664–5.682, P < 0.01), diabetes (HR = 1.833, 95%CI 1.091–3.257, P = 0.02), N classification (N1, HR = 4.464, 95%CI 2.551–7.813, P < 0.01) (N2, HR = 2.315, 95%CI 1.101–4.878, P = 0.03), type of reconstruction (Pedicled flap, HR = 0.413, 95%CI 0.236–0.722, P = 0.02) (free flap, HR = 0.354, 95%CI 0.148–0.801, P = 0.01), and unplanned reoperation (HR = 2.864, 95%CI 1.181–7.401, P = 0.02) were independent predictors of outcome (Table ​(Table5).5). UR was significantly associated with shortened cancer-specific survival in this study (Log-rank test, P = 0.024) (Fig. 2).

Table 5

Prognostic factors for cancer-specific survival after curative oral cancer resection in univariate and multivariable analyses

Variable	Univariate survival analysis			Multivariate survival analysis
	Hazard ratio	95% CI	p-value	Hazard ratio	95% CI	p-value
Gender	0.987	0.633–1.541	0.955
Smoking	0.927	0.446–1.927	0.838
Alcohol use	0.950	0.413–2.186	0.904
BMI (kg/m2)	0.651	0.400–1.060	0.084
Hypertension	1.263	0.780–2.047	0.342
Age	2.312	1.297–4.123	0.005*	3.077	1.664–5.682	< 0.001*
Diabetes	2.693	1.583–4.582	< 0.001*	1.833	1.091–3.257	0.023*
Preoperative anemia	2.006	1.246–3.229	0.004*	0.678	0.415–1.109	0.121
Tumor size	2.074	1.257–3.421	0.004*	0.638	0.379–1.074	0.091
Cervical nodal metastasis
N0	Ref
N1	4.878	2.873–8.264	< 0.001*	4.464	2.551–7.813	< 0.001*
N2	2.667	1.300–5.464	0.007*	2.315	1.101–4.878	0.027*
Type of reconstruction
Local flap	Ref
Pedicled flap	0.433	0.257–0.729	0.002*	0.413	0.236–0.722	0.002*
Free flap	0.336	0.148–0.763	0.009*	0.345	0.148–0.801	0.013*
Cancer subsites
Oral cavity	Ref
Oropharynx	1.658	0.605–4.545	0.325
Larynx	1.390	0.254–7.590	0.704
Salivary Gland	1.041	0.116–9.350	0.971
URO	2.768	1.118–6.854	0.028*	2.864	1.181–7.401	0.020*

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Numbers in boldface indicate statistically significant values (P < 0.05)

^*P < 0.05

UR, unplanned reoperation; BMI, body mass index

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Fig. 2

Kaplan–Meier curves for cancer-specific survival. UR, unplanned reoperation

Discussion

The incidence of oral cancer is increasing year by year, which has become a global concern [23]. The sooner OC is diagnosed, the better the therapeutic efficacy was detected. The fluorescence method is a non-invasive way of diagnosing oral cancer, but it is still in clinical exploration due to the occurrence of false positives [24]. Histopathological examination currently remains the diagnostic gold standard. At present, physicians and scholars are devoted to the study of oral prognosis, but it is affected by many factors [25]. In recent years, UR is garnering more and more attention.

Over the last dozen years, the incidence of UR has decreased with the advances in surgical technique. Nevertheless, the poor prognosis among patients with UR remains a serious threat to global health. UR often is associated with higher postoperative morbidity, mortality and consequent high medical costs [26, 27]. In the current medical and health institutions, the UR rates was recognized as one of the evaluation indicators of surgical quality, attracting the attention of clinicians [8]. According to Choi et al.’s study, the incidence of unplanned reoperation in head and neck cancer surgery was 10.5% [18]. Zhao et al. reported that the overall unplanned reoperation rate in oral and maxillofacial surgery was 1.52% [19]. The incidence of UR was found to be 15.7 percent in this study, which enrolled over 400 patients. UR is typically correlated with complex surgical procedures such as radical surgery of oral cancer. To further lower risk factors and indications for UR, it is meaningful for surgeons to understand preoperative, perioperative, and postoperative risk factors. Meanwhile, we found that diabetes, tumor size, N classification (N2), and pedicled flap reconstruction were independent risk factors for UR.

Flap failure was the most dominant cause of unplanned reoperations in our study. Thomas’s comparative study showed a reoperation rate of 20.2% in the head and neck free flap reconstructions [28]. Recently, Kwok and Agarwal had investigated the reoperation rate of all microvascular free tissue transfers, and showed the overall reoperation rate was 12.9% and a head and neck reoperation rate was 18.0% [29]. Blockage of blood arteries owing to thrombus development was discovered to be a major cause of flap failure [30]. Anastomosis of a secondary vein has been proven beneficial to the survival of the flap and reduces venous congestion [30]. However, microscopic vascular anastomoses required enormous amounts of time to expend. Moreover, multiple studies showed that a single venous anastomosis can provide enough drainage while maintaining flap survival and reducing operation time, with no significant difference compared to two venous anastomosis [31, 32]. To prevent venous thrombosis, Matti Sievert et al. suggested that low molecular weight heparin can effectively improve the survival rate of the flap [33]. The above literature showed that one venous anastomosis combined with low molecular weight heparin applied could be attributed to an increased survival rate of flap.

Previous studies have found that postoperative bleeding is the most common reason for unplanned reoperation for a variety of diseases, including maxillofacial surgery [17, 34, 35]. Our data revealed that postoperative bleeding was the second most common complication after radical oral cancer surgery. There were only 9 cases of postoperative hemorrhage in UR group, accounting for nearly 13.6 percent of the total number of UR patients. Early postoperative bleeding is associated with hemostasis failure or coagulation defects [19]. Taking NSAIDS and hypertension together is a common cause of postoperative bleeding [36, 37]. In our opinion, preoperative coagulopathy should be given particular attention, and blood pressure should be maintained normal in individuals. Moreover, controlling hemostasis and blood pressure under anesthesia is critical intraoperatively [38]. In this study, delayed hemorrhages were more common in tiny arteries and muscle or connective tissue in the surgical area. To prevent hemostasis, an electrical knife has been widely used in a variety of surgical specialties. Zhao et al. considered that the postoperative bleeding was caused by inappropriate use of the electrical knife [19]. Electrical knives with a high frequency should stay in the tissue for a long enough time to establish effective hemostasis. The ultrasonic scalpel can be effective for providing a relative bloodless field in muscle or connective tissue, which facilitates saving surgical time [39]. Persistent postoperative pain promotes high blood pressure, which also leads to arrhythmia or small blood vessel hemorrhage. Sufficient postoperative analgesia is more conducive to reducing the risk of UR.

Marra et al. found that extra-nodal extension and perineural invasion are prognostic factors associated with reduced disease-free survival for oral tongue cancer [40]. Hussain et al. showed that nodal stage was the most important poor prognostic factor in terms of disease-free survival in T1, T2 oral tongue cancer [41]. Our research showed that UR may have a significant impact on oral cancer patients' long-term survival rates following surgery. In addition, multivariate analyses revealed that unplanned reoperation may be poor prognostic factors for cancer-specific survival.

Despite our efforts to subject it to a comprehensive analysis, the present study still has a few limitations. First, our study was based on retrospective single-center study. Further prospective multicenter studies may be warranted to further validate the findings. Second, the relatively small sample size of UR should be taken into consideration. Third, due to the complex condition of patients, different clinical decision-making for the same disease might affect our results. Therefore, a more comprehensive investigation is needed for further confirmation in the context of big data. Despite these limitations, the research confirmed the clinical importance of an unplanned reoperation in oral cancer surgery.

Conclusion

This study suggests that tumor size, diabetes, N classification (N2), and pedicled flap reconstruction might be risk factors for UR after oral cancer radical surgery. UR was associated with worse long-term survival, and may be a novel prognostic factor for OC patients. These findings may help identify high-risk patients for UR, optimize surgical planning, strengthen perioperative management, and reduce the incidence of unplanned reoperations.

Acknowledgements

Abbreviations

Author contributions

MW conceived the study, carried out the design and coordination, wrote the manuscript, and gave the final approval of the version to be submitted. PY and HZ critically revised the manuscript for important intellectual content. WZ and PY collected the clinical data and drafted the article. All authors read and approved the final manuscript.

Funding

This study did not receive any funding and there are no financial conflicts of interest.

Availability of data and materials

The data are available from the corresponding author on reasonable request.

Declarations

Footnotes

Contributor Information

Wei Zhang, Email: moc.361@04068605951m.

Hong Zhu, Email: moc.361@gnohuhzyyah.

Pu Ye, Email: moc.361@260774678py.

Meng Wu, Email: nc.ude.umjn@mwyyah.

References