Analysis of the Therapeutic Effectiveness of Segmental Lung Resection Versus Lobectomy in Patients with Isolated Lung Metastases from Colorectal Cancer

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Analysis of the Therapeutic Effectiveness of Segmental Lung Resection Versus Lobectomy in Patients with Isolated Lung Metastases from Colorectal Cancer

https://doi.org/10.21203/rs.3.rs-4323469/v1

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In patients with solitary pulmonary metastasis from colorectal cancer, surgical resection is considered a standard treatment protocol and routinely performed in thoracic surgery. However, there is a paucity of studies that delve into the detailed discussion of the efficacy and safety of lobectomy and segmentectomy in the treatment of pulmonary metastatic cancer. Our study retrospectively analyzed the surgical outcomes of 62 patients from a single center and reported the findings. In comparison to the group undergoing lung segmental resection, the cohort receiving lobectomy exhibited significantly larger tumor diameters (P < 0.001), prolonged operative durations (P < 0.001), increased intraoperative bleeding (P = 0.002), augmented drainage volume on the first postoperative day (P < 0.001), greater total postoperative drainage (P < 0.001), and elevated operative costs (P < 0.001). Pulmonary segmentectomy offers superior advantages in terms of operative time, intraoperative blood loss, drainage volume on the first postoperative day, total postoperative drainage volume, and surgical costs.

Health sciences/Diseases/Cancer/Cancer therapy

Health sciences/Medical research

Colorectal cancer lung metastasis

Solitary Metastasis

Lobectomy

Segmentectomy

comparative study

Colorectal cancer (CRC) ranks as the third most prevalent cause of cancer-related mortality, despite advancements in adjuvant and surgical therapies, as well as multidisciplinary strategies that have significantly altered long-term survival outcomes. Nevertheless, metastatic dissemination occurs in approximately half of patients following radical resection of the primary tumor ^[1]. Notably, the lungs constitute a frequent site for CRC metastasis, trailing only the liver in frequency. Pulmonary metastasis is observed in 15–20% of CRC cases, highlighting its significant clinical impact^[2]. Surgical resection of metastatic tumors has emerged as a standard therapeutic approach when indicated and is routinely practiced in thoracic surgery^[3]. Case series from renowned cancer centers have demonstrated that approximately 40–55% of patients undergoing resection of lung metastases from CRC achieve favorable long-term survival outcomes ^[4–6].

Among the surgical procedures for removing isolated lung metastases from CRC, lung wedge resection is the most frequently performed, followed by segmental resection and lobectomy^[7]. Lung segmental resection involves a more limited resection of lung tissue compared to lobectomy, offering several advantages. These include greater preservation of lung function, reduced operative mortality, decreased intraoperative bleeding, and shorter hospital stays^[8]. The randomized controlled trial conducted by Kenji Suzuki et al. in 2019 revealed comparable intraoperative and postoperative complication rates between patients undergoing segmental lung resection and those undergoing lobectomy. This suggests that, with the continuous advancements in imaging and other related diagnostic modalities, both procedures can be considered viable therapeutic options^[9] .

Over the past decade, accumulating literature has indicated that patients with lung metastases from colorectal cancer may also benefit from metastatic lung resection. However, the evidence supporting the resection of lung metastases from colorectal cancer is significantly less robust than that for liver metastases^[10]. Few studies have delved into the efficacy and safety of lobectomy versus segmentectomy for the treatment of lung metastases. Our retrospective analysis examined 62 clinical cases of thoracoscopic treatment for solitary lung metastases from colorectal cancer performed in our hospital's thoracic surgery department from March 2015 to March 2024. These cases were divided into a lobectomy group (31 cases) and a segmentectomy group (31 cases). We compared the efficacy and safety of the two surgical approaches and discussed their prognostic outcomes.

Patient baseline characteristics

The mean age of patients in the lobectomy group was 60.97 years, with 18 males and 13 females. Two patients were found to have liver metastases preoperatively, and one patient had bone metastases preoperatively. In the segmentectomy group, the mean age of patients was 61.16 years, including 20 males and 11 females. One patient in this group was found to have liver metastases preoperatively. There was a statistically significant difference in tumor diameter between the two groups, with the data derived from postoperative pathological examination reports. Specifically, the tumor diameter in the lobectomy group (1.75 ± 0.33cm) was larger than that in the segmentectomy group (1.30 ± 0.30cm). However, no significant statistical differences were observed in other baseline data between the two groups. Detailed information is presented in Table 1.

Table 1

Comparison of baseline data between the 2 groups
baseline data	lobectomy	segmentectomy	P-values
Average age (years)	60.97 ± 7.99	61.16 ± 8.69	0.928
Sex (male/female)	18/13	20/11	0.602
DFI(month)	24(15,40)	21(14,32)	0.375
BMI	22.54 ± 1.41	22.57 ± 1.89	0.946
Complementary therapies (yes/no)	12/19	15/16	0.442
Metastasis to other sites (yes/no)	3/28	1/30	0.612 ^*
Tumor diameter (cm)	1.75 ± 0.33	1.30 ± 0.30	<0.001
Smoking (yes/no)	9/22	12/19	0.421
DFI: The disease-free interval refers to the time between the patient's initial diagnosis of colorectal cancer and the subsequent diagnosis of colorectal cancer lung metastases; BMI: body mass index; ^* : Fisher's exact test

Short-term efficacy and safety

All 62 patients successfully completed the surgical procedures, including intraoperative lymph node dissection and subsequent testing, with no perioperative mortalities. Among the 31 patients in the lobectomy group, one patient required conversion to open thoracotomy with a blood loss of 1000ml. Lymph node metastases were detected in four patients, specifically one case in groups 7, 9, and 10, one case in group 9, one case in group 4, and one case in group 7. Nine patients experienced postoperative complications, including four with persistent low-grade fever, two with fatigue and dizziness, two with sinus tachycardia, and one with hemoptysis. With appropriate treatment, all complications resolved before discharge.

In the segmentectomy group, there were no cases of conversion to open thoracotomy. Lymph node metastases were found in two patients, both in group 4. Seven patients experienced postoperative complications, including three with persistent fever, two with hemoptysis, and one with fatigue and dizziness. As with the lobectomy group, all complications resolved before discharge following appropriate treatment.

The lobectomy group had significantly higher surgical time, intraoperative blood loss, postoperative day 1 drainage volume, total postoperative drainage volume, and surgical costs compared to the segmentectomy group. However, there were no significant differences between the two groups in terms of postoperative pain scores, postoperative extubation time, postoperative complications, time to ambulation, postoperative discharge time, and lymph node metastasis. Detailed information is presented in Table 2.

Table 2

Comparison of surgery-related data between the 2 groups
Surgical Information	lobectomy	segmentectomy	P-values
Surgical time (minutes)	205.03 ± 66.65	129.26 ± 22.76	<0.001
Intraoperative bleeding (ml)	148.55 ± 162.23	38.87 ± 27.80	0.002
Intermediate open chest (yes/no)	1/30	0/31	/
Postoperative pain score	3.97 ± 1.11	3.87 ± 1.31	0.755
Postoperative day 1 drainage (ml)	196.29 ± 102.80	101.13 ± 72.41	<0.001
Total postoperative drainage (ml)	1044.84 ± 317.96	616.94 ± 426.16	<0.001
Postoperative extubation time (days)	5.39 ± 1.05	5.48 ± 1.26	0.744
Postoperative Complications (yes/no)	9/22	7/24	0.562
Postoperative time out of bed (h)	31.03 ± 8.28	31.77 ± 9.37	0.742
Postoperative discharge time (days)	7.06 ± 1.46	6.97 ± 2.93	0.870
Cost of surgery (RMB)	9665.55 ± 1589.75	7782.97 ± 999.85	<0.001
Lymph node metastasis (yes/no)	4/27	2/29	0.671^*
^* : Fisher's exact test

Survival and recurrence rates

Survival rate

The median follow-up time in the lobectomy group was 43 (20, 66) months, with a total of 9 patient deaths, including 7 deaths within 5 years. The median survival time estimated by the Kaplan-Meier curve was 92 months. In the segmentectomy group, the median follow-up time was 36 (20, 55) months, with a total of 10 patient deaths, including 9 deaths within 5 years. The median survival time estimated by the Kaplan-Meier curve was 79 months. See Fig. 1 for a graphical representation of these data.

Statistical tests were conducted to compare the survival rate between the two groups. In this study, there was no statistically significant difference in survival rate between the two treatment methods (P-values for all three tests were > 0.05). This indicates that there was no statistically significant difference in survival rates between the lobectomy group and the segmentectomy group. See Table 3 for details.

Table 3

Statistical test was conducted tocompare the survival rates of the two groups
	chi-square	degrees of freedom	significance
Log Rank (Mantel-Cox)	.358	1	.550
Breslow (Generalized Wilcoxon)	.696	1	.404
Tarone-Ware	.581	1	.446

Recurrence-free survival rate

In the lobectomy group, a total of 15 patients survived without recurrence, and the median recurrence-free survival time estimated by the Kaplan-Meier curve was 79 months. In the segmentectomy group, a total of 12 patients survived without recurrence, and the median recurrence-free survival time estimated by the Kaplan-Meier curve was 68 months. See Fig. 2 for a graphical representation of these data.

Statistical tests were conducted to compare the recurrence-free survival rates between the two groups. In this study, there was no statistically significant difference in recurrence-free survival rates between the two treatment methods (P-values for all three tests were > 0.05). This indicates that there was no statistically significant difference in recurrence-free survival rates between the lobectomy group and the segmentectomy group. See Table 4 for details.

Table 4

Statistical test was conducted tocompare the Recurrence-free survival rates of the two groups
	chi-square	degrees of freedom	significance
Log Rank (Mantel-Cox)	.557	1	.456
Breslow (Generalized Wilcoxon)	.121	1	.728
Tarone-Ware	.311	1	.577

Relapse rate

In the lobectomy group, a total of 12 patients experienced recurrence, with a median recurrence time of 54 months estimated by the Kaplan-Meier curve. In the segmentectomy group, a total of 16 patients experienced recurrence, with a median recurrence time of 39 months estimated by the Kaplan-Meier curve. See Fig. 3 for a graphical representation of these data.

Statistical tests were conducted to compare the recurrence rates between the two groups. In this study, there was no statistically significant difference in recurrence rates between the two treatment methods (P-values for all three tests were > 0.05). This indicates that there was no statistically significant difference in recurrence rates between the lobectomy group and the segmentectomy group. See Table 5 for details.

Table 5

Statistical test was conducted tocompare the relapse rate of the two groups
	chi-square	degrees of freedom	significance
Log Rank (Mantel-Cox)	.966	1	.326
Breslow (Generalized Wilcoxon)	.230	1	.631
Tarone-Ware	.500	1	.479

Colorectal cancer, the third most common malignancy globally, has a relatively high mortality rate, with a 5-year survival rate of approximately 65.1%^[11]. Surgical resection is generally considered for the treatment of isolated pulmonary metastases from colorectal cancer^[12]. However, there are currently no randomized controlled trials comparing the postoperative outcomes of the three surgical approaches^[13]. The postoperative benefits of segmentectomy and lobectomy for the treatment of pulmonary metastases from colorectal cancer remain inconclusive. While thoracotomy was once the standard surgical approach for pulmonary metastases from colorectal cancer, recent advancements in minimally invasive video-assisted thoracoscopic surgery (VATS) have led to its development as a clinical standard^[14], resulting in significant improvements in the prognosis of patients with pulmonary metastases from colorectal cancer. Segmentectomy can achieve adequate surgical margins with minimal impairment to lung function but may carry a risk of local recurrence. Lobectomy, on the other hand, can significantly reduce the risk of postoperative recurrence but may affect lung function. To date, it is unclear which surgical approach, segmentectomy or lobectomy, offers better prognosis after resection of pulmonary metastases. Therefore, we conducted a retrospective study to analyze the data of patients who underwent resection of solitary pulmonary metastases from colorectal cancer at the Department of Thoracic Surgery, Gansu Provincial People's Hospital, from March 2015 to March 2024. The aim of this study was to investigate the efficacy, safety, and recurrence rates of segmentectomy and lobectomy for the treatment of solitary pulmonary metastases from colorectal cancer.

Except for tumor diameter, there were no statistically significant differences in baseline characteristics between the two groups of patients. The median disease-free interval (DFI) was 24 months in the lobectomy group and 21 months in the segmentectomy group, and there was no statistically significant difference in DFI between the two groups. Previous research^[15] has identified a DFI of 36 months or longer as an important prognostic factor after resection of pulmonary metastases from colorectal cancer, with a statistically significant difference in final survival rates compared to patients with a DFI of less than 36 months who underwent resection of pulmonary metastases.

In our study, 8 patients in the lobectomy group and 7 patients in the segmentectomy group had a DFI of 36 months or longer. We statistically validated the relevant outcome indicators for these 15 patients compared to patients with a DFI of less than 36 months within the same group and did not find any statistically significant differences. Additionally, we identified another potential prognostic factor: patients with a DFI significantly longer than 36 months and normal preoperative CEA levels who have a single metastasis may be more suitable for resection of colorectal lung metastases^[16]. However, our study did not analyze preoperative CEA levels, and the number of patients with a DFI greater than 36 months was too small to validate this conclusion. Further research with a larger sample size is needed to investigate whether DFI affects the resection of pulmonary metastases from colorectal cancer.

According to the Chinese guidelines for the diagnosis and treatment of colorectal cancer^[7], wedge resection is commonly used for the surgical management of pulmonary metastases from colorectal cancer, followed by segmentectomy and lobectomy. In some cases, pneumonectomy may also be considered. However, the guidelines do not clearly specify the conditions for the use of segmentectomy and lobectomy. Based on our experience with surgical approach selection in a single center, lobectomy is often used for deeper, more centrally located metastases when wedge resection is not feasible.

A randomized controlled trial conducted in 2022^[17]demonstrated that for lung cancer lesions with a diameter of ≤ 2 cm, segmentectomy is non-inferior to lobectomy in terms of survival rates. A recent meta-analysis comparing segmentectomy and lobectomy also mentioned that for lung cancer lesions under 3 cm, both procedures can achieve similar outcomes, and there were no statistically significant differences in prognostic indicators such as survival rates^[18].The results of our study showed that there was a statistically significant difference in tumor size between the segmentectomy and lobectomy groups, but no difference in outcome indicators. Although the tumor diameter in the lobectomy group was larger than that in the segmentectomy group, the average size was still below 2 cm. Therefore, we can conclude that the difference in tumor diameter between the two groups did not affect our results. We believe that the difference in tumor diameter between the two groups is associated with the subjective preferences of surgeons in terms of tumor location and surgical approach selection. Tumors located closer to the center tend to have larger diameters, and when the surgical approach cannot be clearly determined based on tumor location, surgeons often prefer to use lobectomy to treat relatively larger lung cancer lesions.

The lobectomy group exhibited significantly higher values in operative time, intraoperative blood loss, postoperative day 1 drainage volume, total postoperative drainage volume, and surgical costs compared to the segmentectomy group, with statistically significant differences. These findings are consistent with conclusions drawn from multiple studies^[19–21]. Since segmentectomy preserves more lung tissue, it results in less postoperative lung function loss, reduced intraoperative bleeding and postoperative drainage, and faster patient recovery with less compromised lung function. However, there were no statistically significant differences between the two groups in terms of postoperative drainage duration, postoperative pain, and discharge time. We believe that the differences in efficacy and safety between different surgical procedures for patients with colorectal cancer lung metastases are insufficient to influence surgeons' choice of surgical approach. In clinical diagnosis and treatment, the selection of the appropriate surgical resection method for lung metastases should be based on the patient's condition and individual circumstances.

Surgery is the primary treatment for colorectal cancer with lung metastases, with a reported 5-year survival rate ranging from 27–68%. However, recurrences are still common after surgery, with a high recurrence rate. In particular, wedge resection of the lung has been reported to have a local recurrence rate of 28%^[22], while the recurrence rate after segmentectomy has reached 11%^[23]. Although there is limited mention of the recurrence rate following lobectomy for solitary lung metastases from colorectal cancer, due to its more extensive resection range, we anticipated a lower recurrence rate in the lobectomy group compared to the segmentectomy group prior to our study. The results showed a recurrence rate of 38.71% in the lobectomy group and 51.61% in the segmentectomy group, but statistical testing indicated no significant difference. This may be related to individual differences among patients in our center and the sample size. Although there were no significant differences in baseline characteristics between the two groups, factors such as preoperative physical condition, postoperative quality of life, use of anticancer drugs, and uncertainties during long-term follow-up may have led to bias in some information.Additionally, the difficulty in collecting cases for our study was due to the fact that most patients with colorectal cancer lung metastases still opt for wedge resection as their treatment, resulting in a limited number of cases that may not have been sufficient to demonstrate a significant difference between the two groups. In the future, multi-center collaborative studies with larger sample sizes or even large-scale randomized trials could be conducted to verify the impact of different resection techniques on patient outcomes. The impact of local recurrence on survival rates has not been fully studied. Since the type of surgical procedure seems to affect the recurrence rate at the resection margin, every effort should be made to prevent recurrences at the resection margin. In cases where obtaining a satisfactory resection margin is not feasible, lobectomy may be an optimal choice.

Our study has several limitations. First, as a comparative study between two surgical techniques, we did not collect detailed preoperative imaging staging or postoperative pathological staging data for lung metastases. Instead, we only included tumor diameter in our analysis, and the impact of metastatic tumor staging on the prognosis of patients in both surgical groups was not discussed. Second, this study is retrospective and involved a relatively small sample size of 62 cases from a single center, potentially introducing a degree of bias in our results. Third, due to issues such as missing data and retrospective bias, we did not collect statistics on the TNM staging of colorectal cancer or surgical approach. Finally, follow-up was conducted primarily through telephone, and there may be issues with patient dropout or information bias, which could potentially affect the results of survival analysis.

For patients with solitary pulmonary metastases from colorectal cancer, the current clinical treatment strategy primarily involves wedge resection of the lung. However, postoperative recurrence is more common following wedge resection compared to segmentectomy and lobectomy. Whether lobectomy can achieve a lower recurrence rate and whether this difference in recurrence rates translates into a survival advantage for patients remains to be validated through larger-scale, multicenter randomized trials. In our study, segmentectomy achieved equally satisfactory clinical outcomes as lobectomy, while demonstrating better short-term effects. Nevertheless, this conclusion still requires further investigation and confirmation through additional studies.

In summary, for patients with solitary pulmonary metastases from colorectal cancer, segmentectomy and lobectomy exhibit comparable safety profiles. Segmentectomy demonstrates relatively better short-term outcomes, while there are no significant differences in long-term effectiveness between the two procedures. However, both segmentectomy and lobectomy offer superior recurrence rates compared to wedge resection. In clinical practice, for patients who are unable to undergo wedge resection, the choice between segmentectomy and lobectomy should be made based on the patient's preferences and the physician's assessment.

clinical data

We selected 62 patients with solitary lung metastases from colorectal cancer who underwent surgical treatment in the thoracic surgery department of Gansu Provincial People's Hospital from March 2015 to March 2024. The inclusion criteria were as follows: (1) patients with a histopathological diagnosis of colorectal cancer; (2) patients with radiographic or pathological evidence of lung malignancy and positive postoperative genetic testing for villin and CDX2; (3) patients aged 18 to 80 years who had undergone preoperative evaluations and were deemed to be able to tolerate lung surgery; (4) patients who underwent surgery using thoracoscopic techniques. The exclusion criteria were: (1) patients with multiple lung metastases detected on preoperative imaging; (2) patients with cardiopulmonary or general conditions that precluded lung surgery; (3) patients who had undergone multiple lung surgeries or had recurrent lung disease; (4) to eliminate unnecessary bias, patients who underwent robot-assisted surgery or traditional open thoracotomy were excluded.

Finally, 62 patients were included in the study, with 31 patients in the lobectomy group (mean age: 60.97 ± 7.985 years; male-to-female ratio: 18/13) and 31 patients in the segmentectomy group (mean age: 61.16 ± 8.688 years; male-to-female ratio: 20/11).

Surgical techniques

Lobectomy Group: The two-port thoracoscopic technique was employed. Taking the right upper lobe as an example, the patient was anesthetized with general anesthesia and intubated with a double-lumen endotracheal tube. The patient was placed in the left lateral decubitus position, and the right surgical field was disinfected and draped. An observation port was established at the 8th intercostal space along the right axillary midline, and an operating port was established at the 4th intercostal space along the right anterior axillary line. After thoracoscopic exploration, the anterior segmental artery, posterior ascending branch artery, and upper lobe vein were freed, and a linear cutter stapler was used to transect them. Subsequently, the upper lobe bronchus was freed and transected. During the operation, a non-traumatic grasping clamp was used to gently retract the lung tissue and tumor, with care taken to avoid injuring surrounding blood vessels and nerves. The right upper lobe was resected intact, mediastinal lymph nodes were dissected, hemostasis was achieved, and the specimen was retrieved through the operating port. A chest tube was placed, the lung was inflated, and the thoracic cavity was irrigated to check for air leaks. The thoracotomy incision was closed in layers.

Segmentectomy Group: The two-port thoracoscopic technique was also utilized. Taking the dorsal segment of the left lower lobe as an example, the patient was anesthetized with general anesthesia and intubated with a double-lumen endotracheal tube. The patient was placed in the right lateral decubitus position, and the left surgical field was disinfected and draped. An observation port was established at the 8th intercostal space along the posterior axillary line on the left side, and an operating port was established at the 6th intercostal space along the anterior axillary line. Thoracoscopic exploration was performed, the posterior mediastinal pleura was opened, and the dorsal segmental artery, vein, and bronchus were freed. A linear cutter stapler was used to transect and close each structure. The lung was inflated to determine the intersegmental plane, and the dorsal segment was resected intact along this plane using a linear cutter stapler. The specimen was retrieved using a retrieval bag, hemostasis was thoroughly achieved, and a closed chest tube was placed. After verifying that all instruments and dressings were accounted for, the lung was inflated to ensure good re-expansion of the remaining lung tissue. The thoracotomy incision was then closed in a routine manner.

Observation target

Basic information

gender, age, BMI, disease-free interval, adjuvant chemotherapy, preoperative clinical staging, multiple site metastases, smoking, and tumor size.

Surgical data

surgical time, intraoperative bleeding, lymph node dissection, surgical cost, intermediate open heart, postoperative pain, postoperative extubation time, postoperative drainage, postoperative complications, postoperative time out of bed, and postoperative length of stay.

(The information above was obtained from the patient's medical and surgical records during hospitalization.)

prognostic factor

survival rate, survival relapse rate, and recurrence rate. (The information above was obtained by regularly following up with patients and reviewing their outpatient records.)

Statistical analyses

Statistical analysis of the collected data was conducted using SPSS 26.0 software. Continuous variables were expressed as mean ± standard deviation (x ± s), and intergroup comparisons were performed using independent sample t-tests. Categorical variables were compared between groups using chi-square tests (with Fisher's exact test used when appropriate). Kaplan-Meier methodology was employed to estimate overall survival, recurrence-free survival, and recurrence rates. Univariate analysis, including the construction of Kaplan-Meier survival curves and Logrank tests, was conducted to determine the relationship between overall survival, recurrence-free survival, recurrence rates, and the study groups. A P-value of less than 0.05 was considered statistically significant, indicating a meaningful difference between groups.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, [Y.J Gou，[email protected]]，upon reasonable requestDeclaration of competing interest.

All authors do not have any competing interests to disclose.

Ethics approval and consent to participate

Prior to participating in the study, all patients provided written informed consent. The study adhered to the principles outlined in the Declaration of Helsinki and aligned with the International Conference on Harmonisation guidelines for Good Clinical Practice, as well as complied with all applicable local laws and regulations. The protocol and any subsequent amendments were approved by the respective Ethics Committees/Independent Review Boards.

Funding

This study did not receive any form of external funding.

Funding

This study did not receive any form of external funding.

Author Contribution

Author contributionsChang-Hao Que: Methodology, Validation, Formal analysis, Writing - Original Draft, Writing - Review & Editing.Da-Cheng Jin: Conceptualization, Formal analysis, Writing - Review & Editing, Visualization.Qi Wang: Validation, Investigation, Data Curation, Visualization.Zhibo-Ye: Validation, Data Curation.Cheng-Fang Li: Validation, Data Curation.Pei-Yuan Lu: Software, Data Curation.Ya-Ping Wang: Software, Data Curation.Yun-Jiu Gou: Conceptualization, Supervision, Project administration, Funding acquisition.

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No competing interests reported.

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Analysis of the Therapeutic Effectiveness of Segmental Lung Resection Versus Lobectomy in Patients with Isolated Lung Metastases from Colorectal Cancer

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Abstract

Figures

Introduction

Result

Patient baseline characteristics

Short-term efficacy and safety

Survival and recurrence rates

Survival rate

Recurrence-free survival rate

Relapse rate

Discussion

Methods

clinical data

Surgical techniques

Observation target

Statistical analyses

Declarations

Ethics approval and consent to participate

Funding

Author Contribution

References

Additional Declarations

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