Introduction
The best therapeutic option for localized renal tumours is surgical removal amongst other therapeutic options (1). As a standard treatment option, a partial nephrectomy (PN) provides better oncological and functional results for T1 renal tumours (≤7 cm); with the advantage of healthy renal parenchyma preservation (1,2). An open PN (OPN) has been a safe technique for many years, with high cancer-free survival rates, a better quality of life results, and low local recurrence rates (3). Due to, OPN technique requires longer hospitalisation rates, the need for longer surgical incisions, higher analgesic requirements and an increased comorbidity rate, minimally invasive techniques have become more popular. Advancements in minimally invasive procedures have increased the potential for laparoscopic and robot-assisted PNs, increasing the number of nephron sparing surgeries for T1 tumours. The evolution of imaging techniques (4) have led to the diagnosis of asymtomatic renal masses (up to 27%), with an risk of residual tumours (0.1%-10.7%) (5,6). The surgical technique applied, the skill of the surgeon, and tumour characteristics, such as the location, stage, and grade determines the recurrence rate of the tumour (5,7). No matter the technique, the main goal of a successful tumour management is to remove the renal tumour completely, with lower warm ischaemia times (WITs) (8) and minimal postoperative complication rates (9).
In this study, the positive surgical margin (PSM) rates mean ischaemic times, perioperative complication rates, and associated risk factors were compared between OPNs and laparoscopic partial nephrectomies (LPNs) in patients undergoing PNs for kidney tumours.
Materials and Methods
After obtaining Institutional Board Approval from the Clinical Research and Ethics Committee of Zonguldak Bülent Ecevit University (Zonguldak, Turkey) (approval number: 2019-94-12/06, date: 12.06.2019). We then retrospectively reviewed the data of 315 patients with kidney tumours who had undergone LPNs or OPNs, done in a high volume experienced centre between January 2008 and December 2016. We excluded patients with bilateral kidney tumours (n=16) and with a less than two year follow-up (n=14) from the study. Seventy patients with tumours higher than 7 cm, with lymph nodes or distant metastases, and with a history of PNs for benign diseases of the kidney were also excluded from the study.
Finally, the preoperative and postoperative data from 215 patients with complete data were evaluated. The demographic, surgical reports, clinical charts, laboratory results and histopathological reports were reviewed. In addition, detailed medical histories and physical examination findings were obtained in all of the cases.
Patients with T1 kidney tumours were divided into two groups according to the applied surgical technique: an OPN group (group 1, n=46) and an LPN group (group 2, n=169). We assessed the recurrence using radiological methods and additional histopathological examinations where needed. The cancer recurrences were clinically or radiologically assessed in both groups. The presence of a contralateral non-functional kidney or the presence of a tumour in an anatomically solitary kidney was accepted as imperative indications for a PN. The LPN criteria were based on the computed tomography (CT) findings, including the size, localization, and accessibility of the mass, in addition to the general health status and comorbidities of the patient.
Surgical Procedure
The LPN procedure was performed transperitoneally with the patient in a lateral decubitus position. A 12 mm optical camera port was inserted 5 cm lateral at the level of the umbilicus after the pneumoperitoneum was created using a Veress needle. The 10 mm subxiphoidal trocar and 5 mm trocar were placed approximately 2 cm medially and superior to the anterior superior iliac crest to create a triangularly shape under direct vision. For tumours on the right side, an additional 5 mm port was used to retract the liver. The colon was then mobilised medially, and the renal vascular pedicle was exposed. The main renal artery was clamped using a bulldog clamp and the tumour was resected within a safe margin, and put into an endo bag. The renal parenchyma was sutured using 2-0 monofilament poliglecaprone (Monocryl®, Ethicon) sutures in a running manner.
For the OPN, a flank incision was made in patients with lower pole kidney tumours. A subcostal approach was used for those who had upper pole or middle tumours. The renal artery was clamped and the resection of the tumour with the surrounding normal parenchyma was completed and figure eight knots were used for closing the collecting system and the renorrhaphy.
The follow-up protocol was defined as follows:
1. Complete physical examinations and serum creatinine measurements were done at the postoperative first, third and twelfth months and annually thereafter.
2. Plain chest X-rays and CT scans of the abdomen were obtained in the sixth postoperative month and annually after that.
Histopathological Investigation
All the PN specimens were evaluated by the same pathologist. Tumour grading and pathological staging were done according to the Fuhrman et al. (10) nuclear grading system and the 2016 World Health Organization classification (11). The presence of malignant cells at the surgical margin was defined as surgical margin positivity.
Statistical Analysis
The demographic variables, including age, gender and indication for surgery, laterality, diameter and location of the tumour was assessed. The mean follow-up periods, histopathological diagnoses, tumour grades and recurrence rates of the groups were compared using IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, NY, USA). An Independent Sample t-test and chi-squared test was used to compare the variables and ratios between the two groups. A p value of less than 0.05 was considered statistically significant. Binary regression analysis was performed to assess the impact of the tumor diameter, laterality, polarity and localization for PSM.
Results
The demographic and clinical characteristics of the LPN and OPN groups, including the age, body mass index, gender, glomerular filtration rate, American Society of Anaesthesiologists score, and comorbidity, presence of surgical margin positivity, tumour location and diameter are given in Table 1. The mean preoperative and postoperative haemoglobin, blood loss, and creatinine levels and the mean surgical time and follow-up periods were similar between the groups (p>0.05). The mean warm ischaemia time in the OPN group was significantly lower when compared to the LPN group (p<0.05). Other variables, such as the recurrence rate and the clinical and histopathological findings are shown in Table 2.
One patient with a surgical margin positivity in the LPN group had local recurrence. One patient in the OPN group with negative surgical margins (NSMs) and two patients (1.2%) in the LPN group with NSMs had local recurrences within a mean follow-up period of 29.8 months. Two patients in the LPN group with NSMs (1.2%) had bone and lung distant metastases in the 19th and 54th months. The overall recurrence or metastasis rate was 2.8%.
Binary logistic regression analysis was performed to assess the impact of the tumor diameter, laterality, polarity and localization for PSM (p>0.05). The individual characteristics of the patients with recurrences or metastases following the PNs are given in Table 3. Three of the patients had recurrence in the LPN group with Fuhrman grade 3, and two had Fuhrman grade 2 tumours.
Discussion
PN has become the standard surgical method for the treatment of T1 renal tumours with similar oncological results; however, there are still debates with regards to its relationship with PSMs and local recurrences. Our results showed that the tumor diameter, laterality, polarity and localization were not associated with PSM. Kwon et al. (12) showed that local recurrence after a PN was related to the high malignant potential of the tumour and the presence of a PSM. Irrespective of the tumour complexity, a PSM was found to be associated with a higher Nephrometry score, the presence of bilateral tumours, a prior renal cell carcinoma treatment history, local recurrence and distant metastasis when compared to patients with NSMs (13). On the contrary, many institutional data have shown that the surgical margin status did not influence the tumour recurrence risk in pT1 tumours after a PN (14). In a comparative meta-analytical study analyzing the data of 45,786 patients, a larger tumour size, a pT3a stage, nuclear grade 3-4 and minimally invasive procedures, were found to be potential risk factors for a local recurrence. However, cancer-specific and overall survival rates were not increased by the use of minimally invasive procedures (15). Our results showed that local recurrence was observed only in one patient with a PSM in the LPN group, a very low number of patients with NSM showed that there was no association with surgical margin positivity and local recurrence or distant metastasis in both groups. Two of the patients in the LPN group had bone and lung metastasis respectively. One of the patients with distant metastasis had a tumour necrosis (Fuhrman grade 3) and the other had a relatively endophytic mass close to the collection system with microvascular invasion. Histopathological and morphological findings such as high tumour grade and endophytic location of the tumour, may explain the distant metastases in our patients with NSM as reported earlier.
In this study, three patients (6.5%) in the OPN group showed PSM with no local recurrence. Although only a patient in the OPN group and two patients in the LPN group had local recurrence, no difference was observed in cancer-specific or overall survival which is consistent with the literature (16). A previous cohort study of 11,587 patients, showed that the PSM rates were 4.9%, 8.7% and 8.1% for open, robotic and laparoscopic PNs respectively (17). Considering PSM ratios, our results in the OPN group were similar to those of the previously published reports, which may be attributed to the cumulative skills of the urologists in open surgery. The 7.7% PSM rate recorded for the LPN group was similar to that found in literature. However, when a detailed analysis was done, the PSM rate was the highest for the first 50 cases (10.0%), and it decreased to a rate of 8% for the second 50 cases. As previously reported, this can be explained by the need for more complex skills and a relatively long learning curve (18). Consistent with literature, the PSM ratio was only 4.3% in the last 69 patients in the LPN group (19).
Nevertheless, the primary goal should be not to leave a PSM during a PN (7). A healthy parenchymal margin of 1 cm has been suggested for optimal cancer control (20,21). Due to the likelihood of a PSM, challenging cases require close follow-ups and careful surveillance and salvage procedures should be reserved for patients with locally advanced or high-grade tumours.
Only two of our patients showed distant metastases in the LPN cases with NSM, but no metastasis was observed in the participants in the OPN group or the LPN patients with PSM. At first glance, although the absence of metastasis in PSM seemed unreasonable, as previously reported, distant metastasis was not only related to the presence of PSM, but also tumour grade, subtype, microvascular invasion, necrosis and tumoural invasion to the collecting system (22).
The WIT is an essential parameter for postoperative kidney function (23). Studies have shown that a lower WIT was associated with better kidney function postoperatively (9). When compared to an OPN, a longer WIT is expected for an LPN (24). This study’s result showed that the mean WIT values were significantly less than 25 minutes, particularly in the OPN group.
Study Limitations
Oncological outcomes and PSM rates between LPNs and open partial nephrectomies at a single tertiary referral centre were compared in this study. This study had some limitations including;
1. Lack of a long-term follow-up period
2. The retrospective design of the study
3. Many studies have been done in literature about surgical margin positivity.
Conclusions
The presence of a PSM, although considered to be a risk factor for distant metastasis, was not associated with an increased risk of distant metastasis in this study. Nevertheless, the early stages of the learning curve for an LPN may be associated with higher PSM rates, and this may be a risk factor for distant metastases when combined with other histological and morphological features, such as the nuclear grade of the tumour, the presence of necrosis and endophytic localization.
Acknowledgements
Publication: This study was presented in the 14th International Urooncology Congress on November 6-10 in 2019, Antalya.
Contribution: There is not any contributors who may not be listed as authors.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.
Ethics
Ethics Committee Approval: After obtaining Institutional Board Approval from the Clinical Research and Ethics Committee of Zonguldak Bülent Ecevit University (Zonguldak, Turkey) (approval number: 2019-94-12/06, date: 12.06.2019).
Informed Consent: Retrospective study.
Peer-review: Internally and externally peer-reviewed.
Authorship Contributions
Supervision: H.V., Concept Ö.Ç., Design: Ö.Ç., M.Ç.Ç., Ç.G.Ö., Data Collection or Processing: M.Ç.Ç., Ç.G.Ö., B.A.V., Analysis or Interpretation: Ö.Ç., Literature Search: M.S.B., Writing: Ö.Ç.