AIMOM—auditing the introduction of minimally-invasive oesophagectomy in Malta

Introduction

The treatment of oesophageal and oesophagogastric junctional (OGJ) cancer has evolved dramatically over the past three decades. A number of diagnostic, physiological, surgical and oncological developments led to significant improvements in survival outcomes. Surgical resection retains an important role in the curative treatment of adenocarcinomas, and the salvage treatment of choice for squamous cell cancer cases that fail primary curative chemo-radiotherapy. The late 1990s signalled the slow but steady transition from open procedures (OP) to minimally invasive surgery (MIS) (1,2). Technical variations of minimally invasive oesophagogastric resections appear to be safe alternatives to OP with a favourable major complication and mortality profile (3-6). The TIME, MIRO, ROBOT, and MIOMIE trials suggest that hybrid or total variations of the minimally invasive Ivor-Lewis approach improve major complication profiles, chest sepsis, and quality of life (7-11). Lymph node harvest and survival also appear to be equivalent in both approaches, with a suggestion that MIS may offer a better chance of complete resection (12,13). This accrued body of evidence supporting MIS oesophagagogastric resections has also been acknowledged by European [European Society for Medical Oncology (ESMO)] and United Kingdom [National Institute for Health and Care Excellence (NICE)] guidelines (14,15).

This prospective audit assesses the transition from OP to MIS for oesophageal and junctional cancers in a national university hospital over an 11-year period with regard to operative safety, outcomes, and survival. Furthermore, this work identified criteria from published literature against which clinical performance can be benchmarked. We present this article in accordance with the STROBE reporting checklist (available at https://ales.amegroups.com/article/view/10.21037/ales-23-65/rc).

Methods

This audit was conducted at a national university hospital covering a catchment population of 500,000, with an oesophageal cancer incidence which is slightly higher than neighbouring southern Mediterranean countries but lower than northern European nations such as the United Kingdom and the Netherlands (16). With institutional approval (Department of Surgery, Mater Dei Hospital, Msida, Malta), a registry was established in 2013 and included all patients undergoing oesophagectomies for neoplasia following a multidisciplinary team (MDT) meeting. As a quality improvement exercise, this clinical audit was deemed to be exempt from ethical approval and not requiring individual consent by the institution (Department of Surgery, Mater Dei Hospital, Msida, Malta).

OP was the standard of care between February 2013 to May 2017, and once supporting evidence was accrued (see Table 1), MIS was introduced in June 2017. Before 2019, all procedures were carried out by the lead author, with a second consultant surgeon (CC) being appointed in the unit (see Table 2 for procedural transition over the 11-year period). The unit’s operators are experienced endoscopic and laparoscopic surgeons (trained in high-volume units elsewhere) and engaged in training, mentoring, fellowships, courses, and conferences abroad.

Data were collected until October 2023 from patient records, including routine follow-up which included tumour markers and 6-monthly trunk computerised tomography (CT) scan or positron-emission tomography (PET)-CT for 2 years then yearly.

Treatment pathway

Staging

Following endoscopic assessment, initial staging was performed with a trunk CT scan and a concurrent assessment of fitness status. Any obvious hepatic lesion was assessed by contrast ultrasound and/or magnetic resonance imaging (MRI). When these preliminary tests were negative for metastatic disease, PET-CT was performed for further assessment. In patients with suspected early lesions, endoscopic ultrasound (EUS) was used to confirm T1N0 staging, to be able to offer endoscopic mucosal resection or endoscopic submucosal dissection. Patients with more invasive (greater than T1N0) lesions of the distal oesophagus and junction were staged via laparoscopy [briefly gasless during the coronavirus disease 2019 (COVID-19) pandemic] with peritoneal washout for cytology.

Following staging, the MDT meeting determined further management. Patients with acceptable lung function test plus echocardiography results, with resectable, non-metastatic disease (with negative peritoneal cytology and tumour stage less than T4b), were referred for neo-adjuvant oncological treatment. Oesophagectomy was offered to patients with adenocarcinomas that were stable or responsive to neo-adjuvant treatment. Surgery was also offered as a salvage procedure for patients with squamous cancers with escape disease after radical chemo-radiotherapy. Up-front surgery was offered as primary treatment only to those patients who refused pre-operative oncological treatment and those with contra-indications to chemotherapy and/or radiotherapy.

MIS techniques

Minimally invasive McKeown oesophagectomy (MIMO)

For MIMO, following double-lumen endotracheal intubation, patients were placed in the prone position with a 15° right-shoulder-up tilt. Right-sided 3-port thoracoscopy was performed. This permits a right-sided thoracoscopic approach through two 12-mm non-bladed ports and one 5 mm non-bladed port. A low-flow carbon dioxide pneumothorax was maintained at 5 mmHg.

Lymph node mapping was standardised using Japanese Esophageal Society lymph node station mapping, recently simplified by Liang et al. (17,18). Dissection was started posteriorly in order to free the oesophagus en-bloc with the pre-aortic tissue (station 112), thus skeletonising the descending aorta alongside the azygos vein and including the thoracic duct, divided between Hem-o-lok^® (Teleflex, USA) clips. The dissection was subsequently carried anteriorly to divide the azygos arch between twin Hem-o-lok^® clips. Lymph node stations 106tbR, 107, 108, 109R, 110, 111 and 112 were removed en-bloc.

Subsequently, the patient was placed in the supine position and the abdominal phase was performed through a 4-port laparoscopy with Nathanson liver retraction. After identification and sparing of the right gastroepiploic pedicle and arcade, the gastrosplenic omentum was incised to include lymph node stations 4sa, 19, and 2 with a margin of the left crus. On the right, simple kocherisation of the duodenum was carried out selectively and the lesser omentum was incised sparing the right gastric pedicle and carrying the dissection to include stations 8, 3 and 1 with a margin of the right crus. The stomach was then lifted to bowstring the left gastric pedicle, which was skeletonised by excising lymph node stations 11p, 7, and 9. The pedicle was incised between Hem-o-lok^® clips, flush with the coeliac trunk. Concurrently, through a left sternomastoid incision, the cervical oesophagus was mobilised and incised after threading a vein stripper distally into the stomach. The mobilised oesophagus was delivered through the diaphragmatic hiatus using traction onto the stripper, with the pre-aortic route maintained by an attached chest drain.

Through an 8 cm midline mini-laparotomy stretched with a medium-sized wound protector (Alexis^®), the oesophagus and stomach were delivered, and the stomach tube was constructed with a linear stapler (Endo GIA^TM, Medtronic, Ireland). The gastric tube was subsequently lubricated and pulled through the chest and into the neck by traction onto the drain. An oesophagogastric anastomosis was fashioned in the neck.

Laparoscopic transhiatal extended total gastrectomy (LTHETG)

For Siewert type III lesions, a LTHETG was extended through the partially excised crura, with en-bloc dissection of the oesophagus and lymph node stations 108, 110, 111 and 112. A stapled end-to-side oesophagojejunal anastomosis was fashioned using the Orvil^TM (Medtronic, Ireland) in the sub-carinal region.

Benchmarking

Departmentally set benchmarks were supplemented using reports by the international Esophageal Complications Consensus Group (ECCG), the Dutch DUCA group, and the Oesophago-Gastric Anastomosis Audit (OGAA) (19-21). Selected national audits and other studies were also used to complement and complete our platform (22-27) (see Table 3 for details of the benchmark platform).

Statistics

The data were analysed using SPSS (IBM, USA) version 26. In order to compare OP versus MIS, continuous variables were assessed with the parametrically appropriate tests following Shapiro-Wilk test. Additionally, medians were compared with median test, while frequencies, were compared with Fischer’s exact (two-tailed) test and significance was ascribed as a P value of less than 0.05. Kaplan-Meier curves were plotted for survival and recurrences from diagnosis up to 5 years with the same software and compared with Mantel-Cox log rank test. Curves were also plotted and contrasted for elderly (over 70 years of age) patients versus younger ones.

Results

Fifty-nine consecutive and unselected patients (mean age 66.4 years, male:female = 4:1) underwent variations of oesophagectomy for malignant disease of the oesophagus and oesophagogastric junction over the period from January 2013 to October 2023 (see Table 4 for clinical and operative demographics of this cancer series). Staging investigations were completed for all patients. Following the introduction of MIS, only two patients underwent OP due to COVID restrictions on laparoscopy.

MIS and OP (n=32 and n=27 respectively) were not significantly different with regard to age, gender, administration of pre-operative chemotherapy, pathological tumour characteristics (tumour type and T and N stage), lymph node harvest, completeness of resection and time to discharge. Significant heterogeneity was registered in the procedure type. The administration of pre-operative radiotherapy was significantly higher in the MIS group, as this modality became the standard of care in 2017 (P=0.02).

An overall postoperative complication rate of 42.4% was recorded (see Table 5 for morbidity and mortality data, and selected benchmarks), with 32% (n=19) suffering more than one complication. At 5.1%, the incidence of post-operative cardiac complications was lower than the benchmark of 17.2%. However, the rate of postoperative pneumonia at 30.5% was much higher than the expected 16%. Pulmonary embolism (5.1%) and stroke (1.7%) were likewise commoner than reported in larger series. Haemorrhagic complications, pleural effusion requiring intervention and renal dysfunction were similar in both groups and compared well with the benchmarks. For anastomotic failure, the overall rates for cervical and thoracic leaks and stricture formation were also comparable to larger series. Leaks in the neck [type II, Dindo-Clavien grade 2 (28)] occurred significantly more frequently in MIS when compared to OP (24% vs. 0%, P=0.001). Conversely, wound complications [Dindo-Clavien grade 1 (28)] were significantly higher in the open group (P<0.001), and this was itself much higher than the benchmark (40.7% vs. 1.1%), but none were reported in the MIS group.

No statistically significant difference in mortality was observed between the MIS and OP groups. It is important to note, however, that a 65-year-old male patient suffered major haemorrhage and refractory cardiac arrest during an aortic arch repair, during the thoracic phase of a MIMO procedure. This constituted the unit’s only open conversion, death on table, significant haemorrhage and 30-day mortality (1.7%, n=1, see Table 6).

Follow-up was greater but not significantly so for OP for both survival (OP: 89.5±29.2 versus MIS: 41.8±23.1 months, P=0.07) and recurrences (OP: 98.9±27.4 versus MIS: 42.7±23.3 months, P=0.10), reflecting the transition to MIS in 2017. There was no statistically significant difference in overall survival between the MIS and OP groups (log-rank test, P=0.80, see Figure 1). Similarly, there was no significant difference in recurrence plots (log-rank test, P=0.79). Subgroup analysis of the whole series to assess survival and recurrences between elderly patients (over 70 years) and younger patients confirmed no significant difference (log-rank test, P values of 0.90 and 0.08, respectively).

Figure 1 Kaplan-Meier curves. (A,C) Equivalence in overall survival and recurrence (log rank P=0.80 and P=0.79, respectively) between MIS and OP from time of diagnosis. (B,D) In the whole series, there was no difference in these outcomes based on age for 70 years and older versus those who were younger (log-rank, P=0.90 and 0.08, respectively). MIS, minimally invasive surgery; OP, open procedure.

Discussion

The concept of high-volume surgeons undertaking high-risk and complex surgery in high-volume centres is well-established and universally accepted, with considerable and convincing backing from various landmark studies that confirm lower trends in morbidity and mortality, as well as improved long-term survival (19,29,30). In a small island state, embarking on new techniques to provide high-risk complex surgery is challenging. The timing of introducing such emerging procedures also requires a balance between the data in hand, awaiting robust evidence, and the timely implementation to meet patient needs and interests (31). Furthermore, published prospective trial data may feature highly selected groups of patients, undergoing procedures in high-volume academic centres with established expertise in the field.

This audit fulfils a principle of clinical governance, scrutinising the outcomes of this new service and presenting unselected patient data covering the transition to MIS. Furthermore, in the absence of previously set national key performance indicators for such a service, benchmarks were assimilated from trials and other national guidelines (32), with the literature also monitored for emergent evidence, especially cautionary results from more recent trials (see Table 1). These benchmarks were divided into five subsets covering the entire patient experience in a holistic manner, including: the staging and pre-operative period, oncological parameters, the intra-operative phase, post-operative complications, and survival.

Regarding the operative transition, rather than opting for a hybrid (two-step) approach to implementation, this unit decided on the one-step approach to MIS. In our experience, this transition to minimally invasive oesophagectomy was reliant on three important principles. Firstly, the institution committed the required investment in procurement. Secondly, the operating theatre team engaged in training, and thirdly this endeavor was supported by the intensive care, high-dependency, and ward staff.

Within our dataset, this audit suggests that MIS was not inferior to OP with regard to overall complication rate, oncological parameters, and survival outcomes. Older age did not appear to be associated with worse outcomes. Use of neo-adjuvant chemo-radiotherapy was higher in the MIS group because our unit adopted this modality as the standard of care in 2016, following publication of the results from the CROSS trial (33).

With regard to complications, our data does draw caution to the high rate of postoperative pneumonia, which was higher than the benchmark, and this trend persisted despite the introduction of MIS. The team may have been too liberal with the clinical diagnosis of pneumonia, when the condition might well have consisted of collapse/atelectasis. Be that as it may, the results prompted a review of the prevailing analgesic, physiotherapy, and anti-microbial protocols. The unit is increasingly employing cardio-pulmonary exercise testing (in preference to the dated regime of lung function tests and echocardiography) for pre-operative assessment. Over the past year, more patients are being referred for pre-operative cardio-pulmonary prehabilitation in the neo-adjuvant phase. The team looks forward to re-auditing the pulmonary complication rates to assess the impact of these changes.

Interestingly, the introduction of MIS drastically reduced (practically eliminated) the high wound infection rate prevalent in the OP group. Conversely, the cervical anastomotic leak rate in MIS was significantly higher than in the OP group. As the anastomotic technique is identical in both MIS and OP, it is plausible that MIMO may result in relative ischaemia of the tip of the gastric tube, leading to localized and limited conduit necrosis. In addition to fasting, cervical leaks are managed with total parenteral nutrition and intravenous antimicrobials, and this leads to prolonged hospitalisation. These protracted hospital stays may have denied the expected advantage of the short hospitalisations inherent to MIS. Nonetheless, cervical leaks have been found easier to manage, and were treated conservatively with a subsequently high rate of cases needing later endoscopic dilatation, in line with the set benchmark (see Table 5). This contrasts with the severity of outcomes relating to thoracic anastomotic leak. Although these were less common, the management of these proved to be more difficult. Specifically for one case where a radiological leak led to catastrophic fatal haemorrhage from stent erosion (included in 90-day mortality, see Tables 5,6) following endoscopic stenting.

Indocyanine green fluorescence angiography perfusion assessment is a technique under investigation which seeks to diminish anastomotic leaks post-oegophagectomy. This tool is available in our unit, however, expertise in its use is still lacking, and it is not used. This technique is also still under investigation (34) and evidence suggests that the interpretation of these angiograms can be inconsistent when used by inexperienced users (35).

While informative, the overall results of this audit cannot be compared to trial data. No randomisation was carried out, and recruitment was not prospectively tested for statistical power, thus lack of significant differences between the two groups could be attributed to type-two errors rather than non-inferiority. Furthermore, statistical matching was not employed in this work and thus this audit is prone to bias due to confounding factors.

The duration of follow-up in the MIS group was also obviously shorter as the procedure was introduced in 2017, and this may too have impacted our results. Furthermore, technique heterogeneity is present with a mix of procedures, heavy in McKeown procedures. This mix is unlike previously reported and therefore, cannot be readily compared to any of these completed randomized trials. In this respect, the publication of the results of a Chinese trial comparing MIMO to open McKeown oesophagectomy are awaited (36).

Although the decade-long audit period permitted post-operative survival assessment, it also meant that other practices (e.g., neoadjuvant treatments described above) concurrently also changed. This was not assessed/controlled for and may have confounded our outcomes. Additionally, the survival benefits from newer medical oncology techniques were potentially not reflected in the MIS group due to lack of statistical power.

Disease epidemiology has also not been studied here, and this may limit the generalisability of our findings. The incidence of oesophageal cancer is lower than other countries. This may be due to disease factors or socioeconomic factors such as a workforce mobility related to remote and digital working having skewed incidence rates. This work also does not take into consideration the ratio of short versus long segment Barrett’s oesophagus. With short segment disease having been reported to be increasing in Spain (37) but is yet to be investigated in our unit. Additionally, lower third oesophageal tumours not related to the gastro-oesophageal junction were not prospectively segregated.

As with any other operative techniques, learning curves (including those of the operator, assistants, and theatre staff) are difficult to gauge and may have also impacted our measured outcomes. The patient’s perspective has also not been considered in this governance exercise, and future audits should include patient-reported outcome measures.

Robotic surgery portends to be the next iterative step in minimal access surgery. Whereas thoraco-laparoscopy has proven invaluable in reducing wound size and pain whilst providing the surgeon with a magnified image allowing careful dissection, robotic surgery offers other advantages. When seated at the console, the operator benefits from a digitally enhanced view, three-dimensional experience, seven degrees of freedom of articulation, and comfort. These platforms may also offer meticulous and intricate dissection, with the potential to improve lymph node harvest and respective performance. Indeed, a robot is available in our unit and mentored experience in the surgical treatment of benign disease is being accrued. The ROBOT-2 trial is expected to shed light on whether robotic lymphadenectomy will supersede the thoracoscopic yield (38). Whether the unit will introduce this via a two-step approach (hybrid robotic chest and laparoscopic abdomen) remains to be determined.

Conclusions

This audit suggests that, except for pneumonia rates (which have remained relatively high), our transition to MIS oesophagectomy has not negatively impacted morbidity, mortality, and survival outcomes when compared to our OP data or MIS results from higher volume centres.

Acknowledgments

The authors would like to thank Ms Sharon Young for her support with data collection.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://ales.amegroups.com/article/view/10.21037/ales-23-65/rc

Data Sharing Statement: Available at https://ales.amegroups.com/article/view/10.21037/ales-23-65/dss

Peer Review File: Available at https://ales.amegroups.com/article/view/10.21037/ales-23-65/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ales.amegroups.com/article/view/10.21037/ales-23-65/coif). J.E.A. reports that he is a member of parliament of the Republic of Malta and Cabinet Minister for Health and Active Ageing. He is also a visiting senior lecturer at the University of Malta, an honorary consultant surgeon at Mater Dei Hospital (Malta) and College Tutor for the Royal College of Surgeons of Edinburgh (United Kingdom). J.D. reports that he is a recipient of the Tertiary Education Scholarship Scheme scholarship (Malta); was previously employed on research funded by the Disruptive Technologies and Innovation Fund (Ireland); has been an invited speaker (expenses only covered) at Med-Tech world conference (Malta EU, 2022 and 2023); and is named on a patent application relating to tissue perfusion assessment. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. As a quality improvement exercise, this clinical audit was deemed to be exempt from ethical approval and not requiring individual consent by the institution (Department of Surgery, Mater Dei Hospital, Msida, Malta).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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