Systemic inflammatory response after endoscopic surgery of Zenker's diverticulum.

Introduction

Zenker’s diverticulum is an acquired pulsion diverticulum of the mucosa which develops in the so-called Killian triangle, a triangular shaped area between the oblique muscle fibres of the inferior pharyngeal constrictor muscle and the horizontal muscle fibres of the cricopharyngeus muscle. Zenker’s diverticula typically present in middle-aged and elderly individuals, especially during the seventh and eighth decades of life. Dysphagia is the main presenting symptom; other symptoms are regurgitation of undigested food, choking, cough, halitosis, globus, aspiration, pneumonia and oesophageal obstruction.

Zenker’s diverticulum was first reported in 1767 by Ludlow [1], but named after the German pathologist Friedrich Albert von Zenker who published a case series in 1877 [2]. Since the first report of successful open surgical treatment by Wheeler in 1886 [3], many options have been described for the treatment of Zenker’s diverticulum. The external approach was the treatment of choice for many years. Mosher in 1917 introduced the treatment by rigid endoscopy, sectioning the septum of the diverticulum [4]. In the last decades, endoscopic treatment has gained more popularity also due to the use of carbon dioxide laser, which was introduced by van Overbeek et al. [5]. In 1993, Collard at al. introduced diverticulotomy by using the endostapler [6].

Since the invention of the carbon dioxide laser and the linear stapling device, these methods have become widely used once they were demonstrated to be secure and precise [7-9]. Compared with classic surgery the main advantages of the endoscopic approach are shorter operative time, less surgical trauma and lower morbidity rate [10].

Until now, it is unclear which technique is superior in terms of outcomes. It is controversial if the open wound after laser surgery leads to bacterial penetration into the mediastinum and if closure of the wound by stapler prevents a mediastinal bacterial invasion, and therefore minimises complication rates like mediastinitis. Therefore, the issue of early diagnosis of inflammatory changes in the post-operative period is important. Post-operative serial screening of white blood cell count (WBC) and C-reactive protein (CRP) is useful as an indicator of infectious complications. CRP is an acute-phase protein synthesised by hepatocytes, largely in response to pro-inflammatory cytokines [11]. CRP is not specific for a particular disease, but can arise due to inflammation, trauma, malignancy and tissue infarction. In bacterial infection, CRP levels increase within 6 hours [12]. CRP is considered to be useful for detection of an inflammatory response early in its course, and also for monitoring disease activity [11]. Leukocytosis also commonly accompanies infection and may serve as an early marker for a developing infection. Normal WBC and CRP responses can rule out almost all early infectious complications.

There is no study that has investigated inflammatory changes after rigid endoscopic surgery of Zenker’s diverticulum by laser or stapler. The objective of the present study was to investigate whether endoscopic stapler surgery causes a less pronounced release of inflammatory cytokines compared to endoscopic laser surgery.

Materials and methods

This retrospective study included patients having elective endoscopic surgery for Zenker’s diverticulum by carbon dioxide laser or stapler from 2001 to 2011 and fulfilled the following inclusion criteria:

The diagnosis of Zenker’s diverticulum was made through clinical and radiologic examination.

Patients had a baseline examination 1 or 2 days before the procedure. Blood samples for biochemistry were obtained as part of the preoperative examination (day 0) and subsequently at day 1, 2, 3 and 5 upon completion of the procedure.

C-reactive protein (CRP) and white blood cell count (WBC) at baseline were in the normal range (CRP < 5 mg/l, WBC 4000-10,000/μl). Therefore, any inflammatory situations due to comorbidity could be excluded.

The procedures were performed under general anaesthesia. Patients were placed supine with their neck overextended. The diverticular sac was exposed with a Weerda distending operation laryngoscope. After transoral positioning of the laryngoscope in the hypopharynx, the wall containing cricopharyngeus muscle fibers between the diverticular sac and hypopharynx lumen was visualised. Then, division of the septum was performed by CO2 laser or stapler. By endoscopically dividing the cricopharyngeal muscle the diverticula were marsupialised to become one cavity with the hypopharynx. Post-operatively, patients were kept on total parenteral nutrition for a period of at least 48 hours. A liquid oral diet was introduced at first, followed by solids according to the patients’ acceptance. No post-operative routine radiological swallow examination was performed. All patients received intravenous fluid infusion, peri- and post-operative intravenous antibiotics [cefuroxime (1.5 g per 8 h) and metronidazole (500 mg per 12 h)], a proton pump inhibitor and analgesics.

The ASA score is a subjective assessment of a patient’s overall health that is based on six classes (I to VI). I: A normal healthy patient; II: A patient with mild systemic disease; III: A patient with severe systemic disease; IV: A patient with severe systemic disease that is a constant threat to life; V: A moribund patient who is not expected to survive without the operation; VI: A declared brain-dead patient whose organs are being removed for donor purposes [13].

Statistical analysis

The Mann-Whitney-U-test was used to compare sex, age, ASA grade, and WBC and CRP levels of both patient groups. Results were considered statistically significant if p ≤ 0.05.

Results

In all, 34 patients fulfilled the inclusion criteria and were investigated. Of these, 18 patients underwent stapler-assisted diverticulotomy, and the remaining 16 patients were subjected to diverticulotomy by carbon dioxide laser. All procedures were performed by an experienced surgeon, who was defined as one having more than 5 years experience as an attending surgeon. In each group, 3 patients were endoscopically treated for Zenker’s diverticulum in other hospitals before. Basic parameters of both patient groups prior to Zenker’s diverticulum surgery are shown in Table I. There was no significant difference between the two groups of patients in terms of age, sex ratio and ASA grade.

Table I.

Demographic details of patients.

	Stapler	Laser
Patients	18	16
Gender
Male	11	7
Female	9	7
Age mean (range)	68.4 (46-86)	70.9 (56-85)
ASA grade (mean)	2.4	2.5
Primary surgery	15	13
Revision surgery	3	3

The mean operative time was 15 minutes shorter in the stapler group (53 vs 68 minutes); however, this difference was not statistically significant. No serious post-operative complications such as mediastinitis or pneumonia occurred in either group.

Before the operation, the levels of neither CRP nor WBC were significantly different between two groups. In both groups the WBC peaked as early as one day post-surgery, returning to normal range at the third day after surgery in all patients of both groups. However, there was a significant difference on the first day after surgery between the groups regarding the mean WBC. The patient group who was subjected to carbon dioxide laser diverticulotomy had a significant higher WBC than patients after stapler-assisted surgery (p < 0.05) (Fig. 1).

Fig. 1.

WBC at baseline (0) and days 1, 2, 3 and 5 after surgery (mean values) in the carbon dioxide laser and stapler groups.

Mean CRP levels reached their maximum 2 days after surgery in both groups and did not decline to preoperative levels at day 5 after the operation. The increase in the carbon dioxide laser group was significantly higher than in the stapler group. Significant differences between both groups were seen on day 1, 2 and 3 after surgery (p < 0.05). Figure 2 shows the chronological change in the mean CRP level after surgery.

Fig. 2.

CRP at baseline (0) and days 1, 2, 3 and 5 after surgery (mean values) in the carbon dioxide laser and stapler groups.

In one patient of the stapler group revision surgery was performed 6 months later due to recurrence of the diverticulum. In the other patients, no recurrence was observed.

Discussion

Due to its good safety and long-term efficacy, rigid endoscopic surgery of Zenker’s diverticulum has become increasingly popular, although there is some controversy about the optimal surgical method [14-16]. A recent meta-analysis demonstrated increased non-dental complications in patients treated by CO2 laser compared to patients treated by stapler, but no difference in overall complications or revision surgery [17]. Endoscopic surgery for Zenker’s diverticulum can be complicated by inflammatory processes and mediastinitis [18]. An elevated WBC and elevated CRP have been associated with an increased risk of inflammatory events. Until now, there are no studies on the inflammatory response after laser surgery or stapler surgery for Zenker’s diverticulum. Therefore, the influence of carbon dioxide laser surgery and stapler surgery of Zenker’s diverticulum on WBC and CRP were retrospectively investigated.

The present study shows no differences in pre-operative clinical parameters between the two groups. The results showed that endoscopic surgery for Zenker’s diverticulum whether performed by carbon dioxide laser or stapler is associated with an inflammatory response. There were no differences between CRP and WBC count at baseline between both groups since values within the normal range at baseline were defined as inclusion criteria. The stapler group was superior to the carbon dioxide laser group in terms of post-operative systemic inflammation. There was a significant lower mean WBC on the first post-operative day and significant lower CRP levels on days 1, 2 and 3 after surgery in patients treated by stapler.

The reason for the lower inflammatory response in the stapler group may is that carbon dioxide laser diverticulotomy causes greater tissue trauma since the stapler has the advantage of simultaneously cutting and sealing the wound edge. It is possible that the inflammatory reactions were the result of possible unnoticed leakages. In order for a leak to occur, the peri-oesophageal fascia must be violated. Because the fascial planes in the neck are continuous with the mediastinum, leakage of oesophageal contents into the neck can cause mediastinitis. The greater physical trauma due to laser surgery may lead to an increased liberation of inflammatory cytokines and enhancing post-operative systemic inflammation. Another cause for the higher inflammatory response in the CO2 laser group could be the longer mean operative time which was 15 minutes longer in the CO2 laser group. This difference was not statistically significant although the longer duration of tissue injury can lead to a greater amount of released mediators resulting in a higher inflammatory response. However, in our patients no inflammatory complications occurred and there were no significant differences in outcomes. In one patient in the stapler group a recurrence of the diverticulum occurred, while in the laser group there were no recurrences.

There are some limitations to our study. The first and most obvious is that it consists of a relatively small number of patients who were studied retrospectively. We know that laser surgery is possible when stapler surgery is not, for example in cases with cricopharyngeal dysfunction or small diverticulum. Due to the retrospective nature of the study, we do not know what influences the decision for stapler or laser surgery. Additionally, all patients were treated with intravenous antibiotics in the post-operative period since these antibiotics were part of our treatment scheme. This affected post-operative inflammatory reaction, although antibiotic treatment was the same in both groups.

Conclusions

The inflammatory response in the early period after carbon dioxide laser diverticulotomy of Zenker’s diverticulum is higher than after stapler-assisted surgery of Zenker’s diverticulum. Prospective studies with larger numbers of patients are needed to further address this issue.