Core Topics in General & Emergency Surgery: Companion to Specialist Surgical Practice (28 page)

While the relationship between
Helicobacter pylori
infection and uncomplicated peptic ulcers is indisputable, the role of the bacteria in ulcer perforation was once enigmatic. Reported infection rates in earlier series varied markedly from 0% to 100%.
^35
–
37
The difference in the number, timing and types of diagnostic test used to diagnose
H. pylori
infection in these studies may have accounted for the widely different findings. Furthermore, the frequency of NSAID intake can be an important confounding factor. In one consecutive series of 73 patients with perforated duodenal ulcers, intraoperative antral biopsies for rapid urease test and histopathology were taken. These revealed an
H. pylori
infection rate of 70%,
³⁸
the figure rising to 80% if NSAID users were excluded. Some studies also reported a high proportion of NSAID use among patients with perforated gastric ulcers, especially in those without
H. pylori
infection, suggesting that these drugs may represent a factor of relevance to
H. pylori
-negative ulcer perforation.
^39,
40

The more affirmative evidence confirming a causal relationship between
H. pylori
infection and non-NSAID peptic ulcer perforation comes from long-term follow-up studies. A study of 163 consecutive patients with perforated peptic ulcer managed by simple closure confirmed the strong association between persistent
H. pylori
infection and ulcer.
⁴¹
Of the 163 patients, 47.2% were found to have
H. pylori
infection during endoscopy at a mean follow-up of 6 years. Male gender and
H. pylori
were the only two independent predictive factors of ulcer relapse in the study.

In a randomised study, 99 patients with perforated duodenal ulcers and confirmed
H. pylori
infection received either 1 week of anti-
Helicobacter
therapy or 4 weeks of omeprazole.
⁴²
Endoscopic surveillance after 1 year showed that ulcer recurrence rate decreased significantly from 38% in the control group to 4.8% in the eradication group. A recent meta-analysis has further consolidated the efficacy of
H. pylori
eradication in the prevention of ulcer relapse after simple repair of duodenal ulcer perforation.
⁴³
The pooled incidence of 1-year ulcer relapse from three prospectively randomised trials was only 5.2% in patients treated with
H. pylori
eradication, which was significantly lower than that of the control group (35.2%).

Selective COX-2 inhibitors have been approved for symptomatic treatment of arthritis for nearly two decades. In contrast to conventional NSAIDs, COX-2 inhibitors provide anti-inflammatory effects without suppressing synthesis of prostaglandins essential for maintenance of mucosal integrity.
⁴⁴
In the Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind randomised controlled trial, selective COX-2 inhibitor was confirmed to be associated with a significantly lower annualised incidence of peptic ulcer complications when compared to non-selective NSAIDs (0.44% vs 1.27%,
P
 = 0.04).
⁴⁵
However, such a protective effect was negated if the patient used aspirin concomitantly.
^45,
46
In another population-based study, a 44% increase in the annual number of prescriptions for NSAIDs (both selective and non-selective) had been recorded since the introduction of COX-2 inhibitors, but the annual hospitalisation rates for perforated peptic ulcer decreased from 17 per 100 000 person-years to 12 per 100 000 person-years during the study period.
⁴⁷

The impact of COX-2 inhibitor and traditional NSAIDs on perforation-related death was recently determined in a population cohort study.
⁴⁸
While the observed 30-day mortality of the entire cohort of 2061 patients with ulcer perforation was 25%, that among NSAID and COX-2 inhibitor users was much higher, amounting to 35%. The increase in mortality associated with use of COX-2 inhibitors was similar to that of traditional NSAIDs, with an adjusted mortality rate ratio (compared to non-users of NSAIDs) of 2.0 and 1.7, respectively. COX-2 inhibitors, although being able to reduce the overall incidence of perforated ulcers, do not confer any advantage in clinical outcomes if perforation occurs. Such an observation may be related to the poor underlying comorbid condition of the patients who require extended use of NSAIDs or COX-2 inhibitor therapy.

As a result of knowing that the mortality risk is high once perforation occurs in the long-term NSAID users, protective measures against development of peptic ulcer in this group of patients have been extensively investigated. In an economic evaluation study using the Markov model and data extracted from a systematic review, the prescription of a proton-pump inhibitor (PPI) was shown to be cost-effective for people with osteoarthritis no matter whether they are taking a traditional NSAID or COX-2 selective inhibitor.
⁴⁹
Importantly, the cost-effectiveness of adding a PPI remained valid even in patients at low risk of gastrointestinal adverse events.

As the ulcer diathesis is readily corrected by
H. pylori
eradication and cessation of NSAID usage, most patients with ulcer perforation can now be treated with a simple patch repair together with a thorough peritoneal washing. These operations used to mandate a midline laparotomy, but developments in minimally invasive surgery have revolutionised the surgical approach. The first laparoscopic closure of peptic ulcer perforation was reported in 1992.
⁵⁰
Since then several series have been published.
^51
–
53
However, interpretation of these data is difficult due to marked heterogeneity in the study designs, patients' demographics and the laparoscopic techniques used. With the exception of the two truly randomised trials from Hong Kong, all the others are either single-centre series or retrospective non-randomised comparative studies.
^54,
55
Most of them reported significantly better, albeit marginal, outcomes in the laparoscopic group, which could be due to selection bias when choosing the surgical approach for individual patients.

In a systematic review of 15 publications, the laparoscopic closure was found to be associated with significantly less analgesic use, shorter hospital stay, less wound infection and lower mortality rate compared to open surgery.
⁵⁶
However, shorter operating time and less suture-site leakage were clear advantages of the open technique. Interestingly, in a more updated review comprising data extracted from 56 studies, apart from confirming the above-mentioned findings, the issue of conversion to open surgery was addressed.
⁵⁷
The overall conversion rate was 12.4%, with the main reason being the size of perforation and inadequate localisation of the perforated pathology. The authors also identified that patients with a Boey score of 3, age over 70 years and symptoms persisting longer than 24 h were associated with a higher morbidity and mortality, and recommended these factors to be relative contraindications for laparoscopic intervention.

Giant duodenal perforation (> 2 cm in diameter) remains a challenge to most surgeons because failure of omental patch repair is not uncommon (2–10%), which can lead in turn to increased morbidity rates and a resultant higher mortality (10–35%).
^58,
59
Converting the perforation into a controlled fistula by suturing the perforated site around an indwelling Foley catheter or T-tube was once advocated as a salvage measure. However, leakage remains a major concern with this technique and it should be reserved for patients with overtly unstable physiology to which the operative time is limited. For patients who are haemodynamically stable, a distal gastrectomy incorporating resection of the perforation-bearing duodenum is considered to be a viable option by some surgeons. However, due to pre-existing scarring and recent tissue loss, the duodenal stump thus created can be difficult to manage. Various procedures have been described, keeping in mind the friability of tissues. Nissen's double-layer closure technique,
⁶⁰
catheter duodenostomy (
Fig. 6.3
),
⁶¹
lateral duodenostomy through the third part of the duodenum,
⁶²
and making a duodenojejunostomy with a Roux-en-Y segment of jejunum
⁶³
have all been mentioned. Nevertheless, it is noteworthy that the best way to avoid a difficult duodenal closure is to avoid an unnecessary gastrectomy, even in the presence of giant duodenal perforation. The alternatives to gastrectomy in these situations include converting the large perforation into a Finney pyloroplasty, use of omental plugging technique
⁶⁴
or fashioning a controlled tube duodenostomy after primary closure of the perforation.
⁶⁵
It cannot be overemphasised that most of the technical advocates are based on level III evidence only because of the rare nature of giant perforations. However, if there is no option but to proceed with a distal gastrectomy, a Roux-en-Y reconstruction is preferable as this will permit enteral nutrition in the postoperative period while the (inevitable, but hopefully controlled) duodenal fistula is allowed to close.

Reports pertaining to gastric ulcer perforation only are scarce.
⁶⁶
On a statistical basis, gastric perforation tends to cluster among the elderly and is more likely to be associated with use of NSAIDs, but other possible causes include carcinoma, lymphoma and gastrointestinal stromal tumours. Perforation in the older age group carries a less favourable prognosis, partly related to their impaired physiological response to the septic insult, and more so to the delay in presentation, which is not uncommon. While simple omental patch remains the best option (after biopsying the lesion – see below), most surgeons prefer an ulcer excision if this can easily be carried out and without compromise to the stomach lumen. Formal gastric resection is not indicated unless either of these options is not possible, and this is rare.

Because a small minority of gastric perforations are malignant, and the possibility of gastric lymphoma needs to be remembered, it is essential to biopsy the ulcer edge, if it is not being excised.
⁶⁷
Definitive surgery, if then required, can be carried out at a later date once the pathology has been reviewed, full staging investigations carried out, and after a full and frank discussion with the patient regarding prognosis and alternative treatment options. This is particularly true for gastric lymphoma, which can now be managed almost entirely by chemotherapy, radiotherapy or a combination of the two.

Though surgery for a perforated gastric cancer was once considered to be invariably palliative in nature, recent evidence suggests that long-term survival is still achievable in selected patients (stage I and II). A systematic review based on nine published articles encompassing 127 patients surgically treated for gastric cancer perforation reveals that the diagnosis of malignancy was known in 14–57% during the preoperative and intraoperative phases.
⁶⁸
While mortality rates for emergency gastrectomy ranged from 0 to 50%, a two-stage approach was adopted in five of the nine series, and patients able to receive an R0 gastrectomy during the second-stage operation demonstrated significantly better long-term survival (median 75 months, 50% 5-year) compared with patients who had only simple closure. It highlights the importance of not taking a too pessimistic stance if the biopsy of a repaired gastric ulcer turns out to be carcinoma.