Helicobacter Pylori Infections in Peptic Ulcer Perforations: A Retrospective Analysis in Two Referral Hospitals in Douala, Cameroon

Background: Perforations are major complications of peptic ulcer disease and surgical emergencies with important mortality and morbidity. Helicobacter pylori (H. pylori) has been identified as one of the commonest factors associated with peptic ulcer disease. However, little is known about its implication in cases of perforations in Cameroon. We aimed to determine the frequency of Helicobacter pylori infections in cases of perforated peptic ulcers, describe clinical features and outcomes of these cases in Cameroon. Method: A hospital-based retrospective cross-sectional study was conducted through the review of patients’ records admitted for peptic ulcer perforations in Laquintinie and Douala General Hospitals over a period of 5 years (January 2014 December 2018). We defined H. pylori infection as; positive result on tissue biopsy at time of surgery. We used SPSS version 23.0 to analyse data and set an alpha value at P = 0.05. Results: We reviewed 115 cases of peptic ulcer perforation, with a mean age of 40 years and sex ratio (M:F) of 5:1. All patients underwent emergency laparotomy, 48 (41%) cases had a biopsy report and the prevalence of H. pylori infection in these cases was 47.9 %. Smoking, alcohol consumption and Non-Steroidal Anti-inflammatory Drugs (NSAIDs) use, were not associated with peptic ulcer perforation. The morbidity was at 43.7% and mortality at 14%. Mortality was increasing with a higher Mannheim Peritonitis Index score (OR: 23.51, 95% CI: 4.197 How to cite this paper: Bokalli, F.A.M., McWright, C.F., Aseneh, J.B.N., Mbachan, T.M., Mokake, N.D., Nguedia, J.C.A. and Ngowe, M.N. (2020) Helicobacter Pylori Infections in Peptic Ulcer Perforations: A Retrospective Analysis in Two Referral Hospitals in Douala, Cameroon. Surgical Science, 11, 298-311. https://doi.org/10.4236/ss.2020.1110032 Received: September 17, 2020 Accepted: October 25, 2020 Published: October 28, 2020 Copyright © 2020 by author(s) and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access F. A. M. Bokalli et al. DOI: 10.4236/ss.2020.1110032 299 Surgical Science 143.003, P-value: 0.000). Conclusion: We observed a high prevalence of H. pylori infection in patients with peptic ulcer perforations. We recommend systematic H. pylori screening in cases of perforations and that larger studies should be carried out to evaluate the association of H. pylori infection with peptic ulcer perforation in Sub-Saharan Africa.


Introduction
Peptic ulcer disease (PUD) refers to a break in the mucosal lining of the stomach or duodenum and occasionally the lower part of the oesophagus [1]. There are five major complications of PUD; bleeding, perforation, penetration, obstruction and malignancy [2].
In 1983, the whole thinking regarding the pathophysiology and management of this disease was revolutionized when Warren and Marshall [3] reported Helicobacter pylori (H. pylori) infection plays a crucial role in the pathogenesis of PUD. The revolution in PUD treatment that occurred with the discovery of the role of H. pylori is yet to lead to any detectable changes in incidence or treatment of peptic ulcer perforations (PUP) [4] [5].
PUP occurs in 2% -10% of patients with ulcer disease, it is the second most frequent complication after bleeding [7]. Gastroduodenal perforation, with leakage of alimentary contents into the peritoneal cavity, is a common surgical emergency associated with morbidity and mortality in 50% and 30% of cases respectively [8] [9]. PUP present as acute abdominal emergency conditions, with localized or generalized peritonitis and a high risk for further development of sepsis and death [10].
About 50% of the global population is colonized by H. pylori in the gastric mucosa, yet it causes diseases in only 10% -20%. Nonetheless, it shows a variable prevalence (0 -90%) in perforated ulcers [5] [11]. In addition, studies done in Africa have shown that the rate of H. pylori infections in patients with PUP ranges from 50% -80% and H. pylori infections, as a risk factor for PUP, appear to be more relevant in younger patients [12] [13].
H. pylori is highly endemic in Cameroon [14] with a prevalence estimated at 72.5% with a slight male predominance and affecting the young adults of less than 40 years. It was also higher among people living in urban cities, with low level of education and of low socioeconomic status. The prevalence of H. pylori infections was 63% among patients with gastric ulcers and 50% among those  [15].
Despite diagnostic and therapeutic advancements [16] [17], the role of H. pylori in the incidence of perforations and possible interactions with other known risks is yet to be ascertained. However, there is paucity of data regarding its burden in peptic ulcer perforations in Cameroon. Therefore, we sought to determine the influence of H. pylori infections in cases of peptic ulcer perforations in the city of Douala.

Study Area
We carried out this study in two referral hospitals in Douala (the economic capital of Cameroon); the Douala General and Laquintine Hospitals. They host an extensive technical plateau and experimented specialists.

Study Design
This study was a hospital-based cross-sectional retrospective study carried out over a period from January 2014 -December 2018.

Study Population
We reviewed all records of patients hospitalized for peptic ulcer perforation in both hospitals from 1 st January 2014 to 31 st December 2018, excluded cases of perforations resulting from trauma and all cases managed conservatively (not surgically), as well as records with incomplete data. Where histopathology records were available, cases were classified as; infected with H. pylori if positive or not infected with H. pylori if negative.

Study Procedure
The study involved the use of patients' records who had been treated for PUP.
Additional information was obtained from ward registers, histopathology reports and theatre records. Morbidity was considered as medical complications sustained postoperatively during the hospital stay. The Mannheim Peritonitis Index [18] was the scoring system used to predict outcome, we classified into 3 groups; those with a score <21, 21 to 28 and >28 corresponding to mild, moderate and severe respectively. These were collected with the help of a pre-established data collection form (Appendix).

Data Management and Analysis
The Data collection forms were checked on a daily basis to ensure correct entry of information and codes used to ensure confidentiality. Data were keyed into a computer, secured by a password known only to the primary investigator. Data  Data were summarized as frequencies and proportions for categorical variables. Continuous variables were summarized using means and standard deviation for parametric variables and median and interquartile range for nonparametric variables. Group comparison for categorical variables was done using Chi-square (χ 2 ) test and Fisher's exact test (where appropriate). The p-value < 0.05 was considered statistically significant.
The prevalence was determined by counting the number of patients in whom the bacteria were isolated divided by the overall number patients who were biopsied.

Ethical Statement
We obtained administrative clearance from the Faculty of Health Sciences of the University of Buea, followed by ethical clearance from the Institutional Review Board of the Faculty of Health Science. Then proceeded to obtain authorization from the administration of the Douala General and Laquintinie Hospitals.

Results
In, total, 176 cases of perforations were identified. 61 files were excluded (42 Traumatic perforations, 17 incomplete records and 2 conservatively managed).
Of the 11 with history of smoking, 5 were found to be H. pylori positive. Among 37 non-smokers, 18 were H. pylori positive. 24 persons had a known history of PUD or recurrent dyspepsia, among them 12 were H. pylori positive and among those with neither history, 11 were H. pylori positive. Among 11 patients with history of alcoholism, 8 were H. pylori positive and among 37 non alcoholics 15 had H. pylori infection. Among 15 patients with history of NSA-IDs, 8 were positive for H. pylori and among 33 patients with no history of NSAIDs 15 tested positive for H. pylori. No significant association was found between the presence of H. pylori infection in peptic ulcer perforation with smoking, alcohol intake, history of PUD/dyspepsia or NSAIDS use ( Table 3).
The mortality in our study was 17% (7/48), with just one case registered as H. pylori positive. Mortality was found to be higher in patients with MPI greater than 29 compared to those with less (p = 0.000) ( Table 5).

Discussion
Of the 115 patients treated for PUP, 48 (42%) were screened for the presence of H. pylori infection. This was relatively low and could be explained by financial    [19]. This is likely owing to the fact that men are the breadwinners in the family, and are consequently prone to stress, drugs and alcohol abuse.
The mean age at presentation was 40 years with an age range of 17 to 80 years.
Afuwape et al. [19] reported a mean age of 42.5 years and the highest incidence in the fifth decade. These results differed from those of Ghosh et al. in India [10] who showed most (45.1%) patients were in the 15 -30 age group. In Europe however, majority (68%) of patients belonged to a much older age group (>60 years) [20]. These variations in the age may be attributed to the age at which the patients are exposed to various risk factors predisposing for peptic ulcer disease and subsequently perforation.  [22]. This discrepancy could be accounted for by the fact that other diagnostic methods were used in that study.
Although the age groups 15 -30 and 31 -45 had equal number of participants, the percentage of 31 -45 year positive for H. pylori infection was highest and agrees with the findings of Dogra et al. [22].
The association of H. pylori infection with gastric ulcer perforation was slightly more striking in that out of 43 cases of gastric ulcer perforation, H. pylori was detected in 22 cases (48.9%). But was less striking in cases of duodenal ulcer perforations where 1 out of 3 (33.3%) had H. pylori detected. These results were similar to the study of Rashim et al. [23] where H. pylori was isolated in 48.7% of gastric ulcer perforation.
Although treatment of patients with history of chronic dyspepsia should be individualized, a cost-effective initial approach is to test for H. pylori and treat the infection if the test is positive. If the H. pylori test is negative, empiric therapy with an acid suppressant is recommended. In our study, patients having history of dyspepsia had a high prevalence rate of 50% though Ullah et al. had a higher prevalence at 87% [24]. The differences in cultures could be an explanation to this. that allows the surgeon to easily determine the outcome risk during initial surgery. In theory the lower the score the lower the chances of morbidity or mortality from peritonitis and this was seen in practice in our study as the mortality rate was 1/48 (2%) for those with a score < 21 and 6/48 (12.5%) for those > 21.
Those who were H. pylori positive had a better prognosis of survival from perforation peritonitis as shown by a Mannheim peritonitis index < 21 for a majority (60%) when compared to H. pylori negative and over 91% among those who tested positive. This could help conclude that H. pylori infection does not worsen the prognosis in cases of perforated peptic ulcer as this observation attained statistical significance. The mortality rate was higher compared to similar studies [21] [22].
All the cases in which the bacteria were isolated were systematically placed on H. pylori eradication therapy for 2 weeks, but follow up on this was not documented.

Study Limitations
1) The retrospective nature of this work made retrieval of some important data that would have been added value to the study difficult.
2) We assumed that all patients entered during the study had been subject to a fairly standard treatment commensurate with the individual diagnosis. Inadequate treatment could have negatively impacted on outcome, yet it was not a subject of evaluation in this study.

Conclusion
Peptic ulcer perforations are common findings in the male population of the fourth and fifth decades of life. Also, gastric perforations were more common than duodenal. The prevalence of H. pylori infection in cases of peptic ulcer perforations in which histopathologic biopsies were done was 47.9%. This is quite high given that H. pylori eradication therapy is systematically prescribed in PUD. However, smoking, NSAIDs use and alcohol ingestion were not associated with H. pylori infection.

Recommendations
Raise awareness on the importance of H. pylori screening in cases of peptic ulcer perforations.
To always send excised body tissues for histopathologic analysis.