peptic ulcer, gastric perforation, peritonitis, laparoscopy, minimally invasive surgery, emergency surgery.

Treatment outcomes for peptic ulcer disease (PUD) have been substantially improved over the past few decades, first of all in the 1970s with the introduction of H2-blockers followed by proton pump inhibitors in the 1980s and the introduction of antibacterial therapy to eradicate Helicobacter pylori, leading to a decrease in elective surgical procedures for this disease[1].

However, there are discordant results in the literature, while the Scandinavian groups[2, 3] reported a reduced incidence of perforated peptic ulcer due to these treatments, several studies reported no change or even an increase in the incidence of perforated peptic ulcer[4, 5].

Improved medical management of PUD has virtually eradicated the need for acid-reducing surgery, such as proximal selective vagotomy, gastric resection and surgery performed for benign gastric outlet obstruction[6, 7].

However gastric or duodenal perforation remains a life threatening complication of PUD; it is one of the commonest causes of emergency hospitalization and surgery in PUD and develops in 2-14% of patients[8, 9]. Most authors consider perforated gastric and duodenal ulcer as a single disease entity. However, Hodnett et al.[10] reported that perforated gastric ulcer has a higher morbidity and mortality than perforated duodenal ulcer. Moreover, perforated gastric ulcer is more commonly associated with older patients, larger ulcer size, and more severe intraperitoneal contamination than duodenal one[11, 12].

Although predominantly benign nature of peptic ulcer, underlying gastric cancer can occasionally present with perforation, as reported in over 13% of patients in one series[13].

The incidence of perforated peptic ulcer is approximately 7-10 per 10.000 population per year[5, 14]. An estimated 2% to 10% of patients with PUD will present with perforation of the stomach or the duodenum in their lifetimes, with a high risk for mortality in the elderly[15, 16]. Acute perforations of the duodenum are estimated to occur in 2–10% of patients with PUD[17, 18].

In addition, most patients with a perforated peptic ulcer are elderly with considerable comorbidity[19], among those patients a higher mortality rate (up to 25%) and a morbidity rate of up to 50% have been reported, even in recent studies[20-22]. In particular, for patient ≥ 60 years, the incidence increased over 10-fold, and mortality more than 50-fold, compared to younger ages[17, 23]. Overall prevalence of perforation is about 5% with mortality ranging from 8.5% to 25%[9, 24].

Consequently, perforated peptic ulcer remains a frequent challenge to surgeons and optimal treatment strategies are needed.

The aim of this study is to analyze the post-operative outcomes of our series from a single center comparing open and laparoscopic repair.

Ninety-four patients met inclusion criteria. Preoperative characteristics, surgical procedures and postoperative outcomes of the patients included in this study are listed in Table 1, Table 2, Table 3.

Figure 3

Values in parentheses are percentages unless indicated otherwise; *values are mean±SD.

The overall median operative time was 92.9±34.4 [35-255] minutes, no significant difference was shown between the two groups (p=0.90). In all cases warm saline was used for intraoperative peritoneal lavage until clear fluid was obtained and the overall average amount of it was 1798.8±1213.9 ml.

The reintroduction of oral diet varied across the groups and was dependent on the first bowel movement and the severity of peritonitis. The naso-gastric tube and surgical drainage were removed earlier in the LG than OG with statistically significant differences (p<0.01).

Eighteen patients (19.1%) died in hospital after surgery: 2 in LG and 16 in OG, respectively (p=<0.01). In particular, 15 patients had a Boey score 2 and one patient had a Boey score 3. Among these patients, in two cases the death occurred after a re-operation; in one patient due to a gastric suture leakage, in the other one due to an evisceration.

Post-operative complications occurred in 19 patients (20%) of our study cohort. In particular, mild complications (Clavien grade I-II) were more prevalent than severe complications (Clavien grade III-IV). However, no significant differences were recorded between the two groups. Five patients had a re- operation. In two patients the reoperation was due to a gastric suture leakage, in the remaining three cases due to an evisceration.

The overall median hospital stay was 9.49±8.72 [1- 60] days and was significantly affected by surgical procedure; not surprisingly the median hospital stay was longer in OG compared to LG, with a difference of

about 7 days (p<0.01).

The impact of laparoscopic procedure on the overall occurrence of complications, postoperative death and discharge at home in relation to other variables considered in the logistic regression model is shown in Table 4.

Mortality showed to be more favourable in LG in the unadjusted model. However, after adjusting for co- variables, this difference was not found to be statistically significant.

The first recorded description of a peptic ulcer perforation was by the Princess Anne Henriette of England, the daughter of King Charles I of England and Princess Marie Henriette of France[27].

Since that description, peptic perforation was a serious complication of PUD affected by worse outcome. The overall mortality due to perforation peritonitis ranges between 6% and 27%. One of the most important factors responsible for mortality is septicemia[28].

Perforated peptic ulcer can mimic acute cholecystitis, acute pancreatitis, or appendicitis when gastroduodenal contents spread out causing pain in abdomen[29].

The perforation leads to chemical peritonitis, with or without contamination with micro-organisms. Spillage of gastroduodenal contents is usually diffuse but may be localized in the upper abdomen. After 6 to 12 hours many patients may obtain some spontaneous relief of the pain due to dilution of the irritating gastroduodenal contents by the ensuing peritoneal exudate. The intra- abdominal infection appears after 12 to 24 hours[30].

Definitive surgical procedures have been routinely performed for decades in Japan, other Asian countries, and Eastern Europe; nowadays, non-definitive surgical procedures like simple closure with or without omentoplasty and drainage are the most popular in case of perforation[31].

Notwithstanding aggressive surgical procedures such as gastric disconnection, antrectomy, gastrostomy, lateral duodenostomy and feeding jejunostomy with restoration of intestinal continuity were described in literature; nowadays the surgical options are suture of the perforation with or without omentoplasty[32].

However, it is controversial whether laparoscopic approach or conventional open surgery should be chosen.

In literature, negative factors for the laparoscopic approach are shock at the diagnosis, delayed presentation (> 24 h), confounding medical conditions, age > 70 years, ASA (American Society of Anesthesiologists) score 3–4 and Boey score of ≥ 2, ulcer location or large perforation size (> 6–10 mm). The most accepted but discussed contraindication is signs of shock due to the negative impact of increase duration of surgery and negative influence of pneumoperitoneum on renal function[33]. For the laparoscopic approach the concern is the CO2 pneumoperitoneum who leads to increased intra-abdominal pressure intraoperatively: it is related to growing risk of bacteremia and sepsis due to the increased chance of bacterial translocation from peritoneal cavity into the bloodstream, increasing the occurrence of pneumonia in patients selected for this

approach[34].

In our cohort of patients, the OG presented more fragile patients with more severe ASA score and a greater number of Boey 2-3 than the LG.

The most common cause of conversion to open surgery was an inability to repair the ulcer due to either technical difficulties or size of perforation. The conversion rates are directly influenced by the laparoscopic skills and experience of the surgeon. In the literature it ranges between 2.6% to 7.7%[35].

Overall complications rate in our series was 20% which is comparable to other reports[36, 37].

A recent study by Teoh et al.[38] found that a laparoscopic approach in high-risk patients was not associated with increased morbidity and mortality when compared to an open approach, particularly if the ASA grading was below 3.

A Cochrane meta-analysis[32] showed a trend in reducing intra-abdominal septic complications, wound infections, postoperative ileus, pulmonary complications, and mortality with laparoscopy.

A previous meta-analysis by Lau[39] showed a lower incidence of post-operative complications in the laparoscopic group but even a higher rate of reoperation. In our cohort of patients, there were 5 reoperations in the 2 groups. One patient in the LG and 4 patients in the OG, respectively (p=0.16).

The main limitation of the present study is the relatively low sample of patients. However, all our data were prospectively collected, and all surgical procedures were performed by the same group of surgeons.

Gastric perforation is a severe complication of PUD. Early diagnosis and surgical treatment are mandatory to avoid peritonitis progression with consequent high mortality risk. Laparoscopy is a valid alternative to open surgery in selected patients and in centers with experience in minimally invasive surgery.