DD as a benign digestive tract disease is widely distributed in the population. Patients with DD are usually asymptomatic and therefore often receive insufficient attention[14], but in our study, more than half of the patients (53.3%) had a combination of various symptoms. Meanwhile, the most common clinical symptoms (such as epigastric pain, nausea, vomiting, and abdominal distension) of DD patients often lack specificity and are often combined with multiple symptoms at the same time, making them easy to misdiagnose in the clinic and preventing them from receiving appropriate treatment.
By comparing the differences in clinical characteristics between patients in the symptomatic and asymptomatic groups, we found that patients with DD located in periampullary and ≥ 1 cm seemed to be more likely to have clinical symptoms. It is well known that DD is more common in the 2nd portion and periampullary, and different hypotheses[15, 16] have also been proposed that DD in this area is more likely to be combined with various pathological states. Our results firstly provide the evidence of this association, meanwhile we suggesting a possible association between diverticular size and the presence of clinical symptoms.
Previous studies lacked a unified standard for the classification of DD size because it was difficult to accurately measure diverticular size even under endoscopy. Kim et al. [8] chose 1.5 cm and 3.0 cm as the judgment bounds, because the diameter of a commonly used endoscopic stone picking balloon was exactly 1.5 cm, and the size of PAD could be more accurately measured with this reference. Based on our precise measurements of all measurable imaging pictures, we chose 1 cm, 3 cm, and 5 cm as the measured value of diverticular size, then found that smaller DD with the size of < 1 cm and 1–3 cm were the majority (78.0%). Interestingly, there were also lots of patients in our study who had no obvious clinical symptoms, so this phenomenon can be partially explained by the above conclusions, as we all know usually a small DD is less likely to cause symptoms because it has little effect on the primary physiological function.
Patients with DD usually have symptoms that do not arise directly from the diverticula, but rather from various types of diverticula-related complications and comorbidities. In addition to comorbidities such as diverticulitis, various complications related to the biliary system and the pancreas are also included. The association between DD and Biliopancreatic disorders has been confirmed by many previous studies. Karn et al. [17] recently completed a meta-analysis including 11 related studies and concluded that patients with PAD had a significantly increased risk of choledocholithiasis about 2.3 times that of normal people. Bruno et al. [18] conducted a 2475 EUS examination on patients with PAD and showed that the prevalence of cholangitis, bile duct dilatation, and choledocholithiasis was significantly higher than those in the control group without DD.
In our study, patients with DD combined with different types of biliopancreatic comorbidities were significantly more common in PAD and DD > 1 cm, again confirming our previous findings. As for the reasons for the association, there are several possible hypotheses in previous studies: (1) Mechanical pressure exerted by the diverticula on the distal portion of the common bile duct can impede bile excretion [19]; (2) The diverticula may cause sphincter dysfunction of Oddi. It may be due to sphincter stenosis due to the accumulation of food or bezoar in the diverticula. Or chronic ampullary inflammation caused by diverticula can lead to chronic fibrosis of the nipple and subsequent stenosis [20]; (3) Bile stasis and abnormal tension and contractile activity of Oddi sphincter may lead to the spread of overgrown bacteria in the diverticula to the biliary tract system more easily, and produce β-glucuronidase and debinding bile salts, thus forming stones [21, 22].
Given high proportion of patients in the symptomatic group in our study, the management of this group of patients deserves high attention. In our study, conservative treatment (65.2%) was predominant in the treatment of DD, which suggests that a high number of smaller-sized or single DD are not usually associated with a serious outcome. Depending on the type and severity of the complications, endoscopic treatment and cholecystectomy may be options for complications only, in addition to surgical treatments that directly target DD.
Our univariate analysis found that a greater number of clinical characteristics may be associated with the choice of treatment modality. Further, we performed a multivariate Logistics regression analysis and the results showed that patients with combined smaller-sized DD may prefer conservative treatment, while patients with combined biliary system stones and cholangitis without bile duct stones may prefer surgical treatment (direct or indirect). Previous studies on the treatment of patients with DD are scarce, and our findings will be very helpful in making decisions on the treatment for these patients.
The main surgical treatment modalities for patients with DD in previous studies[23] include diverticulectomy, duodenal resection, and diverticular inversion, and surgical treatment for DD is considered safe. In our study, DD patients were operated on more frequently with choledochojejunostomy (43.8%) and gastrojejunostomy (20.3%), next by diverticulectomy (14.1%). Based on a review of the indications for each procedure, we summarized the more frequent indications of each procedure for the reference of subsequent operators. As for postoperative complications, our results are consistent with those reported[23, 24], with a low probability of postoperative complications in diverticulosis patients (10.9%). Complications occur mostly in middle-aged and elderly female patients and are non-fatal, and all improved after conservative treatment.
As mentioned earlier, our study mainly focuses on two questions: What kind of DD patients deserve attention and management; and what kind of management is appropriate for this type of DD patient? Although it was a retrospective study, we suggest possible explanations by analyzing a large number of case data. Our study is also the only detailed and in-depth study done to date on the evaluation and management of DD.
Still, our study needs to be improved in the following aspects: groups based on DD size may be slightly biased from the true situation because we cannot ensure that the data measured by the electronic caliper is completely accurate, especially when it is influenced by the diverticular contents. More importantly, limited by the nature of retrospective studies, our answers to the two questions can only provide possible interpretations. As for the exact causal relationship, further confirmation is needed in subsequent multicenter, prospective studies.
In conclusion, DD is a common clinical pathology frequently occurring in the 2nd portion, mostly small in size and single in number. Patients with DD ≥ 1 cm or located in the periampullary are more likely to be combined with various types of comorbidities and complications, thus presenting as symptomatic. The size of the DD and the combination of specific biliary comorbidities may have an impact on the choice of treatment modality. Although most patients with symptomatic DD can be treated conservatively only, surgical treatment is also a safe and effective approach when the appropriate procedure is chosen. Our findings will provide important ideas for the clinical diagnosis and treatment of DD, but further prospective studies are needed to confirm that.