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A 10-Year Retrospective Study in 13680 Patients

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AbstractBackgroundMethodsResultsDiscussionData AvailabilityConflicts of InterestReferencesCopyrightRelated Articles

Introduction. Shared by certain epidemiological and etiological characteristics, diverticulosis and colorectal cancer (CRC) as well as colonic polyps has long been linked. This association was studied in several heterogeneous studies but has reported inconsistent results. Clarifying the association is clinically relevant for endoscopist awareness and potential modification of screening and surveillance intervals for diverticulosis patients. Methods. In this retrospective single-center study, patients diagnosed with diverticulosis on colonoscopy over a 10-year period were included. Each diverticulosis patient was matched with 1 control by age, gender, setting (inpatient/outpatient), and procedure’s indication. CRC and polyp detection rates were recorded and compared between the groups before and after adjustment for bowel preparation quality and exam completion. CRC location was recorded and compared between groups. Results. A cohort of 13680 patients (6840 patients with diverticulosis and 6840 matched controls) was included. Diverticulosis was located mainly to the sigmoid and left colon (94.4%). The CRC diagnosis rate was lower in the diverticulosis group (2% vs. 4.5%, , , and ). Moreover, location of CRC was unrelated to diverticulosis location, as more CRCs in the diverticulosis group were located proximal to the splenic flexure as compared to the control group (42.5% vs 29.5%, respectively; ). Diverticulosis, however, was associated with an increased polyp detection rate compared to controls (30.5% vs. 25.5%; , , and ). Conclusion. We demonstrated that diverticulosis was not associated with an increased risk for CRC. A possible increased polyp detection rate, however, warrants further evaluation in large prospective studies.

1. Background

Diverticulosis is considered as one of the most common and burdensome GI disorders [1, 2]. The underlying pathological mechanisms resulting in diverticular formation of a colonic wall is still largely unknown. Diverticula develop at well-defined points of weakness in the circular muscle of colon and are likely to be the result of complex interactions between environmental and heritable factors including diet, increased age, and decreased colonic motility, among others [3, 4]. Typically, diverticulosis is identified incidentally at colonoscopy or imaging studies performed for various indications, and the majority of patients with diverticulosis remain asymptomatic throughout their lifetime [5].

Several observations hold that certain epidemiological and etiological characteristics are shared between colonic diverticulosis and colorectal cancer, suggesting a possible association between these two conditions. The prevalence of these conditions is markedly on the rise in the last decades, and they both are detected frequently in aged people as well as western population and industrialized countries [6–8]. Western diet, namely, low dietary fiber and high total fat, has been largely regarded to play a major role in the pathogenesis and was epidemiologically associated with an increased risk of both conditions [9–13].

The abovementioned connection is of great clinical relevance, as several reports demonstrated that patients with diverticular disease have a higher risk of harboring colonic cancer [14–16]. Above and beyond, one meta-analysis demonstrated that diverticular disease was associated as well with increased detection of colorectal adenomas [17].

However, data are still controversial and inconclusive as other recent studies failed to confirm this association [18–20]. Moreover, the vast majority of the studies inspecting a possible link between both conditions were limited by small patient numbers and did not account for multiple confounders that are known to affect CRC and polyp detection such as patients’ demographics, procedure’s indication, setting, quality of bowel preparation, and exam completion.

Taken together, unraveling the dilemma and clarifying the association between both conditions appear to be clinically relevant, as modifying screening or surveillance intervals for CRC and polyp follow-up may be warranted accordingly in patients with diverticular disease.

The present study is aimed at comparing the CRC diagnosis rate and location as well as polyp detection rate between patients with diverticular disease and a matched group without diverticulosis with adjustment for abovementioned confounders.

2. Methods and Settings

We conducted a retrospective, large cohort study, which examined consecutive patients who underwent colonoscopies over a 10-year period within the gastroenterology department at the Hillel Yaffe Medical Center, a university-affiliated hospital in Israel. All patients’ data were collected from our department’s electronic record system. We searched endoscopy reports to identify all patients with a diagnosis of diverticulosis to create a study group. For a control group, each patient from the study group was matched with 1 control patient by age, gender, setting (inpatient/outpatient), and procedure’s indication. Patients were excluded if they were less than 18 years, had prior diagnosis of colon cancer, or if full data set is missing. Endoscopy findings including cancer diagnosis and location as well as polyp detection were recorded in both groups. Diverticulosis location was documented as well in the diverticulosis group. Whenever an endoscopic diagnosis of colorectal cancer was encountered, histology reports were reviewed to confirm diagnosis.

We compared the rate of CRC and polyp diagnosis between both groups and use multivariable analysis to adjust for adequacy of bowel preparation (adequate/inadequate) and depth of examination (cecal intubation confirmed or not), in order to identify independent association of diverticulosis with CRC and polyp detection. CRC location was documented according to endoscopy reports, and we compared its location between both groups. Diverticulosis and CRC location was classified as proximal (proximal to splenic flexure) or distal (splenic flexure or distal). The local institutional Helsinki ethics board approved the study and granted exemption from informed consent in this retrospective study as patients were receiving standard care without relation to the study.

3. Statistical Analysis

This statistical analysis is dealing with cohort of “big data” (40128 patients), of them 6840 patients with diverticulosis (study group). We used the Propensity Score Matching in R program version 3. 3 to divide the total cohort to 1 : 1 ratio (study and control group). Descriptive statistics in terms of mean, SD, and percentiles were preformed to the whole parameters in the study. Differences between the two groups (diverticulosis diagnosed vs. matched group) in the quantitative parameters were demonstrated by -test. For the categorical parameters, we used fisher exact tests. Multivariate logistic regression model was used to determine the effect of the independent parameters associated with CRC. SPSS version 25 was also used for statistical analysis. was considered as significant.

4. Results

We included a large cohort of 40128 patients who underwent colonoscopy at our hospital. We searched endoscopy reports and identified 6840 patients (17%) with diverticulosis diagnosed during the study period. A matched group of 6840 control patients (at 1 : 1 ratio) was included for final analysis. Baseline characteristics of both groups were similar and are provided in Table 1. The overall mean age was years (range: 18-101), with a slight male predominance (52. 1%). The vast majority of the procedures (78.4%) were performed in the outpatient setting. Procedures’ indications did not differ significantly between groups. The most common indications for colonoscopy were abdominal pain and diarrhea (21.1%), rectal bleeding (14.2%), and anemia (13.2%).

The CRC diagnosis rate was lower in the diverticulosis group (2% vs. 4.5%; ) while the polyp detection rate was surprisingly higher (30.5% vs. 25.5%; ) as compared to the matched group (Table 2). Cecal intubation rate (92.8% vs. 84.1%; ), adequate bowel preparation rate (90.7% vs. 84.1%; ), and terminal ileum intubation rate (2.2% vs. 1.6%; and ; ) were significantly higher in the diverticulosis group (Table 2). Multivariate analysis (Table 3) to account for these variables revealed similar trends as diverticulosis patients were associated with less CRC diagnosis (, , and ) but increased polyp detection rate (, , and ).

Diverticulosis and CRC locations are demonstrated in Table 4. Diverticulosis was located mainly to the distal colon (94. 4%). Location of CRC was unrelated to diverticulosis location, as more CRCs in the diverticulosis group were located proximally compared to the control group (42.5% vs. 29.5%, respectively; ).

5. Discussion

The current study was designed to clarify several aspects of diverticulosis and its possible association with CRC and polyp diagnosis. This association has long been studied in observational, cross-sectional, and case-control studies and has reported inconsistent results. Moreover, small patient numbers and heterogeneous study design contributed to conflicting conclusions. In the current study, we included a large cohort over a 10-year period and performed group matching followed with multivariate analysis in order to account for as many confounders as possible that may have influenced results of preceding studies.

We found that diverticulosis patients were not associated with an increased rate of CRC diagnosis compared to a matched group (2% vs. 4.5%; , , ). Our findings confirm the findings from other recent studies that diverticulosis is not associated with increased CRC diagnosis. A nationwide case-control study found that diverticular disease does not increase the risk of colon cancer in the long term, and a history of diverticular disease does not affect colon cancer mortality [18]. Our findings are also in concordance with a study by Meurs-Szojda et al. on more than 4200 colonoscopies which demonstrated a negative correlation between colon cancer and diverticulosis [21].

Moreover, we provided detailed location of diverticulosis and colon cancer in our cohort. Similar to different reports in western population [6, 7, 9], diverticulosis was located predominantly to the distal colon as more than 94% of diverticula were located to sigmoid and descending colon. In this regard, not only we demonstrated that CRC was located into sigmoid and descending colon in less than 35% but also we showed that more CRCs in the diverticulosis group were located proximally compared to the control group (Table 3) (42.5% vs. 29.5%, respectively; ). Consistent findings were reported by Cooper et al. who showed that diverticulosis associated interval cancers were somewhat more likely to be in the proximal colon and less likely to be in the distal colon [15]. Taken together, these findings reinforce the conclusion that CRC and diverticulosis are unrelated.

One worth mentioning finding in this study, however, is the increased polyp detection rate in diverticulosis patients (30.5% vs. 25.5%; 2, , ). This observation is supported by several other studies reporting that patients with diverticulosis have a higher risk of colorectal polyps as compared to those without [22, 23]. One meta-analysis found a significant 1.67-fold increased odds of developing adenomas in patients with diverticulosis [17]. Unfortunately, we were unable to determine the location and histologic type of these polyps in the current study. However, given the lower CRC diagnosis rate in the diverticulosis patients, this may point out that the majority of the detected polyps were of low dysplastic progression potentials (diminutive/hyperplastic polyps), thus explaining the low CRC diagnosis albeit the high PDR. Nevertheless, this observation needs further validation by a large prospective cohort study.

Furthermore, we demonstrated that diverticulosis has no significant effect on the outcome of colonoscopy. Linked with suboptimal bowel preparation, it is thought that diverticulosis may cause technical difficulty to perform a complete colonoscopy as a result of a spastic colon and luminal narrowing [24–26]. However, we demonstrated the contrary as quality indicators such as the cecal intubation rate (92.8% vs. 84.1%; and ; ) and the adequate bowel preparation rate (90.7% vs. 84.1%; and ; ) as well as the terminal ileum intubation rate (2.2% vs. 1.6%; and ; ) which were even better in diverticulosis patients compared to those without. Similar findings were reported by Gohil et al. who found that diverticulosis did not adversely affect the cecal intubation rate, withdrawal times, or sedation requirements [27].

One of the strengths of the current study includes the large number of participants involved as well as the inclusion of multiple factors such as procedures’ settings and indications reflecting real daily practice. Our study has limits inherent in its retrospective nature. Besides, other possible factors that may have affected endoscopy findings such as withdrawal time and variable endoscopist experience could not be obtained and were not included.

In conclusion, diverticulosis apparently is not linked with an increased risk of CRC but is possibly associated with an increased polyp detection rate. Prospective studies to clarify these findings are warranted.

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Conflicts of Interest

The authors certify that they have no affiliations with or involvement in any organization or entity with any financial or nonfinancial interest in the subject matter or materials discussed in this manuscript. The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Copyright

Copyright © 2019 Fadi Abu Baker et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Intestinal diverticulosis – treatment of the sigmoid colon and colon

Diverticular disease (diverticulosis) is characterized by a latent, conceived insidious course of this disease, when, against the background of complete well-being, a person suddenly finds himself in a hospital bed in intensive care units and, often, in the operating room. The reason for this situation is diverticular disease with a complicated course.

Currently remains the subject of numerous discussions, seminars, conferences, due to the fact that the problem has not been finally resolved. Many problems can be avoided if a person understands what diverticular disease is, whether he belongs to the risk group for diverticulosis, how to prevent the development of the disease and its complications.

Epidemiology

Applicable to Russia and the former USSR, a rapid increase in the incidence of diverticular disease can be noted. In 1970, the incidence of the disease did not exceed 2-3 per 100,000 people. In 1979 this number increased almost 6 times. According to the data published by the GNCC in 2002, the number of diverticulosis detected during X-ray examination was 14.2% of all coloproctological patients, and already in 2012 this figure doubled and amounted to 28.8%.

The growth of this disease is clearly seen along with the process of industrialization and urbanization due to changes in the way of life, lifestyle and nutrition of people. A decrease in the amount of dietary fiber consumed, a large amount of carbohydrate food with the use of red meat led to a significant jump in cases of diverticulosis.

In contrast, in developing agricultural countries, diverticular disease is characterized by isolated cases, which is determined by the nature of the diet, which includes a significant amount of plant foods. Aging society is another reason for the increase in the incidence of diverticular disease. It is noted that at the age of 40 years, the risk of developing diverticulosis varies within 5-10%. Whereas at the age of 60, the percentage of detected cases of the disease is already 30%, and by the age of 80 it exceeds 66%.

Thus, diverticular disease was, is and remains a serious problem that poses challenges for doctors and patients. To understand the term diverticular disease, a brief description of the anatomy of the colon is necessary.

Anatomy of the colon

The colon consists of the following sections: cecum, ascending colon, transverse colon, descending colon, sigmoid colon. The cecum has the widest lumen, the sigmoid colon has the smallest. The junction of the sigmoid colon with the rectus is referred to as the rectosigmoid junction. It is important to note that this section of the intestine has the narrowest diameter.

The wall of the colon consists of three layers: serous, muscular and mucous. The function of the mucous membrane of the colon is the absorption of water, the formation of fecal masses, preparing them for evacuation by secreting a large amount of mucus and the synthesis of vitamins B and K. Under the epithelium of the colon mucosa there is a submucosa, represented by a loose fibrous connective tissue in which blood and lymphatic vessels and submucosal nerve plexus.

The muscular coat has a skeletal function and is responsible for the progressive movement of stool to the rectum. The muscular coat consists of a continuous inner circular layer, divided into three ribbons of the outer longitudinal layer.

The serous membrane consists of a connective tissue base covered with mesothelium, into which outgrowths of adipose tissue penetrate from the side of the muscular membrane, the so-called fatty pendants

What is a diverticulum of the intestine intestinal wall.

There are true diverticula, which have all the layers of the intestinal wall in the structure, and false ones, in which there is no muscle layer.

In the diverticulum, the mouth, neck, body and bottom of the diverticulum are distinguished. The blood supply of the diverticulum is carried out from the vessels of the submucosal layer, from which thin vascular branches depart, perforating the intestinal wall and heading to the bottom of the diverticulum.

When a diverticulum is formed in the projection of the fat suspension and the mesentery of the colon, it is covered on the outside with adipose tissue, when a diverticulum is formed in the free edge of the intestinal wall, it is covered on the outside only with a serous membrane.

• The number distinguishes between a single diverticulum and multiple diverticula of the colon.
• According to the localization of diverticula, right-sided, left-sided and total lesions of the colon are distinguished.
• Right-sided diverticulosis is usually congenital with a predominance of true diverticula.
• With left-sided localization, diverticulosis in most cases is acquired and there is no muscle layer in the structure of diverticula.

Causes of diverticulosis

Causes of diverticular disease is still the subject of numerous discussions. There are several theories for the occurrence of diverticula. The most likely and most often discussed causes include: increased intraluminal pressure in the intestine, increasing weakness of the intestinal wall, impaired motility of the colon, and congenital predisposition.

Increased intraluminal pressure in the colon:

Currently, the most recognized factor in the occurrence of diverticulosis is food. A decrease in the diet of plant fibers in the proper amount reduces the volume of feces, which in turn leads to a violation of their evacuation with an increase in intraluminal pressure in the intestine. The evidence is based on observations of vegetarians and residents of agrarian countries who consume a significant amount of fiber, in which the risk of diverticula is 42% lower than in a group of people who do not consume vegetable fibers in sufficient quantities.

Increasing weakness of the intestinal wall:

The fact of the appearance of diverticula in old age confirms the theory of weakness of the intestinal wall, which is a consequence of the aging process, when degenerative changes in muscle tissue and collagen fibers develop in the intestinal wall.

Colonic dysmotility:

Intestinal dysmotility leads to constipation and increased pressure in the intestinal lumen when stool evacuation is required. The loss of elasticity of the intestinal wall leads, when it is stretched, to micro-ruptures of the circular muscles, through which diverticula begin to form.

Vascular disorders in the intestinal wall:

It is impossible not to indicate the vascular component in the formation of the diverticulum. Violation of the blood supply leads to structural changes in the intestinal wall, while at the place where the vessel passes the muscle layer to the intestine, an expansion is formed, which over time transforms into the mouth of the diverticulum.

Congenital predisposition:

Various congenital systemic connective tissue diseases, collagenoses are a provoking factor in the development of diverticulum disease.

Diagnosis of diverticulosis

Irrigoscopy:

One of the most accessible diagnostic methods is irrigoscopy, which allows to reliably identify the location, size and number of diverticula. This method is not recommended for use in complicated cases due to the high risk of perforation of the inflamed diverticulum.

Colonoscopy:

A method to visualize diverticula and identify complications is colonoscopy. With this procedure, with sufficient reliability, it is possible to diagnose inflammatory changes in the region of the mouth of the diverticulum and detect bleeding from the diverticulum. ! This method cannot be recommended as a mandatory procedure if the patient has a clinical picture of an acute surgical disease of the abdominal organs.

Multislice computed tomography:

The safest method for diagnosing diverticular disease, both during the latent course and in diagnosing complications, is computed tomography, which allows not only to confirm the presence of diverticula in a patient, but also to determine the nature of complications. These include acute diverticulitis with perforation, abscess, peritonitis.

! despite the safety, this method is used to a limited extent due to the high cost of the study and inaccessibility, due to the lack of a MSCT machine in a number of hospitals.

Ultrasonography (ultrasound of the abdominal cavity):

An effective and affordable method for diagnosing complications of diverticular disease, reveals inflammatory changes in the colon wall, signs of abscess and peritonitis.

Laparoscopy:

Of the invasive methods for diagnosing complications of diverticular disease, laparoscopy should be noted, which can be considered not only as a diagnostic procedure, but also be of a therapeutic nature. With this method, it is possible to perform sanation measures for local peritonitis, drainage of the abdominal cavity.

Mechanism of development of diverticulum complications

Diverticular disease is a progressive disease. Diverticula do not undergo reverse development. The risk of developing diverticulitis with a 5-year existence of a diverticulum is approximately 10%. With a disease duration of more than 10 years, the risk increases to 25%.

Diverticulitis:

In diverticular disease, inflammatory changes develop in the wall of the diverticulum. The absence of a muscular layer leads to the fact that intestinal contents stagnate in them without the possibility of evacuation. This leads to the formation of fecalite (fecal stone) in the lumen of the diverticulum, followed by inflammation in the wall of the diverticulum.

Diverticulum perforation:

Inflammatory changes may be limited to the wall of the diverticulum with its edema and infiltration. With an aggressive microbial flora, inflammation takes on a malignant course and can lead to perforation of the diverticulum wall, which in turn can be delimited by the adjacent fatty tissue of the intestine or mesentery with the formation of an abscess. Violation of the integrity of the wall of the diverticulum can lead to serious complications in the form of peritonitis when the diverticulum is located on the free edge of the intestine.

Relapses of diverticulitis:

When acute inflammation is relieved, the diverticulum wall does not recover. The damaged mucosa is replaced by granulation tissue, which comes into close contact with the tissues surrounding the diverticulum, creating favorable conditions for a chronic inflammatory process and subsequent relapses of acute diverticulitis.

Bleeding from the diverticulum

Damage to the inflamed mucosa of the diverticulum by fecal matter when it exits the mouth or the development of a pressure sore can lead to bleeding.

Fistula formation:

Fistula formation may occur if inflammation spreads to nearby abdominal organs and/or the anterior abdominal wall. Through such fistulas, intestinal contents can spread into the lumen of the bladder, the uterine cavity, and even to the anterior abdominal wall.

Classification and treatment of complicated diverticular disease

The Hinchey E.J. classification is widely used to characterize the complicated course of diverticular disease. proposed at 1978 year. ! Only a DOCTOR can establish the nature of the complication and prescribe the appropriate treatment. Do not self-medicate, this can lead to serious consequences!

Hinchey I.

Pericolic abscess or infiltrate: an acute condition caused by inflammation of the diverticulum with the possible formation of a limited abscess (abscess) in the mesentery of the colon or in its fatty suspension. The treatment of this complication is conservative, it consists in prescribing a strict diet and antibacterial drugs

Hinchey II.

Pelvic, intra-abdominal or retroperitoneal abscess. This condition is characterized by the formation of an abscess in a limited space in the abdominal cavity or in the retroperitoneal space outside the intestinal wall. Treatment consists of hospitalization in a surgical or coloproctological hospital, the appointment of bed rest, a strict diet, antibiotic therapy and detoxification treatment. If there is no effect, surgical treatment is indicated. As a rule, a sufficient volume of surgical intervention is the puncture of the abscess in order to evacuate it. However, in case of inefficiency, an emergency operation is indicated to remove the source of purulent infection. At this stage of the development of the disease, it is possible to perform a one-stage resection intervention with the restoration of intestinal continuity.

Hinchey III.

Generalized purulent peritonitis. A formidable complication that develops when an abscess breaks into the free abdominal cavity. Treatment is surgical only. With this complication, resection of the affected area of ​​the colon is performed with the formation of a stoma, sanitation and drainage of the abdominal cavity. Subsequently, a reconstructive intervention is performed aimed at restoring the natural passage through the intestines.

Hinchey IV.

Generalized fecal peritonitis. The most severe complication that develops in advanced cases, with late treatment of patients for medical care, in debilitated patients, people of senile age. The volume of the surgical operation is similar to the treatment for Hinchy III, however, the postoperative period requires long-term intensive care in the intensive care unit.

What to do if you have already undergone surgery for complicated diverticulosis with stoma removal

If you have already undergone emergency surgery and stoma removal, do not despair. Currently, methods for performing reconstructive interventions aimed at eliminating the stoma and restoring the natural passage through the intestine with good functional results have been developed and implemented. As a rule, these operations are recommended to be performed in specialized coloproctological hospitals.

Elective surgery for diverticulosis

Generally, surgery is not indicated after a single episode of diverticulitis, but may be recommended for people younger than 45 years of age. The decision to perform the operation is made individually. After successful conservative treatment of two or more episodes of diverticulitis, elective surgery is recommended.