2018 Volume 65 Issue 2 Pages 151-157
This study aimed to determine the prevalence of colorectal neoplasms and to investigate the rate of and time required for cecal intubation in patients with acromegaly. A database search performed at our institution identified 29 patients with acromegaly who underwent colonoscopy. Data regarding the endoscopic, biological, and pathological examinations performed were retrospectively reviewed from the clinical records. Subsequently, the rate of and time required for cecal intubation were investigated in 23 patients with acromegaly and compared with the corresponding data of the control group. Control subjects were selected from a 2:1 matched historical control cohort, according to baseline characteristics. The mean age of the acromegaly group (17 female and 12 male) was 60.4 ± 12.6 years. Twelve patients had adenoma (41.4%), eight patients had hyperplastic polyps (27.6%), three patients had sessile serrated adenoma/polyps (10.3%), and three patients had colon cancer (10.3%). Successful cecal intubation was achieved in all patients in both groups. The difference in the time required for successful intubation between the acromegaly group (15.7 ± 9.8 minutes) and the control group (8.7 ± 6.0 minutes) was statistically significant. Linear regression analysis revealed that increased patient age was significantly related to longer colonoscope insertion times. In conclusion, although cecal intubation during colonoscopy was successful in all participants, it required a longer time in patients with acromegaly. Our results underscore the importance of and certain technical difficulties involved in colonoscopy procedures in patients with acromegaly, especially in older patients.
ACROMEGALY is a hormonal abnormality caused by excessive levels of growth hormone, which typically results in enlargement of the hands, feet, forehead, jaw, and nose. Patients with acromegaly have increased morbidity and mortality associated with diabetes mellitus, cardiovascular and cerebrovascular diseases, and respiratory complications [1-3]. More significant comorbidities include malignant diseases, mainly colorectal cancer [3-6]. Owing to the high prevalence and worse overall prognosis of colorectal cancer, evaluation of the colorectum is strongly recommended for patients with acromegaly. For example, colonoscopy at the time of diagnosis of acromegaly is suggested in the acromegaly treatment guidelines published by the American Association of Clinical Endocrinologists and the Endocrine Society [7-9]. Moreover, cecal intubation during colonoscopy may be challenging in patients with acromegaly, because the bowel is generally redundant and tortuous [8]. However, to our knowledge, the technical difficulties associated with colonoscopy in patients with acromegaly have not been investigated. In this study, we comparatively analyzed the rate of successful cecal intubation and the time required for cecal intubation between patients with acromegaly, and control subjects.
A database search identified 62 patients with acromegaly who were treated at our hospital between January 2006 and February 2017. Among them, 29 patients (46.8%) who underwent colonoscopy were analyzed in this study. The sex of the patient, age at the time of colonoscopy examination, time elapsed between the initial diagnosis of acromegaly and the colonoscopy examination, levels of growth hormone and insulin-like growth factor I (IGF-I) at colonoscopy, the presence or absence of conditions such as impaired glucose tolerance/diabetes, hypertension, and dyslipidemia, existing medical treatment, the presence or absence of colorectal neoplasms, the results of esophagogastroduodenoscopy, and the existence of concomitant and/or history of neoplastic diseases were retrospectively reviewed.
Subsequently, the time required for the inserted colonoscope to reach the cecum was analyzed. Four patients with acromegaly were excluded from this analysis, since their detailed information including the elapsed time during colonoscopy examination was not available. Two patients were further excluded, as they underwent colonoscopy after surgical resection of the colon. Consequently, the remaining 23 patients constituted the acromegaly group. Historical control subjects for the non-acromegaly group were selected from the database at the Department of Endoscopy. Two controls per case of acromegaly group were matched with a margin of 20% in terms of age. The sex of the control patients and the operator of colonoscopy examination were thoroughly matched to those of the acromegaly group. Finally, a 2:1 matched-control group was formed by sampling 46 cases. The rate of successful cecal intubation and the time required for the inserted colonoscope to reach the cecum was compared between the acromegaly group and control group. The two groups were compared using t-tests, chi-square tests, and F-tests. A scatter diagram for the acromegaly patient group was generated, comparing patient characteristics and the time required for the inserted colonoscope to reach the cecum. Linear regression analyses were applied to investigate the relationship between the variables.
Statistical analyses were performed using JMP 12.0.1 software (SAS Institute, Cary, NC, USA). p-values <0.05 were considered statistically significant. The study design was approved by the ethics committee of Okayama University Hospital (No. 1704-006) and it adhered to the Declaration of Helsinki.
The patient backgrounds (17 female and 12 male) are summarized in Table 1. The mean age of the patients was 60.4 ± 12.6 (range: 32–78) years. The patients underwent colonoscopy an average of 10.0 ± 9.7 (range: 0–38) years after the initial diagnosis of acromegaly; four patients underwent colonoscopy during the initial diagnostic workup of acromegaly, while the remaining 25 patients underwent colonoscopy during the course of their acromegaly monitoring and/or treatment. On average, growth hormone levels were 4.61 ± 7.01 ng/mL at colonoscopy, while average IGF-I levels were 325.1 ± 311.1 ng/mL. As comorbidities of acromegaly, 17 patients (58.6%) had impaired glucose tolerance/diabetes, 14 patients (48.3%) had hypertension, and 5 patients had dyslipidemia (17.2%). Treatments included transsphenoidal surgery (N = 22, 75.9%), cabergoline (N = 13, 44.8%), octreotide (N = 8, 27.6%), and bromocriptine (N = 2, 6.9%). Two patients had been followed up without any specific treatment for acromegaly.
| Characteristic | No. (N = 29) |
|---|---|
| Sex | |
| Female | 17 |
| Male | 12 |
| Age (years) | 60.4 ± 12.6 (32–78)* |
| Years between initial diagnosis of acromegaly and colonoscopy | 10.0 ± 9.7 (0–38)* |
| GH levels at colonoscopy (ng/mL) | 4.61 ± 7.01 (0.28–28.83)* |
| IGF-I levels at colonoscopy (ng/mL) | 325.1 ± 311.1 (60–1,420)* |
| Comorbidities | |
| Impaired glucose tolerance/diabetes | 17 (58.6%) |
| Hypertension | 14 (48.3%) |
| Dyslipidemia | 5 (17.2%) |
| Treatments | |
| Transsphenoidal surgery | 22 (75.9%) |
| Cabergoline | 13 (44.8%) |
| Octreotide | 8 (27.6%) |
| Bromocriptine | 2 (6.9%) |
| None† | 6 (20.7%) |
| Colorectal lesions | |
| Adenoma | 12 (41.4%) |
| Hyperplastic polyps | 8 (27.6%) |
| Sessile serrated adenoma/polyps | 3 (10.3%) |
| Cancer | 3 (10.3%) |
| Upper GI lesions‡ | |
| Brunner gland hyperplasia of the duodenum | 2 (6.9%) |
| Subepithelial tumor in the stomach | 1 (3.4%) |
GI: gastrointestinal, GH: growth hormone, IGF-I: insulin like growth factor I
* mean ± SD (range)
† Treatment had not been initiated in four patients at the time of the study, because colonoscopy was performed during the initial diagnostic workup of acromegaly. Two patients did not require treatment for acromegaly.
‡ Twenty-three patients underwent esophagogastroduodenoscopy
Colonoscopy examination revealed adenoma (Fig. 1A) in 12 patients (41.4%), hyperplastic polyps (Fig. 1B) in eight patients (27.6%), and sessile serrated adenoma/polyp in three patients (10.3%). Two patients were diagnosed and surgically treated with colon cancer before undergoing colonoscopy at our institution. In one patient, ascending colon cancer was identified during colonoscopy (Fig. 1C). Thus, three patients had colon cancer (10.3%). Overall, 16 patients (55.2%) had polyps and/or cancer in the large intestine (i.e., cecum, colon, and rectum), whereas no neoplastic lesions were found in the other 13 patients. All the 16 patients had two or more polyps. Fig. 2 shows the anatomical distribution of polyps identified during colonoscopy. Although hyperplastic polyps were most frequently identified in the rectum, other neoplastic polyps, including sessile serrated adenoma/polyps, adenomas, and cancers, were found in the ascending colon, followed by the transverse colon and descending colon.
Endoscopic images
Representative image of an adenoma (A), hyperplastic polyp (B), and cancer (C) identified in the colorectum during colonoscopy
Anatomical distribution of polyps identified during colonoscopy. White rectangles represent the number of patients having hyperplastic polyps in that segment of the large intestine. Yellow rectangles represent the number of patients with sessile serrated adenoma/polyps (SSA/P), blue rectangles represent the number of patients with adenomas, and rectangles with diagonal lines represent the number of patients with a cancer.
In total, 23 patients underwent esophagogastroduodenoscopy examination. Among them, one patient had Brunner gland hyperplasia in the duodenum, and another patient had a gastric subepithelial tumor and Brunner gland hyperplasia in the duodenum. Other concomitant and/or history of neoplastic diseases included adenomatous goiter (N = 3), follicular adenoma of the thyroid (N = 1), myelodysplastic syndrome (N = 1), gingival cancer (N = 1), bronchioalveolar carcinoma (N = 1), breast cancer (N = 1), renal angiomyolipoma (N = 1), hemangioma of the liver (N = 1), intraductal papillary mucinous neoplasm of the pancreas (N = 1), uterine myoma (N = 1), adenomyosis of the uterus (N = 1), polycystic ovary syndrome (N = 1), chocolate cyst of the ovary (N = 1), and atheroma cutis (N = 1).
Table 2 shows the characteristics of the patients in the acromegaly group and control group. As described previously, patient age and gender, and the operator of colonoscopy were matched between the groups. Successful cecal intubation was achieved in all patients in both groups. Fig. 3 shows the dot plot of time required for the inserted colonoscope to reach the cecum. The colonoscope required 15.7 ± 9.8 (range: 5–37) minutes to reach the cecum in patients in the acromegaly group, whereas it required 8.7 ± 6.0 (range: 2–31) minutes to reach the cecum in subjects in the control group. The time difference between the groups was statistically significant.
| Acromegaly | Control | p-value | |
|---|---|---|---|
| N | 23 | 46 | |
| Sex | 1.000 | ||
| Female | 14 | 28 | |
| Male | 9 | 18 | |
| Age (years, mean ± SD) | 59.6 ± 13.1 | 60.7 ± 10.9 | 0.711 |
| Successful cecal intubation | 23 (100%) | 46 (100%) | 1.000 |
| Time to reach the cecum (min., mean ± SD) | 15.7 ± 9.8 | 8.7 ± 6.0 | <0.001 |
Dot plot diagram showing the time (min) required for the inserted colonoscope to reach the cecum
The time required for the colonoscope to reach the cecum was not significantly different between male patients (mean ± SE: 13.6 ± 3.3 minutes) and female patients (17.1 ± 2.6 minutes, p = 0.40). Furthermore, the cecal intubation time was not significantly different between groups of patients with and without impaired glucose tolerance/diabetes (17.1 ± 2.6 minutes vs. 13.7 ± 3.3 minutes, p = 0.21), hypertension (17.0 ± 2.9 minutes vs. 14.4 ± 3.0 minutes, p = 0.27), or dyslipidemia (10.5 ± 4.8 minutes vs. 16.8 ± 2.2 minutes, p = 0.88) as well. Fig. 4 shows scatter diagrams comparing patient characteristics and the time required for the inserted colonoscope to reach the cecum. Linear regression analysis determined that in older patients, age was significantly related to the longer colonoscope insertion times (Fig. 4A). Although the colonoscope insertion times tended to be longer in patients with longer time between the initial diagnosis of acromegaly and colonoscopy, this was determined not to be statistically significant (Fig. 4B). Patient levels of growth hormone and IGF-I at colonoscopy did not affect the time for inserted colonoscope to reach the cecum (Fig. 4C, D).
Scatter diagrams and regression lines with respect to acromegaly patient characteristics and the time (min) required for the inserted colonoscope to reach the cecum
In the present study, we observed that 41.4% of patients with acromegaly had adenoma, 27.6% patients had hyperplastic polyps, 10.3% patients had sessile serrated adenoma/polyps, and 10.3% patients had colorectal cancer. In a multicenter study in Italy including 235 patients with acromegaly, adenoma was identified in 55 patients (23.4%) and carcinoma was found in 10 patients (4.3%) during colonoscopy [10]. Another group in England reported similar findings [11]. The overall incidence of colorectal cancer among patients with acromegaly ranges from 1.07% to 20% [12]. In one study, patients with acromegaly have been shown to have an eight-fold increased risk for hyperplastic polyps, a four-fold increased risk for colonic adenoma, and a 13.5-fold increased risk for colon cancer, compared with control subjects [11, 13]. Such an increased prevalence of colorectal neoplasms has been considered to be caused by a high level of serum IGF-I [11, 14, 15]. IGF-1 functions as the major mediator of growth hormone-stimulated somatic growth in many cells and tissues. Based on the mitogenic and anti-apoptotic properties, IGF-1 stimulates the proliferation of colorectal cancer cells in vitro [3, 16, 17]. Several researchers reported that patients with acromegaly showed increased proliferation of colonic epithelial cells [3, 13, 18]. Dutta et al. reported that elevated levels of serum IGF-1 were particularly associated with increased proliferation of the superficial crypt cells in vivo. Such accelerated colonic mucosal proliferation likely contributes to the increased prevalence of hyperplastic polyps, adenomas, and adenocarcinomas in the colorectum [15].
In patients with acromegaly, colorectal adenomas tend to be multiple and are present proximal to the splenic flexure [19, 20]. The present study also showed that neoplastic lesions such as sessile serrated adenoma/polyps, adenomas, and cancers were most frequently identified in the ascending colon, followed by identification of lesions in the transverse colon and descending colon (Fig. 2). Therefore, observation of the entire colorectum is important. The present study revealed that cecal intubation was successful in all patients with acromegaly. However, colonoscopists required 15.7 ± 9.8 minutes to reach the cecum. The time required for cecal intubation was significantly longer in patients with acromegaly than that required in control subjects (8.7 ± 6.0 minutes). As described previously, because patients with acromegaly show increased length and circumference of the colon, insertion up to the cecum and evaluation of the entire length of the colorectum during colonoscopy is often challenging [3, 21, 22]. In addition, this study revealed that older patients require more time for the colonoscope to reach the cecum during colonoscopy. In contrast, age was not related to the time required for the colonoscope to reach the cecum in the control group (R2 = 0.046, p = 0.152; data not shown). Although the time required for cecal intubation was not directly related to the technical difficulty of the colonoscopy, it is recommended that seasoned endoscopists perform colonoscopy examinations for acromegaly patients, especially when the patient is of advanced age.
It is well known that bowel transit is prolonged in patients with acromegaly. Veysey et al. investigated the mean transit time from the mouth to cecum and revealed that it was 175 minutes in patients with acromegaly who were untreated with octreotide, and 225 minutes in patients on long-term octreotide treatment. The time in both groups was significantly longer than that required in control subjects without acromegaly or constipation (113 minutes) and in patients with simple constipation (125 minutes) [21]. This result indicates that in patients with acromegaly, bowel preparation before performing colonoscopy likely requires a longer time and results in inadequate intestinal lavage. Lower-quality bowel preparation is another factor that leads to suboptimal assessment during colonoscopy [3]. Our approaches to improve the quality of bowel preparation are as follows: i) hospitalize patients with acromegaly several days before colonoscopy and monitor their bowel habits, ii) prescribe purgative medicine two to three days before colonoscopy to stimulate defecation, and iii) use commercially available foods designed for colonoscopy on the day before examination.
There were several limitations associated with this study. Firstly, the sample size was relatively small. Secondly, biases may have existed during the selection process of control subjects without acromegaly. Thirdly, this study was conducted in a single, tertiary care center. As colonoscopy was performed by experts in endoscopic examinations in most cases, the results obtained in this study may not be directly interpreted for general hospitals or clinics.
In conclusion, we reviewed 29 patients with acromegaly and found adenoma in 41.4%, hyperplastic polyps in 27.6%, sessile serrated adenoma/polyps in 10.3%, and colon cancer in 10.3% of them. Although cecal intubation during colonoscopy was successful in all patients, it required a longer time. These results reinforce the importance of and certain technical difficulties involved in colonoscopy procedure in patients with acromegaly, especially older patients. Although acromegaly is an endocrine disorder, periodical systemic screening of the gastrointestinal tract is necessary to proactively identify systemic complications that can potentially increase the risk of death of acromegaly patients [23]. In this context, it is essential for endocrinologists and gastroenterologists to share a common understanding of the importance and potential difficulty of colonoscopy examination in the treatment of acromegaly patients.
None of the authors have any potential conflicts of interest associated with this research.
