ABSTRACT
Colorectal carcinomas are the most common malignancies of the gastrointestinal tract. The incidence of synchronous primary appendicular neoplasms associated with colorectal cancer has been reported as 0.3-4.1%, but most of the studies are case reports and the actual incidence still remains unclear. Appendix embryologically originates from the large intestine, so the actual incidence of synchronous appendix tumors may increase. In this study, we aimed to report three patients who underwent right hemicolectomy for ascending colon adenocarcinoma and who had synchronous primary appendicular neoplasia determined histopathologically.
Historic Considerations
To the best of our knowledge, transanal advancement flap repair (TAFR) for perianal fistulas was first described by Elting.1 Interestingly, he stated that “while the treatment of practically every other surgical malady has been improved in the past few decades, the treatment of fistula in ano remains about where it was twenty years ago, and the general results of such treatment are but little if any more satisfactory than they were then”. Interestingly, a few surgeons would be surprised if this statement was expressed today. Throughout the years, many modifications have been made to the technique, originally described by Elting.1 Nonetheless, most authors have published their techniques under a similar name (“endorectal” or “transanal” advancement flap). Elting.1 described a large series of 96 patients with perianal fistula. The surgery was successful in all cases and he described fecal incontinence in only four cases (4%). Several small series were published throughout the 20th century, but the first large series in recent years was published by Aguilar et al.2 Interestingly, like Elting.1 he described a very dissimilar flap design to the flap most authors have described in the past 20 years. We have published our technique extensively in earlier reports.3,4
Effectiveness of Technique
Even though the reported recovery rate of TAFR varies widely, ranging from 30% to 100%, most author surgeons state an approximately 2/3 improvement rate for their patients. As with many techniques, the reported initial recovery rates are very high. The large series by Aguilar et al.2 in the 1980s described an almost perfect recovery rate of 98%. This high recovery rate motivated many others to start utilizing the technique in order to improve the outcome of fistula surgery. Unfortunately, other authors failed to reproduce these results. Decreased success rates were published in the 1990s, reporting more realistic recovery rates varying between 68 and 87%.4,5,6 In an excellent review of 35 studies including over 2000 patients, Soltani and Kaises7 presented a weighted average recovery rate of 80.8% for cryptoglandular fistulas. A later similar review by Balciscueta et al.8 found a similar pooled rate of recurrence of 21%, although it included several large-scale new studies and ignored low-quality studies. Due to these findings, we think that the expected recovery rate of TAFR is around 80%.
Impact on Fecal Continence
Interestingly, the first series at the end of the 20th century hardly entail detailed reports of the impact on fecal continence. The series of Aguilar et al.2 described an impairment of continence in approximately 10% of cases, whereas Schouten et al.4 reported a significantly higher rate of impaired continence of 35%. It is unclear why exactly patients who undergo TAFR may encounter impaired continence. Although the external anal sphincter is preserved in all patients, they frequently experience minor effects on fecal continence. Although overt fecal incontinence is rare, minor impairment is a frequent finding. Aguilar attributed this effect to the inclusion of circular muscle fibers in the flap.2 Zimmerman et al.9 postulated that the use of the Parks retractor was a major contributing factor. This phenomenon was also described by other authors.10 It is difficult to draw meaningful conclusions on this subject; however, there are some indications in the literature that the use of this retractor is a major contributing factor to fecal continence impairment. It is rare for published results of flap repair to contain detailed information about the effect on fecal continence. However, authors describing the use of different retractors (such as Hill-Ferguson, Eisenhammer or Scott retractors) reported a rate of impaired continence varying between 0 and 12%, whereas authors who used the Parks retractor reported a rate of impaired continence varying between 28 and 40%.4, 11,12,13,14,15 Moreover, in our early study, we compared the use of the Parks retractor to the use of the Scott retractor, and we found a statistically significant difference both in Rockwood Fecal Incontinence Severity index and postoperative anal resting pressure.9 Finally, the rate of impaired continence in our patients decreased from 35% to 4% after discontinuation of the use of Parks retractor.4,16 The review of Soltani and Kaiser7 calculated a weighted average incontinence rate of 13%. In conclusion, approximately one in 10 patients will encounter impaired continence after this surgery. The inclusion of circular muscle fibers and the use of Parks retractor may play a major contributing role in this regard.
Aspects of Surgical Technique
Type of Flap
The original description of the technique (as described by both Elting1 and Aguilar et al.2) encompasses the creation of an elliptical (or even straight?) flap as opposed by more recent authors, who create a more rhomboid flap. The main difference between these techniques is the vertical incisions on the lateral sides of the flap (Figure 1). These authors do not describe why they chose different types of flap design. Most likely, training or trainers may play a role in this. Not all authors have described their exact choice of flap type; therefore, it is impossible to draw any meaningful conclusions into the benefit of one flap type over the other. Yellinek et al.17 performed an interesting study in which they compared the results of a heterogeneous group of fistula repairs (including many different types and etiologies of fistulas) by a rather large group of six colorectal surgeons who rarely performed advancement flap repair (about two procedures per surgeon per year). They compared patients with a rhomboid flap to patients with an elliptical flap. They concluded that there was no difference between these two groups of patients in terms of recovery. On theoretical grounds, it can be advocated that elliptical flaps allow better blood supply to the tip of the flap due to the absence of corners, however, the literature does not support this belief sufficiently, so we recommend that one should not choose the type of flap on the grounds of expected improved recovery.17 In our experience, when a relatively large part of the distal end of the flap has to be excised (due to suppuration), a rhomboid flap is usually indicated in order to achieve a tension-free closure.
Shape of Flap
Over the last two decades, various different shapes have been described, including wide-angular flaps (Figure 2a), relatively narrow round flaps (Figure 2b), and relatively wide round flaps (Figure 2c).4,12,18 It is rare for authors to describe the reason for their choice of flap shape. Moreover, most often flap shape has to be deduced from schematic drawings supplied with the article. Therefore, it is impossible to draw meaningful conclusions about the preferred shape of the flap.
Thickness of Flap
More robust research has been performed on the optimal thickness of the flap. Different methods have been described over time ranging from the formation of pure mucosal flaps to the use of full thickness rectal wall. Both prospective and retrospective investigations were performed. The difference in approach was first identified by the Dubsky et al.19 Their retrospective review suggested an improvement in recovery rates without higher rates of impaired continence after full mobilization of the rectal wall. Khafagy et al.20 performed a prospective analysis and randomized flap designs consisting of mucosa and submucosa with (Group 1) or without (Group 2) inclusion of circular muscle fibers. They noticed a statistically significant difference between these two groups in terms of recurrence in favor of full thickness flaps. The recovery rate in Group 1 was 90%, whereas only 60% recovered in Group 2. Even though there was a minor difference in terms of impairment of continence (0% vs. 10%) in favor of Group 2, this difference did not reach statistical significance. Balciscueta et al.8 investigated this issue by performing a systematic review and meta-analysis. This group meticulously investigated reports on full and partial thickness flaps and their influence on recovery and fecal continence. They identified not two but three types of flaps, namely mucosal, partial thickness and full thickness flaps. Some criticism on this classification is warranted in our opinion, since many reports do not offer detailed descriptions of their technique. Moreover, most reports are retrospective and many describe surgeries by different surgeons, making full standardization of technique unlikely. Nonetheless, this systematic review elegantly shows an explicit suggestion that there is a strong correlation between the increasing thicknesses of the flap and improved recovery rates. It is noteworthy that they also showed a higher rate of continence impairment after the use of thicker flaps, even though statistical significance was not reached. Intuitively, it is easy to accept that thicker flaps may lead to both high recovery rates and poorer continence. It is however not entirely clear why it affects continence. Khafagy et al.20 performed anorectal manometry and did not identify differences between the effects of the two techniques on resting- or squeeze pressure. It is likely that all intra-anal surgery will have an effect on anorectal continence; however, it may be minor. As stated before, selective use of retractors may play a role. Also, some surgeons advocate that the type of anesthesia (resulting in different levels of pelvic relaxation) may play a role. No objective data about this issue are available. Sensibility of the anal verge may be impaired after formation of advancement flap, possibly deteriorating fecal continence in some patients. More extensive dissection when creating thicker flaps may contribute to this. In conclusion, it seems clear that creating advancement flaps that encompass circular fibers, or even the full thickness of the rectal wall will lead to higher recovery rates at the cost of a seemingly higher rate of (minor) continence impairment. We advocate the use of thicker flaps where possible, while recognizing the fact that individualized flap design, based on the pathology and anatomy of the patient is mandatory.
Addition of Accessory Techniques (Or the “Icarus Syndrome”)
An interesting phenomenon observed in many different types of fistula surgeries is the desire of individual authors to combine different treatment modalities in order to improve the outcomes of said treatment. Regrettably, these additions dilute the available data on operative techniques, often before their exact role is clarified. Moreover, authors often attempt to improve their own imperfect results when compared to initial reports without reporting the imperfect results, thereby inadvertently inflating the publicly available results. Ellis and Clark21 published a small series of 60 patients who underwent anocutaneous or mucosal advancement flap repair, and in half of these patients, an attempt was made to improve the outcomes by adding obliteration of the external tract with fibrin glue. A contrary effect was noted. The authors concluded that the study failed to improve outcome, but interestingly they did not consider that obliteration of the tract with fibrin glue might also have a negative effect. Interestingly, not only were the outcomes of the flap repair poorer than expected, the recovery rates were also much worse than those initially published for fibrin glue treatment (75 to 81%).22,23 Other authors have also attempted to augment the putcomes of flap repair by obliterating the external fistula tract. Several authors reported small series of combined treatment of TAFR and fistula plugs, yielding varying results (recovery rates between 25-75%).24,25,26, These outcomes are unimpressive compared to series reporting the outcome of plug alone.27 An attempt by our group to augment outcomes of flap repair by obliterating the external fistula tract using BioGlue® was discontinued after including eight patients in a pilot study and noticing adverse events (severe pain and/or abscess formation) in seven patients. Wilhelm et al.28 published their large series of patients who underwent laser-assisted fistula treatment (LAFT). Fifty-three patients underwent LAFT in combination with mucosal advancement flap repair. Primary recovery was achieved in 35 patients (67%). This recovery rate does not seem to differ from the reported recovery rates of Giamundo et al.29 through LAFT alone (without the addition of a flap repair).30 Finally, the outcomes of flap repair has also been attempted to be augmented by additional ligation of the intersphincteric fistula tract (LIFT). van Onkelen et al.31 disappointingly described that recovery was observed in only 21 patients (51%) out of 41 patients. Again, this recovery rate was lower than expected in the TAFR as well as what has been reported in studies using LIFT alone (a reported pooled recovery rate of 71%).32 These findings are summarized in Figure 3. In conclusion, it should be noted that, to date, no additional treatment to TAFR has ever shown improved results, both when compared to the expected results of TAFR as well as to the expected results of the augmentative procedure. In our opinion, attempts at augmenting the well-investigated and predictable results of TAFR should be undertaken with extreme caution and should only be attempted when a very solid theoretical basis for the expected improvement of outcomes can be formulated. Furthermore, these attempts should be considered experimental and can only be undertaken within studies, after careful and detailed patient informed consent and shared decision making where applicable.
Factors Contributing to Successful Recovery
Several studies have investigated which factors contribute to recovery or failure of TAFR (Table 1). Upon reviewing these different factors, it is clear that there is no consensus on which factors can predict failure. Besides, different authors used different definitions and aspects of complexity to describe the fistulas they treated.
Effect of Covering Ostomy
Sonoda et al.40 compared patients who underwent flap repair with and without a covering colostomy in a heterogeneous retrospective group of patients. Sixty-four patients underwent TAFR with a covering stoma, resulting in a recovery rate of 72%. Twenty-five patients had a covering colostomy. In these patients, TAFR was only 60% successful. Even though this difference was not statistically significant, and it seems likely the more challenging cases may have been offered a stoma, this study did not suggest an advantage of a covering stoma. Similar findings were reported by Mizrahi et al.41 even though they had only three patients who had a covering ostomy.
The “Seton Paradox”
Interestingly, as stated before, none of the authors who investigated the role of preoperative seton drainage showed a statistically significant higher recovery rate in patients in whom a seton was placed before undergoing TAFR. Our group has reported on this subject several times throughout the years (Figure 4).33,34,42 Even though these investigations have led us to refrain from prior seton placement more frequently (Figure 4), still a considerable percentage of patients will undergo seton drainage before TAFR either in the referring hospital or because of excessive inflammation on preoperative magnetic resonance imaging. Paradoxically, this suggests that the most difficult cases will be prone to undergo seton drainage. Remarkably, not only the recovery rate in these patients was not higher than in patients without prior seton drainage, some authors have found it to be lower.40 Seton placement prior to TAFR is a well-accepted treatment regimen. Many surgeons advocate seton placement as an important preparatory step before flap repair. Due to the reasonable use of setons, good results can be obtained in the more complex group of patients. In addition to the conclusion that the benefit of previous seton drainage has not been proven and therefore questionable, it is very hard to draw meaningful conclusions from the available literature. In our opinion, seton placement may still be part of an adequate treatment plan. A thorough curettage followed by placement of a comfortable seton may reduce the amount of active inflammation and thereby minimize the size of external wounds at a later time. However, there should be a good reason for seton placement. The placement of setons as part of a standardized treatment regimen is not supported by the literature in our opinion.
In conclusion, TAFR is a well-investigated technique that yields good results in the treatment of perianal cryptoglandular fistulas. It may be expected that 80% of fistulas will recover after TAFR. The effect on fecal continence is predictable and will affect about 13% of patients. We advocate the use of thicker flaps, where possible. There are few modifiable factors that seem to affect recovery. Smoking cessation and weight loss may be considered. There is no evidence to support the use of diverting stomas. The placement of setons as part of a standardized treatment regimen is not supported by the literature. It is unadvisable to combine flap repair with other techniques.
Introduction
The most common malignancies of the gastrointestinal tract are colorectal tumors. It has been reported that synchronous colorectal neoplasms are 3-5% and metachronous colorectal neoplasms are 2-3%.1
Neoplastic lesions of the appendix are rare, and approximately 25% of patients with appendix tumors are reported to be synchronous or metachronous colon tumors.2 The appendix is originated embryologically from large intestine and has a similar mucosal pattern to the colon and rectum, therefore, any neoplastic alteration of colon and rectum will affect appendix.3,4 Appendiceal tumors are usually detected incidentally in patients who were operated for acute appendicitis and preoperative diagnosis is rare.3 We present three cases of appendix tumors, which we detected incidentally in the right hemicolectomy specimens of ascending colon tumor cases.
Case Reports
Case 1
A 73-year-old female patient was diagnosed as adenocarcinoma of cecum by colonoscopy performed for anemia etiology. In terms of regional and distant organ metastasis, whole body radiological examination was performed and it revealed no additional pathology except for wall thickening of cecum. Right hemicolectomy was performed. Histopathological examination of the specimen revealed a moderately differentiated subserosal adenocarcinoma of cecum of 3x2.5x0.7 cm and a synchronous 0.3 cm neuroendocrine tumor (NET) of appendix (Figure 1). Tumor was considered as T3N1aM0 (stage 3b-AJCC 2017) due to one metastasis from 30 removed lymph nodes. Postoperative adjuvant chemotherapy was performed and 37th month follow-up continues without any complications or recurrence.
Case 2
A 58-year-old male patient was admitted to our clinic with complaints of abdominal pain, change in defecation habits and weight loss (20 kg/3 months). Colonoscopy showed an ulcerovegetant mass at hepatic flexure and biopsy was reported as adenocarcinoma. Right hemicolectomy was performed. Histopathological evaluation of the right hemicolectomy specimen revealed 8x2.5 cm, moderately differentiated subserosal adenocarcinoma with a mucinous component located at hepatic flexure. In addition, a 0.4 cm NET of appendix invading the superficial muscle layer was reported (Figure 1). Metastatic involvement was one out of 46 removed lymph nodes. The patient was considered as T3N1aMO (stage 3b-AJCC 2017). Postoperative adjuvant chemotherapy was performed and 34th month follow-up continues without any complications or recurrence.
Case 3
An 80-year-old female patient was admitted to our clinic with complaints of weakness, colic-type abdominal pain and weight loss (5 kg/2 months). Colonoscopy showed an ulcerovegetant mass that narrowed the lumen of the ascending colon. Abdominal CT revealed wall thickening of cecum without any metastasis. Right hemicolectomy was performed and histopathological examination of the right hemicolectomy specimen revealed 5.5x5 cm moderately differentiated serosal adenocarcinoma of cecum and a low-grade mucinous neoplasia of appendix (Figure 1). There was no metastasis in 27 removed lymph nodes. The patient was considered as T4aN0M0 (Stage 2b-AJCC 2017). Twelfth month follow-up without adjuvant chemotherapy continues without any complications or recurrence.
Discussion
Tumors of the appendix are very rare. Preoperative diagnosis is difficult and most of them are diagnosed incidentally after histopathologic examination of appendectomy specimens of acute appendicitis cases. The incidence of appendiceal tumors was reported as 1%, but actual incidence was accepted up to 5% because of missed histopathologic examination of appendectomy specimens.4 There are studies reporting that appendix tumors are more common in colorectal tumor patients,2,5 because the appendix originates embryologically from the colon and has a similar mucosal structure like colon and rectum.6,7 Tumors of the appendix are NET, mucoceles and adenocarcinomas. NETs, commonly referred to as carcinoid tumors, are the most common tumors of the appendix. They constitute 80% of all appendiceal masses and 0.5% of appendectomy materials.8 NET mostly originates from appendix in gastrointestinal system at a rate of 40-50%.9 The clinical importance of NET is being synchronous with other gastrointestinal malignancies at a rate of 55%.10 Mucocele constitutes 0.2-0.5% of all appendiceal neoplasms.11 Appendiceal adenocarcinoma accounts for 6% of appendiceal tumors and 0.2-0.5% of all gastrointestinal tumors.12 The appendix tumors with these clinical features do not have any pathognomonic signs or symptoms, and it is difficult to diagnose them preoperatively. In our study, two cases were NET and one was mucinous neoplasia.
Recently, some studies have recommended incidental appendectomy during colorectal cancer operations because of the difficulties in the diagnosis of synchronous appendix tumors preoperatively. Khan and Moran13 reported the incidence of synchronous appendiceal and colorectal cancer as 4.1% in 169 patients with colorectal cancer who had incidental appendectomy. In the same study, the authors reported that more appendix tumors were diagnosed histopathologically for rectal cancers than right hemicolectomy surgeries13 and it was considered that separate appendectomy specimens were examined more carefully than appendix in a right hemicolectomy specimen.
Albright et al.14 defined a lifetime appendectomy risk of 6-7%. They considered that additional appendectomies for colorectal malignancies were cost effective because additional appendectomy would not prolong operative time and future appendectomies would be more difficult because of previous abdominal operations. Lohsiriwat et al.15 reported that the rate of synchronous primary appendix tumor was 0.3%, and the secondary appendix tumor/appendix metastasis was 1% in 293 cases who underwent incidental appendectomy. Some authors recommend incidental appendectomy in colorectal tumor surgery, defining that appendectomy does not cause an additional risk of infection in major bowel surgery, and some authors argue this association as coincidental because of they are being the most common gastrointestinal tumors. In our study, we detected only three appendix tumors in the last 5 years in patients who underwent right hemicolectomy due to colon tumors. We deliberated that prospective studies consisting of large case series are needed for the decision of incidental appendectomy in colorectal tumor surgery. Incidental appendectomies during colorectal malignancy surgeries will not affect wound infection rates and mortality or morbidity rates, so that incidental appendectomies can be added for all colorectal malignancy surgeries.
