25 Rectal Resection

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Introduction

The frequency of fecal incontinence (FI) in patients submitted to rectal resection (RR) for cancer ranges between 2% and 40% [1–6]. In fact, despite the significant improvements registered over the last few decades in the treatment of rectal cancer, not only in the control of the neoplasm itself and sparing of the anal sphincters but also in the preservation of urinary and sexual function [6–19], FI can occur, with severe detrimental effects on patients’ quality of life.

In these patients, FI is a disabling clinical condition, the etiology of which is complex and not yet fully elu- cidated. It is regarded as a component of “anterior resection syndrome,” including an increased number of daily bowel movements, clustering, FI, and soiling after this operation [20–22]. In some cases, urinary incontinence also contributes to worsening of the clinical condition. Even if these patients are comfort- ed by the fact that they have won their fight against the cancer, their personal and social life suffers con- siderably. Unfortunately, the minimalist attitude of some physicians prevents these patients from explor- ing the possibilities of treatment other than an appropriate diet or stimulating systems to empty the bowel completely.

Hypothesis of Pathophysiology

Various causes (including reduction of the rectal ampulla, iatrogenic internal sphincter lesions, autonomic nerve lesions, influence of chemoradiation) could play a role in determining this dysfunction.

A sphincter-saving RR significantly reduces the rectal ampulla; frequently, excision of the entire rectum is necessary, and coloanal anastomosis is performed [5, 23–27]. Even if a colonic pouch is con- structed, FI may still occur [5, 23, 28]. However, the role of methods of reconstruction appears essential.

At present, the J-pouch remains the gold standard for routine clinical practice, thanks to good results at long-term follow-up, but the transverse coloplasty

and side to end anastomosis assure a superposable intestinal function in many trials [29–34].

The transanal introduction of a stapler or anal dilatation may be a cause of iatrogenic lesion of the internal anal sphincter in a high percentage of patients (18% at endoanal ultrasound evaluation) [2, 35, 36], but the external sphincter does not appear lesioned by the procedure. Internal anal sphincter fragmentation can cause a decrease of resting anal pressure. On the other hand, transabdominal anastomosis minimized the risk of sphincter damage and showed a good degree of continence [36–38].

Despite the warning that great care should be taken regarding nerve sparing, sympathetic and parasympathetic fibers can be interrupted, with significant deregulation of the nervous inputs and out- puts to and from the pelvis, particularly the remain- ing rectum, anus, and perirectal structures [11]. On the other hand, the preservation of autonomic nerve structures during total mesorectal excision (TME) can decrease the risk of FI and urogenital disturbances. The pelvic organs are innervated by sympathetic and parasympathetic nerve fibers. The sympathetic supply arises from L1 to L3, which contribute to the superior hypogastric plexus that extends to the sacral promontory. This plexus gives origin to the right and left hypogastric nerves. The parasympathetic nerve fibers arise from S2 to S4. They emerge through the sacral foramina (nerves erigentes) and join the sympathetic hypogastric nerves to constitute the right and left inferior pelvic plexuses sited at the pelvic sidewall anteriorly and laterally to the lower third of the rectum. From each pelvic plexus, nerve fibers (both sympathetic and parasympathetic) reach the pelvic viscera.

Identification of the nerve fibers is more difficult for the parasympathetic nerves that extend deep into the pelvis, whereas visualization of the sympathetic system is easier. However, damage could occur along the entire nerve fiber branchings: periaortic/pericav- al, superior hypogastric plexus, hypogastric nerves, S2–S4 parasympathetic nerves, inferior pelvic plexuses, and distal nerve fibers. Other factors can

Rectal Resection

Giovanni B. Doglietto, Carlo Ratto, Angelo Parello, Lorenza Donisi, Francesco Litta

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also influence nerve sparing: male gender, tumor size, intraoperative blood loss, and surgeon expert- ise. When urinary incontinence and/or disturbances of sexual function occur as secondary effects of nerve damage, they contribute to worsening of the patient’s clinical condition [39].

Pelvic radiotherapy can play an important role in the pathogenesis of functional disturbances of continence [40–42]. In patients treated with pelvic radiotherapy for prostate, gynecological, bladder, anal, or rectal cancer, the incidence of FI is 3–53% [43]. This is despite progress in irradiation procedure. The patient’s age and presence of “anal symptoms” are described as risk factors. In their review article, Putta and Andreyev [43] assessed that rectal cancer seems to present the highest incontinence rate, probably due to the additive effects of surgery to those of radiotherapy. In this work, only 8–56% of incontinent patients were found affected in their quality of life. The authors interpreted this finding because patients “do not feel or seem ill, will not report symptoms, as they believe they are inevitable conse- quences of radiotherapy treatment, of being old, or that there is nothing that can be done”. With the aim of investigating bowel dysfunctions, Peeters et al.

[44] sent a questionnaire to 597 patients enrolled in the prospective randomized TME trial (5×5 Gy before TME surgery vs. TME surgery alone), with a median follow-up of 5.1 years after the treatment.

Irradiated patients compared with nonirradiated patients reported increased rates of FI (62% vs. 38%, respectively; p<0.001), pad wearing as a result of incontinence (56% vs. 33%, respectively; p<0.001), anal blood loss (11% vs. 3%, respectively; p=0.004), and mucus loss (27% vs. 15%, respectively; p=0.005).

Satisfaction with bowel function was significantly lower and the impact of bowel dysfunction on daily activities was greater in irradiated patients compared with patients who underwent TME alone. Pollack et al. [45] recently reported results of a randomized trial within the Stockholm Radiotherapy Trials on 64 patients submitted to low anterior resection with or without preoperative radiotherapy (21 and 43 patients, respectively) followed up with quality-of- life questionnaires, clinical examination, anorectal manometry, and endoanal ultrasound. An impaired anorectal function was common after low anterior resection for rectal cancer, and the risk was increased after radiotherapy. Irradiated patients had signifi- cantly more symptoms of FI (57% vs. 26%, p=0.01), soiling (38% vs. 16%; p=0.04), and bowel movements per week (20 vs. 10; p=0.02). Significantly lower rest- ing (35 mmHg vs. 62 mmHg; p<0.001) and squeeze pressures (104 mmHg vs. 143 mmHg; p=0.05) and more scarring of the anal sphincters (33% vs. 13%;

p=0.03) were documented in irradiated patients. A

worse quality of life affected incontinent patients.

Multiple factors are supposed to produce the effects of radiotherapy on the pelvic structures involved in the continence mechanisms, including radiotherapy dose as well as physical, patient-related, treatment, and genetic factors [43]. Effects could be found on both anal canal structures and the rectum.

In most studies, anal maximum resting pressure decreased following pelvic irradiation [46–54], hypo- thetically due to damage of endovascular cushions, internal anal sphincter thinning or atrophy, or both.

However, disagreement exists on manometric assessment of resting pressure, as it was unchanged in other reports [50, 55–57]. Even if pressure increment due to squeezing is decreased in most studies [47, 48, 50, 51–54, 57, 58] and thickness of the external anal sphincter has been reported after radiotherapy for prostate cancer [54], the influence of pudendal neu- ropathy in a change of muscle morphology is unclear. A significant prolonged pudendal nerve terminal motor latency (PNTML) has been observed in patients treated with neoadjuvant chemoradiation (irrespective to the inclusion or not of the anal canal to the irradiation field) and is associated to the FI severity score [57]. Moreover, being that the pudendal nerve is also responsible for anal sensitivity, damage to it can be a significant cause of fecal seepage.

A lumbosacral plexopathy may be a concomitant cause of incontinence and can cause perianal anesthesia and alterations to the pudendal nerve [59].

Myenteric plexus degeneration within the bowel wall has been thought to influence continence [46]. The rectal sensation to distension is primarily transmit- ted along the S2, S3, and S4 parasympathetic nerves, which traverse the pelvic splanchnic nerves. Damage to these nerves induced by radiotherapy could alter rectal compliance. Regarding rectal physiology, most studies report a significant decrease in threshold volume and maximum tolerated volume in incontinent patients following pelvic irradiation [46–52, 54, 56, 58]. Moreover, radiotherapy induces an inflammato- ry response within the pelvic vessels and an increased secretion of growth factors, with consequent damage to the microcircle of the rectum.

Diagnostic Assessment

In patients submitted to RR for cancer, clinicians must dedicate attention in investigating defecation disorders. In fact, a variety of dysfunctions can occur considering the multifactorial etiology of FI in these patients, particularly when integrated therapies have been associated to surgery. Increased bowel frequency only or associated with fecal soiling or seepage should be of concern. Tenesmus is not infrequent,

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and incontinence to gas could coexist. In more severe cases, incontinence to liquid and/or solid feces is reported, up to many episodes per day, altering significantly daily activities and quality of life. FI severity index could be very high in these patients. Calcu- lation of a specific score is usually useful not only to measure baseline FI severity but also to compare this to the condition reached after a given treatment. In each case, special efforts must be made to assess alteration of rectoanal sensitivity, and patients must be asked about their ability to distinguish gas from liquid and solid stools, defer defecation, and feel the bowel completely empty.

The aim of clinical examination is to investigate perianal/perineal scars, patulous anus, perineal soiling, anal ectropion, sphincter deficit, loss of perineal body, and perineal descent. During digital examination, resting and squeeze tones must be evaluated, whereas the puborectalis muscle needs to be assessed at rest, squeezing, and straining. Proctoscopy or, if necessary, colonoscopy is needed to ascertain absence of tumor recurrence or other bowel neo- plasms. Physiology evaluation is of utmost impor- tance. Anorectal manometry can offer information about alterations in resting and squeeze pressures, sphincter asymmetry by vector manometry, anom- alies of rectoanal inhibitory reflex (sometimes absent, sometimes normal, sometimes not identifi- able when resting pressure is very low), and rectal compliance. Assessment of rectal sensation (measur- ing threshold, urge, and maximum tolerated vol- umes) could be of help in interpreting pathophysiology in these patients. Endoanal ultrasound (or mag- netic resonance, as an alternative) is mandatory to detect sphincter lesions. Electrophysiology study can investigate anal and rectal sensory and PNTML.

Treatment

Due to the multifactorial pathogenesis of FI following RR with or without (chemo)radiotherapy, primary aims of any treatment should be intervention on the underlying causes to restore or, at least, significantly improve continence. Although various therapies (medical and surgical) are available as effective treatment of FI, a gold standard has not yet been estab- lished.

Medical Therapy

A number of therapeutic agents and options have been proposed (bulking agents and high-fiber diet, valproate sodium, diazepam, topical phenylephrine, biofeedback [60–65]). Theoretically, loperamide

should have the best mechanism of action when compared with other antidiarrheal drugs, because it potentially can improve internal anal sphincter pressure [66]. Biofeedback and pelvic floor training could have the best possibilities of success if dysfunctional external anal sphincter or puborectalis is one of the main reasons of FI following RR, although only few reports have been published in this specific clinical condition [65].

Surgery

When intractable FI occurs, surgical treatment must be considered. Traditionally, two assumptions have guided treatment choice. First, stoma formation rep- resents the “radical” approach, but the impact on patient’s quality of life, as yet undetermined, should be questioned. Second, a few alternatives for surgical sphincter repair (sphincteroplasty) or substitution (gracilis/gluteus transposition, artificial sphincter) could be considered, but this approach is often thought hazardous because of the high risk of non- healing, infection, chronic pain, and fistula formation [43, 67]. Finally, a palliative approach, i.e., anal plugs and rectal irrigation, will only minimize the effects of FI. A new, promising treatment could be sacral nerve stimulation.

Dynamic Graciloplasty

In 1990, Baeten and Spaans and Williams et al. [68, 69] introduced a new technique for the treatment of FI in the presence of large sphincter defects: the dynamic graciloplasty. Cavina applied this therapy after abdominoperineal resection of the rectum [70].

This “sphincterial” substitution can be achieved as a synchronous procedure or after several years and can involve one or both gracilis muscles [71–73]. The primary reconstruction is more frequently applied because more technical difficulties can be encoun- tered during such a sphincter restoration in a previ- ously “mutilated” pelvic floor. At the long-term follow-up, about two thirds of the patients with dynamic graciloplasty after abdominoperineal resection of the rectum achieved satisfactory continence. Howev- er, no reports are available on the application of dynamic graciloplasty following sphincter-saving RR for cancer.

Artificial Sphincter

Indications for application of an artificial sphincter are very similar to those for dynamic graciloplasty.

Even if reports on this approach have documented positive impact on restoration of continence in the

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majority of patients [74–77], postoperative and short-term morbidity as well as long-term results reduce the overall efficacy of this treatment. Unfortu- nately, no series has been reported of FI patients treated with artificial sphincter following RR for rectal cancer. Only a case report is documented, in which the device needed to be explanted due to intense perineal pain [74].

Sacral Nerve Stimulation

Electrical stimulation of sacral nerves has been thought to excite these nerves and thus “modulate”

specific functions due to this complex nerve supply.

Expected results of such stimulation should be to stimulate additional impulses not only to an inade- quate pelvic floor musculature and pelvic organs but also to the sensitive pelvic fibers. This therapeutic approach is called sacral nerve stimulation (SNS). It presents peculiar characteristics if compared with other surgical options for FI treatment. The first step, the percutaneous nerve evaluation (PNE), is both a diagnostic procedure and a test of therapeutic efficacy. It permits implantation of an electrode adjacent to the sacral nerves (through the sacral foramina, the S3 foramen being generally preferred (Fig. 1) to both evaluate the nerves’ response to stimulation during the implantation procedure and during the following

period and to assess the clinical efficacy on defecation disturbances. Indeed, the PNE test, when affecting significant improvement, allows a 100% positive predictive value of response to permanent chronic stimulation. Actually, there is a tendency to use the new-model self-fixing definitive quadripolar electrode for the PNE test. The electrode can be implanted by a percutaneous technique (Fig. 2) under local anesthesia and connected to the external stimulator during the test period. The second step is permanent implant of the sacral neuromodulation (SNM) system. Only if the PNE test produced good results in improving FI can a permanent implant be considered. When the quadripolar electrode has already been implanted, only the definitive electrostimulator has to be placed into a subcutaneous pocket located in the gluteal area (Fig. 3) and connected to the electrode. This procedure is usually performed under local anesthesia. One or two electrodes can be placed, which are connected to a single electrostimulator.

Primarily, inclusion criteria for SNS were poor FI (at least one episode of either solid or liquid stool leakage per week) and failure of conservative treatment. Thereafter, functional defects of the striated pelvic musculature (without sphincter lesion) were the main criteria used in the early studies [20].

Enrolled patients had decreased manometric squeeze pressure but normal PNTML. More recently, other, more precise, indications have been investigated suc-

Fig. 1.Schema of percutaneous implantation of self-fixing definitive quadripolar electrode for sacral nerve stimulation (SNS). Courtesy of Medtronic S.p.A, Italy

Fig. 2. Percutaneous implantation of self-fixing definitive quadripolar electrodes for sacral nerve stimulation (SNS), under local anesthesia, in a patient with fecal incontinence (FI) following chemoradiotherapy and rectal resection (RR) for rectal cancer. Reprinted with permission from [80]

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cessively, including FI due to idiopathic sphincter degeneration, iatrogenic internal sphincter damage, partial spinal cord injury, scleroderma, limited lesions of internal or external anal sphincters, rectal prolapse repair, and low anterior resection of the rectum.

In the 2002, Matzel et al. [78] described a single case report of SNS for FI after low anterior rectum resection. Two sacral electrodes were used. Complete resolution of FI was reported 18 months after the implant, with significant improvement not only in the continence score but also in the quality-of-life score. Moreover, squeeze pressure improved, and resting pressure and neorectal sensation parameters appeared not to be affected. Our preliminary experience concerning definitive SNS implant in four patients has been published [79]. After device implantation, the mean FI scores decreased, and the mean number of incontinence episodes dropped from 12.0 to 2.5 per week (p<0.05). Permanent implant resulted in a significant improvement in fecal continence in three patients, and incontinence was slightly reduced in the fourth. Manometric parameters agreed with clinical results: maximum and mean resting tone and the squeeze pressure were normal in three patients and reduced in one. In these same three patients, neorectal sensation parameters increased when the preoperative value was normal or below normal and decreased when the preoperative value was higher than normal, whereas in one patient in whom extremely low values were record- ed, all parameters decreased significantly.

At present, in our series, a PNE test was performed in eight patients after chemoradiation and RR for rectal cancer. Patients were evaluated with anorectal manometry (Fig. 4), endoanal ultrasound (Fig. 5), and electrophysiology study. In one of these patients, functional results were poor and the PNE test was interrupted; in another, they were not very good, and the test was also stopped. The other six patients had an excellent functional recovery of FI, so the definitive implant was completed. At long-term follow-up, the results are very good and have been stable over time (unpublished data).

Conclusion

Patients presenting with FI following RR with or without neoadjuvant therapy must be carefully evaluated. Skepticism by patients and clinicians nega- tively affects the possibility to rightly assess the clinical condition and to plan therapy. In this view, an accurate clinical and physiological evaluation is mandatory. Even if traditional therapeutic proce- dures are not always successful, they can be attempted in selected patients. If suspected “neuro- genic” FI is confirmed by the physiological tests, SNS may be proposed and tested. Positive results of the PNE test suggest that a permanent SNM device must be implanted. Long-term results of SNS are encouraging. Failure of this approach does not pre- vent the use of other, more aggressive, forms of treatment.

Fig. 4.Anorectal manometry: normal resting and squeeze pressure profiles in a patient with fecal incontinence (FI) following chemoradiotherapy and rectal resection (RR) for rectal cancer

Fig. 3.Electrostimulator implant for sacral nerve stimulation (SNS) in a patient with fecal incontinence (FI) following chemoradiotherapy and rectal resection (RR) for rectal cancer. Reprinted with permission from [80]

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