Automatic muscle impedance and nerve analyzer (AMINA) as a novel approach for classifying bioimpedance signals in intraoperative pelvic neuromonitoring.

Frequent complications arising from low anterior resections include urinary and fecal incontinence, as well as sexual disorders, which are commonly associated with damage to the pelvic autonomic nerves during surgery. To assist the surgeon in preserving pelvic autonomic nerves, a novel approach for intraoperative pelvic neuromonitoring was investigated that is based on impedance measurements of the innervated organs. The objective of this work was to develop an algorithm called AMINA to classify the bioimpedance signals, with the goal of facilitating signal interpretation for the surgeon. Thirty patients included in a clinical investigation underwent nerve-preserving robotic rectal surgery using intraoperative pelvic neuromonitoring. Contraction of the urinary bladder and/or rectum, triggered by direct stimulation of the innervating nerves, resulted in a change in tissue impedance signal, allowing the nerves to be identified and preserved. Impedance signal characteristics in the time domain and the time-frequency domain were calculated and classified to develop the AMINA. Stimulation-induced positive impedance changes were statistically significantly different from negative stimulation responses by the percent amplitude of impedance change Amax in the time domain. Positive impedance changes and artifacts were distinguished by classifying wavelet scales resulting from peak detection in the continuous wavelet transform scalogram, which allowed implementation of a decision tree underlying the AMINA. The sensitivity of the software-based signal evaluation by the AMINA was 96.3%, whereas its specificity was 91.2%. This approach streamlines and automates the interpretation of impedance signals during intraoperative pelvic neuromonitoring.

Technical aspects of a new approach to intraoperative pelvic neuromonitoring during robotic rectal surgery.

It has been found that rectal surgery still leads to high rates of postoperative urinary, fecal, or sexual dysfunction, which is why nerve-sparing surgery has gained increasing importance. To improve functional outcomes, techniques to preserve pelvic autonomic nerves by identifying anatomic landmarks and implementing intraoperative neuromonitoring methods have been investigated. The objective of this study was to transfer a new approach to intraoperative pelvic neuromonitoring based on bioimpedance measurement to a clinical setting. Thirty patients (16 male, 14 female) involved in a prospective clinical investigation (German Clinical Trials Register DRKS00017437, date of first registration 31/03/2020) underwent nerve-sparing rectal surgery using a new approach to intraoperative pelvic neuromonitoring based on direct nerve stimulation and impedance measurement on target organs. Clinical feasibility of the method was outlined in 93.3% of the cases. Smooth muscle contraction of the urinary bladder and/ or the rectum in response to direct stimulation of innervating functional nerves correlated with a change in tissue impedance compared with the pre-contraction state. The mean amplitude (Amax) of positive signal responses was Amax = 3.8%, negative signal responses from a control tissue portion with no stimulation-induced impedance change had an amplitude variation of 0.4% on average. The amplitudes of positive and negative signal responses differed significantly (statistical analysis using two-sided t-test), allowing the nerves to be identified and preserved. The results indicate a reliable identification of pelvic autonomic nerves during rectal surgery.

Resection rectopexy as part of the multidisciplinary approach in the management of complex pelvic floor disorders.

Objectives: Pelvic floor disorders are frequently caused by an organ prolapse involving multiple pelvic floor compartments. In such cases, a multidisciplinary strategy for diagnostic work-up and therapy is required. Methods: All patients who underwent transabdominal rectopexy/resection rectopexy alone or in combination with simultaneous gynecological pelvic floor reconstruction at our institution between 01/2006 and 12/2021 were included in this retrospective study. The study aimed to evaluate the functional outcome and postoperative complications. Results: Two hundred and eighty seven patients were assigned to one of the following groups: PG1 - patient group one: after resection rectopexy (n=141); PG2 - after ventral rectopexy (n=8); PG3 - after combined resection rectopexy and sacro (cervico)colpopexy (n=62); PG4 - after combined resection rectopexy and trans-vaginal pelvic floor repair (n=76). The duration of follow-up was 14 months for PG1 (median, IQR 37 months), 11 months for PG2 (mean, SD 9 months), 7 months for PG 3 (median, IQR 33 months), and 12 months for PG 4 (median, IQR 51 Months). The surgical procedure resulted in improvement of symptoms related to obstructed defecation in 56.4 % (22/39) of the patients in PG1, 25 % in PG2 (1/4), 62.5 % (20/32) in PG3, and 71.8 % (28/39) in PG4. "De novo" constipation was reported by 2.4 % (2/141) of patients from PG1. Improvement in fecal incontinence symptoms was reported by 69 % (40/58) of patients in PG1, 100 % in PG2 (2/2), 93.1 % (27/29) in PG3, and 87.2 % (34/39) in PG4. The recurrence rate for external rectal prolapse was 7.1 % in PG1, 50 % in PG2 (1/2), 2.7 % in PG3, and 6.3 % in PG4. A significant difference in terms of severe morbidity (grade ≥ IIIb) and mortality could not be determined between the non-interdisciplinary (PG1 with PG2) and interdisciplinary surgery (PG3 with PG4) (p=0.88, p=0.499). Conclusions: Based on our results, we can assume that combined surgery is as feasible as rectal surgery alone. In our study, combined interventions were effective and not associated with an increased risk of postoperative complications.

[Stoma-associated complications-Prevention strategy and treatment concepts]. / Stomaassoziierte Komplikationen ­ Vermeidungsstrategie und Therapiekonzepte.

Postoperative complications after the creation of an intestinal stoma have a considerable impact on the patient's quality of life. The accurate surgical technique is very important for their prevention and requires profound surgical knowledge as well as sufficient experience. The importance of the preoperative consultation as well as the postoperative care by stoma therapists is clearly proven. Depending on the severity of the complication, outpatient conservative treatment is initially indicated. A surgical local revision or laparotomy should only be considered if conservative treatment is no longer sufficient, whereby the indications for surgery should be set very cautiously. This article provides an overview of the current evidence regarding the prevention and treatment of postoperative stoma complications.

The Indications for and Timing of Surgery for Diverticular Disease.

BACKGROUND: Diverticular disease is one of the more common abdominal disorders. In 2016, approximately 130 000 patients received inpatient treatment for diverticular disease in Germany. The disease has a number of subtypes, each of which has an appropriate treatment. In this article, we present the current surgical indications and optimal timing of surgery for diverticular disease. METHODS: This review is based on publications that were retrieved by an extensive, selective search in Medline and the Cochrane Library (1998-2018) for studies and guidelines with information on the indications for surgery in diverticular disease. RESULTS: Studies of evidence grades 2 to 4 were available. Patients receiving a diagnosis of freely perforated diverticulitis and peritonitis (Classification of Diverticular Disease [CDD] type 2c) should be operated on at once. Covered perforated diverticulitis with a macroabscess (>1 cm, CDD type 2b) may be an indication for elective surgery after successful conservative treatment. New evidence from a randomized, controlled trial suggests that elective surgery should also be considered for patients with chronic recurrent diverticulitis (CDD type 3b). The decisive factor in such cases is the impairment of the quality of life for the individual patient. Elective surgery is indicated in chronic recurrent diverticulitis with complications (fistulae, stenoses). Asymptomatic diverticulosis (CDD type 0) and uncomplicated diverticulitis (CDD type 1) are not surgical indications. Likewise, in diverticular hemorrhage (CDD type 4), surgery is only indicated in exceptional cases, when conservative treatment fails. CONCLUSION: The surgical indication and the proper timing of surgery depend on the type of disease that is present. Future studies should more thoroughly investigate the effect of surgery on the quality of life in patients with the various types of diverticular disease.

Intraoperative fluorescence angiography with indocyanine green: retrospective evaluation and detailed analysis of our single-center 5-year experience focused on colorectal surgery.

OBJECTIVES: Assessing bowel perfusion with indocyanine green fluorescence angiography (ICG-FA) shows positive effects on anastomotic healing in colorectal surgery. METHODS: A retrospective evaluation of 296 colorectal resections where we performed ICG-FA was undertaken from January 2014 until December 2018. Perfusion of the bowel ends measured with ICG-FA was compared to the visual assessment before and after performing the anastomosis. According to the observations, the operative strategy was confirmed or changed. Sixty-seven low anterior rectal resections (LARs) and 76 right hemicolectomies were evaluated statistically, as ICG-FA was logistically not available for every patient in our service and thus a control group for comparison resulted. RESULTS: The operative strategy based on the ICG-FA results was changed in 48 patients (16.2%), from which only one developed an anastomotic leakage (AL) (2.1%). The overall AL rate was calculated as 5.4%. Within the 67 patients with LAR, the strategy was changed in 11 patients (16.4%). No leakage was seen in those. In total three AL happened (4.5%), which was three times lower than the AL rate of 13.6% in the control group but statistically not significant. From the 76 right hemicolectomies a strategy change was undertaken in 10 patients (13.2%), from which only one developed an AL. This was the only AL reported in the whole group (1.3%), which was six times lower than the leakage rate of the control group (8.1%). This difference was statistically significant (p=0.032). CONCLUSIONS: Based on the positive impact by ICG-FA on the AL rate, we established the ICG-FA into our clinical routine. Although randomized studies are still missing, ICG-FA can raise patient safety, with only about 10 min longer operating time and almost no additional risk for the patients.

The modified Blumgart anastomosis after pancreaticoduodenectomy: a retrospective single center cohort study.

OBJECTIVES: The postoperative pancreatic fistula (POPF) is a major complication after pancreatic head resection whereby the technique of the anastomosis is a very influencing factor. The literature describes a possible protective role of the Blumgart anastomosis. METHODS: Patients after pancreatic head resection with reconstruction through the modified Blumgart anastomosis (a 2 row pancreatic anastomosis through mattress sutures of the parenchyma and duct to mucosa pancreaticojejunostomy, Blumgart-group) were compared with patients after pancreatic head resection and reconstruction through the conventional pancreatojejunostomy (single suture technique of capsule and parenchyma to seromuscularis, PJ-group). The Data were collected retrospectively. Depending on the propensity score matching in a ratio of 1:2 comparison groups were set up. Blumgart-group (n=29) and PJ-group (n=56). The primary end point was the rate of POPF. Secondary goals were duration of operation, length of hospital stay, length of stay on intermediate care units and hospital mortality. RESULTS: The rate of POPF (biochemical leak, POPF "grade B" and POPF "grade C") was less in the Blumgart-group, but without statistical relevance (p=0.23). Significantly less was the rate of POPF "grade C" in the Blumgart-group (p=0.03). Regarding the duration of hospital stay, length of stay on intermediate care units and hospital mortality, there was no relevant statistical difference between the groups (p=0.1; p=0.4; p=0.7). The duration of the operation was significantly less in the Blumgart-group (p=0.001). CONCLUSIONS: The modified Blumgart anastomosis technique may have the potential to decrease major postoperative pancreatic fistula.

[Influence of Local Insufflation of Warm Humidified CO2 on the Wound Surface and Body Core Temperature as well as on Wound Healing in Open Colorectal Surgery]. / Einfluss einer lokalen Insufflation von befeuchtetem und erwärmtem CO2 auf die Wundoberflächen- und Körperkerntemperatur sowie auf die Wundheilung in der offenen Kolorektalchirurgie.

BACKGROUND: Perioperative hypothermia may lead to serious complications. This study aims to investigate whether intraoperative insufflation of warmed and humidified carbon dioxide (W-H-CO2) into the open wound during open colorectal surgery influences body core and wound surface temperatures or the incidence of wound healing disorders (WHD). METHODS: Between 02/2018 and 07/2019, 50 patients intended to undergo open resection for colorectal cancer were recruited and randomised to a control group (n = 25) and an experimental group (n = 25). In the experimental group, a device for insufflation of W-H-CO2 was used. Body core and wound surface temperatures were recorded at the beginning and before finishing the procedure. IL-6 serum levels were determined preoperatively and during the postoperative course. Clinical observation of wound healing was performed until the 30th day post-op. RESULTS: Both groups were homogeneous in terms of risk factors for WHD. In the control group, the median body core temperature (1. quartile/3. quartile) was 36.2 °C (36/36.4 °C) when the operation started and 36.2 °C (35.9/36.45 °C) at the end, while in the experimental group it was initially 36.2 °C (35.7/36.4 °C) and 36.4 °C (36/36.7 °C) at the end. There was no significant difference between the two groups (p = 0.08). The wound temperature in the control group dropped from 32.8 °C (median; 31.85/34.05 °C) to 30.7 °C (median; 29.85/32.15 °C). In the experimental group, we recorded a drop from 31.9 °C (median; 30.25/32.95 °C) to 31.6 °C (median; 30.25/31.85 °C), which was statistically significant (p = 0.000475). The dynamic of the IL-6 serum levels in both groups suggest that there was no significant difference (p = 0.66; p = 0.88; p = 0.88). In the control group, 8 patients experienced superficial WHD, 2 anastomotic leakages (AL), while in the experimental group, superficial WHD were observed in 5 patients and AL in 1 patient. This differences between the groups regarding in WHD were not significant (p = 0.42). CONCLUSION: The established measures for prevention of perioperative hypothermia in elective procedures are sufficient. However, the local wound surface temperature is not preserved satisfactorily. Deployment of a device for intraoperative insufflation of W-H-CO2 into open wounds may be suitable for maintaining local normothermia. Further studies are needed to determine the influence of warm and humid CO2 on wound healing.

German S3 guidelines: anal abscess and fistula (second revised version).

BACKGROUND: The incidence of anal abscess and fistula is relatively high, and the condition is most common in young men. METHODS: This is a revised version of the German S3 guidelines first published in 2011. It is based on a systematic review of pertinent literature. RESULTS: Cryptoglandular abscesses and fistulas usually originate in the proctodeal glands of the intersphincteric space. Classification depends on their relation to the anal sphincter. Patient history and clinical examination are diagnostically sufficient in order to establish the indication for surgery. Further examinations (endosonography, MRI) should be considered in complex abscesses or fistulas. The goal of surgery for an abscess is thorough drainage of the focus of infection while preserving the sphincter muscles. The risk of abscess recurrence or secondary fistula formation is low overall. However, they may result from insufficient drainage. Primary fistulotomy should only be performed in case of superficial fistulas. Moreover, it should be done by experienced surgeons. In case of unclear findings or high fistulas, repair should take place in a second procedure. Anal fistulas can be treated only by surgical intervention with one of the following operations: laying open, seton drainage, plastic surgical reconstruction with suturing of the sphincter (flap, sphincter repair, LIFT), and occlusion with biomaterials. Only superficial fistulas should be laid open. The risk of postoperative incontinence is directly related to the thickness of the sphincter muscle that is divided. All high anal fistulas should be treated with a sphincter-saving procedure. The various plastic surgical reconstructive procedures all yield roughly the same results. Occlusion with biomaterial results in lower cure rate. CONCLUSION: In this revision of the German S3 guidelines, instructions for diagnosis and treatment of anal abscess and fistula are described based on a review of current literature.

German S3-Guideline: rectovaginal fistula.

BACKGROUND: Rectovaginal fistulas are rare, and the majority is of traumatic origin. The most common causes are obstetric trauma, local infection, and rectal surgery. This guideline does not cover rectovaginal fistulas that are caused by chronic inflammatory bowel disease. METHODS: A systematic review of the literature was undertaken. RESULTS: Rectovaginal fistula is diagnosed on the basis of the patient history and the clinical examination. Other pathologies should be ruled out by endoscopy, endosonography or tomography. The assessment of sphincter function is valuable for surgical planning (potential simultaneous sphincter reconstruction). Persistent rectovaginal fistulas generally require surgical treatment. Various surgical procedures have been described. The most common procedure involves a transrectal approach with endorectal suture. The transperineal approach is primarily used in case of simultaneous sphincter reconstruction. In recurrent fistulas. Closure can be achieved by the interposition of autologous tissue (Martius flap, gracilis muscle) or biologically degradable materials. In higher fistulas, abdominal approaches are used as well. Stoma creation is more frequently required in rectovaginal fistulas than in anal fistulas. The decision regarding stoma creation should be primarily based on the extent of the local defect and the resulting burden on the patient. CONCLUSION: In this clinical S3-Guideline, instructions for diagnosis and treatment of rectovaginal fistulas are described for the first time in Germany. Given the low evidence level, this guideline is to be considered of descriptive character only. Recommendations for diagnostics and treatment are primarily based the clinical experience of the guideline group and cannot be fully supported by the literature.

German S3 guideline: anal abscess.

BACKGROUND: The incidence of anal abscess is relatively high, and the condition is most common in young men. METHODS: A systematic review of the literature was undertaken. RESULTS: This abscess usually originates in the proctodeal glands of the intersphincteric space. A distinction is made between subanodermal, intersphincteric, ischioanal, and supralevator abscesses. The patient history and clinical examination are diagnostically sufficient to establish the indication for surgery. Further examinations (endosonography, MRI) should be considered in recurrent abscesses or supralevator abscesses. The timing of the surgical intervention is primarily determined by the patient's symptoms, and acute abscess is generally an indication for emergency treatment. Anal abscesses are treated surgically. The type of access (transrectal or perianal) depends on the abscess location. The goal of surgery is thorough drainage of the focus of infection while preserving the sphincter muscles. The wound should be rinsed regularly (using tap water). The use of local antiseptics is associated with a risk of cytotoxicity. Antibiotic treatment is only necessary in exceptional cases. Intraoperative fistula exploration should be conducted with extreme care if at all; no requirement to detect fistula should be imposed. The risk of abscess recurrence or secondary fistula formation is low overall, but they can result from insufficient drainage. Primary fistulotomy should only be performed in case of superficial fistulas and by experienced surgeons. In case of unclear findings or high fistulas, repair should take place in a second procedure. CONCLUSION: In this clinical S3 guideline, instructions for diagnosis and treatment of anal abscess are described for the first time in Germany.

Cryptoglandular anal fistulas.

BACKGROUND: Cryptoglandular anal fistula arises in 2 per 10 000 persons per year and is most common in young men. Improper treatment can result in fecal incontinence and thus in impaired quality of life. METHOD: This S3 guideline is based on a systematic review of the pertinent literature. RESULTS: The level of evidence for treatment is low, because relevant randomized trials are scarce. Anal fistulae are classified according to the relation of the fistula channel to the sphincter. The indication for treatment is established by the clinical history and physical examination. During surgery, the fistula should be probed and/or dyed. Endo-anal ultrasonography and magnetic resonance imaging are of roughly the same diagnostic value and may be useful as additional studies for complex fistulae. Surgical treatment is with one of the following operations: laying open, seton drainage, plastic surgical reconstruction with suturing of the sphincter, and occlusion with biomaterials. Only superficial fistulae should be laid open. The risk of postoperative incontinence is directly related to the thickness of sphincter muscle that is divided. All high anal fistulae should be treated with a sphincter-saving procedure. The various plastic surgical reconstructive procedures all yield roughly the same results. Occlusion with biomaterials yields a lower cure rate. CONCLUSION: This is the first German S3 guideline for the treatment of cryptoglandular anal fistula. It includes recommendations for the diagnostic evaluation and treatment of this clinical entity.

[Principles and quality control of surgical therapy of rectal carcinoma]. / Chirurgische Therapie des Rektumkarzinoms. Richtig resezieren und rekonstruieren.

During the past years, it has been possible to achieve impressive success in the treatment of rectal carcinoma through standardized therapeutic concepts. Through the consistent application of total mesorectal excision (TME) as a therapeutic procedure, a dramatic improvement in local recurrence rate has been attained. Future strategies are now aimed at improving postoperative quality of life and moreover, at reducing the incidence of distant metastasization. The positive development during recent years is ultimately also the result of increasing quality control. Hence, surgery with its specific quality criteria has been integrated into a broad spectrum of various individual factors that must be taken into consideration in a multimodal therapeutic concept.

Increased serum levels of complement C3a anaphylatoxin indicate the presence of colorectal tumors.

BACKGROUND & AIMS: Late diagnosis of colorectal carcinoma results in a significant reduction of average survival times. Yet despite screening programs, about 70% of tumors are detected at advanced stages (International Union Against Cancer stages III/IV). We explored whether detection of malignant disease would be possible through identification of tumor-specific protein biomarkers in serum samples. METHODS: A discovery set of sera from patients with colorectal malignancy (n = 58) and healthy control individuals (n = 32) were screened for potential differences using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Candidate proteins were identified and their expression levels were validated in independent sample sets using a specific immunoassay (enzyme-linked immunosorbent assay). RESULTS: By using class comparison and custom-developed algorithms we identified several m/z values that were expressed differentially between the malignant samples and the healthy controls of the discovery set. Characterization of the most prominent m/z values revealed a member of the complement system, the stable form of C3a anaphylatoxin (ie, C3a-desArg). Based on a specific enzyme-linked immunosorbent assay, serum levels of complement C3a-desArg predicted the presence of colorectal malignancy in a blinded validation set (n = 59) with a sensitivity of 96.8% and a specificity of 96.2%. Increased serum levels were also detected in 86.1% of independently collected sera from patients with colorectal adenomas (n = 36), whereas only 5.6% were classified as normal. CONCLUSIONS: Complement C3a-desArg is present at significantly higher levels in serum from patients with colorectal adenomas (P < .0001) and carcinomas (P < .0001) than in healthy individuals. This suggests that quantification of C3a-desArg levels could ameliorate existing screening tests for colorectal cancer.

Do geographic and educational factors influence the quality of life in rectal cancer patients with a permanent colostomy?

PURPOSE: This study was designed to evaluate possible social and geographic factors that could have an impact on quality of life in patients after abdominoperineal excision of the rectum. Although the number of patients with rectal cancer who need to be treated with abdominoperineal excision of the rectum and construction of permanent colostomy has greatly decreased in the past, there is still controversy about the influence on quality of life caused by this procedure. METHODS: In a prospective trial, patients operated on for low rectal cancer by abdominoperineal excision of the rectum were evaluated by a quality of life questionnaire, modified from The American Society of Colon and Rectal Surgeons questionnaire, to assess fecal incontinence. The results for the four domains of quality of life (lifestyle, coping behavior, embarrassment, depression), as well as for subjective general health, were evaluated with regard to age, gender, education, and geographic origin in univariate and multivariate analyses. RESULTS: Thirteen institutions in 11 countries included data from 257 patients. Although the analysis of general health did not reveal any significant differences, the analysis of the four quality of life domains showed the significant influence of geographic origin. The presence of a permanent colostomy showed a consistently negative impact on patients in southern Europe as well as for patients of Arabic (Islamic) origin. On the other hand, age, gender, and educational status did not reveal a statistically significant influence. CONCLUSIONS: This is the first study to show the influence of geographic origin on quality of life of patients with a permanent colostomy. Possible factors that may influence the outcome of patients after surgical treatment of rectal cancer, such as weather, religion, or culture, should be taken into account when quality of life evaluations are considered.

Diagnosis and monitoring of colorectal cancer by L6 blood serum polymerase chain reaction is superior to carcinoembryonic antigen-enzyme-linked immunosorbent assay.

PURPOSE: The aim of this study was to compare carcinoembryonic antigen levels with detection of messenger ribonucleic acid coding for the tumor-associated antigen L6 in patients with colorectal cancer. Not only are carcinoembryonic antigens expressed by the corresponding tumor cell, but the messenger ribonucleic acid of tumor-associated antigens, in contrast, is produced exclusively by viable tumor cells. METHODS: L6 messenger ribonucleic acid was determined by reverse-transcription polymerase chain reaction. Carcinoembryonic antigen was measured by the enzyme-linked immunosorbent assay technique, with a cutoff value of 40 microg/l. Blood serum was sampled from 187 patients with colorectal cancer. Statistical significance was calculated with the McNemar chi-squared test. RESULTS: Preoperatively, 79 percent of patients in all stages were positive for L6 messenger ribonucleic acid, whereas only 35 percent had elevated carcinoembryonic antigen titers (P < 0.001). In Dukes A tumors, 84.9 percent of patients were positive for L6 messenger ribonucleic acid, whereas carcinoembryonic antigen was elevated in only 16.9 percent of patients. Only in Dukes D tumors did the enzyme-linked immunosorbent assay for carcinoembryonic antigen exhibit the same sensitivity as reverse-transcription polymerase chain reaction for L6 messenger ribonucleic acid. Recurrence was detected significantly earlier by reverse-transcription polymerase chain reaction for L6 messenger ribonucleic acid than by enzyme-linked immunosorbent assay for carcinoembryonic antigen. CONCLUSION: L6 is more sensitive and precise than carcinoembryonic antigen in diagnosing and monitoring colorectal cancer.

Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon.

BACKGROUND & AIMS: A variety of gastrointestinal motility disorders have been attributed to alterations of interstitial cells of Cajal and malformations of the enteric nervous system. This study evaluates both the distribution of interstitial cells of Cajal and the pathohistology of the enteric nervous system in 2 severe human colorectal motility disorders. METHODS: Colonic specimens obtained from patients with slow-transit constipation (n = 11), patients with megacolon (n = 6), and a control group (n = 13, nonobstructing neoplasia) were stained with antibodies against c-kit (marker for interstitial cells of Cajal) and protein gene product 9.5 (neuronal marker). The morphometric analysis of interstitial cells of Cajal included the separate registration of the number and process length within the different regions of the muscularis propria. The structural architecture of the enteric nervous system was assessed on microdissected whole-mount preparations. RESULTS: In patients with slow-transit constipation, the number of interstitial cells of Cajal was significantly decreased in all layers except the outer longitudinal muscle layer. The myenteric plexus showed a reduced ganglionic density and size (moderate hypoganglionosis) compared with the control group. Patients with megacolon were characterized by a substantial decrease in both the number and the process length of interstitial cells of Cajal. The myenteric plexus exhibited either complete aganglionosis or severe hypoganglionosis. CONCLUSIONS: The enteric nervous system and interstitial cells of Cajal are altered concomitantly in slow-transit constipation and megacolon and may play a crucial role in the pathophysiology of colorectal motility disorders.