Multistain deep learning for prediction of prognosis and therapy response in colorectal cancer.

Although it has long been known that the immune cell composition has a strong prognostic and predictive value in colorectal cancer (CRC), scoring systems such as the immunoscore (IS) or quantification of intraepithelial lymphocytes are only slowly being adopted into clinical routine use and have their limitations. To address this we established and evaluated a multistain deep learning model (MSDLM) utilizing artificial intelligence (AI) to determine the AImmunoscore (AIS) in more than 1,000 patients with CRC. Our model had high prognostic capabilities and outperformed other clinical, molecular and immune cell-based parameters. It could also be used to predict the response to neoadjuvant therapy in patients with rectal cancer. Using an explainable AI approach, we confirmed that the MSDLM's decisions were based on established cellular patterns of anti-tumor immunity. Hence, the AIS could provide clinicians with a valuable decision-making tool based on the tumor immune microenvironment.

Senescence-Associated Molecules and Tumor-Immune-Interactions as Prognostic Biomarkers in Colorectal Cancer.

Background and Aims: The initiation of cellular senescence in response to protumorigenic stimuli counteracts malignant progression in (pre)malignant cells. Besides arresting proliferation, cells entering this terminal differentiation state adopt a characteristic senescence-associated secretory phenotype (SASP) which initiates alterations to their microenvironment and effects immunosurveillance of tumorous lesions. However, some effects mediated by senescent cells contribute to disease progression. Currently, the exploration of senescent cells' impact on the tumor microenvironment and the evaluation of senescence as possible target in colorectal cancer (CRC) therapy demand reliable detection of cellular senescence in vivo. Therefore, specific immunohistochemical biomarkers are required. Our aim is to analyze the clinical implications of senescence detection in colorectal carcinoma and to investigate the interactions of senescent tumor cells and their immune microenvironment in vitro and in vivo. Methods: Senescence was induced in CRC cell lines by low-dose-etoposide treatment and confirmed by Senescence-associated ß-galactosidase (SA-ß-GAL) staining and fluorescence activated cell sorting (FACS) analysis. Co-cultures of senescent cells and immune cells were established. Multiple cell viability assays, electron microscopy and live cell imaging were conducted. Immunohistochemical (IHC) markers of senescence and immune cell subtypes were studied in a cohort of CRC patients by analyzing a tissue micro array (TMA) and performing digital image analysis. Results were compared to disease-specific survival (DSS) and progression-free survival (PFS). Results: Varying expression of senescence markers in tumor cells was associated with in- or decreased survival of CRC patients. Proximity analysis of p21-positive senescent tumor cells and cytotoxic T cells revealed a significantly better prognosis for patients in which these cell types have the possibility to directly interact. In vitro, NK-92 cells (mimicking natural killer T cells) or TALL-104 cells (mimicking both cytotoxic T cells and natural killer T cells) led to dose-dependent specific cytotoxicity in >75 % of the senescent CRC cells but <20 % of the proliferating control CRC cells. This immune cell-mediated senolysis seems to be facilitated via direct cell-cell contact inducing apoptosis and granule exocytosis. Conclusion: Counteracting tumorigenesis, cellular senescence is of significant relevance in CRC. We show the dual role of senescence bearing both beneficial and malignancy-promoting potential in vivo. Absence as well as exceeding expression of senescence markers are associated with bad prognosis in CRC. The antitumorigenic potential of senescence induction is determined by tumor micromilieu and immune cell-mediated elimination of senescent cells.

Local excision followed by early radical surgery in rectal cancer: long-term outcome.

BACKGROUND: In rectal cancers, radical surgery should follow local excisions, in cases of unexpected, unfavorable tumor characteristics. The oncological results of this completion surgery are inconsistent. This retrospective cohort study assessed the clinical and long-term oncological outcomes of patients that underwent completion surgery to clarify whether a local excision compromised the results of radical surgery. METHODS: Forty-six patients were included, and the reasons for completion surgery, intraoperative complications, residual tumors, local recurrences (LRs), distant metastases, and cancer-specific survival (CSS) were assessed. The results were compared to 583 patients that underwent primary surgery without adjuvant therapy, treated with a curative intention during the same time period. RESULTS: The median follow-up was 14.6 years. The reasons for undergoing completion surgery were positive resection margins (24%), high-risk cancer (30%), or both (46%). Intraoperative perforations occurred in 10/46 (22%) cases. Residual tumor in the rectal wall or lymph node involvement occurred in 12/46 (26%) cases. The risk of intraoperative perforation and residual tumor increased with the pT category. Intraoperative perforations did not increase postoperative complications, but they increased the risk of LRs in cases of intramural residual tumors (p = 0.003). LRs occurred in 2.6% of pT1/2 and 29% of pT3 tumors. Both the 5- and 10-year CSS rates were 88.8% (95% CI 80.0-98.6). Moreover, the LRs of patients with pT1/2 cancers were lower in patients with completion surgery than in patients with primary surgery. CONCLUSIONS: Rectal wall perforations at the local excision site and residual cancer were the main risks for poor oncological outcomes associated with completion surgery. Local excisions followed by early radical surgery did not appear to compromise outcomes compared to patients with primary surgery for pT1/2 rectal cancer. Improvements in clinical staging should allow more appropriate selection of patients that are eligible for a local excision of rectal cancer.

The Link Between Local Recurrence and Distant Metastases in Patients With Rectal Cancer.

BACKGROUND/AIM: The relationships between local recurrence (LR), the development of distant metastases (DM) and prognosis in patients with rectal cancer remain unclear. PATIENTS AND METHODS: In 606 patients who underwent curative resection, the role of LR was assessed retrospectively by time-dependent multivariate Cox models with inverse probability of treatment weighting taking into account competing risks. RESULTS: Patients with LR had more DM than patients without LR (49/79, 62% vs. 86/524, 16.4%; p<0.001); 37% of LR-associated DM developed before or at LR, 63% after diagnosis of LR. Fifty-five percent of patients without DM at diagnosis of LR later developed DM. In these patients, the incidence of DM significantly exceeded the incidence in patients without LR. DM risk was most strongly associated with preceding LR and stage UICC III and II. CONCLUSION: There is a causal link between LR and DM in patients with rectal cancer.

Analysis of local recurrences after transanal endoscopic microsurgery for low risk rectal carcinoma.

AIM: Rates of local recurrence (LR) after transanal endoscopic microsurgery (TEM) for rectal carcinoma vary; the reasons remain unclear. We analyzed LR after TEM for low-risk pT1 (G1/2/X, L0/X) rectal carcinoma to investigate the influence of completeness of resection and occult lymph node metastasis on risk of LR. METHOD: LR location and stage, completeness of resection of primary carcinoma (minimal distance between tumor and resection line ≤1 mm vs >1 mm), and incidence of involved lymph nodes in resected LR specimens were collected, and tumor characteristics of LR were compared with primary carcinoma. Distant metastasis and overall and cancer-specific survival were determined. RESULTS: LR developed in 14 patients; in 2/4 with R1/X resection, in 3/8 (38%) with clear margins (R0) but a minimal distance of ≤1 mm, and in 9/88 (10%) with formally complete resection. Six of nine patients with formally complete resection underwent radical surgery for LR; in five out of these six, lymph nodes were not involved. In 5/14 patients, LR was poorly differentiated compared to primary carcinoma. Main LR causes were incomplete tumor resection or tumor persistence after formally complete resection. Overall (p = 0.008) and cancer-specific (p < 0.001) survival was lower in LR patients compared to non-LR patients, even if lymph nodes were uninvolved. CONCLUSIONS: The results suggest that most LRs after TEM for low-risk rectal cancer were caused by residual tumor at the previous excision site and not by undetected lymph node metastases. By improved standardization of surgical techniques to ensure complete resection of carcinomas and thorough pathological assessments, most LRs seem to be avoidable.

Influence of Local Recurrence and Distant Metastasis on Prognosis After Local Excision of Rectal Carcinoma.

BACKGROUND: Influence of local recurrence (LR) on prognosis after a local excision (LE) for rectal cancer is unclear. PATIENTS AND METHODS: A total of 152 patients were retrospectively assigned to one of three groups: Groups 1 and 2: complete and incomplete resection respectively, for low-risk carcinoma; group 3: high-risk carcinoma. We evaluated LR, distant metastasis (DM), overall survival, and cancer-specific survival (CSS). RESULTS: LR rates were 10.4%, 43% and 29% for groups 1-3, respectively (p=0.002). In all three groups, DM incidence was low in patients without LR, but high in patients with LR (p<0.0001). Prior LR was an important risk factor for DM (hazard ratio: 14.1, 95% confidence interval=4.3-45.8, p<0.0001). DM significantly reduced CSS. CONCLUSION: There is a strong association between LR and DM independently in the cause of LR. Avoiding LE for high-risk carcinoma and complete LE of low-risk carcinoma are essential to reduce LR and DM.

Long-term Oncologic Outcome After Transanal Endoscopic Microsurgery for Rectal Carcinoma.

BACKGROUND: Transanal endoscopic microsurgery is superior to other methods of local excision of rectal cancer, but few studies report long-term follow-up data. OBJECTIVE: This study investigated the use of transanal endoscopic microsurgery alone as curative and compromise therapy based on long-term disease recurrence and mortality. DESIGN: This was a retrospective review of prospectively collected data. SETTINGS: The study was conducted at a tertiary care university medical center. PATIENTS: The study included 133 patients treated between 1985 and 2007. There were 3 groups, including transanal endoscopic microsurgery in curative intent (low-risk rectal carcinoma, including pT1, G1/2, L0, and LX with clear margins and a minimal distance between tumor and resection margin of >1 mm (N = 64) or clear margins only (N = 18 ))) and as compromise therapy (high-risk or incompletely resected rectal carcinoma; N = 51). MAIN OUTCOME MEASURES: Log-rank tests were used to compare overall and cancer-specific survival. RESULTS: The median follow-up time was 8.6 years (range, 0.2-25.1 years), and a total of 131 of 133 patients (98.5%) were followed >5 years or until death. The preoperative diagnosis of carcinoma was not associated with belonging into 1 of the 3 categories. In patients with low-risk completely (>1 mm) resected carcinoma, the 5- and 10-year local recurrence rates were 6.6% and 11.6%. In patients with high-risk or incompletely resected carcinoma, the rates were 32.5% and 35.0% (p = 0.006). The 5- and 10-year cancer-specific survival rates for low-risk patients were 98.0% and 91.0% and 84.3% and 74.3% for high-risk patients (p = 0.05). LIMITATIONS: The study was limited by its retrospective design and small subgroups. CONCLUSIONS: The high cancer-specific survival justifies transanal endoscopic microsurgery alone as curative treatment in low-risk rectal carcinoma. Complete resection is essential to lower the risk of local recurrence. The high local recurrence rate in patients with high-risk rectal carcinoma restricts the use of TEM alone as compromise therapy.

Rectal cancer: assessment of response to neoadjuvant chemoradiation by dynamic contrast-enhanced MRI.

PURPOSE: To assess pretreatment functional and morphological tumor characteristics with magnetic resonance imaging (MRI) in advanced rectal carcinoma and to identify factors predicting response to neoadjuvant chemoradiation. MATERIALS AND METHODS: In a prospective study, 95 patients with rectal carcinoma underwent dynamic contrast-enhanced MRI before and after chemoradiation. Quantitative parameters were derived from a pharmacokinetic two-compartment model. Tumors were also characterized with regard to mucinous status at pretreatment high-resolution MRI as nonmucinous or mucinous. Response to treatment was defined as a downshift in the local tumor stage. RESULTS: The parameter k21 (contrast medium exchange rate) was higher at pretreatment MRI in nonmucinous compared with mucinous carcinomas (P < 0.001). The effect of chemoradiation on dynamic MR parameters was higher in nonmucinous carcinomas than in the mucinous subtype (P < 0.001). A higher rate of response to treatment was linked with nonmucinous morphology (P < 0.001). Multivariate analysis revealed an association between mucinous tumor morphology and poor response (odds ratio [95% confidence interval]: 0.113 [0.032-0.395], P < 0.001) as well as an association between a high 75th percentile of k21 and a higher response rate (odds ratio: 1.043 [1.001-1.086], P = 0.019). CONCLUSION: Functional and morphological parameters of pretreatment MRI can assess tumor characteristics associated with the effectiveness of chemoradiation before treatment initiation.

Rectal Cancer: MR imaging of the mesorectal fascia and effect of chemoradiation on assessment of tumor involvement.

PURPOSE: To evaluate the impact of chemoradiation on the reliability of MRI in assessing tumor involvement of the mesorectal fascia in patients with rectal cancer. MATERIALS AND METHODS: Presurgical MRI was performed in 150 patients; among them 85 had received neoadjuvant long-course chemoradiation. A standardized imaging protocol (1.5 Tesla [T] system, image voxel size 0.6 × 0.4 × 3 mm(3) ), standardized surgery, and histopathological examination were applied for the entire patient population. Images were analyzed to identify potential tumor involvement of the mesorectal fascia (minimum tumor distance to fascia ≤1 mm) and compared with histopathology as the reference standard. Results of nonirradiated and irradiated patients were compared to define the impact of chemoradiation on imaging reliability. RESULTS: In nonirradiated patients, MRI was reliable in predicting or excluding tumor involvement of the mesorectal fascia, positive predictive value 80%, negative predictive value 89%. The frequency of overestimating tumor involvement was significantly higher in irradiated patients (P = 0.005, positive predictive value 42%). CONCLUSION: Discussions about MRI assessment of tumor involvement of the mesorectal fascia as a basis for recommending neoadjuvant chemoradiation should focus on investigations that excluded irradiated patients, because MRI is less reliable after chemoradiation and tends to overestimate mesorectal tumor involvement.

Rectal cancer: mucinous carcinoma on magnetic resonance imaging indicates poor response to neoadjuvant chemoradiation.

PURPOSE: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). METHODS AND MATERIALS: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgical specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). RESULTS: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p ≤ 0.001). Positive resection margins (ypCRM ≤ 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p ≤ 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). CONCLUSION: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.

Laparoscopic anterior semifundoplication in patients with intrathoracic stomach.

The laparoscopic management of the intrathoracic stomach is still controversial. Laparoscopic semifundoplication in gastroesophageal reflux disease results in effective long-term reflux control and is, as compared with 360 degrees Nissen fundoplication, associated with less frequent side effects such as dysphagia and gas bloat syndrome. The aim of our study was to evaluate the results of laparoscopic anterior semifundoplication in patients with intrathoracic stomach. Enrolled in this study are 19 patients (67.1 years of age; range, 37.5-83.7 years) with intrathoracic stomach undergoing laparoscopic anterior semifundoplication and a minimal follow up of 5 months postoperatively. The study covers the interval between August 1999 and March 2006. Including criterion was a minimum percentage of herniated intrathoracic stomach of 33 per cent. A standardized questionnaire was used for follow up and the modified symptomatic DeMeester score (0-9) was assessed. The median percentage of herniated stomach in the chest was 87.5 per cent (range, 33-100%). Seven patients revealed organo-axial volvulus of the stomach. Duration of preoperative symptoms was 24 months (range, 1-266 months) with a median follow up of 18 months (range, 5-76 months) postoperatively. The modified symptomatic DeMeester score was 0 (0-3). Thirteen of 19 patients were on no postoperative proton pump inhibitor medication. One patient had anatomic recurrence on late follow up at 27 months. The overall contentment with the surgical treatment on an analog scale from 0 to 10 was a median of 9. Although laparoscopic anterior semifundoplication yields satisfactory symptomatic results in patients with intrathoracic stomach, the incidence of failures and anatomical recurrences is higher than expected from subjective data. Prospective, randomized long-term studies are essential to gain further information about the "ideal" type of laparoscopic repair in large hiatal hernia with intrathoracic stomach.

Transanal endoscopic microsurgical excision of pT2 rectal cancer: results and possible indications.

PURPOSE: In previous studies, local excision was predominantly established for "low-risk" pT1 rectal cancer. The results obtained with T2 tumors are unclear; recurrence rates of 0 to 67 percent were reported. This study was designed to determine the value of local excision for T2 rectal carcinomas, prognostic factors, and the need for reoperation. METHODS: After local excision of 649 patients with rectal tumors, pT2 carcinoma was found in 44 patients. In general, immediate reoperation was recommended; however, 24 patients declined further surgery or were not reoperated because of comorbidities. The results were analyzed separately for local R0 resection of low-risk carcinomas and for prognostically unfavorable criteria (R1/RX/R < or = 1mm/G3-4/L1/V1). Reoperation was performed within four weeks. Recurrences also were divided by previous local R0 resection of low-risk tumors as well as by unfavorable results and were analyzed in a long-term, follow-up study. Patients with palliative therapy were excluded, and follow-up was obtained in 90 percent (20 transanal endoscopic microsurgical excision alone, 17 transanal endoscopic microsurgical excision and reoperation). RESULTS: Local recurrence rates after local R0 resection alone of low-risk T2 carcinomas were 29 percent, whereas patients with unfavorable criteria developed recurrences in 50 percent. After immediate reoperation, the local recurrence risk in patients without lymph node filiae was significantly reduced to 7 percent. CONCLUSIONS: Local R0 resection of low-risk pT2 carcinomas represents an inadequate therapy. In pT2N0M0 rectal carcinomas, the recurrence rate can be reduced through immediate reoperation to a level similar to primary radical surgery. An initial poor local resection result (R1/RX/R < or = 1 mm/G3-4/L1/V1) has no negative influence on further oncologic outcome.

The influence of histopathologic criteria on the long-term prognosis of locally excised pT1 rectal carcinomas: results of local excision (transanal endoscopic microsurgery) and immediate reoperation.

PURPOSE: Local excision of early rectal cancer is a controversial issue, which is in part because of differences in the evaluation of histopathologic criteria. This prospective study was designed to determine prognostic factors for recurrences and the need for reoperation. METHODS: In 105 of 118 patients with pT1 carcinomas and local excision, results of recurrence rates and ten-year cancer-free survival were studied separately according to different histologic criteria (R0, R1, Rx, R < or = 1 mm, high-/low-risk situation), tumor localization (anterior, posterior, lateral wall and third of rectum), size, and degree of resection (full-thickness/partial wall). Patients were grouped into local excision (n = 89) and local excision followed by reoperation (n = 21). Risk classification was performed by division into "low-risk" carcinomas after local R0-resection (Group A) and unfavorable histologic results after local resection (R1, Rx, R < or = 1 mm, high-risk situation; Group B). RESULTS: Local recurrence rates after local R0-resection of low-risk carcinomas were 6 percent, whereas patients in Group B with local resection were 39 percent. The recurrence risk in those patients was significantly reduced to 6 percent by reoperation (P = 0.015). In addition, ten-year, cancer-free survival was 93 percent in Group B after reoperation compared with 89 percent in patients of Group A after local excision alone. CONCLUSIONS: Local R0-resection in cases with low-risk pT1 carcinomas represents an oncologically adequate therapy, which results in similar survival rates compared with primary radical surgery of pT1N0M0 rectal carcinomas. High recurrence rates are observed in tumors with unfavorable histologic result (Group B) requiring further treatment. In these cases immediate reoperation reduces the recurrence rate to 6 percent.

Adrenalectomy for bilateral and recurrent pheochromocytoma: increased intraoperative risk?

Adrenalectomy for pheochromocytoma is per se associated with a specific intraoperative cardiovascular risk caused by catecholamine secretion during manipulation of the tumor. Bilateral or multiple, and recurrent chromaffine tumors are special subentities with a potentially more intensified and longer surgical preparation. The aim of our study was to examine these effects on hemodynamic changes compared with those observed for primary, solitary tumors. Of the 82 studied interventions between February 1992 and May 2005, 58 were seen to involve primary, unilateral tumors, 17 involved bilateral (1 trilateral) findings, and there were 7 cases of recurrency. The hemodynamic changes related to primary, solitary pheochromocytomas revealed a higher frequency of intraoperative blood pressure crises (37%) compared with the comparative groups (11.8% in bilateral and 0% in recurrent tumors), as well as higher maximum pCO2 values noted. The intraoperative blood loss was more pronounced in interventions involving recurrencies. Aside from an appropriate preliminary therapy using an alpha-blocker and the careful surgical preparation of the adrenal gland, the different hemodynamic changes possibly may be related to the presence of smaller tumors in bilateral pheochromocytoma, as well as being based upon the already existent ligature of the draining vein in the event of recurrent procedures. The extent to which the adrenergic effect of the increased maximum pCO2 value plays a role on the development of higher maximum blood pressure values and more frequent intraoperative blood pressure crises continues to remain unclear.

Laparoscopic gastric banding as a universal method for the treatment of patients with morbid obesity.

INTRODUCTION: This study analyzed the influence of potentially negative predictors such as sweet-eating behavior, super-obesity, social and psychological status, family and education situation, intake of sedative drugs, and the distance between hospital and home on the outcome of laparoscopic adjustable gastric banding (LAGB). METHODS: 77 women and 29 men with mean age 40.6 years (28-47) underwent LAGB. Preoperative mean body weight was 146 kg (99-179), and mean BMI was 48.1 kg/m2 (36.4-73.5). The influence of the above-mentioned potentially negative predictors on weight loss was the primary end point. RESULTS: Mean follow-up was 44.6 +/- 19.7 months. Follow-up was possible in all but 6 patients. Median excess weight loss (EWL) was 52.1% (range 28.6-72.2%). Univariate analysis revealed no influence of the investigated negative predictors on the weight reduction. Median EWL in 24 sweet-eater patients was 55.6% compared to 55.4% in 82 non-sweet-eaters (P=0.65). A significant difference in the weight reduction was found between super-obese and non-superobese groups (P <0.001). CONCLUSIONS: LAGB should be recommended without limitation as the operation of choice for morbidly obese patients. Gastric bypass operations should be recommended only in cases of unsuccessful LAGB.

Intraoperative identification and neurophysiologic parameters to verify pelvic autonomic nerve function during total mesorectal excision for rectal cancer.

BACKGROUND: Preservation of parasympathetic and sympathetic nerves is required to avoid urogenital function disturbances after total mesorectal excision (TME) for rectal carcinoma. This study sought to determine whether intraoperative stimulation of parasympathetic nerves with monitoring of bladder contraction is useful in meeting this demand. STUDY DESIGN: In a prospective pilot study, 17 patients, 11 men and 6 women, underwent TME with pelvic autonomic nerve preservation performed by an experienced surgeon. The parasympathetic nerves were stimulated by an electrostimulation device (Screener 3625, Medronic), and the resulting bladder contraction was measured manometrically in all patients. Variations in pulse rate and voltage were measured to determine optimal stimulation parameters. A standardized questionnaire was used to record urogenital function disturbances. Residual urine volume was measured by ultrasound pre- and postoperatively. Shortterm outcomes data were evaluated to establish a possible association between intraoperative test results and postoperative bladder function. RESULTS: In 15 of 17 patients undergoing TME with pelvic autonomic nerve preservation for rectal carcinoma, the parasympathetic nerves were identified based on nerve stimulation-induced bladder contraction. Two patients with negative results on intraoperative nerve stimulation had persisting bladder dysfunction requiring an indwelling catheter after discharge from hospital. In spite of a short median followup of 2 months (range 1 to 4 months), in 7 of 10 men with intact erectile function prior to surgery, postoperative erectile dysfunction could be excluded. The study showed a pulse rate of 35 Hz and an electric potential of 12 V to be optimal stimulation parameters, associated with a mean intravesical pressure rise of 12.7 cm H(2)O (range 2.8 to 18.0 cm H(2)O). CONCLUSIONS: Intraoperative nerve stimulation with monitoring of intravesical pressure represents a technically simple procedure for the identification and verification of function of pelvic parasympathetic nerves during TME for rectal carcinoma.