INSPIRA: study protocol for a randomized-controlled trial about the effect of spirometry-assisted preoperative inspiratory muscle training on postoperative complications in abdominal surgery.

BACKGROUND: Rehabilitation strategies after abdominal surgery enhance recovery and improve outcome. A cornerstone of rehabilitation is respiratory physiotherapy with inspiratory muscle training to enhance pulmonary function. Pre-habilitation is the process of enhancing functional capacity before surgery in order to compensate for the stress of surgery and postoperative recovery. There is growing interest in deploying pre-habilitation interventions prior to surgery. The aim of this study is to assess the impact of preoperative inspiratory muscle training on postoperative overall morbidity. The question is, whether inspiratory muscle training prior to elective abdominal surgery reduces the number of postoperative complications and their severity grade. METHODS: We describe a prospective randomized-controlled single-centre trial in a tertiary referral centre. The primary outcome is the Comprehensive Complication Index (CCI) at 90 days after surgery. The CCI expresses morbidity on a continuous numeric scale from 0 (no complication) to 100 (death) by weighing all postoperative complications according to the Clavien-Dindo classification for their respective severity. In the intervention group, patients will be instructed by physiotherapists to perform inspiratory muscle training containing of 30 breaths twice a day for at least 2 weeks before surgery using Power®Breathe KHP2. Depending on the surgical schedule, training can be extended up to 6 weeks. In the control group, no preoperative inspiratory muscle training will be performed. After the operation, both groups receive the same physiotherapeutic support. DISCUSSION: Existing data about preoperative inspiratory muscle training on postoperative complications are ambiguous and study protocols are often lacking a clear design and a clearly defined endpoint. Most studies consist of multi-stage concepts, comprehensively supervised and long-term interventions, whose implementation in clinical practice is hardly possible. There is a clear need for randomized-controlled studies with a simple protocol that can be easily transferred into clinical practice. This study examines the effortless adjustment of the common respiratory physiotherapy from currently postoperative to preoperative. The external measurement by the device eliminates the diary listing of patients' performances and allows the exercise adherence and thus the effect to be objectively recorded. TRIAL REGISTRATION: ClinicalTrials.gov NCT04558151 . Registered on September 15, 2020.

Artificial intelligence for detection of microsatellite instability in colorectal cancer-a multicentric analysis of a pre-screening tool for clinical application.

BACKGROUND: Microsatellite instability (MSI)/mismatch repair deficiency (dMMR) is a key genetic feature which should be tested in every patient with colorectal cancer (CRC) according to medical guidelines. Artificial intelligence (AI) methods can detect MSI/dMMR directly in routine pathology slides, but the test performance has not been systematically investigated with predefined test thresholds. METHOD: We trained and validated AI-based MSI/dMMR detectors and evaluated predefined performance metrics using nine patient cohorts of 8343 patients across different countries and ethnicities. RESULTS: Classifiers achieved clinical-grade performance, yielding an area under the receiver operating curve (AUROC) of up to 0.96 without using any manual annotations. Subsequently, we show that the AI system can be applied as a rule-out test: by using cohort-specific thresholds, on average 52.73% of tumors in each surgical cohort [total number of MSI/dMMR = 1020, microsatellite stable (MSS)/ proficient mismatch repair (pMMR) = 7323 patients] could be identified as MSS/pMMR with a fixed sensitivity at 95%. In an additional cohort of N = 1530 (MSI/dMMR = 211, MSS/pMMR = 1319) endoscopy biopsy samples, the system achieved an AUROC of 0.89, and the cohort-specific threshold ruled out 44.12% of tumors with a fixed sensitivity at 95%. As a more robust alternative to cohort-specific thresholds, we showed that with a fixed threshold of 0.25 for all the cohorts, we can rule-out 25.51% in surgical specimens and 6.10% in biopsies. INTERPRETATION: When applied in a clinical setting, this means that the AI system can rule out MSI/dMMR in a quarter (with global thresholds) or half of all CRC patients (with local fine-tuning), thereby reducing cost and turnaround time for molecular profiling.

Experiences with the Kono-S anastomosis in Crohn's disease of the terminal ileum-a cohort study.

PURPOSE: The most frequent long-term complication after ileocecal resection in Crohn's disease is anastomotic recurrence and subsequent stenosis. Recurrence typically begins at the site of the anastomosis, raising the question of whether the surgical technique of the anastomosis could affect recurrence rates. Kono-S anastomosis is a hand-sewn antimesenteric functional end-to-end anastomosis that offers a wide lumen that is well accessible for endoscopic dilatation. The purpose of our study is to review the rate of postoperative complications almost 2 years after the introduction of this technique. MATERIALS AND METHODS: This is a prospective single-center cohort study of all consecutive patients with Crohn's disease undergoing ileocecal resection. Patients' characteristics as well as specific data for the surgical procedure and short-term outcome were evaluated. RESULTS: Thirty patients were operated for Crohn's disease of the terminal ileum (n = 24) or anastomotic recurrence (n = 6). Postoperative complications with a Clavien-Dindo Score ≥ IIIb were observed in three patients. One patient showed a hemorrhage and underwent surgical hemostasis. Two patients developed anastomotic leakage; in both cases, ileostomy was created after resection of the anastomosis. The median hospital stay was 9 days (IQR 7-12). A comparison with a historic group of conventionally operated patients of our hospital revealed no differences in short-term results except for the duration of surgery. CONCLUSION: The Kono-S anastomosis is associated with acceptable short-term results, complications, and recurrence rates comparable with the established anastomotic techniques. Longer operation times are observed, but the few published studies concerning long-term recurrence are promising.

Resection enterostomy versus Hartmann's procedure for emergency colonic resections.

BACKGROUND: If a primary anastomosis is considered too risky after emergency colon resection either a resection enterostomy or an end stoma with closure of the distal bowel (Hartmann's procedure) is possible. This study analyzes the rate of restoration of intestinal continuity and other surgical outcomes after resection enterostomy placement versus Hartmann's procedure for emergency colon resections. METHODS: All patients who underwent emergency colorectal resections between August 2009 and June 2014 at the University Medical Center Mannheim were reviewed in regard to therapeutic approach, rate of restoration of bowel continuity, and surgical morbidity after the primary operation and after reversal surgery. RESULTS: Fifty-five patients in whom both studied interventions would have been technically feasible were further analyzed. The rate of revisional surgery was significantly higher in the resection enterostomy cohort after the primary operation. There were no significant differences regarding morbidity, mortality, and the rate of restoration of intestinal continuity. Overall, bowel continuity could be restored in 63% (29/46) of the surviving patients. The median time of surgery of the initial as well as of the reversal surgery was significantly longer in the Hartmann's group. Five of 13 patients underwent protective ileostomy placement in the Hartmann's group at the time of the reversal (vs. none in the resection enterostomy group). CONCLUSIONS: The bowel continuity can be restored in the majority of patients after emergency colonic resection. Conclusive evidence which surgical option should be preferred when a primary anastomosis is considered too risky-Hartmann's procedure or resection enterostomy-is still lacking.

Laparoscopic ventral mesh rectopexy in complex pelvic floor disorder.

AIM: For the treatment of complex pelvic organ prolapse, many different surgical procedures are described without any comparative studies available. Laparoscopic ventral mesh rectopexy after D'Hoore is one of the methods, which is publicized to treat patients with symptomatic rectocele, enterocele and rectal prolapse. METHOD: All patients who received ventral mesh rectopexy since 07/10 for symptomatic rectocele, enterocele and possible rectal prolapse I ° or II ° in terms of a complex pelvic floor disorder were included in this follow-up study. The Wexner score for incontinence was recorded (range 0-20), the constipation score of Herold (r6-30) was evaluated as well as supplementary questions compiled by D'Hoore concerning outlet symptoms (r0-20). In addition, the quality of life (SF-12) was requested. RESULTS: Thirty-one women were operated in the period, and 27 were eligible to be included in the present study. Median follow-up was 22 months (2-39). The preoperative Wexner score was in median 8 (0-20), going down to 6 (0-20) without significance (p = 0.735). The constipation score decreased significantly from median 14 (9-21) to 11 (6-25) (p = 0.007). The median score after D'Hoore was preoperatively 8 (4-16) and 4.5 (0-17) postoperatively (p = 0.004). The SF-12 values were preoperatively significantly reduced compared to the normal population; postoperatively, they equalized. CONCLUSION: Two years after laparoscopic ventral mesh rectopexy, constipation and quality of life improve significantly in patients with complex pelvic organ prolapse. The grade of incontinence remains essentially the same, but was not the dominant clinical problem in the treated patients of our study. STATEMENT: The improvement in constipation and quality of life after laparoscopic ventral mesh rectopexy for obstructive defecation is encouraging. However, the impact on sexual life differs; some patients improve but a relevant number reports a change for the worse.

[Surgery in Crohn's disease]. / Chirurgie beim M. Crohn.

Surgical treatment is primarily used to treat complications of Crohn's disease but also to improve the quality of life. An adequate preoperative preparation including improvement of the nutritional status, weaning off or stopping immunosuppressive medication and preoperative drainage of abscesses can decrease the complication rate. With the exception of when neoplasia is present, bowel-sparing techniques (e. g. strictureplasty and limited resection) are now standard, which has resulted in a low risk of short bowel syndrome. The laparoscopic approach is possible for most indications even in the case of recurrent disease, in primary ileocecal resection the laparoscopic approach has been shown to be superior to the open approach. None of the available techniques for anastomotic reconstruction of the bowels has been shown to be superior. A drainage seton is a good option to retain the quality of life in complex fistulas and reconstructive repair should only be considered when the rectum is free from inflammation.

Ischemic and injured bowel evaluation by Fluorescence imaging.

AIM: Although fluorescence has been proposed for estimation of bowel perfusion decades ago it is still not widely used. In emergency situations like mesenteric ischemia, fluorescence might give objective criteria to evaluate the perfusion and guide the decisions of surgeons. METHOD: The use of near-inrafrared angiography by PinPoint (Novadaq) in a serial of four emergency situations of acute mesenteric ischemia has been evaluated in a university hospital setting. RESULTS: The use of the near-infrared tool is in emergency situations easy to handle and little time-consuming. The angiography showed clearly the perfusion in regions that were not estimated as recoverable by the surgeons. In one of the cases a significant amount of bowel could be spared by use of the system. CONCLUSION: Although the assessment of the perfusion with the applied system is comprehensible, it would be desirable to evaluate a threshold level in order to further objectify it. While the surgeons who used the tool were subjectively assured by the expressiveness it would need a randomized and maybe experimental setting to evaluate objectively the amount of spared bowel length.

Does the Addition of Cetuximab to Radiochemotherapy Improve Outcome of Patients with Locally Advanced Rectal Cancer? Long-Term Results from Phase II Trials.

Purpose. The addition of cetuximab to radiochemotherapy (RCT) failed to improve complete response rates in locally advanced rectal cancer (LARC). We report the long-term results in patients treated within two sequential clinical trials. Methods. Patients receiving neoadjuvant RCT using capecitabine and irinotecan (CapIri) within a phase I/II trial or CapIri + cetuximab within a phase II trial were evaluated for analysis of disease-free survival (DFS) and overall survival (OS). KRAS exon 2 mutational status had been analyzed in patients receiving cetuximab. Results. 37 patients from the CapIri trial and 49 patients from the CapIri-cetuximab treatment group were evaluable. Median follow-up time was 75.2 months. The 5-year DFS rate was 82% (CapIri) and 79% (CapIri-cetuximab) (P = 0.62). The median OS was 127.4 months. 5-year OS was 73% for both groups (CapIri and CapIri-cetuximab) (P = 0.61). No significant difference in DFS (P = 0.86) or OS (P = 0.39) was noticed between patients receiving CapIri and those receiving CapIri-cetuximab with KRAS wild-type tumors. Conclusions. As the addition of cetuximab did not improve neither DFS nor OS it should not play a role in the perioperative treatment of patients with LARC, not even of patients with (K)RAS WT tumors.

Impaired continence function five years after intensified chemoradiation in patients with locally advanced rectal cancer.

AIMS: While the influence on survival is only seen in patients with complete regression after neoadjuvant treatment in locally advanced rectal cancer the impairment of the continence capacity weighs even more for patients with little oncological benefit. METHODS: Patients treated with intensified preoperative radiochemotherapy patients treated only by TME surgery were asked five years after treatment to complete the Wexner and SF-12 quality of life questionnaire. RESULTS: 25 after neoadjuvant treatment had a median Wexner score of 14 [3-20] after 63 [42-78] months. Histopathological stage or grade of regression did not influence the Wexner score (p = 0.76, resp. p = 0.9). 12% describe themselves as being permanently continent; 40% are stool incontinent "always" or "most of the time". 68% are always wearing pads. 29 patients after TME only showed a median Wexner score of 5 [range 0-17] after 66 months [26-133]. SF-12 showed significantly lower values in physical (p = 0.02) as well as mental summary scales (p = 0.015) in patients after RCTX while patients after radical surgery showed no difference to the norm population. CONCLUSION: This study shows that continence is significantly worse five years after neoadjuvant treatment. Moreover, patients after neoadjuvant treatment and surgery have impaired quality of life compared to norm population. These results may contribute to the discussion of only applying neoadjuvant chemoradiation selectively in patients with advanced rectal cancer.

Influence of type of mesh fixation in endoscopic totally extraperitoneal hernia repair (TEP) on long-term quality of life.

INTRODUCTION: Laparoscopic total extraperitoneal mesh repair (TEP) of inguinal hernia has become well accepted with low recurrence and high patient satisfaction rates. However, inguinal pain has also been reported. Source of this pain has been suggested to be the fixation method, especially the use of tacks. Introduction of fibrin glue and absorbable tacks were suggested to lower chronic pain and inguinal discomfort rates. This study analyses the different methods of fixation. PATIENTS AND METHODS: 201 patients were analysed. Primary end-points were patients' satisfaction, health-related quality of life, and specific inguinal conditions (e.g. pulling, swelling, troubles at coughing). Secondary endpoints were duration of operation, length of hospital stay, and material costs. RESULTS: Fibrin glue was used in 101 patients and tacks in 100 patients, in 21 of those absorbable tacks. Patients were fully satisfied with the results in more than 90%, irrespective of the fixation method. Health-related quality of life along the SF-12(®) questionnaire attested no differences. Inguinal pulling occurred significantly more often after fibrin glue (25.7 %) than after tack fixation (11 %; p = 0.026), whereas no differences in the other specific inguinal sensations occurred. CONCLUSION: Mesh fixation in TEP can be performed either by tacks or by fibrin glue with similar long-term results concerning satisfaction, health-related quality of life, and pain. No advantage of fibrin glue could be found, in fact, a higher percentage of patients had inguinal pulling and burning sensations after the use of fibrin glue. The use of absorbable tacks showed no advantage.

[Transabdominal procedures for functional bowel diseases]. / Transabdominelle Verfahren bei funktionellen Darmerkrankungen.

Incontinence and constipation can occur in cases of pelvic floor dysfunction. Purely morphological changes without severe clinical symptoms are not an indication for surgery. Abdominal operations can be classified into procedures with dorsal (with or without bowel resection and with or without mesh implantation) and procedures with ventral rectopexy (with mesh). With respect to constipation and incontinence suture rectopexy alone is inferior to all other procedures. Dorsal and ventral mesh rectopexy and resection rectopexy are all comparable with respect to improvement of incontinence. Ventral rectopexy without dorsal mobilization and resection rectopexy are superior to mesh rectopexy with respect to constipation. Due to poor evidential status treatment is carried out from a pragmatic viewpoint.

Intensified neoadjuvant chemoradiotherapy in locally advanced rectal cancer -- impact on long-term quality of life.

AIMS: In spite of advances in rectal cancer surgery and the use of preoperative 5-fluorouracil-(5-FU) based chemoradiotherapy (CRT) in stage II and III disease distant metastases still occur in about 35-40% of the patients. Intensified preoperative CRT (ICRT) using other drugs in conjunction with 5-FU has been investigated in order to improve the pathological complete remission (pCR) rate and thereby prognosis of patients with locally advanced rectal cancer. However, acute toxicity, especially diarrhea, was reported to be high and no improvement in pCR rates has been observed in randomized trials. Long-term results of these trials are pending. In the present analysis we investigated the impact of ICRT on health related quality of life and long term toxicity. METHODS: The present study included 119 patients with locally advanced rectal cancer who underwent neoadjuvant CRT followed by surgery within controlled clinical trials. Patients received ICRT (n = 83) or standard CRT (n = 36). Evaluation of HRQoL was performed using EORTC QLQ-C30 and QLQ-CR29 questionnaires. RESULTS: The overall rating of global health status/QLQ scale of the EORTC QLQ-C30 questionnaire was identical in both patient groups but patients in the CRT group showed better results in four out of nine function scales. Concerning symptom scales, patients in the CRT arm exhibited significantly less diarrhea (p = 0.028) and less disorders with taste (0.042). CONCLUSIONS: This data suggests that higher gastrointestinal acute toxicity caused by ICRT might lead to a higher risk of long-term deterioration of "gastrointestinal QoL". Future results of randomized trials investigating ICRT versus CRT should be discussed in the light of long-term QoL data.

Local excision of early rectal cancer: is transanal endoscopic microsurgery an alternative to radical surgery?

OBJECTIVE: Transanal endoscopic microsurgery (TEM) allows locally complete excision of rectal neoplasms and provides an alternative to conventional surgery for benign tumours. However, its role in the curative treatment of invasive carcinoma is controversial. This paper examines the results of TEM compared with radical surgery (RS) for T1 rectal cancer. METHODS: 51 patients with T1 rectal tumours treated by RS, or local excision by means of TEM were included. The following parameters were evaluated: operating time, blood loss, hospital stay and complications, as well as local recurrence rate and survival. RESULTS: 17 patients were treated by RS and 34 by TEM. Operative time, blood loss, and duration of hospitalization were significantly lower in the TEM group compared with the RS group. In the RS group there were 4 patients with complications which required an operative revision (23.5%), compared to 1 reintervention (2.9%) in the TEM group. Local recurrence was 5.88% (n = 2) in the TEM group compared with none after RS (p = 0.547). The overall survival and disease-free survival showed not significant statistical differences between both groups (p = 0.59; p = 1.000, resp.). CONCLUSIONS: Although local recurrence was only observed after local excision, patients treated with TEM showed no significant differences in terms of overall survival and disease-free survival compared with patients who underwent RS. Inasmuch as local excision represents a minimally invasive technique in terms of morbidity, mortality and functional outcome, TEM should be offered as a valid option for well selected patients with early rectal cancer.

Local excision of early rectal cancer: is transanal endoscopic microsurgery an alternative to radical surgery?

Objetivo: la cirugía transanal endoscópica (TEM) permite la resección completa de neoplasias de recto siendo una alternativa a la cirugía convencional para tumores benignos. Existe controversia sobre su papel en el tratamiento curativo del cáncer de recto. Esta publicación compara los resultados entre la resección radical (RS) y la exéresis local vía TEM del cáncer de recto en estadio precoz. Métodos: se evaluaron 51 pacientes con neoplasia de recto cuya infiltración se limitaba a la submucosa (T1) y que fueron tratados mediante RS o TEM. Se evaluaron los siguientes parámetros: tiempo quirúrgico, pérdidas sanguíneas, estancia hospitalaria y complicaciones así como recidiva local y supervivencia. Resultados: 17 pacientes fueron tratados mediante RS y 34 vía TEM. El tiempo quirúrgico, el posible sangrado y la estancia hospitalaria fueron significativamente menores en el grupo TEM. En el grupo RS, 4 pacientes presentaron complicaciones que obligaron a una revision quirúrgica (23,5%), comparado con sólo 1 reintervención (2,9%) en grupo TEM. La recidiva local sólo fue observada en dos pacientes (5,88%) del grupo TEM (p = 0,547). La supervivencia global y libre de enfermedad no mostró diferencias estadísticamente significativas entre ambos grupos (p = 0,59 y p = 1,000, respectivamente). Conclusiones: si bien el grupo tratado con TEM advirtió dos recidivas locales, no se observaron diferencias en términos de supervivencia global y libre de enfermedad entre los dos grupos analizados. En tanto la resección local representa una técnica mínimamente invasiva en términos de morbilidad, mortalidad y resultados funcionales, la exéresis mediante TEM debe ser ofertada como una opción válida para pacientes muy bien seleccionados con carcinoma de recto en estadio precoz(AU)

Objective: transanal endoscopic microsurgery (TEM) allows locally complete excision of rectal neoplasms and provides an alternative to conventional surgery for benign tumours. However, its role in the curative treatment of invasive carcinoma is controversial. This paper examines the results of TEM compared with radical surgery (RS) for T1 rectal cancer. Methods: 51 patients with T1 rectal tumours treated by RS, or local excision by means of TEM were included. The following parameters were evaluated: operating time, blood loss, hospital stay and complications, as well as local recurrence rate and survival. Results: 17 patients were treated by RS and 34 by TEM. Operative time, blood loss, and duration of hospitalization were significantly lower in the TEM group compared with the RS group. In the RS group there were 4 patients with complications which required an operative revision (23.5%), compared to 1 reintervention (2.9%) in the TEM group. Local recurrence was 5.88% (n = 2) in the TEM group compared with none after RS (p = 0.547). The overall survival and disease-free survival showed not significant statistical differences between both groups (p = 0.59; p = 1.000, resp.). Conclusions: although local recurrence was only observed after local excision, patients treated with TEM showed no significant differences in terms of overall survival and disease-free survival compared with patients who underwent RS. Inasmuch as local excision represents a minimally invasive technique in terms of morbidity, mortality and functional outcome, TEM should be offered as a valid option for well selected patients with early rectal cancer(AU)

Tumor response to neoadjuvant chemoradiation in rectal cancer: predictor for surgical morbidity?

BACKGROUND: Increasing the rate of pathological complete remissions after neoadjuvant chemoradiation of rectal cancer has become a strategy to further improve the long-term oncological outcome of patients. This report evaluates the influence of preoperative intensified radiochemotherapy on the rate and outcome of surgical complications. MATERIALS AND METHODS: Patients with primary rectal cancer at stages cT3/4cNx or N+ without metastasis were preoperatively treated either with capecitabine and irinotecan or with capecitabine, irinotecan and ceutximab with a concurrent radiation (50.4 Gy). Surgery was scheduled 4-7 weeks after completion of the chemoradiation. Perioperative complications were prospectively documented during the patient's hospital stay. RESULTS: Fifty-nine patients (median age 60; male/female: 46/13) undergoing surgery at a single center were analysed. The median distance of the tumour from the dentate line was 5 cm. The operations performed were low anterior resection (n=45), Hartmann's procedure (n=4) and abdominoperineal resection (n=10). Total mesorectal excision with R0-resection was accomplished in all but one patients. Histopathological regression was described in four grades (0-3) as defined by the Japanese Society for Cancer of the Colon and Rectum. Tumors were called major responsive when assigned to the regression grades 3 or 2, and minor or nonresponsive at regression grades 1 or 0. In total, 33 patients (55.9%) had a regression grade 2 or 3. Among them, 12 patients showed a pathological complete response without any residual cancer cell (20.3%). Seven out of 45 patients (15.5%) with sphincter-preserving surgery suffered from suture breakdown; they all had previously shown a major response of the resected tumor. Two of them died during the hospital stay. CONCLUSIONS: While in general, patients undergoing neoadjuvant intensified treatment suffer from a slight increase in surgical complications, this is markedly enhanced in patients with good treatment responses. Our results underline the oncological benefit of intensified neoadjuvant chemoradiation, but the severity of complications in low rectal anastomosis of patients with good response after neoadjuvant therapy should alert surgeons and oncologists.

Retrorectal tumors: excision by transanal endoscopic microsurgery.

Tumours within the retrorectal space are uncommon. Due to their rarity and diverse symptoms they are often misdiagnosed or mistreated. We report three cases of women presenting a variety of symptoms including increased rectal pain, recurrent abscesses/fistulas and constipation. Upon clinical examination and further investigations using MR scan, endorectal ultrasound and endoscopy, a retrorectal mass was suspected in all three cases. In order to achieve a complete excision of the tumor while minimizing trauma, transanal endoscopic microsurgery (TEM) was performed. The histology of the multicystic tumor revealed in all three cases a tailgut cyst. As far as we know this is the first report describing the use of TEM for surgical treatment of tumors located in the retrorectal space.

Retrorectal tumors: Excision by transanal endoscopic microsurgery

Los tumores del espacio retrorrectal representan una patologíapoco frecuente. Debido a su singularidad incluida la amplia sintomatologíacon la que debutan, son a veces causa de diagnósticos ytratamientos erróneos.Esta nota clínica informa sobre tres casos surgidos en mujerescon variada sintomatología donde se incluía dolor rectal, enfermedadsupurada anal recidivada y estreñimiento. La masa retrorrectalfue diagnosticada tras exploración clínica y pruebas de imagendonde se incluía ecografía endorrectal, resonancia magnética yendoscopia.La exéresis quirúrgica se realizó mediante microcirugía transanalendoscópica, en un intento de combinar una visualización mejoradade la disección y una técnica mínimamente invasiva. Laanatomía patológica demostró en los tres casos quistes caudales.Esta nota clínica describe por primera vez en la literatura la resecciónquirúrgica de tumores localizados en el espacio retrorrectalmediante microcirugía transanal endoscópica

Tumours within the retrorectal space are uncommon. Due totheir rarity and diverse symptoms they are often misdiagnosed ormistreated.We report three cases of women presenting a variety of symptomsincluding increased rectal pain, recurrent abscesses/fistulasand constipation. Upon clinical examination and further investigationsusing MR scan, endorectal ultrasound and endoscopy, a retrorectalmass was suspected in all three cases.In order to achieve a complete excision of the tumor while minimizingtrauma, transanal endoscopic microsurgery (TEM) wasperformed. The histology of the multicystic tumor revealed in allthree cases a tailgut cyst. As far as we know this is the first reportdescribing the use of TEM for surgical treatment of tumors locatedin the retrorectal space (AU)

A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer.

We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial. Patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive irinotecan (50 mg m(-2) weekly) and capecitabine (500 mg m(-2) bid days 1-38) with a concurrent RT dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the completion of chemoradiation. A total of 36 patients (median age 62 years; m/f: 27:9) including three patients with local recurrence were enclosed onto the trial. The median distance of the tumour from the anal verge was 5 cm. The main toxicity observed was (NCI-CTC grades 1/2/3/4 (n)): Anaemia 23/9/-/-; leucocytopenia 12/7/7/2, diarrhoea 13/15/4/-, nausea/vomiting 9/10/2/-, and increased activity of transaminases 3/3/1/-. One patient had a reversible episode of ventricular fibrillation during chemoradiation, most probably caused by capecitabine. The relative dose intensity was (median/mean (%)): irinotecan 95/91, capecitabine 100/92). Thirty-four patients underwent surgery (anterior resection n=25; abdomino-perineal resection n=6; Hartmann's procedure n=3). R0-resection was accomplished in all patients. Two patients died in the postoperative course from septic complications. Pathological complete remission was observed in five out of 34 resected patients (15%), and nine patients showed microfoci of residual tumour (26%). After a median follow-up of 28 months one patient had developed a local recurrence, and five patients distant metastases. Three-year overall survival for all patients with surgery (excluding three patients treated for local relapse or with primary metastatic disease) was 80%. In summary, preoperative chemoradiation with CapIri-RT exhibits promising efficacy whereas showing managable toxicity. The local recurrence and distant failure rates observed after a median 28 months are low compared with standard 5-fluorouracil based therapy.

[Neoadjuvant treatment of rectal cancer: towards an individualised therapy]. / Neoadjuvante Therapie beim Rektumkarzinom: Auf dem Weg zur individuellen Therapie.

Neoadjuvant radiation or chemoradiation followed by oncological resection is the current treatment of choice for locally advanced rectal cancer. Profound diagnostics are mandatory to stratify patients for neoadjuvant treatment or primary surgery. Here, magnetic resonance tomography most probably will become the standard modality due to its ability to predict involvement of the circumferential resection margin during surgery. While the initiation of chemoradiation in T4 rectal cancer and patients with distal tumours potentially undergoing sphincter-preserving surgery is unequivocal, the treatment of choice for the remaining patients is undecided. Here, short-term radiotherapy (5 x 5 Gy) competes with chemoradiation of different intensity. In surgical oncology, minimally invasive surgery of the rectum needs further evidence before it can be accepted as an equivalent. Finally, the increase in multimodality treatment will ultimately increase the incidence of late functional sequelae which, up to now, are underrepresented in most reports due to the priority of oncological results. Since responders to neoadjuvant treatment are the ones who benefit most from these therapies, research related to prediction of treatment response has a fundamental role.

Aldosterone blunts human baroreflex sensitivity by a nongenomic mechanism.

BACKGROUND: Impaired baroreflex sensitivity (BRS) is a negative predictive factor of mortality in cardiovascular disease. Aldosterone has been shown to decrease BRS in humans and animal models. However, the mode of aldosterone action, whether genomic or nongenomic has not been determined. Therefore, we conducted a clinical study to examine whether BRS, as measured by the phenylephrine method, is impaired in humans by aldosterone by a nongenomic mechanism. METHODS: In a randomised, double-blinded, fourfold cross-over trial in 16 healthy male volunteers, BRS was tested 15 minutes after initiation of a continuous infusion of aldosterone (3 microg/minute) or placebo. 6 hours earlier, this period was preceded by an injection of either canrenoate (400 mg) or placebo. RESULTS: BRS was 34.6 +/- 4.7 ms/mm Hg in the placebo/placebo period. It was significantly blunted in the placebo/aldosterone (25.5 +/- 1.8 ms/mm Hg) as well as in the canrenoate/placebo (24.0 +/- 1.5 ms/mm Hg) and the canrenoate/aldosterone (25.4 +/- 2.5 ms/mm Hg) periods. CONCLUSION: These data suggest that the decreased BRS caused by aldosterone is due to a rapid, thus presumably nongenomic mechanism, as these effects occur in a time frame that excludes genomic aldosterone effects at large. The mineralocorticoid receptor (MR) antagonist canrenoate does not block these effects, but blunts BRS by itself.