The other colon cancer: a population-based cohort study of appendix tumour trends and prognosis.

AIM: Appendiceal neoplasms are rare subtypes of colorectal tumours that mainly affect younger patients some 20 years earlier than other colon tumours. The aim of this study was to gain more insight into the histological subtypes of this rare disease and include cases previously excluded, such as mucinous neoplasia. METHOD: The cohort study included 1097 patients from the Munich Cancer Registry (MCR) diagnosed between 1998 and 2020. Joinpoint analysis was used to determine trend in incidence. Baseline demographic comparisons and survival analyses using competing risk and univariate/multivariate methods were conducted according to tumour histology: adenocarcinoma (ADENO), neuroendocrine neoplasia (NEN), mixed adeno-neuroendocrine carcinoma (MANEC), and low- (LAMN) and high-grade mucinous neoplasia (HAMN). RESULTS: Up to 2016 the number of cases increased significantly [annual per cent change (APC) = 6.86, p < 0.001] followed by a decline in the following years (APC = -14.82, p = 0.014; average APC = 2.5, p = 0.046). Comparison of all patients showed that NEN (48.4%) and mucinous neoplasms (11.6%) had a considerably better prognosis than ADENO (36.0%) and MANEC (3.0%, p < 0.0001). A multivariate analysis within the NEN and ADENO subgroups revealed that further histological classification was not prognostically relevant, while older age and regional tumour spread at diagnosis were associated with a poor prognosis. ADENO histology with high tumour grade and appendectomy only was also associated with poorer survival. CONCLUSION: Appendiceal neoplasms are histologically heterogeneous; however, this diversity becomes less relevant compared with the marked difference from cancers of the remaining colon. The previously observed increase in cases appears to be abating; fewer cases of appendicitis and/or appendectomies or changes in histopathological assessment may be behind this trend.

Patients with colorectal cancer and brain metastasis: The relevance of extracranial metastatic patterns predicting time intervals to first occurrence of intracranial metastasis and survival.

The aim of the study was to investigate the predictive impact of extracranial metastatic patterns on course of disease and survival in patients with colorectal cancer (CRC) and brain metastasis (BM). A total of 228 patients (134 male [59%], 94 female [41%]) with histologically proven CRC and BM were classified into different groups according to extracranial metastatic patterns. Time intervals to metastatic events and survival times from initial CRC diagnosis, extracranial and intracranial metastasis were analyzed. Extracranial organs mostly affected were liver (102 of 228 [44.7%]) and lung (96 of 228 [42.1%]). Liver and lung metastases were detected in 31 patients (13.6%). Calculated over the entire course of disease, patients with lung metastasis showed longer overall survival (OS) than patients with liver metastasis or patients without lung metastasis (43.9 vs 34.6 [P = .002] vs 35.0 months [P = .002]). From the date of initial CRC diagnosis, lung metastasis occurred later in CRC history than liver metastasis (24.3 vs 7.5 months). Once lung metastasis was diagnosed, BM occurred faster than in patients with liver metastasis (15.8 vs 26.0 months; Δ 10.2 months). Accordingly, OS from the diagnosis of liver metastasis was longer than from lung metastasis (27.1 vs 19.6 months [P = .08]). Once BM was present, patients with lung metastasis lived longer than patients with liver metastasis (3.8 vs 1.1 months [P = .028]). Shortest survival times in all survival categories analyzed revealed patients with concurrent liver and lung metastasis. Patients with CRC and BM form a heterogeneous cohort where extracranial metastasis to liver or lungs predicts survival.

MRI-Based Use of Neoadjuvant Chemoradiotherapy in Rectal Carcinoma: Surgical Quality and Histopathological Outcome of the OCUM Trial.

BACKGROUND: Preoperative magnetic resonance imaging (MRI) allows highly reliable imaging of the mesorectal fascia (mrMRF) and its relationship to the tumor. The prospective multicenter observational study OCUM uses these findings to indicate neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma. METHODS: nCRT was indicated in patients with positive mrMRF (≤ 1 mm) in cT4 and cT3 carcinomas of the lower rectal third. RESULTS: A total of 527 patients (60.2%) underwent primary total mesorectal excision, and 348 patients (39.8%) underwent long-term nCRT followed by surgery. The mrMRF was involved in 4.6% of the primary surgery group and 80.7% of the nCRT group. Rates of resections within the mesorectal plane (90.8%), sparing of pelvic nerves on both sides (97.8%), and number of regional lymph nodes (95.3% with ≥ 12 lymph nodes examined) are indicative of high-quality surgery. Resection was classified as R0 in 98.3%, the pathological circumferential resection margin (pCRM) was negative in 95.1%. Patients in the nCRT group had more advanced carcinomas with a significantly higher rate of abdominoperineal excision. Independent risk factors for pCRM positivity were advanced stage (T4), metastatic lymph nodes, resection in the muscularis propria plane, and location in the lower third. CONCLUSIONS: The risk classification of rectal cancer patients by MRI seems to be highly reliable and allows the restriction of nCRT to approximately half of the patients with clinical stage II and III rectal carcinoma, provided there is a high-quality MRI diagnostic protocol, high-quality surgery, and standardized examination of the resected specimen.

Reducing Patient Burden and Improving Data Quality With the New Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire.

BACKGROUND: The Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire was developed in response to the need for a new, fast, and comprehensive tool for evaluating quality of life in patients who have colorectal cancer. Available surveys such as the SF-12, SF-36, Functional Assessment of Cancer Therapy-Colorectal, and European Organization for Research and Treatment of Cancer are either too general to be informative or too lengthy to complete. OBJECTIVE: The aim was to validate the Cleveland Clinic Foundation Colorectal Quality of Life Questionnaire. DESIGN: Data were obtained as part of a prospective randomized controlled trial. SETTINGS: This was a worldwide multicenter study with 2 domestic and 5 international locations. PATIENTS: This study randomly assigned 190 patients between the ages of 18 and 80 undergoing surgery for low rectal cancer. Of those randomly assigned, 142 with partially complete surveys were analyzed for selection bias and acceptability, and 95 with complete surveys were analyzed for survey validity. INTERVENTIONS: Patients received either a J-pouch, side-to-end anastomosis, or straight anastomosis. MAIN OUTCOME MEASURE: The study evaluated survey validity measures such as standardized Cronbach α for internal consistency and Spearman correlation coefficients for construct validity, convergent validity, and responsiveness. Univariate analyses were used to assess discriminative validity. RESULTS: Sufficient acceptability, construct, and convergent validity and responsiveness were achieved. All scores showed great internal consistency (Cronbach α >0.8). Superior discriminative ability was demonstrated by significant differences (p < 0.05) in 2 of 7 scores between neoadjuvant treatment groups, and in 6 of 7 scores between complication groups, none of which were detected by the SF-12 or Functional Assessment of Cancer Therapy-Colorectal surveys. LIMITATIONS: Limitations included a small sample size, cultural differences, and failure to assess test-retest ability of the questionnaire. CONCLUSIONS: The Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire is an efficient and reliable quality-of-life measure that better incorporates factors specific to colorectal cancer surgery. See Video Abstract at http://links.lww.com/DCR/B155. REDUCIENDO LA CARGA AL PACIENTE Y MEJORANDO LA CALIDAD DE DATOS CON EL NUEVO CUESTIONARIO DE CALIDAD DE VIDA EN CÁNCER COLORRECTAL DE CLEVELAND CLINIC (CCF-CAQL): El cuestionario de calidad de vida en cáncer colorrectal de Cleveland Clinic se desarrolló en respuesta a la necesidad de una herramienta nueva, rápida e integral para evaluar la calidad de vida en pacientes con cáncer colorrectal. Los cuestionarios disponibles como SF-12, SF-36, FACT-C y EORTC son demasiado generales para ser informativas o demasiado largas para completar.El objetivo fue validar el cuestionario de calidad de vida colorrectal de la Cleveland Clinic Foundation.Los datos se obtuvieron como parte de un ensayo prospectivo aleatorizado y controlado.Este fue un estudio multicéntrico mundial con dos sedes nacionales y cinco internacionales.Este estudio aleatorizó a 190 pacientes entre las edades de 18 y 80 sometidos a cirugía por cáncer rectal bajo. De aquellos aleatorizados, 142 con encuestas parcialmente completas se analizaron para determinar el sesgo de selección y la aceptabilidad, y 95 con encuestas completas se analizaron para determinar la validez de la encuesta.Los pacientes recibieron un reservorio en J, anastomosis latero-terminal o anastomosis termino-terminal.El estudio evaluó medidas de validez de la encuesta, como el Alfa de Cronbach estandarizado para la consistencia interna y los coeficientes de correlación de Spearman para la validez de construcción, la validez de convergencia y la capacidad de respuesta. Se utilizaron análisis univariados para evaluar la validez discriminativa.Se obtuvo suficiente aceptabilidad, construcción, validez de convergencia, y capacidad de respuesta. Todos los puntajes mostraron una gran consistencia interna (alfa de Cronbach > 0.8). Una capacidad discriminativa superior fue demostrada por diferencias significativas (p < 0.05) en dos de siete puntajes entre grupos de tratamiento neoadyuvante, y en seis de siete puntajes entre grupos de complicaciones, ninguno de los cuales fue detectado por SF-12 o FACT-C.Las limitaciones incluyeron un tamaño de muestra pequeño, diferencias culturales y la falta de evaluación de la confiabilidad test-retest del cuestionario.El Cuestionario de Calidad de Vida en Cáncer Colorrectal de Cleveland Clinic es una medida de calidad de vida eficiente y confiable que incorpora mejor factores específicos asociados a la cirugía de cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B155.

Better Function With a Colonic J-Pouch or a Side-to-end Anastomosis?: A Randomized Controlled Trial to Compare the Complications, Functional Outcome, and Quality of Life in Patients With Low Rectal Cancer After a J-Pouch or a Side-to-end Anastomosis.

BACKGROUND INFORMATION: We aimed to compare prospectively the complications and functional outcome of patients undergoing a J-Pouch (JP) or a side-to-end anastomosis (SE) for treatment of low rectal cancer at a 2-year time point after resection for rectal cancer. METHODS: A multicenter study was conducted on patients with low rectal cancer who were randomized to receive either a JP or SE and were followed for 24 months utilizing SF-12 and FACT-C surveys to evaluate the quality of life (QOL). Fecal incontinence was evaluated using the Fecal Incontinence Severity Index (FISI). Bowel function, complications, and their treatments were recorded. RESULTS: Two hundred thirty-eight patients (165 males) were randomized with 167 final eligible patients, 80 in the JP group and 87 in the SE group for evaluation. The mean age at surgery was 61 (range 29 to 82) years. The overall mean recurrence rate was 12 of 238, 5% and similar in both groups. COMPLICATIONS: Overall, 37 of 190 (19%) patients reported complications, 14 of these were Clavien Dindo Grade 3b and 2 were 3a: leak 3 (2 JP,1 SE), fistula 4 (1 JP, 3 SE), small bowel obstruction 4 (3JP, 1 SE), stricture 4 (3 SE, 1 SA), pouch necrosis 2 (JP), and wound infection 5 (2 JP, 3 SE). QOL scores using either instrument between the 2 groups at 12 and 24 months were similar (P > 0.05). Bowel movements, clustering, and FISI scores were similar. CONCLUSION: At time points of 1 and 2 years after a JP or a SE for low rectal cancer, QOL, functional outcome, and complications are comparable between the groups. Although choosing a particular procedure may depend on surgeon/patient choice or anatomical considerations at the time of surgery, SE functions similar to JP and may be chosen due to the ease of construction.

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.

Pretherapeutic MRI for decision-making regarding selective neoadjuvant radiochemotherapy for rectal carcinoma: interim analysis of a multicentric prospective observational study.

PURPOSE: To study the accuracy of different cutoffs for an involved circumferential resection margin (CRM) compared with T and N categories measured by MRI as basis for selective application of neoadjuvant radiochemotherapy (nRCT) in rectal carcinoma. MATERIALS AND METHODS: In a prospective multicenter observational study involving 153 primarily operated patients, the preoperative results of MRI with pathohistological findings of resected specimens were compared. RESULTS: For a cutoff of ≤1 mm for involvement of the CRM, the accuracy of preoperative MRI was 90.9% (139/153). The negative predictive value was 98.5% (134/136). The four participating departments did not differ significantly. For a cutoff of >2 mm and >5 mm, the rates of false-positive findings increased significantly from 5% to 12% and 35% with a decrease in accuracy to 82% and 62%, respectively. In contrast, the accuracy in predicting T (69.3%) and N categories (61.4%) was much lower. CONCLUSION: The indication for nRCT should be based on the determination of the minimal distance of the tumor from mesorectal fascia with a cutoff point of >1 mm as measured by MRI.

Risk-Adapted Neoadjuvant Chemoradiotherapy in Rectal Cancer: Final Report of the OCUM Study.

PURPOSE: We investigated whether neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer can be restricted to those at high risk of locoregional recurrence (LR) without compromising oncological outcomes. PATIENTS AND METHODS: In a prospective multicenter interventional study, patients with rectal cancer (cT2-4, any cN, cM0) were classified according to the minimal distance between the tumor, suspicious lymph nodes or tumor deposits, and mesorectal fascia (mrMRF). Patients with a distance >1 mm underwent up-front total mesorectal excision (TME; low-risk group), whereas those with a distance ≤1 mm and/or cT4 and cT3 tumors in the lower rectal third received nCRT followed by TME surgery (high-risk group). The primary end point was 5-year LR rate. RESULTS: Of the 1,099 patients included, 884 (80.4%) were treated according to the protocol. A total of 530 patients (60%) underwent up-front surgery, and 354 (40%) had nCRT followed by surgery. Kaplan-Meier analyses revealed 5-year LR rates of 4.1% (95% CI, 2.7 to 5.5) for patients treated per protocol, 2.9% (95% CI, 1.3 to 4.5) after up-front surgery, and 5.7% (95% CI, 3.2 to 8.2) after nCRT followed by surgery. The 5-year rate of distant metastases was 15.9% (95% CI, 12.6 to 19.2) and 30.5% (95% CI, 25.4 to 35.6), respectively. In a subgroup analysis of 570 patients with lower and middle rectal third cII and cIII tumors, 257 (45.1%) were at low-risk. The 5-year LR rate in this group was 3.8% (95% CI, 1.4 to 6.2) after up-front surgery. In 271 high-risk patients (involved mrMRF and/or cT4), the 5-year rate of LR was 5.9% (95% CI, 3.0 to 8.8) and of metastases 34.5% (95% CI, 28.6 to 40.4); disease-free survival and overall survival were the worst. CONCLUSION: The findings support the avoidance of nCRT in low-risk patients and suggest that in high-risk patients, neoadjuvant therapy should be intensified to improve prognosis.

[Minimum volume requirements-perspective of a tertiary care hospital]. / Mindestmengen aus der Sicht einer Klinik der Schwerpunktversorgung.

BACKGROUND: The increase of minimum volumes for complex esophageal resections decided by the Federal Joint Committee (GBA) in Germany is currently the subject of intensive discussions. OBJECTIVE: To shed light on the effects of minimum volume requirements from the perspective of a tertiary care hospital. RESULTS: Strict adherence to the valid minimum volume requirements for esophageal surgery would significantly reduce the number of hospitals offering these procedures in Germany. The associated loss of revenue should not have any relevant negative economic consequences for most hospitals; however, the loss of complex esophageal surgery may result in a competitive disadvantage for these hospitals in times of shortage of qualified medical personnel. Another point of criticism is the assumption that the treatment quality can be recognized based solely on the numbers of patients. CONCLUSION: Despite the well-known volume-outcome relationship, minimum volume requirements do not define the lower limit of quality of surgical treatment. Therefore, additional evidence of treatment quality, such as structural or process quality as well as outcome parameters should be required, e.g. through certification. An obligatory synchronous certification could contribute to increasing the acceptance of minimum volume requirements in Germany.

Selection of patients with rectal cancer for neoadjuvant therapy using pre-therapeutic MRI - Results from OCUM trial.

PURPOSE: No consensus is available on the appropriate criteria for neoadjuvant chemoradiotherapy selection of patients with rectal cancer. The purpose was to evaluate the accuracy of MRI staging and determine the risk of over- and undertreatment by comparing MRI findings and histopathology. METHOD: In 609 patients of a multicenter study clinical T- and N categories, clinical stage and minimal distance between the tumor and mesorectal fascia (mrMRF) were determined using MRI and compared with the histopathological categories in resected specimen. Accuracy, sensitivity, specificity, positive predictive, and negative predictive value (NPV) were calculated. Overstaging was defined as the MRI category being higher than the histopathological category. mrMRF and circumferential resection margin (CRM) were judged as tumor free at a minimal distance > 1 mm. The chi-squared test or Fisher's exact test were used. P < 0.05 was considered significant. RESULTS: The T category was correct in 63.5% (386/608) of patients; cT was overstaged in 22.9% (139/608) and understaged in 13.5% (82/608). MRI accuracy for lymph node involvement was 56.5% (344/609); 22.2% (28/126) of patients with clinical stage II and 28.1% (89/317) with clinical stage III disease were diagnosed by histopathology as stage I. The accuracy for tumor free CRM was 86.5% (527/609) and the NPV was 98.1% (514/524). In 1.7% (9/524) mrMRF was false negative. CONCLUSION: MRI prediction of the tumor-free margin is more reliable than the prediction of tumor stage. MRF status as determined MRI should therefore be prioritized for decision making.

MRI-based indications for neoadjuvant radiochemotherapy in rectal carcinoma: interim results of a prospective multicenter observational study.

BACKGROUND: This study evaluated use of circumferential resection margin status in preoperative MRI (mrCRM) as an indication for neoadjuvant radiochemotherapy (nRCT) in rectal carcinoma patients. MATERIALS AND METHODS: In a multicenter prospective study, nRCT was given to patients with carcinoma of the middle rectum with positive mrCRM (≤1 mm), with cT3 low rectal carcinoma, and all patients with cT4 tumors. The short-term endpoints were pathologic pCRM (≤1 mm) as a strong predictor of local recurrence rate and the quality of total mesorectal excision according to the plane of surgery. These endpoints were compared in patients with and without nRCT. RESULTS: Of 230 patients that met the inclusion criteria, 96 (41.7%) received a long course of nRCT and 134 (58.3%) were primarily operated on. The pCRM was positive in 13 of 230 (5.7%) (primarily operated on, 2 of 134 [1.5%]; after nRCT, 11 of 96 [11%]). In 1 of 134 (0.7%) case, the mrCRM was falsely negative. Patients at participating centers varied in terms of preoperative stage but not in pCRM positivity (0%-13%, P = .340). The plane of surgery was mesorectal (good) in 209 of 230 (90.9%), intramesorectal (moderate) in 16 of 230 (7%), and the muscularis propria plane (poor) in 2.2% (5 of 230). CONCLUSIONS: Low pCRM positivity and the high quality of mesorectal excision support use of MRI-based nRCT in rectal carcinoma. nRCT was avoidable in 45% of patients with stage II and III disease without significant risk of undertreatment. Preoperative MRI thus allows identification of patients with high risk of local recurrence and use of selective nRCT.

The prognostic value of lymph node ratio in a population-based collective of colorectal cancer patients.

OBJECTIVE: We analyzed 3 previously identified cut-off values of lymph node ratios (0.17, 0.41, and 0.69) in a large population-based collective of patients with colorectal cancer for their prognostic value. SUMMARY BACKGROUND DATA: The lymph node ratio (LNR) (relation of tumor-infiltrated to total examined lymph nodes) has a high prognostic impact, but the relevant cut-off values are not determined. METHODS: Patients (N = 27,803) with a primary colorectal cancer diagnosed and operated in the Munich region between 1991 and 2006 were registered in the Munich Cancer Registry. Lymph node numbers and survival data were available for 17,309 patients with a mean follow-up of 5.9 years. RESULTS: The mean number (+/-SD) of resected lymph nodes was 16.8 +/- 8.4. Twelve or more lymph nodes were resected in 76.8%. Estimated 5-year overall survival decreased significantly with increasing LNR: LNR = 0 in 71.4%, LNR 0.01 to 0.17 in 52.4%, LNR 0.18 to 0.41 in 33.3%, LNR 0.42 to 0.69 in 19.8%, and LNR > or = 0.70 in 8.3% (P < 0.001). Multivariable survival analyses identified separately both LNR and pN- category, as well as number of resected lymph nodes, patient's age, tumor location, pT-category, pM-status, R-status, tumor grade, and year of operation as independent prognostic factors. CONCLUSION: : The 3 cut-off values of LNRs had strong independent prognostic value in a population-based collective of patients with colorectal cancer. The LNR should be routinely reported and included in the American Joint Committee on Cancer staging system. Nevertheless, the benefit of lymphadenectomy on survival is still unclear.

Avoidance of Overtreatment of Rectal Cancer by Selective Chemoradiotherapy: Results of the Optimized Surgery and MRI-Based Multimodal Therapy Trial.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer carries a high risk of adverse effects. The aim of this study was to examine the selective application of nCRT based on patient risk profile, as determined by MRI, to find the optimal range between undertreatment and overtreatment. STUDY DESIGN: In this prospective multicenter observational study, nCRT before total mesorectal excision (TME) was indicated in high-risk patients with involved or threatened mesorectal fascia (≤1 mm), or cT4 or cT3 carcinomas of the lower rectal third. All other patients received primary surgery. RESULTS: Of the 1,093 patients, 878 (80.3%) were treated according to the protocol, 526 patients (59.9%) underwent primary surgery, and 352 patients (40.1%) underwent nCRT followed by surgery. The 3-year locoregional recurrence (LR) rate was 3.1%. Of 604 patients with clinical stages II and III, 267 (44.2%) had primary surgery; 337 (55.8%) received nCRT followed by TME. The 3-year LR rate was 3.9%, without significant differences between groups. In patients with clinical stages II and III who underwent primary surgery, 27.3% were diagnosed with pathological stage I. CONCLUSIONS: The results justify the restriction of nCRT to high-risk patients with rectal cancer classified by pretreatment MRI. Provided that a high-quality MRI diagnosis, TME surgery, and standardized examination of the resected specimen are performed, nCRT, with its adverse effects, costs, and treatment time can be avoided in more than 40% of patients with stage II or III rectal cancer with minimal risk of undertreatment. (clinicaltrials.gov NCT325649).

Prognosis of mucinous and signet-ring cell colorectal cancer in a population-based cohort.

PURPOSE: Besides classical colorectal adenocarcinomas (AC), mucinous adenocarcinomas (MAC) and signet-ring cell carcinomas (SC) occur. Controversy remains regarding their prognostic role. Aim of this study was to define prognostic and histopathological specifications of mucinous and signet-ring cell colorectal cancer. METHODS: A total of 28,056 patients with AC, MAC, and SC between 1998 and 2012 in the catchment area of the Munich Cancer Registry were analyzed. Time to locoregional recurrence and distant recurrence was calculated by cumulative incidence. Survival was analyzed by the Kaplan-Meier method, calculation of relative survival, and Cox proportional hazards regression. RESULTS: AC occurred in 25,172 patients (90 %), MAC in 2724 (9.7 %), and SC in 160 (0.6 %). AC were less frequently localized in the proximal colon (34 %) compared to MAC (57 %, p < 0.001) and SC (76 %, p < 0.001). Both, MAC and SC had higher T, N, and M categories, lymphatic invasion, and worse grading (p < 0.001 for each). There were significant differences regarding the 10-year cumulative incidence of locoregional recurrence (p < 0.001), and distant recurrence (p < 0.001). For AC, the 5-year overall survival was 59 % (95 % confidence interval 58.0; 59.3), for MAC 52 % (50.2; 54.2), and for SC 40 % (32.1; 48.5; p < 0.001). However, MAC or SC did not remain independent prognostic factors for overall survival compared to AC upon multivariable analysis (p = 0.981). CONCLUSION: This large cohort reveals specific histopathological and recurrence patterns for patients with colorectal AC, MAC, and SC. MAC and SC are diagnosed at more advanced tumor stages and therefore entail reduced survival rates.

Group A Streptococci: A rare and often misdiagnosed cause of spontaneous bacterial peritonitis in adults.

INTRODUCTION: Acute primary peritonitis due to group A Streptococci (GAS) is a rare but life-threatening infection. Unlike other forms of primary peritonitis it affects predominantly young previously healthy individuals and thus is often confused with the more frequent secondary peritonitis. A case series of three patients is presented as well as a review of the literature focusing on pitfalls in the diagnose and therapy of GAS peritonitis. METHODS: A retrospective analysis of three patients with primary GAS peritonitis was performed. Furthermore a systematic review of all cases of primary GAS peritonitis published from 1990 to 2013 was performed comparing demographics and clinical presentation, as well as radiological imaging, treatment and outcome. RESULTS: All three female patients presented initially with high fever, nausea and severe abdominal pain. Radiological imaging revealed intraperitoneal fluid collections of various degrees, but no underlying cause of peritonitis. Broad antibiotic treatment was started and surgical exploration was performed for acute abdomen in all three cases. Intraoperatively fibrinous peritonitis was observed, but the correct diagnosis was not made until microbiological analysis confirmed GAS peritonitis. One patient died within 24h after admission. The other two patients recovered after multiple surgeries and several weeks on the intensive care unit due to multiple organ dysfunction syndrome. The fulminant clinical course of the three patients resembled those of many of the published cases: flu-like symptoms, high fever, severe acute abdominal pain and fibrinous peritonitis without obvious infectious focus were the most common symptoms reported in the literature. CONCLUSION: GAS primary peritonitis should be considered in particular in young, previously healthy women who present with peritonitis but lack radiological findings of an infectious focus. The treatment of choice is immediate antibiotic therapy. Surgical intervention is difficult to avoid, since the diagnosis of GAS peritonitis is usually not confirmed until other causes of secondary peritonitis have been excluded.

Brain Metastasis in Colorectal Cancer Patients: Survival and Analysis of Prognostic Factors.

BACKGROUND: The purpose of the study was to characterize the rare cohort of patients (pts) with metastatic colorectal cancer (mCRC) and brain metastasis (BM) and to identify prognostic subgroups. PATIENTS AND METHODS: In collaboration with the Munich Cancer Registry, pts with mCRC and BM who were diagnosed between 1998 and 2011 were identified. Survival from the time of first diagnosis of colorectal cancer (CRC) (OS-1), from the time of diagnosis of metastatic disease (OS-2) and of BM (OS-3) was calculated regarding (1) the temporal occurrence of extra- and intracranial metastasis (meta- vs. synchronous) and (2) tumor and patient characteristics. For survival analysis the Kaplan-Meier estimator and Cox regression models were used. RESULTS: A total of 228 pts (134 male [59%], 94 female [41%]) were identified. The median age was 63 years (142 pts [62%] were 65 years of age or younger). Most pts presented with primary tumors staged T3/4, N+, Grade 2. The primary tumor was located predominantly in the left colon (155 pts; 68%), especially in the rectum (95 pts; 42%). Median OS-1 was 35.6 months (95% confidence interval [CI], 30.1-41.1 months), OS-2 was 16.5 months (95% CI, 13.9-19.1 months), and OS-3 was 2.0 months (95% CI, 1.5-2.5 months). Median time from first CRC diagnosis to BM was 29.2 months. Subsequent BM after extracranial metastasis were observed in 184 pts (80.7%), whereas 31 pts (13.6%) presented with solitary BM. Univariate analysis did not reveal a prognostic variable for overall survival after diagnosis of BM. CONCLUSION: This study presents the largest number of pts with mCRC and BM analyzed to date. The results show that most mCRC pts develop BM as a late step in the course of disease. Median time from first CRC diagnosis to BM is 29.2 months. Only a few pts were diagnosed with BM early in the disease or with solitary BM. When BM is present survival is poor.

A randomized multicenter trial to compare long-term functional outcome, quality of life, and complications of surgical procedures for low rectal cancers.

INTRODUCTION: Colonic pouches have been used for 20 years to provide reservoir function after reconstructive proctectomy for rectal cancer. More recently coloplasty has been advocated as an alternative to a colonic pouch. However there have been no long-term randomized, controlled trials to compare functional outcomes of coloplasty, colonic J-Pouch (JP), or a straight anastomosis (SA) after the treatment of low rectal cancer. AIM: : To compare the complications, long-term functional outcome, and quality of life (QOL) of patients undergoing a coloplasty, JP, or an SA in reconstruction of the lower gastrointestinal tract after proctectomy for low rectal cancer. METHODS: A multicenter study enrolled patients with low rectal cancer, who were randomized intraoperatively to coloplasty (CP-1) or SA if JP was not feasible, or JP or coloplasty (CP-2) if a JP was feasible. Patients were followed for 24 months with SF-36 surveys to evaluate the QOL. Bowel function was measured quantitatively and using Fecal Incontinence Severity Index (FISI). Urinary function and sexual function were also assessed. RESULTS: Three hundred sixty-four patients were randomized. All patients were evaluated for complications and recurrence. Mean age was 60 +/-12 years, 71% were male. Twenty-three (7.4%) died within 24 months of surgery. No significant difference was observed in the complications among the 4 groups. Two hundred ninety-seven of 364 were evaluated for functional outcome at 24 months. There was no difference in bowel function between the CP-1 and SA groups. JP patients had fewer bowel movements, less clustering, used fewer pads and had a lower FISI than the CP-2 group. Other parameters were not statistically different. QOL scores at 24 months were similar for each of the 4 groups. CONCLUSIONS: In patients undergoing a restorative resection for low rectal cancer, a colonic JP offers significant advantages in function over an SA or a coloplasty. In patients who cannot have a pouch, coloplasty seems not to improve the bowel function of patients over that with an SA.