Is surgical quality more important than radicality? Long-term outcomes of stage I-III colon cancer (SAKK 40/00).

BACKGROUND: To prospectively determine the influence of variations of surgical radicality and surgical quality on long-term outcome in patients with stage I-III colon cancer. METHODS: From a prospective multicenter cohort study including 1040 patients undergoing surgery for colorectal cancer from 09/2001 to 06/2005 in nine Swiss and one German hospital, 423 patients with stage I-III colon cancer were selected and analyzed. Surgeons and pathologists filled in standardized forms prospectively assessing items of oncosurgical radicality and quality. Patients had standardized follow-up according to national guidelines. RESULTS: Follow-up was median 6.2 years (range 0.3-10.4) showing a 5-year disease-free survival/overall survival of 83 %/87 % in stage I (n = 85), 69 %/77 % in stage II (n = 187), and 53 %/61 % in stage III (n = 151) colon cancer. Despite remarkable variations of oncosurgical radicality and quality, the multivariate model revealed that mainly quality items correlated significantly with disease-free survival (surgical tumor lesion HR 2.12, p = 0.036, perioperative blood transfusion HR 1.67, p = 0.018, emergency resection HR 1.74, p = 0.035) and overall survival (early venous ligation HR 0.66, p = 0.023, surgical tumor lesion HR 2.28, p = 0.027, perioperative blood transfusion HR1.79, p = 0.010, emergency resection HR 1.88, p = 0.026), while radicality parameters (length of specimen, distance of the tumor to nearest bowel resection site, number of lymph nodes, height of resected mesocolon and of central vascular dissection) did not. CONCLUSION: Surgical quality seems to have a stronger impact on oncologic long-term outcome in stage I - III colon cancer than surgical radicality.

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.

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.

Closure of Temporary Ileostomy 2 Versus 12 Weeks After Rectal Resection for Cancer: A Word of Caution From a Prospective, Randomized Controlled Multicenter Trial.

BACKGROUND: The optimum timing for temporary ileostomy closure after low anterior resection is still open. OBJECTIVE: This trial aimed to compare early (2 wk) versus late (12 wk) stoma closure. DESIGN: The study included 2 parallel groups in a multicenter, randomized controlled clinical trial. SETTINGS: The study was conducted at 3 Swiss hospitals. PATIENTS: Patients undergoing low anterior resection and temporary ileostomy for cancer were included. INTERVENTIONS: Patients were randomly allocated to early or late stoma closure. Before closure, colonic anastomosis was examined for integrity. MAIN OUTCOME MEASURES: The primary efficacy outcome was the Gastrointestinal Quality of Life Index 6 weeks after resection. Secondary end points included safety (morbidity), feasibility, and quality of life 4 months after low anterior resection. RESULTS: The trial was stopped for safety concerns after 71 patients were randomly assigned to early closure (37 patients) or late closure (34 patients). There were comparable baseline data between the groups. No difference in quality of life occurred 6 weeks (mean Gastrointestinal Quality of Life Index: 99.8 vs 106.0; p = 0.139) and 4 months (108.6 vs 107.1; p = 0.904) after index surgery. Intraoperative tendency of oozing (visual analog scale: 35.8 vs 19.3; p = 0.011), adhesions (visual analog scale: 61.3 vs 46.2; p = 0.034), leak of colonic anastomosis (19% vs 0%; p = 0.012), leak of colonic or ileal anastomosis (24% vs 0%; p = 0.002), and reintervention (16% vs 0%; p = 0.026) were significantly higher after early closure. The concept of early closure failed in 10 patients (27% vs 0% in the late closure group (95% CI for the difference, 9.4%-44.4%)). LIMITATIONS: The trial was prematurely stopped because of safety issues. The aimed group size was not reached. CONCLUSIONS: Early stoma closure does not provide better quality of life up to 4 months after low anterior resection but is afflicted with significantly adverse feasibility and higher morbidity when compared with late closure. See Video Abstract at http://links.lww.com/DCR/B665. CIERRE DE LA ILEOSTOMA TEMPORAL VERSUS SEMANAS POSTERIOR A LA RESECCIN RECTAL POR CNCER UNA ADVERTENCIA DE UN ESTUDIO MULTICNTRICO CONTROLADO RANDOMIZADO PROSPECTIVO: ANTECEDENTES:El momento óptimo para el cierre temporal de la ileostomía posterior a la resección anterior baja es aun controversial.OBJETIVO:Este estudio tuvo como objetivo comparar el cierre del estoma temprano (2 semanas) versus tardío (12 semanas).DISEÑO:Estudio clínico controlado, randomizado, multicéntrico, de dos grupos paralelos.ENTORNO CLINICO:El estudio se llevó a cabo en 3 hospitales suizos.PACIENTES:Se incluyeron pacientes sometidos a resección anterior baja e ileostomía temporal por cáncer.INTERVENCIONES:Los pacientes fueron asignados aleatoriamente al cierre del estoma temprano o tardío. Antes del cierre, se examinó la integridad de la anastomosis colónica.PRINCIPALES MEDIDAS DE VALORACION:El principal resultado de eficacia fue el Índice de Calidad de Vida Gastrointestinal 6 semanas después de la resección. Los criterios secundarios incluyeron la seguridad (morbilidad), factibilidad y calidad de vida 4 meses posterior a la resección anterior baja.RESULTADOS:El estudio se detuvo por motivos de seguridad después de que 71 pacientes fueron asignados aleatoriamente a cierre temprano (37 pacientes) o cierre tardío (34 pacientes). Hubo datos de referencia comparables entre los grupos. No se produjeron diferencias en la calidad de vida 6 semanas (índice de calidad de vida gastrointestinal, media 99,8 vs. 106; p = 0,139) y 4 meses (108,6 vs 107,1, p = 0,904) después de la cirugía inicial. Tendencia intraoperatoria de supuración (escala analógica visual 35,8 vs 19,3, p = 0,011), adherencias (escala analógica visual 61,3 vs 46,2, p = 0,034), fuga de anastomosis colónica (19% vs 0%, p = 0,012), fuga de anastomosis colónica o ileal (24% vs 0%, p = 0,002) y reintervención (16% vs 0%, p = 0,026) fueron significativamente mayores después del cierre temprano. El concepto de cierre temprano fracasó en 10 pacientes (27% vs ninguno en el grupo de cierre tardío (intervalo de confianza del 95% para la diferencia: 9,4% a 44,4%)).LIMITACIONES:El estudio se detuvo prematuramente debido a problemas de seguridad. No se alcanzó el tamaño del grupo previsto.CONCLUSIÓN:El cierre temprano del estoma no proporciona una mejor calidad de vida hasta 4 meses posterior a una resección anterior baja, esto se ve afectado por efectos adversos significativos durante su realización y una mayor morbilidad en comparación con el cierre tardío. Consulte Video Resumen en http://links.lww.com/DCR/B665.

A systematic review and meta-analysis comparing surgical and oncological outcomes of upper rectal, rectosigmoid and sigmoid tumours.

AIM: Management paradigms for tumours from the sigmoid colon to the lower rectum vary significantly. The upper rectum (UR) represents the transition point both anatomically and in treatment protocols. Above the UR is clearly defined and managed as colon cancer and below is managed as rectal cancer. This study compares outcomes between sigmoid, rectosigmoid and UR tumours to establish if differences exist in operative and oncological outcomes. METHODS: Electronic databases were searched for published studies with comparative data on peri-operative and oncological outcome for upper rectal and sigmoid/rectosigmoid (SRS) tumours treated without neoadjuvant radiation. The search adhered to PRISMA guidelines (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Data was combined using random-effects models. RESULTS: Seven comparative series examined outcomes in 4355 patients. There was no difference in ASA grade (OR, 1.28; 95% CI, 0.99-1.67; P = 0.06), T3/T4 tumours (OR, 1.24; 95% CI, 0.95-1.63; P = 0.12), or lymph node positivity (OR, 0.97; 95% CI, 0.70-1.36; P = 0.87). UR cancers had higher rates of operative morbidity (OR, 0.72; 95% CI, 0.55-0.93; P = 0.01) and anastomotic leak (OR, 0.47; 95% CI, 0.31-0.71; P = 0.0004). There was no difference in local recurrence (OR, 0.63; 95% CI, 0.37-1.08; P = 0.10). SRS tumours had lower rates of distant recurrence (OR, 0.83; 95% CI, 0.68-1.0; P = 0.05). Rectosigmoid operative and cancer outcomes were closer to UR than sigmoid. CONCLUSIONS: Based on existing data, UR and rectosigmoid tumours have higher morbidity, leak rates and distant recurrence than more proximal tumours.

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).

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.

Correction to: Prophylactic Intraperitoneal Onlay Mesh Following Midline Laparotomy-Long-Term Results of a Randomized Controlled Trial.

In the original version of the article, Philippe M. Glauser's, Philippe Brosi's, Benjamin Speich's, Samuel A. Käser's, Andres Heigl's, and Christoph A. Maurer's first and last names were interchanged. The names are correct as reflected here. The original article has been corrected.

Prophylactic Intraperitoneal Onlay Mesh Following Midline Laparotomy-Long-Term Results of a Randomized Controlled Trial.

OBJECTIVES: Incisional hernia, a serious complication after laparotomy, is associated with high morbidity and costs. This trial examines the value of prophylactic intraperitoneal onlay mesh to reduce the risk of incisional hernia after a median follow-up time of 5.3 years. METHODS: We conducted a parallel group, open-label, single center, randomized controlled trial (NCT01003067). After midline incision, the participants were either allocated to abdominal wall closure according to Everett with a PDS-loop running suture reinforced by an intraperitoneal composite mesh strip (Group A) or the same procedure without the additional mesh strip (Group B). RESULTS: A total of 276 patients were randomized (Group A = 131; Group B = 136). Follow-up data after a median of 5.3 years after surgery were available from 183 patients (Group A = 95; Group B = 88). Incisional hernia was diagnosed in 25/95 (26%) patients in Group A and in 46/88 (52%) patients in Group B (risk ratio 0.52; 95% CI 0.36-0.77; p < 0.001). Eighteen patients with asymptomatic incisional hernia went for watchful waiting instead of hernia repair and remained free of symptoms after of a median follow-up of 5.1 years. Between the second- and fifth-year follow-up period, no complication associated with the mesh could be detected. CONCLUSION: The use of a composite mesh in intraperitoneal onlay position significantly reduces the risk of incisional hernia during a 5-year follow-up period. TRIAL REGISTRATION NUMBER: Ref. NCT01003067 (clinicaltrials.gov).

Prophylactic Intraperitoneal Onlay Mesh Reinforcement Reduces the Risk of Incisional Hernia, Two-Year Results of a Randomized Clinical Trial.

BACKGROUND: Incisional hernias still are a major concern after laparotomy and are causing substantial morbidity. This study examines the feasibility, safety and incisional hernia rate of the use of a prophylactic intraperitoneal onlay mesh stripe (IPOM) to prevent incisional hernia following midline laparotomy. METHODS: This prospective, randomized controlled trial randomly allocated patients undergoing median laparotomy either to mass closure of the abdominal wall with a PDS-loop running suture reinforced by an intraperitoneal composite mesh stripe (Group A) or to the same procedure without the additional mesh stripe (Group B). Primary endpoint was the incidence of incisional hernias at 2 years following midline laparotomy. Secondary endpoints are were the feasibility, the safety of the mesh stripe implantation including postoperative pain, and the incidence of incisional hernias at 5 years. RESULTS: A total of 267 patients were included in this study. Follow-up data 2 years after surgery was available from 210 patients (Group A = 107; Group B = 103). An incisional hernia was diagnosed in 18/107 (17%) patients in Group A and in 40/103 (39%) patients in Group B (p < 0.001). A surgical operation due to an incisional hernia was conducted for 12/107 (11%) patients in Group A and for 24/103 (23%) patients in Group B (p = 0.039). In both groups, minor and major complications as well as postoperative pain are reported with no statistically significant difference between the groups, even in contaminated situations. CONCLUSIONS: This first randomized clinical trial indicates that the placement of a non-absorbable IPOM-stripe with prophylactic intention may significantly reduce the risk for a midline incisional hernia. TRIAL REGISTRATION: Ref. NCT01003067 (clinicaltrials.gov).

Prospective multicenter registration study of colorectal cancer: significant variations in radicality and oncosurgical quality-Swiss Group for Clinical Cancer Research Protocol SAKK 40/00.

PURPOSE: This study aimed to investigate in a multicenter cohort study the radicality of colorectal cancer resections, to assess the oncosurgical quality of colorectal specimens, and to compare the performance between centers. METHODS: One German and nine Swiss hospitals agreed to prospectively register all patients with primary colorectal cancer resected between September 2001 and June 2005. The median number of eligible patients with one primary tumor included per center was 95 (range 12-204). RESULTS: The following variations of median values or percentages between centers were found: length of bowel specimen 20-39 cm (25.8 cm), maximum height of mesocolon 6.5-12.5 cm (9.0 cm), number of examined lymph nodes 9-24 (16), distance to nearer bowel resection margin in colon cancer 4.8-12 cm (7 cm), and in rectal cancer 2-3 cm (2.5 cm), central ligation of major artery 40-97 % (71 %), blood loss 200-500 ml (300 ml), need for perioperative blood transfusion 5-40 % (19 %), tumor opened during mobilization 0-11 % (5 %), T4-tumors not en-bloc resected 0-33 % (4 %), inadvertent perforation of mesocolon/mesorectum 0-8 % (4 %), no-touch isolation technique 36-86 % (67 %), abdominoperineal resection for rectal cancer 0-30 % (17 %), rectal cancer specimen with circumferential margin ≤1 mm 0-19 % (10 %), in-hospital mortality 0-6 % (2 %), anastomotic leak or intra-abdominal abscess 0-17 % (7 %), re-operation 0-17 % (8 %). CONCLUSION: In colorectal cancer, surgery considerable variations between different centers were found with regard to radicality and oncosurgical quality, suggesting a potential for targeted improvement of surgical technique.

Liver resections can be performed safely without Pringle maneuver: A prospective study.

AIM: To evaluate liver resections without Pringle maneuver, i.e., clamping of the portal triad. METHODS: Between 9/2002 and 7/2013, 175 consecutive liver resections (n = 101 major anatomical and n = 74 large atypical > 5 cm) without Pringle maneuver were performed in 127 patients (143 surgeries). Accompanying, 37 wedge resections (specimens < 5 cm) and 43 radiofrequency ablations were performed. Preoperative volumetric calculation of the liver remnant preceeded all anatomical resections. The liver parenchyma was dissected by water-jet. The median central venous pressure was 4 mmHg (range: 5-14). Data was collected prospectively. RESULTS: The median age of patients was 60 years (range: 16-85). Preoperative chemotherapy was used in 70 cases (49.0%). Liver cirrhosis was present in 6.3%, and liver steatosis of ≥ 10% in 28.0%. Blood loss was median 400 mL (range 50-5000 mL). Perioperative blood transfusions were given in 22/143 procedures (15%). The median weight of anatomically resected liver specimens was 525 g (range: 51-1850 g). One patient died postoperatively. Biliary leakages (n = 5) were treated conservatively. Temporary liver failure occurred in two patients. CONCLUSION: Major liver resections without Pringle maneuver are feasible and safe. The avoidance of liver inflow clamping might reduce liver damage and failure, and shorten the hospital stay.

Distant Metastasis in Colorectal Cancer is a Risk Factor for Anastomotic Leakage.

PURPOSE: The aim of this study was to investigate whether metastatic colorectal cancer (Union for International Cancer Control stage IV disease) represents a risk factor for anastomotic leakage after colorectal surgery without major hepatic resection. METHODS: This retrospective cohort study was based on an existing prospective colorectal database of all consecutive colorectal resections undertaken at the authors' institution from July 2002 to July 2012 (n = 2104). All patients with colorectal resection and primary anastomosis for colorectal cancer were identified (n = 500). A temporary loop ileostomy was constructed in low rectal anastomosis up to 6 cm from the anal verge (n = 128 cases, 26%). A routine contrast enema was undertaken at the occasion of other prospective studies in 254 patients. UICC stage IV disease was present in 94 patients (19%), while 406 patients (81%) had UICC stage I-III disease. RESULTS: The overall anastomotic leak rate was 2.6% (13/500), 2.2% (11/500) for both clinical and radiological leaks, and 0.8% (2/254) for radiological leaks only. Four were managed conservatively and nine (1.8%) required revision laparotomy. In the case of UICC stage IV disease, the anastomotic leak rate was 6.3% (6/94), while in the case of UICC stage I-III disease the leak rate was 1.7% (7/406). UICC stage IV disease [odds ratio (OR) 4.4, 95% confidence interval (CI) 1.3-14.4; p = 0.015] and diabetes (OR 5.7, 95% CI 1.7-18.7; p = 0.004) were independent risk factors for anastomotic leakage after colorectal surgery. CONCLUSIONS: Patients with stage IV colorectal cancer have an increased anastomotic leak rate after colorectal surgery. Whether this is due to an impaired immune system remains speculative.

Myenteric plexitis: A frequent feature in patients undergoing surgery for colonic diverticular disease.

BACKGROUND: Diverticular disease of the colon is frequent in clinical practice, and a large number of patients each year undergo surgical procedures worldwide for their symptoms. Thus, there is a need for better knowledge of the basic pathophysiologic mechanisms of this disease entity. OBJECTIVES: Because patients with colonic diverticular disease have been shown to display abnormalities of the enteric nervous system, we assessed the frequency of myenteric plexitis (i.e. the infiltration of myenteric ganglions by inflammatory cells) in patients undergoing surgery for this condition. METHODS: We analyzed archival resection samples from the proximal resection margins of 165 patients undergoing left hemicolectomy (60 emergency and 105 elective surgeries) for colonic diverticulitis, by histology and immunochemistry. RESULTS: Overall, plexitis was present in almost 40% of patients. It was subdivided into an eosinophilic (48%) and a lymphocytic (52%) subtype. Plexitis was more frequent in younger patients; and it was more frequent in those undergoing emergency surgery (50%), compared to elective (28%) surgery (p = 0.007). All the severe cases of plexitis displayed the lymphocytic subtype. CONCLUSIONS: In conclusion, myenteric plexitis is frequent in patients with colonic diverticular disease needing surgery, and it might be implicated in the pathogenesis of the disease.

Outcome after surgery for acute right-sided colonic ischemia without feasible vascular intervention: a single center experience of 58 patients over 6 years.

BACKGROUND: The predilection site of non-occlusive mesenteric ischemia is the right-sided colon. Surgical exploration followed by segmental bowel resection and primary anastomosis or ileostomy is recommended, if vascular interventions are not feasible and conservative treatment fails. We assessed the outcome of patients in this life-threatening condition. METHODS: From a prospective database 58 patients with urgent surgery for acute right-sided colonic ischemia without feasible vascular intervention (as a surrogate for non-occlusive mesenteric ischemia) were identified. Retrospectively the patients' characteristics, reason for ischemia, extent of resection, rate of ileostomy creation, 30 day and one year mortality, and rate of ileostomy-reversal at one year postoperative were assessed. RESULTS: Radiologically mesenteric arteriosclerotic disease was present in 54% of the patients. Vaso-occlusive mesenteric disease was suspected in 15% of the patients, but not confirmed intra-operatively. Ten patients underwent (extended) right-sided hemicolectomy with primary anastomosis (30-days mortality 20%, 1-year mortality 30%). Sixteen patients had (extended) right-sided hemicolectomy with creation of an ileostomy (30-days mortality 44%, 1-year mortality 86%, ostomy reversal in one patient). Twenty-five patients had (sub-) total colectomy with ileostomy creation (30-days mortality 60%, 1-year mortality 72%, ostomy reversal in two patients). Seven patients had exploration only (30-days mortality 86%, 1-year mortality 86%). Overall, the 30-days mortality-rate was 52% and the 1-year mortality-rate was 70%. Only 7% of the patients requiring an ostomy experienced ostomy-reversal. CONCLUSIONS: Patients with urgent surgery for acute right-sided colonic ischemia without feasible vascular intervention have a very high short and long-term mortality. The rate of ostomy-reversal is very low.

Enlargement of umbilical incision in standard laparoscopic cholecystectomy is frequently necessary: An argument for the single incision approach?

OBJECTIVE: Cosmetic result after cholecystectomy is up for debate. The aim of this study was to investigate the incidence and extent of enlargement of initial skin and fascia incision in standard laparoscopic cholecystectomy and to detect predictive factors for such an enlargement. MATERIAL AND METHODS: The size of the umbilical incision was measured before and after standard laparoscopic gallbladder removal in 391 patients from August 2009 to October 2012. Predisposing factors for the need of enlargement of the umbilical incision were analysed. RESULTS: Additional enlargement of the umbilical incision for gallbladder removal was required in 35.8% of the patients at skin level, and in 40.4% at fascia level. The median enlargement of the umbilical skin incision was 11 mm, from 25 mm to 36 mm. Gallbladder weight, total stone weight, maximum diameter of largest stone and shorter initial length of incision were independent predisposing factors for enlargement of the incision. CONCLUSIONS: In standard laparoscopic cholecystectomy the umbilical incision frequently requires secondary enlargement, especially if a large stone mass is involved. Therefore, the cosmetic result after laparoscopic cholecystectomy depends on more than only the technique used for access and the surgical technique for cholecystectomy should be chosen individually for each patient according to the stone mass.

Transanal endoscopic microsurgery (TEM) facilitated by video-assistance and anal insertion of a single-incision laparoscopic surgery (SILS(®))-port: preliminary experience.

OBJECTIVE: Transanal endoscopic microsurgery (TEM) is an established method for the resection of benign and early malignant rectal lesions. Very recently, TEM via an anally inserted single incision laparoscopic surgery (SILS(®))-port has been proposed to overcome remaining obstacles of the classical TEM equipment. METHODS: Nine patients with a total of 12 benign or early stage malignant rectal polyps were operated using the SILS(®)-port for TEM. Patients' and polyps' characteristics, perioperative and postoperative complications, as well as operating and hospitalization time were recorded. RESULTS: All 12 polyps (ten low-grade adenoma, one high-grade adenoma, one pT2 carcinoma [preoperatively staged as T1]) were resected. Local full-thickness bowel wall resection was performed for three lesions and submucosal resection for nine lesions. Median operating time was 64 (range 30-180) min. No conversion to laparoscopic or open techniques was necessary. The median maximum diameter of the specimen was 25 (range 3-60) mm, fragmentation of polyps was avoidable in 11 of 12 (92 %) lesions, and resection margins were histologically clear in 11 of 12 (92 %) polyps. Only one patient, in whom three lesions were resected, experienced a complication as postoperative hemorrhage. No mortality occurred. Median hospitalization time was four (range 1-14) days. CONCLUSIONS: SILS(®)-TEM is a feasible and safe method, providing numerous advantages in application, handling, and economy compared with the classical TEM technique. SILS(®)-TEM might become a promising alternative to classical TEM. Randomized, controlled trials comparing safety and efficacy of both instrumental settings will be needed in the future.

Enhanced activity of meprin-α, a pro-migratory and pro-angiogenic protease, in colorectal cancer.

Meprin-α is a metalloprotease overexpressed in cancer cells, leading to the accumulation of this protease in a subset of colorectal tumors. The impact of increased meprin-α levels on tumor progression is not known. We investigated the effect of this protease on cell migration and angiogenesis in vitro and studied the expression of meprin-α mRNA, protein and proteolytic activity in primary tumors at progressive stages and in liver metastases of patients with colorectal cancer, as well as inhibitory activity towards meprin-α in sera of cancer patient as compared to healthy controls. We found that the hepatocyte growth factor (HGF)-induced migratory response of meprin-transfected epithelial cells was increased compared to wild-type cells in the presence of plasminogen, and that the angiogenic response in organ-cultured rat aortic explants was enhanced in the presence of exogenous human meprin-α. In patients, meprin-α mRNA was expressed in colonic adenomas, primary tumors UICC (International Union Against Cancer) stage I, II, III and IV, as well as in liver metastases. In contrast, the corresponding protein accumulated only in primary tumors and liver metastases, but not in adenomas. However, liver metastases lacked meprin-α activity despite increased expression of the corresponding protein, which correlated with inefficient zymogen activation. Sera from cancer patients exhibited reduced meprin-α inhibition compared to healthy controls. In conclusion, meprin-α activity is regulated differently in primary tumors and metastases, leading to high proteolytic activity in primary tumors and low activity in liver metastases. By virtue of its pro-migratory and pro-angiogenic activity, meprin-α may promote tumor progression in colorectal cancer.

Ischemic colitis: clinical presentation, localization in relation to risk factors, and long-term results.

BACKGROUND: Ischemic colitis is commonly thought to occur most often in the left hemicolon close to the splenic flexure owing to insufficient blood supply near Griffith's point. This study investigates the colorectal localization pattern, the risk factors, and the long-term outcome of histologically proven ischemic colitis. METHODS: Between 1996 and 2004, a total of 49 patients with a median age of 69 years (range 26-94 years) with colonoscopically assessed and histologically proven ischemic colitis were identified on behalf of the pathology database. Long-term results of 43 patients were evaluated retrospectively after a median interval of 79 months (range 6-163 months). RESULTS: In 27 patients (55%) more than one location was affected. We found 98 affected locations in 49 patients. The distribution of ischemic colitis in our group shows no significantly preferred location. In an exploratory analysis, the cecum, ascending colon, and right flexure were affected significantly more often if intake of a nonsteroidal antiinflammatory drug (NSAID) is documented. There was no association between the location of ischemic colitis and a history of smoking, peripheral artery occlusive disease, coronary heart disease, diabetes, or malignant tumor. CONCLUSIONS: Ischemic colitis seems not to have a predisposing site of occurrence in the colorectum, especially Griffith's point which was not afflicted significantly more often than other sites. Frequently, ischemic colitis afflicts more than one colonic location. In patients being treated with NSAIDs, ischemic colitis was observed significantly more often in the right hemicolon. Recurrence of ischemic colitis seems to be rare.

Impact of CD39 and purinergic signalling on the growth and metastasis of colorectal cancer.

Despite improvements in prevention and management of colorectal cancer (CRC), uncontrolled tumor growth with metastatic spread to distant organs remains an important clinical concern. Genetic deletion of CD39, the dominant vascular and immune cell ectonucleotidase, has been shown to delay tumor growth and blunt angiogenesis in mouse models of melanoma, lung and colonic malignancy. Here, we tested the influence of CD39 on CRC tumor progression and metastasis by investigating orthotopic transplanted and metastatic cancer models in wild-type BALB/c, human CD39 transgenic and CD39 deficient mice. We also investigated CD39 and P2 receptor expression patterns in human CRC biopsies. Murine CD39 was expressed by endothelium, stromal and mononuclear cells infiltrating the experimental MC-26 tumors. In the primary CRC model, volumes of tumors in the subserosa of the colon and/or rectum did not differ amongst the treatment groups at day 10, albeit these tumors rarely metastasized to the liver. In the dissemination model, MC-26 cell line-derived hepatic metastases grew significantly faster in CD39 over-expressing transgenics, when compared to CD39 deficient mice. Murine P2Y2 was significantly elevated at both mRNA and protein levels, within the larger liver metastases obtained from CD39 transgenic mice where changes in P2X7 levels were also noted. In clinical samples, lower levels of CD39 mRNA in malignant CRC tissues appeared associated with longer duration of survival and could be linked to less invasive tumors. The modulatory effects of CD39 on tumor dissemination and differential levels of CD39, P2Y2 and P2X7 expression in tumors suggest involvement of purinergic signalling in these processes. Our studies also suggest potential roles for purinergic-based therapies in clinical CRC.