Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting.

BACKGROUND: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. METHODS: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either 'node-picking' (the removal of an individual LLN) or 'partial regional node dissection' (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those  undergoing only rectal resection. RESULTS: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7-3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2-2.5, p = 0.874). CONCLUSION: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.

Omentoplasty in Patients Undergoing Abdominoperineal Resection After Long-Course Chemoradiation for Locally Advanced and Locally Recurrent Rectal Cancer: A Comparative Single-Institution Cohort Study.

BACKGROUND: Omentoplasty is a commonly performed procedure after abdominoperineal resection for rectal cancer, but its effectiveness to reduce pelviperineal complications is not firmly established. OBJECTIVE: This study aimed to assess the impact of omentoplasty on postoperative outcomes after long-course (chemo) radiotherapy and abdominoperineal resection in patients with locally advanced and locally recurrent rectal cancer. DESIGN: Retrospective cohort study. SETTINGS: Single center. PATIENTS: All patients with locally advanced and locally recurrent rectal cancer undergoing abdominoperineal resection after neoadjuvant (chemo)radiation in a tertiary referral center between 2008 and 2020 were retrospectively reviewed. MAIN OUTCOME MEASURES: Multivariable logistic and linear regression analyses were performed to analyze the association between omentoplasty and pelviperineal complications, duration of nasogastric tube drainage, and length of hospital stay. RESULTS: A total of 305 patients were analyzed, of whom 245 underwent omentoplasty (80%). Pelviperineal complications occurred in 151 patients (50%) overall, in 125 patients (51%) with omentoplasty, and in 26 patients (43%) without omentoplasty. Independent predictors of pelviperineal complications in multivariable analyses were smoking (OR 2.68; 95% CI, 1.46-4.94) and high BMI (OR 1.68; 95% CI, 1.00-2.83), but not omentoplasty (OR 1.36; 95% CI, 0.77-2.40). The mean duration of nasogastric tube drainage was longer after omentoplasty (6 vs 4 d) with a significant association in multivariable analysis (ß coefficient 1.97; 95% CI, 0.35-3.59). Patients undergoing omentoplasty had a significantly longer hospital stay (14 vs 10 d), and omentoplasty remained associated with a prolonged hospital stay after adjusting for confounding (ß coefficient 3.05; 95% CI, 0.05-5.74). LIMITATIONS: Retrospective design. CONCLUSION: Omentoplasty was not associated with a reduced risk of the occurrence of short-term pelviperineal complications after abdominoperineal resection in patients undergoing long-course (chemo)radiotherapy. Furthermore, in patients undergoing omentoplasty, prolonged duration of nasogastric tube drainage and hospital stay was observed. See Video Abstract at http://links.lww.com/DCR/C124 . OMENTOPLASTIA EN PACIENTES SOMETIDOS A RESECCIN ABDOMINOPERINEAL DESPUS DE QUIMIORRADIOTERAPIA DE CURSO LARGO PARA EL CNCER DE RECTO LOCALMENTE AVANZADO Y LOCALMENTE RECURRENTE ESTUDIO DE COHORTE COMPARATIVO DE UNA SOLA INSTITUCIN: ANTECEDENTES:La omentoplastía es un procedimiento que se realiza comúnmente después de la resección abdominoperineal por cáncer de recto, pero su efectividad para reducir las complicaciones pelvicoperineales no está firmemente establecida.OBJETIVO:Evaluar el impacto de la omentoplastía en las complicaciones pelvicoperineales a corto plazo y los resultados postoperatorios después quimioradioterapia de curso largo y resección abdominoperineal en pacientes con cáncer de recto localmente avanzado y localmente recurrente.DISEÑO:Estudio de cohorte retrospectivo.ESCENARIO:Centro único.PACIENTES:Se revisaron retrospectivamente todos los pacientes con cáncer de recto localmente avanzado y localmente recurrente sometidos a resección abdominoperineal después de quimioradiación neoadyuvante en un centro de referencia de tercer nivel entre 2008 y 2020.PRINCIPALES MEDIDAS DE RESULTADO:Se realizaron análisis de regresión lineal y logística multivariable para examinar la asociación entre la omentoplastía y las complicaciones pelvicoperineales (p. ej., problemas de heridas perineales y abscesos pélvicos), la duración del drenaje por sonda nasogástrica y la duración de la estancia hospitalaria.RESULTADOS:Se analizaron un total de 305 pacientes de los cuales 245 fueron sometidos a omentoplastía (80%). Las complicaciones pelvicoperineales ocurrieron en 151 pacientes (50%) en general, y en 125 (51%) y 26 (43%) de los pacientes con o sin omentoplastía, respectivamente. Los predictores independientes de complicaciones pelvicoperineales en análisis multivariable fueron el tabaquismo (OR 2.68, IC del 95% 1.46 a 4.94) y un IMC alto (OR 1.68, IC del 95% 1.00 a 2.83), pero no la omentoplastía (OR 1.36, IC del 95% 0.77 a 2.40) . La duración media del drenaje por sonda nasogástrica fue mayor después de la omentoplastía (6 frente a 4 días) con una asociación significativa en el análisis multivariable (coeficiente ß 1.97, IC del 95%: 0.35-3.59). Los pacientes que se sometieron a una omentoplastía tuvieron una estancia hospitalaria significativamente más larga (14 frente a 10 días), y la omentoplastía permaneció asociada con una estancia hospitalaria prolongada después de ajustar por factores de confusión (coeficiente ß 3.05, IC del 95%: 0.05-5.74).LIMITACIONES:Diseño retrospectivo.CONCLUSIÓN:La omentoplastía no se asoció con un riesgo reducido de aparición de complicaciones pelvicoperineales a corto plazo después de la resección abdominoperineal en pacientes sometidos a quimioradioterapia de larga duración. Adicionalmente, en los pacientes sometidos a omentoplastía se observó una duración prolongada del drenaje por sonda nasogástrica y la estancia hospitalaria. Consulte Video Resumen en http://links.lww.com/DCR/C124 . (Traducción-Dr. Jorge Silva Velazco ).

Cumulative 5-year Results of a Randomized Controlled Trial Comparing Biological Mesh With Primary Perineal Wound Closure After Extralevator Abdominoperineal Resection (BIOPEX-study).

OBJECTIVE: To determine long-term outcomes of a randomized trial (BIOPEX) comparing biological mesh and primary perineal closure in rectal cancer patients after extralevator abdominoperineal resection and preoperative radiotherapy, with a primary focus on symptomatic perineal hernia. SUMMARY BACKGROUND DATA: BIOPEX is the only randomized trial in this field, which was negative on its primary endpoint (30-day wound healing). METHODS: This was a posthoc secondary analysis of patients randomized in the BIOPEX trial to either biological mesh closure (n = 50; 2 dropouts) or primary perineal closure (n = 54; 1 dropout). Patients were followed for 5 years. Actuarial 5-year probabilities were determined by the Kaplan-Meier statistic. RESULTS: Actuarial 5-year symptomatic perineal hernia rates were 7% (95% CI, 0-30) after biological mesh closure versus 30% (95% CI, 10-49) after primary closure (P = 0.006). One patient (2%) in the biomesh group underwent elective perineal hernia repair, compared to 7 patients (13%) in the primary closure group (P = 0.062). Reoperations for small bowel obstruction were necessary in 1/48 patients (2%) and 5/53 patients (9%), respectively (P = 0.208). No significant differences were found for chronic perineal wound problems, locoregional recurrence, overall survival, and main domains of quality of life and functional outcome. CONCLUSIONS: Symptomatic perineal hernia rate at 5-year follow-up after abdominoperineal resection for rectal cancer was significantly lower after biological mesh closure. Biological mesh closure did not improve quality of life or functional outcomes.

Using guideline-based clinical decision support in oncological multidisciplinary team meetings: A prospective, multicenter concordance study.

BACKGROUND: Multidisciplinary team meetings formulate guideline-based individual treatment plans based on patient and disease characteristics and motivate reasons for deviation. Clinical decision trees could support multidisciplinary teams to adhere more accurately to guidelines. Every clinical decision tree is tailored to a specific decision moment in a care pathway and is composed of patient and disease characteristics leading to a guideline recommendation. OBJECTIVE: This study investigated (1) the concordance between multidisciplinary team and clinical decision tree recommendations and (2) the completeness of patient and disease characteristics available during multidisciplinary team meetings to apply clinical decision trees such that it results in a guideline recommendation. METHODS: This prospective, multicenter, observational concordance study evaluated 17 selected clinical decision trees, based on the prevailing Dutch guidelines for breast, colorectal and prostate cancers. In cases with sufficient data, concordance between multidisciplinary team and clinical decision tree recommendations was classified as concordant, conditional concordant (multidisciplinary team specified a prerequisite for the recommendation) and non-concordant. RESULTS: Fifty-nine multidisciplinary team meetings were attended in 8 different hospitals, and 355 cases were included. For 296 cases (83.4%), all patient data were available for providing an unconditional clinical decision tree recommendation. In 59 cases (16.6%), insufficient data were available resulting in provisional clinical decision tree recommendations. From the 296 successfully generated clinical decision tree recommendations, the multidisciplinary team recommendations were concordant in 249 (84.1%) cases, conditional concordant in 24 (8.1%) cases and non-concordant in 23 (7.8%) cases of which in 7 (2.4%) cases the reason for deviation from the clinical decision tree generated guideline recommendation was not motivated. CONCLUSION: The observed concordance of recommendations between multidisciplinary teams and clinical decision trees and data completeness during multidisciplinary team meetings in this study indicate a potential role for implementation of clinical decision trees to support multidisciplinary team decision-making.

Perineal wound closure using gluteal turnover flap or primary closure after abdominoperineal resection for rectal cancer: study protocol of a randomised controlled multicentre trial (BIOPEX-2 study).

BACKGROUND: Abdominoperineal resection (APR) for rectal cancer is associated with high morbidity of the perineal wound, and controversy exists about the optimal closure technique. Primary perineal wound closure is still the standard of care in the Netherlands. Biological mesh closure did not improve wound healing in our previous randomised controlled trial (BIOPEX-study). It is suggested, based on meta-analysis of cohort studies, that filling of the perineal defect with well-vascularised tissue improves perineal wound healing. A gluteal turnover flap seems to be a promising method for this purpose, and with the advantage of not having a donor site scar. The aim of this study is to investigate whether a gluteal turnover flap improves the uncomplicated perineal wound healing after APR for rectal cancer. METHODS: Patients with primary or recurrent rectal cancer who are planned for APR will be considered eligible in this multicentre randomised controlled trial. Exclusion criteria are total exenteration, sacral resection above S4/S5, intersphincteric APR, biological mesh closure of the pelvic floor, collagen disorders, and severe systemic diseases. A total of 160 patients will be randomised between gluteal turnover flap (experimental arm) and primary closure (control arm). The total follow-up duration is 12 months, and outcome assessors and patients will be blinded for type of perineal wound closure. The primary outcome is the percentage of uncomplicated perineal wound healing on day 30, defined as a Southampton wound score of less than two. Secondary outcomes include time to perineal wound closure, incidence of perineal hernia, the number, duration and nature of the complications, re-interventions, quality of life and urogenital function. DISCUSSION: The uncomplicated perineal wound healing rate is expected to increase from 65 to 85% by using the gluteal turnover flap. With proven effectiveness, a quick implementation of this relatively simple surgical technique is expected to take place. TRIAL REGISTRATION: The trial was retrospectively registered at Clinicaltrials.gov NCT04004650 on July 2, 2019.

Posttreatment Surveillance in Patients with Prolonged Disease-Free Survival After Resection of Colorectal Liver Metastasis.

INTRODUCTION: Posttreatment surveillance protocols most often endure for 5 years after resection of colorectal liver metastasis (CRLM). Most recurrences happen within 3 years after surgical removal of the tumour. This study analysed the need of surveillance for patients with at least 3 years of disease-free survival after potentially curative resection of CRLM. METHODS: A single-centre, retrospective analysis of all consecutive patients who underwent treatment for CRLM with curative intent between 2000 and 2011. RESULTS: In total, 152 of 545 patients (28 %) remained disease-free for 3 years after successful resection of the CRLM. The estimated recurrence rate after 10 years of follow-up in this group of 152 patients was 27 %. More than half of these patients (55 %) could be treated with curative intent for their recurrences. Multivariable analysis revealed that the nodal status of the primary tumour is of significant prognostic value for developing recurrences after 3 years of disease-free survival. A disease-free interval of less than 12 months between resection of primary tumour and detection of CRLM shows a trend towards significance. Both factors were used to create a risk score, showing that patients with a low-risk profile (node-negative status and a disease-free interval <12 months) have an estimated recurrence rate of 5 % and might not benefit from intensive surveillance beyond 3 years of follow-up without a recurrence. CONCLUSIONS: The currently developed risk score shows that follow-up can be stopped in a specific subgroup 3 years after treatment for their CRLM with curative intent.

The Importance of a Minimal Tumor-Free Resection Margin in Locally Recurrent Rectal Cancer.

BACKGROUND: The importance of the circumferential resection margin has been demonstrated in primary rectal cancer, but the role of the minimal tumor-free resection margin in locally recurrent rectal cancer is unknown. OBJECTIVE: The purpose of this work was to evaluate the prognostic importance of a minimal tumor-free resection margin in locally recurrent rectal cancer. DESIGN: This was a single-institution, retrospective study. SETTINGS: This study was conducted in a tertiary referral hospital. PATIENTS: Based on the final pathology report, surgically treated patients with locally recurrent rectal cancer between 1990 and 2013 were divided into 4 groups: 1) tumor-free margins of >2 mm, 2) tumor-free margins of >0 to 2 mm, 3) microscopically involved margins, and 4) macroscopically involved margins. MAIN OUTCOME MEASURES: Local control and overall survival were the main outcome measures. RESULTS: A total of 174 patients with a median follow-up of 27 months (range, 0-144 months) were eligible for analysis. There was a significant difference in 5-year local re-recurrence-free survival in favor of 41 patients with tumor-free margins of >2 mm compared with 34 patients with tumor-free margins of >0 to 2 mm (80% vs 62%; p = 0.03) and a significant difference in 5-year overall survival (60% vs 37%; p = 0.01). The 5-year local re-recurrence-free and overall survival rates for 55 patients with microscopically involved margins were 28% and 16%, and for 20 patients with macroscopically involved margins the rates were 0% and 5%. On multivariable analysis, tumor-free margins of >0 to 2 mm were independently associated with higher re-recurrence rates (HR, 2.76 (95% CI, 1.06-7.16)) and poorer overall survival (HR, 2.57 (95% CI, 1.27-5.21)) compared with tumor-free margins of >2 mm. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Resection margin status is an independent prognostic factor for re-recurrence rate and overall survival in surgically treated, locally recurrent rectal cancer. In complete resections, patients with tumor-free resection margins of >0 to 2 mm have a higher re-recurrence rate and a poorer overall survival than patients with tumor-free resection margins of >2 mm.

The prognostic value of the primary tumor's nodal status after surgery for colorectal liver metastases in the era of effective systemic therapy.

BACKGROUND: The nodal status of primary colorectal cancer is of prognostic value for survival after the resection for colorectal liver metastases (CRLM). However, in the past decade,effective adjuvant chemotherapy for lymph node positive primary colon cancer was introduced. This study evaluated the prognostic value of primary lymph node status in patients with resectable metachronous CRLM in the era of effective systemic therapy. METHODS: Between January 2000 and December 2011, all consecutive patients undergoing curative liver resection for CRLM were retrospectively analyzed. Overall survival (OS) was analyzed by the localization of the primary tumor (colon vs. rectum) and by lymph node status (positive vs. negative) of the primary tumor. RESULTS: A total of 286 patients with metachronous CRLM's were selected. Five-year OS was similar for colon and rectal primaries (42 and 40%, p = 0.62). Lymph node positivity was only a prognostic factor in rectal primaries (N+ 32% vs. N0 49%, p = 0.04) and not in colon primaries (N+ 42% vs. N0 41%, p = 0.99). In multivariate analysis, these results were confirmed. CONCLUSION: The current study demonstrates that the nodal status of primary colon malignancies does not have prognostic value in patients undergoing resection for metachronous CRLM. A possible explanation might be the administration of effective adjuvant chemotherapy in node positive colon cancer.

Outcome in patients with resectable locally recurrent rectal cancer after total mesorectal excision with and without previous neoadjuvant radiotherapy for the primary rectal tumor.

BACKGROUND: The widespread use of neoadjuvant radiotherapy (nRTx) followed by total mesorectal excision (TME) introduced the problem of treating locally recurrent rectal cancer (LRRC) after nRTx and TME. Few data exist on the outcome of the surgical treatment of this type of LRRC and the influence of nRTx for the primary tumor on the outcome is unclear. METHODS: All patients receiving multimodality treatment (including intraoperative radiotherapy) for LRRC in our center between 1996 and 2012 were analyzed retrospectively. The outcome of patients with nonmetastasized resectable LRRC who received nRTx and TME for the primary tumor was compared to the outcome of patients who did not receive nRTx for the primary tumor. RESULTS: During this period, 139 patients underwent surgery for LRRC; 93 of these patients underwent curative surgery for LRRC after TME for the primary tumor. Sixty-five patients did not receive nRTx for the primary tumor, whereas 28 patients received nRTx for the primary tumor. There were no significant differences in the number of incomplete resections or perioperative morbidities. There was no significant difference in 5-year overall survival (28 vs. 43%, p = 0.81), recurrence-free survival (55 vs. 48%, p = 0.5), and disease-free survival (27 vs. 40%, p = 0.59). CONCLUSIONS: Surgical treatment of carefully selected patients with nonmetastasized resectable LRRC after nRTx and TME for the primary tumor is feasible and can result in sustained local control and overall survival. Patients with resectable LRRC who received nRTx for the primary tumor do not have a poorer outcome than patients who did not.

Surgical Outcomes after Full Thickness Chest Wall Resection Followed by Immediate Reconstruction: A 7-Year Observational Study of 42 Cases.

Introduction: Reconstruction of full thickness chest wall defects is challenging and is associated with a considerable risk of complications. Therefore, the aim of this study was to investigate the surgical outcomes and their associations with patient and treatment characteristics following full thickness chest wall reconstruction. Patients and methods: A retrospective observational study was performed by including patients who underwent reconstruction of full thickness chest wall defect at the Erasmus MC between January 2014 and December 2020. The type of reconstruction was categorized into skeletal and soft tissue reconstructions. For skeletal reconstruction, only non-rigid prosthetic materials were used. Patient and surgical characteristics were retrieved and analyzed for associations with postoperative complications. Results: Thirty-two women and 10 men with a mean age of 60 years were included. In 26 patients (61.9%), the reconstruction was performed using prosthetic material and a soft tissue flap, in nine cases (21.4%) only a soft tissue flap was used, and in seven other patients (16.7%) only the prosthetic material was used. Pedicled musculocutaneous latissimus dorsi flaps were used most often (n=17), followed by pectoralis major flaps (n=8) and free flaps (n=8). Twenty-two patients (52.4%) developed at least one postoperative complication. Wounds (21.4%) and pulmonary (19.0%) complications occurred most frequently. Five (11.9%) patients required reoperation. There were no associations between patient and treatment characteristics and the occurrence of major complications. There was no mortality. Conclusions: Reconstruction of full thickness chest wall defects using only non-rigid prosthetic material for skeletal reconstruction appears safe with an acceptable reoperation rate and low mortality, questioning the need for rigid fixation techniques.

Quality of life in patients with a perineal hernia.

INTRODUCTION: Patients who develop a perineal hernia after abdominoperineal resection may experience discomfort during daily activities and urogenital dysfunction, but the impact on quality of life has never been formally assessed. MATERIALS AND METHODS: Patients who underwent abdominoperineal resection for rectal cancer between 2014 and 2022 in two prospective multicenter trials were included. Primary outcome was defined as median overall scores or scores on functional and symptom scales of the following quality of life questionnaires: 5-level version of the 5-dimensional EuroQol, Short Form-36, and European Organization for Research and Treatment of Cancer QoL Questionnaire Colorectal cancer 29 and 30, Urogenital Distress Inventory-6, Incontinence Impact Questionnaire-7. RESULTS: Questionnaires were available in 27 patients with a perineal hernia and 62 patients without a perineal hernia. The 5-dimensional EuroQol score was significantly lower in patients with a perineal hernia (83 vs 87, p = 0.048), which implies a reduced level of functioning. The median scores of pain-specific domains were significantly worse in patients with a perineal hernia as measured by the SF-36 (78 vs. 90, p = 0.006), the EORTC-CR29 (17 vs. 11, p=<0.001) and EORTC-C30 (17 vs. 0, p = 0.019). Also, significantly worse physical (73 vs. 100, p = 0.049) and emotional (83 vs. 100, p = 0.048) functioning based on EORTC-C30 was observed among those patients. Minimally important differences were found for role, physical and social functioning of the SF-36 and EORTC-C30. The urological function did not differ between the groups. CONCLUSION: A symptomatic perineal hernia can significantly worsen quality of life on several domains, indicating the severity of this complication.

Multidisciplinary Virtual Three-Dimensional Planning of a Forequarter Amputation With Chest Wall Resection.

We present the case of a 74-year-old man with a history of a squamous cell carcinoma in the left axilla. The patient underwent a multidisciplinary surgical resection through an extended forequarter amputation with thoracic wall resection and reconstruction. With regard to the complexity of the case, three-dimensional virtual reality-based patient-specific reconstructions were used as a supplemental tool to conventional computed tomography imaging to plan the procedure. With this report, we aim to stimulate further research to improve and automate the workflow and to bring virtual and augmented reality reconstructions into the surgical theater of the future.

Impact of nutritional status and body composition on postoperative outcomes after pelvic exenteration for locally advanced and locally recurrent rectal cancer.

BACKGROUND: Pelvic exenteration for locally advanced rectal cancer (LARC) and locally recurrent (LRRC) rectal cancer provides radical resection and local control, but is associated with considerable morbidity. The aim of this study was to determine risk factors, including nutritional status and body composition, for postoperative morbidity and survival after pelvic exenteration in patients with LARC or LRRC. METHODS: Patients with LARC or LRRC who underwent total or posterior pelvic exenteration in a tertiary referral centre from 2003 to 2018 were analysed retrospectively. Nutritional status was assessed using the Malnutrition Universal Screening Tool (MUST). Body composition was estimated using standard-of-care preoperative CT of the abdomen. Logistic regression analyses were performed to identify risk factors for complications with a Clavien-Dindo grade of III or higher. Risk factors for impaired overall survival were calculated using Cox proportional hazards analysis. RESULTS: In total, 227 patients who underwent total (111) or posterior (116) pelvic exenteration were analysed. Major complications (Clavien-Dindo grade at least III) occurred in 82 patients (36.1 per cent). High risk of malnutrition (MUST score 2 or higher) was the only risk factor for major complications (odds ratio 3.99, 95 per cent c.i. 1.76 to 9.02) in multivariable analysis. Mean follow-up was 44.6 months. LRRC (hazard ratio (HR) 1.61, 95 per cent c.i. 1.04 to 2.48) and lymphovascular invasion (HR 2.20, 1.38 to 3.51) were independent risk factors for impaired overall survival. CONCLUSION: A high risk of malnutrition according to the MUST is a strong risk factor for major complications in patients with LARC or LRRC undergoing exenteration surgery.

Intraoperative Electron Beam Radiation Therapy (IOERT) Versus High-Dose-Rate Intraoperative Brachytherapy (HDR-IORT) in Patients With an R1 Resection for Locally Advanced or Locally Recurrent Rectal Cancer.

PURPOSE: Intraoperative radiation therapy (IORT), delivered by intraoperative electron beam radiation therapy (IOERT) or high-dose-rate intraoperative brachytherapy (HDR-IORT), may reduce the local recurrence rate in patients with locally advanced and locally recurrent rectal cancer (LARC and LRRC, respectively). The aim of this study was to compare the oncological outcomes between both IORT modalities in patients with LARC or LRRC who underwent a microscopic irradical (R1) resection. METHODS: All consecutive patients who received IORT because of an R1 resection of LARC or LRRC between 2000 and 2016 in two tertiary referral centers were included. In LARC, a resection margin of ≤2 mm was considered R1. A resection margin of 0 mm was considered R1 in LRRC. RESULTS: In total, 215 patients with LARC were included, of whom 151 (70%) received IOERT and 64 (30%) received HDR-IORT; in addition, 158 patients with LRRC were included, of whom 112 (71%) received IOERT and 46 (29%) received HDR-IORT. After multivariable analyses, the overall survival was not significantly different between the two IORT modalities. The local recurrence-free survival was significantly longer in patients treated with HDR-IORT, both in LARC (hazard ratio [HR], 0.496; 95% CI, 0.253-0.973; P = .041) and LRRC (HR, 0.567; 95% CI, 0.349-0.920; P = .021). In patients with LARC, major postoperative complications were similar for both IORT modalities (IOERT, 30%; HDR-IORT, 27%), whereas in patients with LRRC, the incidence of major postoperative complications was higher after HDR-IORT (IOERT, 26%; HDR-IORT, 46%). CONCLUSIONS: This study showed a significantly better local recurrence-free survival in favor of HDR-IORT in patients with an R1 resection for LARC or LRRC. Optimization of the IOERT technique seems warranted.

Isolated (hypoxic) hepatic perfusion with high-dose chemotherapy in patients with unresectable liver metastases of uveal melanoma: results from two experienced centres.

Uveal melanoma patients have a poor survival after the diagnosis of metastatic disease. Isolated hepatic perfusion (IHP) was developed to treat patients with unresectable metastases confined to the liver. This retrospective analysis focuses on treatment characteristics, complications, toxicity and survival after IHP. Patients with uveal melanoma metastases confined to the liver treated with IHP in two experienced hepato-pancreatic-biliary surgery centres (Erasmus MC Cancer Institute and Leiden University Medical Center) were included. Between March 1999 and April 2009, 30 patients were treated with IHP. The duration of surgery was 3.7 h (Erasmus MC Cancer Institute) versus 8.7 h (Leiden University Medical Center) and also the dosage of melphalan differed: 1 mg/kg body weight (n=12) versus a dose of 170-200 mg (n=18) or melphalan (100 mg) combined with oxaliplatin (50 or 100 mg) (n=3). The length of hospital stay was 10 days. Two patients developed occlusion of the hepatic artery and died, respectively, 3 days and 1.5 months after surgery. Progression-free survival was 6 (1-16) months and recurrences occurred mainly in the liver. The median overall survival was 10 (3-50) months. IHP is a potentially beneficial treatment modality resulting in a reasonable overall survival for uveal melanoma patients. Because of considerable morbidity related to the open procedure, a percutaneous system has been developed and is currently being investigated.

[The treatment of locally recurrent rectal cancer]. / Behandeling van lokaal recidiverend rectumcarcinoom.

Its incidence has decreased in recent decades due to advances in the treatment of patients with primary rectal cancer, but LRRC still occurs in 6-10% of these patients. LRRC is often accompanied by severe, progressive pain and has a major impact on quality of life. Curative treatment is possible based on surgical resection combined with chemoradiotherapy. Radical resection is the most important prognostic factor in curative treatment. Neo-adjuvant systemic therapy may further improve outcomes in LRRC patients. Many patients are not eligible for surgical treatment due to the presence of metastases or irresectability of the local recurrence. These patients should receive optimal palliative care for the disabling pain. Radiotherapy is effective against local pain in around 75% of patients but the duration of palliation is limited.

A systemic antitumor immune response prevents outgrowth of lung tumors after i.v. rechallenge but is not able to prevent growth of experimental liver tumors.

Although a systemic antitumor immune response by antibodies or T cells is often detected in cancer patients, this response mostly does not result in tumor rejection. The beneficial effect of tumor vaccination on survival rates is limited as tumor response is low. In contrast to solid tumors, circulating tumor cells may be more easily accessible and therefore destroyed by the immune system and thus prevent metastases. This discrepancy is further clarified in our study, by assessing the effect of a systemic immune response on established liver tumors and circulating tumor cells. Male Wag/Rij rats were inoculated with CC531 colorectal tumor cells subcapsulary in the liver, with or without immune suppression (60 mg/kg cyclophosphamide). To study the effect of a systemic immune response, rats received CC531 tumor cells intravenously and three weeks later the number of lung tumors was assessed. Presence of specific anti-CC531 antibodies in serum was determined by flow cytometric analysis at times of inoculation, i.v. tumor cell administration and sacrifice. Rats with liver tumors and subsequent rechallenge produced anti-CC531 IgG antibodies and did not develop lung tumors, whereas without existing liver tumors, rats developed lung tumors upon i.v. administration of CC531 tumor cells. Liver tumors in rats with and without i.v. CC531 tumor cell administration were equal in size. These results showed that a systemic immune response, induced upon liver tumor induction and rechallenge, prevented formation of lung tumors but did not affect tumor growth in the liver. Possibly the immune response lacked the ability to penetrate the protective extracellular matrix surrounding the established liver tumors, which prevented the tumor cells from recognition by and contact with cells of the immune system.

Immunohistochemical detection of melphalan-DNA adducts in colon cancer cells in vitro and human colorectal liver tumours in vivo.

Melphalan is a chemotherapeutic drug that exerts its cytotoxic effect mainly through the formation of DNA adducts. We report the specific immunohistochemical detection and visualisation of melphalan-DNA adducts using the monoclonal antibody MP5/73 in cultured tumour cells and solid tumour tissue from colorectal liver metastases from patients treated with melphalan. The human colon cancer cell lines HT29, SW480 and SW1116, and the rat colon cancer cell line CC531 were exposed to different concentrations of melphalan. In addition, tumour samples from 17 patients with colorectal liver metastases treated by isolated hepatic perfusion with high dose melphalan (200mg) were collected. Cell lines and tumour samples were stained with the MP5/73 antibody against melphalan-DNA adducts and cell viability was determined by an MTT assay. Melphalan-DNA adducts could be visualised by immunohistochemistry in both cultured cells and solid tumour tissue. A correlation between melphalan exposure concentration, the subsequent melphalan-DNA adduct staining intensity, and melphalan cytotoxicity existed for each individual cell line, but the level of both parameters independently differed between cell lines. Specific staining for melphalan-DNA adducts also was feasible in the human solid tumour tissue. There was considerable variation in melphalan-DNA adduct staining, staining intensity, and distribution in the tumour stroma and the tumour epithelium among the different patients. Melphalan-DNA adducts appeared to be more intense in tumour cells at the border of the tumour nodules than in tumour cells in the centre. Thus, visualisation of melphalan-DNA adducts by immunohistochemistry allows the study of distribution of melphalan-DNA adducts in solid tumours.