Development of a reliable surgical quality assurance tool for gastrectomy in oncological trials.

BACKGROUND: Despite its recognized importance, there is currently no reliable tool for surgical quality assurance (SQA) of gastrectomy in surgical oncology. The aim of this study was to develop an SQA tool for gastrectomy and to apply this tool within the ADDICT Trial in order to assess the extent and completeness of lymphadenectomy. METHODS: The operative steps for D1+ and D2 gastrectomy have been previously described in the literature and ADDICT trial manual. Two researchers also performed fieldwork in the UK and Japan to document key operative steps through photographs and semi-structured interviews with expert surgeons. This provided the steps that were used as the framework for the SQA tool. Sixty-two photographic cases from the ADDICT Trial were rated by three independent surgeons. Generalizability (G) theory determined inter-rater reliability. D-studies examined the effect of varying the number of assessors and photographic series they rated. Chi-square assessed intra-rater reliability, comparing how the individual assessor's responses corresponded to their global rating for extent of lymphadenectomy. RESULTS: The tool comprised 20 items, including 19 anatomical landmarks and a global rating score. Overall reliability had G-coefficient of 0.557. Internal consistency was measured with a Cronbach's alpha score of 0.869 and Chi-square confirmed intra-rater reliability for each assessor as < 0.05. CONCLUSIONS: A photographic surgical quality assurance tool is presented for gastrectomy. Using this tool, the assessor can reliably determine not only the quality but also the extent of the lymphadenectomy performed based on remaining anatomy rather than the excised specimen.

Characterizing occupational radon exposure greater than 100 Bq/m3 in a highly exposed country.

Radon is an established lung carcinogen concentrating in indoor environments with importance for many workers worldwide. However, a systematic assessment of radon levels faced by all workers, not just those with direct uranium or radon exposure, has not previously been completed. The objective of this study was to estimate the prevalence of workers exposed to radon, and the level of exposure (> 100-200 Bq/m3, 200-400 Bq/m3, 400-800 Bq/m3, and > 800 Bq/m3) in a highly exposed country (Canada). Exposures among underground workers were assessed using the CAREX Canada approach. Radon concentrations in indoor workplaces, obtained from two Canadian surveys, were modelled using lognormal distributions. Distributions were then applied to the susceptible indoor worker population to yield the number of exposed workers, by occupation, industry, province, and sex. In total, an estimated 603,000 out of Canada's 18,268,120 workers are exposed to radon in Canada. An estimated52% of exposed workers are women, even though they comprise only 48% of the labour force. The majority (68%) are exposed at a level of > 100-200 Bq/m3. Workers are primarily exposed in educational services, professional, scientific and technical services, and health care and social assistance, but workers in mining, quarrying, and oil and gas extraction have the largest number of exposed workers at high levels (> 800 Bq/m3). Overall, a significant number of workers are exposed to radon, many of whom are not adequately protected by existing guidelines. Radon surveys across multiple industries and occupations are needed to better characterize occupational exposure. These results can be used to identify exposed workers, and to support lung cancer prevention programs within these groups.

Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for gastric cancer with peritoneal metastases: A systematic review by the PIPAC UK collaborative.

INTRODUCTION: Gastric cancer with peritoneal metastases (GCPM) carries a poor prognosis. Pressurised Intraperitoneal Aerosolised Chemotherapy (PIPAC) offers pharmacokinetic advantages over intravenous therapy, resulting in higher chemotherapy concentrations in peritoneal deposits, and potentially reduced systemic absorption/toxicity. This review evaluates efficacy, tolerability and impact on quality of life (QOL) of PIPAC for GCPM. METHODS: Following registration with PROSPERO (CRD42021281500), MEDLINE, EMBASE and The Cochrane Library were searched for PIPAC in patients with peritoneal metastases, in accordance with PRISMA standards RESULTS: Across 18 included reports representing 751 patients with GCPM (4 prospective, 11 retrospective, 3 abstracts, no phase III studies), median overall survival (mOS) was 8 - 19.1 months, 1-year OS 49.8-77.9%, complete response (PRGS1) 0-35% and partial response (PRGS2/3) 0-83.3%. Grade 3 and 4 toxicity was 0.7-25% and 0-4.1% respectively. Three studies assessing QOL reported no significant difference. CONCLUSION: PIPAC may offer promising survival benefits, toxicity, and QOL for GCPM.

Safe design and maintenance of bone marrow transplant units: a narrative review.

BACKGROUND: Patients undergoing bone marrow transplantation or chemotherapy for cancer are profoundly immunosuppressed. They are at risk for both endogenous and exogenous infections and require enhanced protection from infection while in hospital. OBJECTIVES: The aim of this narrative review was to determine the optimal design features of bone marrow transplant (BMT) units for reducing infection risk in these vulnerable patients. SOURCES: A literature search was performed on PubMed and other databases for documents published between January 2000 and October 2021. Keywords were: bone marrow transplant unit OR hematopoietic stem cell transplant unit OR haematology unit OR haemato-oncology unit AND design OR design guidelines OR design criteria OR ventilation specification OR HEPA filtration OR water outbreaks OR water system design. CONTENT: Guidelines and other papers pertaining to BMT unit design are discussed. Key design features identified from the literature to reduce infection risks include high efficiency particulate air filtration, positive-pressure ventilation, sufficient air changes and sealed rooms. The evidence for each of these parameters and other findings are discussed. We found no guidelines specific to water quality and control in BMT units. IMPLICATIONS: Guidelines on the various components of design were found, but no comprehensive guidance documents addressing all relevant aspects, such as ventilation, water, and other design features, were found. Literary publications and policy documents were combined and summarised to highlight key design features aimed at reducing infection risk in this vulnerable patient group. We propose the development of international guidance for the design of BMT units encompassing all components.

Association study of candidate DNA-repair gene variants and acute graft versus host disease in pediatric patients receiving allogeneic hematopoietic stem-cell transplantation.

Acute Graft versus Host Disease (aGvHD) grades 2-4 occurs in 15-60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function. We explored 51 variants within 17 DNA-repair genes for their association with aGvHD grades 2-4 in 60 pediatric patients. The cumulative incidence of aGvHD 2-4 was 12% (n = 7) in the exploratory cohort. MGMT rs10764881 (G>A) and EXO rs9350 (c.2270C>T) variants were associated with aGvHD 2-4 [Odds ratios = 14.8 (0 events out of 40 in rs10764881 GG group) and 11.5 (95% CI: 2.3-191.8), respectively, multiple testing corrected p ≤ 0.001]. Upon evaluation in an extended cohort (n = 182) with an incidence of aGvHD 2-4 of 22% (n = 40), only MGMT rs10764881 (G>A) remained significant (adjusted HR = 2.05 [95% CI: 1.06-3.94]; p = 0.03) in the presence of other clinical risk factors. Higher MGMT expression was seen in GG carriers for rs10764881 and was associated with higher IC50 of Busulfan in lymphoblastoid cells. MGMT rs10764881 carrier status could predict aGvHD occurrence in pediatric patients undergoing allo-HSCT.

Investigation of two cases of Mycobacterium chelonae infection in haemato-oncology patients using whole-genome sequencing and a potential link to the hospital water supply.

BACKGROUND: Haemato-oncology patients are at increased risk of infection from atypical mycobacteria such as Mycobacterium chelonae which are commonly found in both domestic and hospital water systems. AIMS: To describe the investigation and control measures following two patient cases of M. chelonae and positive water samples in the study hospital. METHODS: Water testing was undertaken from outlets, storage tanks and mains supply. Whole-genome sequencing (WGS) was used to compare patient and positive water samples. The subsequent infection control measures implemented are described. FINDINGS: The WGS results showed two main populations of M. chelonae within the group of sampled isolates. The results showed that the patient strains were unrelated to each other, but that the isolate from one patient was closely related to environmental samples from water outlets, supporting nosocomial acquisition. CONCLUSIONS: WGS was used to investigate two patient cases of M. chelonae and positive water samples from a hospital water supply. Relevant control measures and the potential for chemical dosing of water systems to enhance proliferation of atypical mycobacteria are discussed.

Investigation and control of an outbreak due to a contaminated hospital water system, identified following a rare case of Cupriavidus pauculus bacteraemia.

BACKGROUND: Cupriavidus pauculus is rare cause of clinical infection. We describe an outbreak of C. pauculus and other Gram-negative bacteraemias in a paediatric haemato-oncology unit secondary to a contaminated water supply and drainage system. AIM: To describe the investigation and control measures implemented for a waterborne infection outbreak in a new build hospital. METHODS: Extensive water testing from various points within the water system was undertaken. Taps, showerheads and components including flow straighteners underwent microbiological analysis. Drains were also swabbed. Surveillance for Gram-negative infections was established on the unit. FINDINGS: Water testing revealed widespread contamination of the water and drainage system. Outlets were also heavily contaminated, including flow straighteners. Drains were found to have underlying structural abnormalities. Water testing enabled us to detect high-risk components within the water system such as the expansion vessels and outlets and the results assisted with hypotheses generation. Review of commissioning data and risk assessments revealed extensive risks present within the water system prior to and after hospital opening. CONCLUSION: Careful design, adequate control measures and maintenance are essential for hospital water systems in order to prevent infections due to waterborne organisms. We discuss what can be learned from this incident with a view to future prevention.

Estimating the burden of lung cancer in Canada attributed to occupational radon exposure using a novel exposure assessment method.

OBJECTIVE: Exposure to radon causes lung cancer. The scope and impact of exposure among Canadian workers have not been assessed. Our study estimated occupational radon exposure in Canada and its associated lung cancer burden. METHODS: Exposed workers were identified among the working population during the risk exposure period (1961-2001) using data from the Canadian Census and Labour Force Survey. Exposure levels were assigned based on 12,865 workplace radon measurements for indoor workers and assumed to be 1800 mg/m3 for underground workers. Lung cancer risks were calculated using the Biological Effects of Ionizing Radiation (BEIR) VI exposure-age-concentration model. Population attributable fractions were calculated with Levin's equation and applied to 2011 Canadian lung cancer statistics. RESULTS: Approximately 15.5 million Canadian workers were exposed to radon during the risk exposure period. 79% of exposed workers were exposed to radon levels < 50 Bq/m3 and 4.8% were exposed to levels > 150 Bq/m3. We estimated that 0.8% of lung cancers in Canada were attributable to occupational radon exposure, corresponding to approximately 188 incident lung cancers in 2011. CONCLUSIONS: The lung cancer burden associated with occupational radon exposure in Canada is small, with the greatest burden occurring among those exposed to low levels of radon.

High dose chemotherapy and autologous hematopoietic cell transplantation for Wilms tumor: a study of the European Society for Blood and Marrow Transplantation.

Survival for subgroups of patients with Wilms tumor (WT), such as those who suffer from relapse, is disappointing. Some patients' treatment plans include high-dose chemotherapy (HDT) with autologous hematopoietic cell transplantation (aHCT), although proof for its benefit is lacking. To increase the level of evidence regarding children with WT receiving aHCT as consolidation of first or second remission (after first relapse), we extracted relevant data from the European Blood and Marrow Transplantation Registry concerning 69 patients. Different HDT regimens were administered, mostly either melphalan-containing (n = 34) or thiotepa-containing (n = 14). For the whole population, 5-year overall survival (OS) and event-free survival (EFS) probabilities were 0.67 (±0.06) and 0.63 (±0.06), respectively (median observation time 7.8 years); for children transplanted in first remission, OS and EFS were 0.69 (±0.09) and 0.72 (±0.08). In univariate analysis, male gender and relapse in multiple sites were associated with lower OS probabilities. The use of a given pretransplant regimen (i.e. melphalan alone versus regimens with multiple drugs) did not seem to influence EFS/OS probability after aHCT, but significantly influenced platelet engraftment (more delayed with thiotepa). We here provide further data to improve the basis for future evidence-based clinical decision-making when using HDT and aHCT in relapsed/refractory WT.

Management of growth failure and growth hormone deficiency after pediatric allogeneic HSCT: Endocrinologists are of importance for further guidelines and studies.

Growth failure (GF) is a frequent problem after pediatric allogeneic hematopoietic stem cell transplantation (HSCT). Growth hormone deficiency (GHD) occurs in 20 to 85%, but published data on the efficacy of growth hormone treatment (GHT) are conflicting. Currently, there are no recommendations on screening for and treatment of GHD after HSCT. We aimed to describe the management of endocrine follow-up (FU)and details of GHT within European Society for Blood and Marrow Transplantation (EBMT) centers.In a retrospective questionnaire study, all EBMT centers performing pediatric HSCT were invited. Results were evaluated in correlation with the structure of endocrine aftercare (HSCT-clinicians and endocrinologists).The majority of centers (80%) reported endocrine FU by an endocrinologist - either within the HSCT-center or in a separate endocrine clinic. Fifty-four percent reported FU outside of the HSCT-center. As diagnostic tests the insulin-like growth factor IGF-I and insulin-like growth factor binding protein IGFBP3, insulin tolerance test and arginine stimulation test were most frequently used. Sixty-four percent of centers performed GHT and endocrinologists were more likely to prescribe GH (74%) compared to HSCT-clinicians (33%). The most frequent indication for GHT was GHD in 60%, with a distinct different approach of endocrinologists in comparison with HSCT-clinicians.Our study reveals substantial variation in practice and emphasizes the need for endocrine aftercare performed by dedicated endocrinologists in close collaboration with the HSCT-center. Our results indicate that the management of GHT depends on the structure of endocrine aftercare, which is important for the future development and distribution of studies and guidelines.

Correction of mildly dysplastic hips with periacetabular osteotomy demonstrates promising outcomes, achievement of correction goals, and excellent five-year survivorship.

AIMS: The aim of this study was to compare patient-reported outcome measures (PROMs), radiological measurements, and total hip arthroplasty (THA)-free survival in patients who underwent periacetabular osteotomy (PAO) for mild, moderate, or severe developmental dysplasia of the hip. PATIENTS AND METHODS: We performed a retrospective study involving 336 patients (420 hips) who underwent PAO by a single surgeon at an academic centre. After exclusions, 124 patients (149 hips) were included. The preoperative lateral centre-edge angle (LCEA) was used to classify the severity of dysplasia: 18° to 25° was considered mild (n = 20), 10° to 17° moderate (n = 66), and < 10° severe (n = 63). There was no difference in patient characteristics between the groups (all, p > 0.05). Pre- and postoperative radiological measurements were made. The National Institute of Health's Patient Reported Outcomes Measurement Information System (PROMIS) outcome measures (physical function computerized adaptive test (PF CAT), Global Physical and Mental Health Scores) were collected. Failure was defined as conversion to THA or PF CAT scores < 40, and was assessed with Kaplan-Meier analysis. The mean follow-up was five years (2 to 10) ending in either failure or the latest contact with the patient. RESULTS: There was no significant difference in PROMs for moderate (p = 0.167) or severe (p = 0.708) groups compared with the mild dysplasia group. The numerical pain scores were between 2 and 3 units in all groups at the final follow-up (all, p > 0.05). There was no significant difference (all, p > 0.05) in the proportion of patients achieving target correction for the LCEA between groups. The mean correction was 12° in the mild, 15° in the moderate (p = 0.135), and 23° in the severe group (p < 0.001). Failure-free survival at five years was 100% for mild, 79% for moderate, and 92% for severely dysplastic hips (p = 0.225). CONCLUSION: Although requiring less correction than hips with moderate or severe dysplasia, we found PAO for mild dysplasia to be associated with promising PROMs, consistent with that of the general United States population, and excellent survivorship at five years. Future studies should compare these results with the outcome after arthroscopy of the hip in patients with mild dysplasia. Cite this article: Bone Joint J 2019;101-B(6 Supple B):16-22.

Robotic excision and ureteroureterostomy of blind-ending ureteral 'Duplication'.

INTRODUCTION: Duplicated ureteral anatomy can be a reconstructive challenge. Blind-ending ureteral duplication has been reported with recommendations for surgical excision. OBJECTIVE: This video reviews the importance of exposure of anatomic landmarks in surgical excision of a blind-ending ureteral duplication. MATERIALS AND METHODS: This is a retrospective case report of a patient who presented with a blind-ending ureteral duplication. DISCUSSION: A 13-year-old female presented with a right-sided abdominal mass. Abdominal and pelvic imaging revealed a tubular structure adjacent to and below the right kidney, possibly connecting to the right lower pole. While initially observed, the patient re-presented with urosepsis. A retrograde pyelogram showed no connection between the right ureter and this structure. The patient underwent robotic-assisted excision of this structure. Intra-operatively, it was connected to the right lower pole calyces. A ureteroureterostomy to the orthotopic ureter was performed. Although the structure was adjacent to the bladder dome, there was no communication distally. Postoperatively, the patient did well; follow-up imaging showed a non-dilated lower pole. The pathology of this structure was benign urothelium. CONCLUSIONS: Surgical management of aberrant ureteral duplications should focus on identifying known landmarks and should be considered to prevent symptomatic infections and renal scarring.

Ten-year survivorship of primary total hip arthroplasty in patients 30 years of age or younger.

Aims: For this retrospective cohort study, patients aged ≤ 30 years (very young) who underwent total hip arthroplasty (THA) were compared with patients aged ≥ 60 years (elderly) to evaluate the rate of revision arthroplasty, implant survival, the indications for revision, the complications, and the patient-reported outcomes. Patients and Methods: We retrospectively reviewed all patients who underwent primary THA between January 2000 and May 2015 from our institutional database. A total of 145 very young and 1359 elderly patients were reviewed. The mean follow-up was 5.3 years (1 to 18). Logistic generalized estimating equations were used to compare characteristics and the revision rate. Survival was evaluated using Kaplan-Meier curves and hazard rates were created using Cox regression. Results: The overall revision rate was 11% (16/145) in the very young and 3.83% (52/1359) in the elderly groups (odds ratio (OR) 2.58, 95% confidence interval (CI) 1.43 to 4.63). After adjusting for the American Society of Anesthesiologists (ASA) score, gender, and a history of previous surgery in a time-to-event model, the risk of revision remained greater in the very young (adjusted hazard ratio (HR) 2.48, 95% CI 1.34 to 4.58). Survival at ten years was 82% (95% CI, 71 to 89) in the very young and 96% (95% CI, 94 to 97) in the elderly group (p < 0.001). The very young had a higher rate of revision for complications related to metal-on-metal (MoM) bearing surfaces (p < 0.001). At last follow-up, the very young group had higher levels of physical function (p = 0.002), lower levels of mental health (p = 0.001), and similar levels of pain (p = 0.670) compared with their elderly counterparts. Conclusion: The overall revision rate was greater in very young THA patients. This was largely explained by the use of MoM bearings. Young patients with non-MoM bearings had high survivorship with similar complication profiles to patients aged ≥ 60 years. Cite this article: Bone Joint J 2018;100-B:867-74.

Association of CTH variant with sinusoidal obstruction syndrome in children receiving intravenous busulfan and cyclophosphamide before hematopoietic stem cell transplantation.

Sinusoidal obstruction syndrome (SOS) is a severe complication of hematopoietic stem cell transplantation (HSCT) that can be fatal, often attributed to the conditioning regimen prior to HSCT. We evaluated the association of SOS risk with gene variants in cystathionase (CTH), an enzyme involved in glutathione synthesis, in 76 children receiving intravenous busulfan (Bu) before HSCT. Our results indicated an association with CTHc.1364 G>T (ORTT=10.6, 95% confidence interval (CI)=2.16, 51.54) and SOS risk, which was sex dependent (female patients, ORTT=21.82, 95% CI=3.590-132.649). The interaction between CTHc.1364 G>T and another risk variant (GSTA1*B) was explored. A recessive model with the use of GSTA1*B*B and CTH c.1364 TT genotypes proved to be useful at predicting SOS occurrence, indicating the possibility of using these gene variants as markers of SOS occurrence and to further individualize preemptive treatment aimed at reducing SOS incidence.

Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European society for blood and marrow transplantation.

The advances in hematopoietic cell transplantation (HCT) over the last decade have led to a transplant-related mortality below 15%. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate >80%. A timely diagnosis of SOS/VOD is of critical importance, given the availability of therapeutic options with favorable tolerability. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children. The aim of this position paper is to propose new diagnostic and severity criteria for SOS/VOD in children on behalf of the European Society for Blood and Marrow Transplantation.

In light of recently published clinical trials and their implication for clinical practice, does a large catchment area acute hospital require 24 hour CT neck and head angiography and/or neuro-interventional services in the setting of acute ischaemic stroke?

BACKGROUND: Recently published clinical trials have resulted in a significant change in the guidelines used to manage patients suffering an acute ischaemic stroke. New neuro-interventional techniques have revolutionised stroke outcomes. Currently, such services are only available in two specialist centres. AIMS: We attempted to evaluate the need for the provision of routine computed tomography (CT) angiography and neuro-interventional services at a university teaching hospital in Limerick. METHODS: A retrospective study was performed based on data collated by the stroke service, University Hospital Limerick (UHL). All patients with a suspected acute ischaemic stroke of anterior circulation and known evolution were included. Baseline clinical and imaging characteristics, thrombolysis data, stroke unit admission rates and discharge destinations were recorded. RESULTS: All 141 patients were suitable for CT angiography and should be performed in accordance with guidelines. Additionally, 165 patients excluded from the study due to an unknown stroke evolution timeframe may have benefitted. Non-contrast CT scan confirmed just 12 anterior circulation strokes. The need for neuro-interventional services proved more difficult to assess, primarily due to the lack of provision of routine CT angiography, employed to confirm anterior circulation occlusion. Secondary results showed a thrombolysis rate of 10.8% and confirmed that time efficiencies result in higher thrombolysis eligibility rates. Stroke unit admissions and discharge destinations were also recorded. CONCLUSION: UHL should provide routine CT angiography to all patients presenting with acute ischaemic stroke in line with current guidelines. The need for provision of neuro-interventional services on-site proved more difficult to assess and requires further analysis.

Prognostic value of the circumferential resection margin and its definitions in esophageal cancer patients after neoadjuvant chemoradiotherapy.

The accepted importance of a positive circumferential resection margin (CRM) (defined as R1 in the TNM classification) is based on histopathology of the resection specimen obtained after primary surgery in esophageal cancer patients. The aim of this study is to look for the prognostic value of CRM after neoadjuvant chemoradiotherapy and to compare the clinical significance of a histologically CRM < 1 mm from the cut margin (Royal College of Pathologists definition of R1) to a positive cut margin (College of American Pathologists definition of R1) and to ≥1 mm margin (R0) resections in patients with ypT3-esophageal tumors after neoadjuvant chemoradiotherapy. Between 2000 and 2014, 458 patients who received esophagectomy after neoadjuvant chemoradiation therapy were selected. Overall (OS) and disease-free survival (DFS) were calculated by means of Kaplan-Meier curves and compared by Cox regression analysis. There were 163 (35.9%) patients who had a ypT3 tumor; in 118 (72.4%) resection was complete (R0). In 37 (22.7%) patients a CRM < 1 mm was found and 8 (4.9%) had a circumferential R1-resection. CRM involvement was inversely correlated with tumor regression grading, lymph node capsular involvement, and number of positive lymph nodes. On univariate analysis, no statistically significant difference was found between R0-resection and CRM < 1 mm (P = 0.103) for OS, but DFS showed a significant difference (P = 0.025). Circumferential R1-resections showed a significant difference compared to R0-resections for OS and DFS (both P = 0.002). In multivariate analysis, extracapsular lymph node involvement and circumferential R1-resection were withheld as independent prognosticators for OS, whereas extracapsular lymph node involvement, absence of regression on the primary tumor and circumferential R1-resection were withheld for DFS. After correcting for different variables in the multivariate model, CRM < 1 mm showed no statistical difference compared to R0-resections neither for OS nor for DFS. After neoadjuvant chemoradiotherapy, CRM is correlated with biological behavior of the tumor and with therapy response. Furthermore it is an independent prognosticator for OS and DFS. However CRM < 1 mm itself is no independent prognosticator for OS nor DFS survival in multivariable analysis. These results suggest that the definition of R1-resection should be limited to true invasion of the section plane.