Evaluation of a Completion Total Mesorectal Excision in Patients After Local Excision of Rectal Cancer: A Word of Caution.

Background: According to Dutch guidelines, locally excised, low-risk, pT1 or ypT0-1 rectal cancer should not necessarily be followed by completion total mesorectal excision (cTME) in contrast to rectal cancers with higher T stages or unfavorable features. This study evaluated cTME after local excision at a national level with possible determinants for decision-making. Methods: All patients in the Dutch Colorectal Audit (DCRA) who underwent local excision of rectal cancer between 2012 and 2015 were included. Guideline adherence for performing cTME was determined with univariate and multivariate analyses to identify factors related to noncompliance. Results: According to the guidelines, of 530 included patients, cTME was indicated in 283 (53%), and among those, was performed in 82 (29%). Guideline adherence for performing cTME improved significantly (P<.001), from 10% in 2012 to 44% in 2015. Lower Charlson comorbidity index in patients with high-risk pT1 rectal cancer and younger patients (aged 61-70 years vs ≥80 years) with pT≥2 rectal cancer were associated with increased performance of cTME (odds ratio [OR], 13.50; 95% CI, 1.39-131.32, and OR, 6.25; 95% CI, 1.83-21.31, respectively). Conclusions: In this population-based study from the Netherlands, only a minority of patients underwent cTME after local excision of rectal cancer with pathologic features indicating the need for further treatment according to the guidelines. Although the percentage of patients undergoing cTME increased over time, the study indicated a tendency toward rectal-preserving treatment with potential oncologic risks.

Using the Comprehensive Complication Index to Assess the Impact of Neoadjuvant Chemoradiotherapy on Complication Severity After Esophagectomy for Cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery for patients with esophageal or junctional cancer has become a standard of care. The comprehensive complication index (CCI) has recently been developed and accounts for all postoperative complications. Hence, CCI better reflects the burden of all combined postoperative complications in surgical patients than the Clavien-Dindo score alone, which incorporates only the most severe complication. This study was designed to evaluate the severity of complications in patients treated with nCRT followed by esophagectomy versus in patients who underwent esophagectomy alone using the comprehensive complication index. STUDY-DESIGN: All patients included in the CROSS trial-a randomized, clinical trial on the value of nCRT followed by esophagectomy-were included. Complications were assessed and graded using the Clavien-Dindo classification. CCI was derived from these scores, using the CCI calculator available online ( www.assessurgery.com ). CCI of patients who underwent nCRT followed by surgery was compared with the CCI of patients who underwent surgery alone. RESULTS: In both groups 161 patients were included. The median (and interquartile range) CCI of patients with nCRT and surgery was 26.22 (17.28-42.43) versus 25.74 (8.66-43.01) in patients who underwent surgery alone (p = 0.58). There also was no difference in CCI between subgroups of patients with anastomotic leakage, pulmonary complications, cardiac complications, thromboembolic events, chyle leakage, and wound infections. CONCLUSIONS: Neoadjuvant chemoradiotherapy according to CROSS did not have a negative impact on postoperative complication severity expressed by CCI compared with patients who underwent surgery alone for potentially curable esophageal or junctional cancer.

Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial.

BACKGROUND: Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years. METHODS: Patients with clinically resectable, locally advanced cancer of the oesophagus or oesophagogastric junction (clinical stage T1N1M0 or T2-3N0-1M0, according to the TNM cancer staging system, sixth edition) were randomly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy (intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m(2) of body-surface area] for 23 days) with concurrent radiotherapy (41·4 Gy, given in 23 fractions of 1·8 Gy on 5 days per week) followed by surgery, or surgery alone. The primary endpoint was overall survival, analysed by intention-to-treat. No adverse event data were collected beyond those noted in the initial report of the trial. This trial is registered with the Netherlands Trial Register, number NTR487, and has been completed. FINDINGS: Between March 30, 2004, and Dec 2, 2008, 368 patients from eight participating centres (five academic centres and three large non-academic teaching hospitals) in the Netherlands were enrolled into this study and randomly assigned to the two treatment groups: 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone. Two patients in the neoadjuvant chemoradiotherapy group withdrew consent, so a total of 366 patients were analysed (178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group). Of 171 patients who received any neoadjuvant chemoradiotherapy in this group, 162 (95%) were able to complete the entire neoadjuvant chemoradiotherapy regimen. After a median follow-up for surviving patients of 84·1 months (range 61·1-116·8, IQR 70·7-96·6), median overall survival was 48·6 months (95% CI 32·1-65·1) in the neoadjuvant chemoradiotherapy plus surgery group and 24·0 months (14·2-33·7) in the surgery alone group (HR 0·68 [95% CI 0·53-0·88]; log-rank p=0·003). Median overall survival for patients with squamous cell carcinomas was 81·6 months (95% CI 47·2-116·0) in the neoadjuvant chemoradiotherapy plus surgery group and 21·1 months (15·4-26·7) in the surgery alone group (HR 0·48 [95% CI 0·28-0·83]; log-rank p=0·008); for patients with adenocarcinomas, it was 43·2 months (24·9-61·4) in the neoadjuvant chemoradiotherapy plus surgery group and 27·1 months (13·0-41·2) in the surgery alone group (HR 0·73 [95% CI 0·55-0·98]; log-rank p=0·038). INTERPRETATION: Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer. This improvement is clinically relevant for both squamous cell carcinoma and adenocarcinoma subtypes. Therefore, neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a standard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer. FUNDING: Dutch Cancer Foundation (KWF Kankerbestrijding).

Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer.

OBJECTIVE: To determine the relation between time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) and pathologically complete response (pCR), surgical outcome, and survival in patients with esophageal cancer. BACKGROUND: Standard treatment for potentially curable esophageal cancer is nCRT plus surgery after 4 to 6 weeks. In rectal cancer patients, evidence suggests that prolonged TTS is associated with a higher pCR rate and possibly with better survival. METHODS: We identified patients treated with nCRT plus surgery for esophageal cancer between 2001 and 2011. TTS (last day of radiotherapy to day of surgery) varied mainly for logistical reasons. Minimal follow-up was 24 months. The effect of TTS on pCR rate, postoperative complications, and survival was determined with (ordinal) logistic, linear, and Cox regression, respectively. RESULTS: In total, 325 patients were included. Median TTS was 48 days (p25-p75=40-60). After 45 days, TTS was associated with an increased probability of pCR [odds ratio (OR)=1.35 per additional week of TSS, P=0.0004] and a small increased risk of postoperative complications (OR=1.20, P<0.001). Prolonged TTS had no effect on disease-free and overall survivals (HR=1.00 and HR=1.06 per additional week of TSS, P=0.976 and P=0.139, respectively). CONCLUSIONS: Prolonged TTS after nCRT increases the probability of pCR and is associated with a slightly increased probability of postoperative complications, without affecting disease-free and overall survivals. We conclude that TTS can be safely prolonged from the usual 4 to 6 weeks up to at least 12 weeks, which facilitates a more conservative wait-and-see strategy after neoadjuvant chemoradiotherapy to be tested.

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

OBJECTIVES: We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. BACKGROUND: Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. METHODS: Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. RESULTS: One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). CONCLUSIONS: The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

Location of lymph node involvement in patients with esophageal adenocarcinoma predicts survival.

BACKGROUND: The location of positive lymph nodes has been abandoned in the seventh classification of the TNM staging system for esophageal adenocarcinoma. The present study evaluates whether distribution of involved nodes relative to the diaphragm in addition to TNM 7 further refines prediction. METHODS: Pathology reports of patients who underwent esophagectomy between 2000 and 2008 for adenocarcinoma of the esophagus were reviewed and staging was performed according to the seventh UICC-AJCC staging system. In addition, lymph node involvement of nodal stations above and below the diaphragm was investigated by endoscopic ultrasonography (EUS) in a separate cohort of patients who were scheduled for esophagectomy between 2008 and 2009 at two institutions. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed with a Cox regression model. RESULTS: Some 327 patients who had undergone esophagectomy for cancer were included. Multivariate analysis revealed that patients with from three to six involved lymph nodes in the resection specimen on both sides of the diaphragm had a twofold higher chance of dying compared to patients with the same number of involved lymph nodes on one side of the diaphragm. EUS assessment of lymph node metastases relative to the diaphragm in 102 patients showed that nodal involvement on both sides of the diaphragm was associated with worse survival than when nodes on one side or no nodes are involved [HR (95 % CI) 2.38 (1.15-4.90)]. CONCLUSIONS: A combined staging system that incorporates distribution of lymph nodes relative to the diaphragm refines prognostication after esophagectomy as assessed in the resected specimen and pretreatment as assessed by EUS. This improved staging has the potential to have a great impact on clinical decision making as to whether to embark upon potentially curative or palliative treatments.

Residual esophageal cancer after neoadjuvant chemoradiotherapy frequently involves the mucosa and submucosa.

OBJECTIVES: To gain insight into the exact location of residual esophageal cancer in the esophageal wall and regional lymph nodes after neoadjuvant chemoradiotherapy (nCRT) and to determine the pattern of regression. BACKGROUND: Data from the recently published chemoradiotherapy for oesophageal cancer followed by surgery study trial showed that 49% of squamous cell carcinomas and 23% of adenocarcinomas had a pathologically complete response (pCR) in the resection specimen after nCRT. These results impose the ethical imperative to reconsider the necessity of esophagectomy with its substantial morbidity and mortality in patients with pCR. However, it remains challenging to accurately identify these patients before resection. METHODS: Between January 2003 and July 2011, all patients with esophageal cancer in a tertiary referral center, who underwent nCRT (5 weekly courses of carboplatin and paclitaxel plus 41.4 Gy concurrent radiotherapy) and surgical resection, were analyzed. The resection specimens were carefully re-evaluated by an experienced gastrointestinal pathologist. Tumor regression grade (TRG) was meticulously scored for each specific layer of the esophageal wall and for all removed lymph nodes. RESULTS: One hundred two consecutive patients were included. Seventy-one (70%) of 102 patients were noncomplete responders (≥TRG2) and in 63 of these patients (89%), residual tumor cells were seen in the mucosa and/or submucosa. Five of 8 patients without involvement of the mucosa and the submucosa had isolated remnants in the muscle layer (5/102 = 5%); the other 3 patients had tumor cells only in a single lymph node (3/102 = 3%). The surrounding stroma showed the highest percentage of TRG1 ( = pCR: 47%). In patients with pretreatment lymph node positivity, the percentage of TRG1 in all lymph nodes was also favorable (52%). Overall regression showed a nonrandom mixed pattern of both concentric regression and regression toward the lumen. CONCLUSIONS: After nCRT for esophageal cancer, both the mucosa and the submucosa show frequent residual malignant involvement. The surrounding stroma and the regional lymph nodes show the highest percentage of pCR and the overall regression pattern is most frequently a mixed pattern of both concentric regression and regression toward the lumen. This overall regression pattern lends support to careful testing of a wait-and-see approach in a subgroup of patients with esophageal cancer after nCRT.

Impact of a multidisciplinary tumour board meeting for upper-GI malignancies on clinical decision making: a prospective cohort study.

BACKGROUND/AIMS: The Dutch guidelines for diagnosis and treatment of upper-GI malignancies recommend review of patients by a multidisciplinary tumour board (MDT). The purpose of this study was to determine the effect on clinical decision making of an MDT for patients with upper-GI malignancies. METHODS: All physicians participating in the MDT completed an electronic standardised case form to delineate their proposed treatment plan for the patients they presented, including the intent of treatment and the modality of treatment. This therapeutic or diagnostic proposal was then compared with the plan on which consensus was reached by the MDT. RESULTS: A total of 252/280 (90.0%) forms were completed and suitable for analysis. In 87/252 (34.5%) of the case presentations, the MDT altered the proposed plan of management. In 29/87 (33.3%) cases, a more extensive diagnostic work-up was decided upon. In 8/87 (9.2%) cases the curative intent of the proposed treatment was altered to palliation only. In 2/75 (2.7%) cases, however, it was decided that a patient could be treated with curative intent instead of the proposed palliative intent. CONCLUSION: In over 1/3 of cases, the diagnostic work-up or treatment plan is altered after evaluation by a multidisciplinary tumour board. This study supports Dutch guidelines recommending discussion of patients with upper-GI malignancies by a multidisciplinary tumour board.

Study on 3D High-Resolution Anorectal Manometry Interrater Agreement in the Evaluation of Dyssynergic Defecation Disorders.

Anorectal manometry measurements exhibit significant interrater variability. Newer techniques like 3D high-resolution anorectal manometry (3D-HRAM) have the potential to enhance diagnostic accuracy and our understanding of defecation disorders. However, the extent of interrater variability in 3D-HRAM is still unknown. Between January 2020 to April 2022, patients referred for pelvic floor physical therapy (PFPT) due to functional defecation complaints underwent 3D-HRAM testing. In a retrospective analysis, three expert raters independently evaluated the 3D-HRAM results in a blinded matter to assess interrater agreement. The evaluation also determined the level of agreement concerning dyssynergic patterns during simulated defecation. The 3D-HRAM results of 50 patients (37 females) were included. Twenty-nine patients had complaints of fecal incontinence, eleven patients had chronic constipation, and ten patients had several other complaints. There was a substantial agreement (kappa 0.612) between the raters concerning the 3D images on dyssynergic patterns during simulated defecation. Our study emphasizes the need for standardized guidelines in evaluating 3D-HRAM test results to reduce subjectivity and further improve agreement among raters. Implementing these guidelines could improve diagnostic consistency and enhance personalized treatment strategies, increasing the reliability and usefulness of 3D-HRAM testing in clinical practice.

Comparison of the 6th and 7th Editions of the UICC-AJCC TNM Classification for Esophageal Cancer.

BACKGROUND: The new 7th edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM) staging system is the ratification of data-driven recommendations from the Worldwide Esophageal Cancer Collaboration database. Generalizability remains questionable for single institutions. The present study serves as a validation of the 7th edition of the TNM system in a prospective cohort of patients with predominantly adenocarcinomas from a single institution. METHODS: Included were patients who underwent transhiatal esophagectomy with curative intent between 1991 and 2008 for invasive carcinoma of the esophagus or gastroesophageal junction. Excluded were patients who had received neoadjuvant chemo(radio)therapy, patients after a noncurative resection and patients who died in the hospital. Tumors were staged according to both the 6th and the 7th editions of the UICC-AJCC staging systems. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed with a Cox regression model. The likelihood ratio chi-square test related to the Cox regression model and the Akaike information criterion were used for measuring goodness of fit. RESULTS: A study population of 358 patients was identified. All patients underwent transhiatal esophagectomy for adenocarcinoma. Overall 5-year survival rate was 38%. Univariate analysis revealed that pT stage, pN stage, and pM stage significantly predicted overall survival. Prediction was best for the 7th edition, stratifying for all substages. CONCLUSIONS: The application of the 7th UICC-AJCC staging system results in a better prognostic stratification of overall survival compared to the 6th edition. The fact that the 7th edition performs better predominantly in patients with adenocarcinomas who underwent a transhiatal surgical approach, in addition to findings from earlier research in other cohorts, supports its generalizability for different esophageal cancer practices.

Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial.

PURPOSE: Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS: From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS: The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION: The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.

IgG4-related diseases: state of the art on clinical practice guidelines.

Immunoglobulin G4-related diseases (IgG4-RD) are a group of chronic relapsing-remitting inflammatory conditions, characterised by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, fibrosis and a usually favourable response to steroids. In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the European Reference Network ReCONNET, aimed at evaluating existing clinical practice guidelines (CPGs) and recommendations in IgG4-RD. From 167 publications initially obtained from a systematic literature search, only one was identified as a systematic multispecialist, evidence-based, consensus guidance statement on diagnosis and treatment of IgG4-RD, which may be recommended for use as CPG in IgG4-RD. With the recognition of a limited evidence based in this increasingly recognised disease, the group discussion has identified the following unmet needs: lack of shared classification criteria, absence of formal guidelines on diagnosis, no evidence-based therapeutic recommendations and lack of activity and damage indices. Areas of unmet needs include the difficulties in diagnosis, management and monitoring and the scarcity of expert centres.

Effect of Neoadjuvant Chemoradiotherapy on Health-Related Quality of Life in Esophageal or Junctional Cancer: Results From the Randomized CROSS Trial.

Purpose To compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL. Patients and Methods Patients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.4-Gy radiotherapy) followed by surgery or surgery alone. HRQOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and -Oesophageal Cancer Module (QLQ-OES24) questionnaires pretreatment and at 3, 6, 9, and 12 months postoperatively. The nCRT group also received preoperative questionnaires. Physical functioning (PF; QLQ-C30) and eating problems (EA; QLQ-OES24) were chosen as predefined primary end points. Predefined secondary end points were global QOL (GQOL; QLQ-C30), fatigue (FA; QLQ-C30), and emotional problems (EM; QLQ-OES24). Results A total of 363 patients were analyzed. No statistically significant differences in postoperative HRQOL were found between treatment groups. In the nCRT group, PF, EA, GQOL, FA, and EM scores deteriorated 1 week after nCRT (Cohen's d: -0.93, P < .001; 0.47, P < .001; -0.84, P < .001; 1.45, P < .001; and 0.32, P = .001, respectively). In both treatment groups, all end points declined 3 months postoperatively compared with baseline (Cohen's d: -1.00, 0.33, -0.47, -0.34, and 0.33, respectively; all P < .001), followed by a continuous gradual improvement. EA, GQOL, and EM were restored to baseline levels during follow-up, whereas PF and FA remained impaired 1 year postoperatively (Cohen's d: 0.52 and -0.53, respectively; both P < .001). Conclusion Although HRQOL declined during nCRT, no effect of nCRT was apparent on postoperative HRQOL compared with surgery alone. In addition to the improvement in survival, these findings support the view that nCRT according to the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study-regimen can be regarded as a standard of care.

Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials.

PURPOSE: To analyze recurrence patterns in patients with cancer of the esophagus or gastroesophageal junction treated with either preoperative chemoradiotherapy (CRT) plus surgery or surgery alone. PATIENTS AND METHODS: Recurrence pattern was analyzed in patients from the previously published CROSS I and II trials in relation to radiation target volumes. CRT consisted of five weekly courses of paclitaxel and carboplatin combined with a concurrent radiation dose of 41.4 Gy in 1.8-Gy fractions to the tumor and pathologic lymph nodes with margin. RESULTS: Of the 422 patients included from 2001 to 2008, 418 were available for analysis. Histology was mostly adenocarcinoma (75%). Of the 374 patients who underwent resection, 86% were allocated to surgery and 92% to CRT plus surgery. On January 1, 2011, after a minimum follow-up of 24 months (median, 45 months), the overall recurrence rate in the surgery arm was 58% versus 35% in the CRT plus surgery arm. Preoperative CRT reduced locoregional recurrence (LRR) from 34% to 14% (P < .001) and peritoneal carcinomatosis from 14% to 4% (P < .001). There was a small but significant effect on hematogenous dissemination in favor of the CRT group (35% v 29%; P = .025). LRR occurred in 5% within the target volume, in 2% in the margins, and in 6% outside the radiation target volume. In 1%, the exact site in relation to the target volume was unclear. Only 1% had an isolated infield recurrence after CRT plus surgery. CONCLUSION: Preoperative CRT in patients with esophageal cancer reduced LRR and peritoneal carcinomatosis. Recurrence within the radiation target volume occurred in only 5%, mostly combined with outfield failures.

Delay in diagnostic workup and treatment of esophageal cancer.

INTRODUCTION: Esophageal cancer should preferably be detected and treated at an early stage, but this may be prohibited by late onset of symptoms and delays in referral, diagnostic workup, and treatment. The aim of this study was to investigate the impact of these delays on outcome in patients with esophageal cancer. METHODS: For 491 patients undergoing esophagectomy for cancer between 1991 and 2007, patients' short- and long-term outcome were analyzed according to different time intervals between onset of symptoms, diagnosis, and surgical treatment. RESULTS: Length of prehospital delay (from onset of symptoms until endoscopic diagnosis) did not affect patient's short- or long-term outcome. A shorter hospital delay between establishing the diagnosis of esophageal cancer on endoscopy and surgery was associated with lower overall morbidity and in-hospital mortality. Patients of ASA classes I and II experienced a shorter hospital delay than patients of ASA classes III and IV. Length of hospital delay between endoscopic diagnosis and surgery did not affect pathological tumor-node-metastasis stage or R0-resection rate. Longer hospital delay did not result in worse survival: Overall survival after esophagectomy for cancer was not significantly different between patients with hospital delay <5, 5-8, or >8 weeks (24.7%, 21.7%, and 32.3%, respectively; p = 0.12). CONCLUSION: A longer hospital delay (between endoscopic diagnosis and surgery) resulted in worse patient's short-term outcome (higher overall morbidity and mortality rates) but not in a worse long-term outcome (overall survival). This may be explained by a more time-consuming diagnostic workup in patients with a poorer physical status and not by tumor progression.

Validation of a nomogram predicting complications after esophagectomy for cancer.

BACKGROUND: A nomogram has been developed recently in order to predict the occurrence and severity of postoperative complications after esophagectomy for cancer. In the present study, we externally validated this nomogram in a new cohort of patients who underwent esophagectomy for cancer in a different high-volume center. METHODS: An independent dataset of 777 patients who underwent esophagectomy for cancer was used for validation. The discriminatory capability of the nomogram was determined by using the concordance index (C statistic). Calibration was evaluated by comparing the observed with the expected number of patients with complications, as predicted by the original nomogram across patients with different risk profiles. We also examined whether adjusting the value of the original coefficients of the predictors or adding new predictors would improve the fit of the nomogram. RESULTS: Discrimination of the original nomogram was similar in the validation cohort: the C statistic hardly decreased from 0.65 in the original cohort to 0.64 in the validation cohort. Observed and expected number of patients with complications were in close agreement, reflecting a good calibration (p = 0.84). Reestimation of the coefficients in the validation cohort did not lead to any significant changes of the original nomogram values. CONCLUSIONS: External validation of a nomogram predicting the occurrence and severity of complications after esophagectomy showed that the model is applicable in other high-volume hospitals. Nevertheless, preoperative prediction of complications in individual patients remains difficult, most likely due to the complexity of mechanisms causing these complications.