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Abstract: Background: Chemoradiotherapy is increasingly applied in patients with oesophageal cancer. The aim of the present study was to determine whether 3D-CT volumetry is able to differentiate between responding and non-responding oesophageal tumours early in the course of neoadjuvant chemoradiotherapy. Patients and methods: Serial CT before and after two weeks of neoadjuvant chemoradiotherapy was performed in the multimodality treatment arm of a randomised trial including patients with oesophageal carcinoma. CT response was measured with the change in tumour volume between baseline and after 14 days of neoadjuvant therapy. Receiver Operating Characteristic (ROC) analysis was used to evaluate the ability of 3D-CT as an early imaging marker of response. Results: CT response analysis was performed in 39 patients, of whom 26 patients were histopathological responders. Median tumour volume increased between baseline and after 14 days of chemoradiotherapy in histopathological responders as well as in non-responders, though changes were not statistically significant. The area under the ROC curve was 0.71. Conclusion: Tumour volume changes after 14 days of neoadjuvant chemoradiotherapy as measured by 3D-CT were not associated with histopathological tumour response. CT volumetry should not be used for early response assessment in patients with potentially curable oesophageal cancer treated with neoadjuvant chemoradiotherapy. [Copyright &y& Elsevier]

Abstract: Aims: In colonic cancer the prognostic significance of extracapsular lymph node involvement (LNI) is not established and is therefore the objective of this study. Methods: Between January 1994 and May 2005, all patients who underwent resection for primary colonic cancer with lymph node metastasis were reviewed. All resected lymph nodes were re-examined to assess extracapsular LNI. In uni- and multivariate analysis disease-free survival (DFS) was correlated with various clinicopathologic factors. Results: One hundred and eleven patients were included. In 58 patients extracapsular LNI was identified. Univariate analysis revealed that pN-stage (5-year DFS pN1 vs. pN2: 65% vs. 14%, p <0.001), extracapsular LNI (5-year DFS intracapsular LNI vs. extracapsular LNI: 69% vs. 41%, p =0.003), and lymph node ratio (5-year DFS <0.176 vs. ≥0.176: 67% vs. 42%, p =0.023) were significant prognostic indicators. Among these variables pN-stage (hazard ratio 3.5, 95% confidence interval [CI]: 1.72–7.42) and extracapsular LNI (hazard ratio 1.98, 95% CI: 1.00–3.91) were independent prognostic factors. Among patients without extracapsular LNI, those receiving adjuvant chemotherapy had a significantly better survival (p =0.010). In contrast, chemotherapy did not improve DFS in patients with extracapsular LNI. Conclusion: Together with pN2 stage, extracapsular LNI reflects a particularly aggressive behaviour and has significant prognostic potential. [Copyright &y& Elsevier]

Abstract: Aims: The impact of extracapsular lymph node involvement (LNI) has been studied for several malignancies, including gastrointestinal malignancies. Aim of this study was to assess the current evidence on extracapsular LNI as a prognostic factor for recurrence in gastrointestinal malignancies. Methods: The Cochrane Database of systematic reviews, the Cochrane central register of controlled trials, and MEDLINE databases were searched using a combination of keywords relating to extracapsular LNI in gastrointestinal malignancies. Primary outcome parameters were incidence of extracapsular LNI and overall five-year survival rates. Findings: Fourteen manuscripts were included, concerning seven oesophageal, three gastric, one colorectal, and three rectal cancer series with a total of 1528 node positive patients. The pooled incidence of extracapsular LNI was 57% (95% CI: 53–61%) for oesophageal cancer, 41% (95% CI: 36–47%) for gastric cancer, and 35% (95% CI: 31–40%) for rectal cancer. In nine of the 14 studies a multivariate analysis was performed. In eight of these nine studies extracapsular LNI was identified as an independent risk factor for recurrence. Conclusion: Extracapsular LNI is a common phenomenon in patients with gastrointestinal malignancies. It identifies a subgroup of patients with a significantly worse long-term survival. This systematic review highlights the importance of assessing extracapsular LNI as a valuable prognostic factor. Pathologists and clinicians should be aware of this important feature. [Copyright &y& Elsevier]

Background: The grade of dysplasia found in Barrett's oesophagus surveillance biopsies is a major factor to determine follow up and treatment. However, it has been reported that the reproducibility of the grading system is not optimal. Aims: To compare routine and expert dysplasia grades in Barrett's oesophagus surveillance biopsies. To evaluate prospectively morphometrical grading support and to assess the pitfalls in its daily application. Methods: Consecutive biopsies (n = 143) were graded routinely by experienced general surgical pathologists as no dysplasia (ND), indefinite for dysplasia, low grade dysplasia (LGD), and high grade dysplasia (HGD). Two expert gastrointestinal pathologists blindly reviewed all sections. The stratification index of nuclei, mean nuclear area, and Ki67 area% were assessed routinely according to a strict protocol. With these features, the previously described morphometrical grade was calculated for each case. The grades provided by the experts, surgical pathologists, and morphometry were compared. Results: The general pathologists graded many more cases as dysplastic than did the experts. Complete agreement between the experts' grades and the original grades was 50 of 143 (35%). Sixty four of the 71 original LGDs and 11 of the 23 original HGDs were downgraded by the experts, whereas one LGD was upgraded. In 93 of the 143 biopsies, at review pitfalls or special characteristics of a technical nature (tangential cutting, severe inflammation, ulcer or the squamocylindrical junction very close by, among others) were seen in the part of the biopsy marked as diagnostic. These probably contributed in part to the original overdiagnoses and could have been prevented or corrected. The morphometrical grading model has not been developed to compensate for this; application of the current morphometrical grading method is not allowed and may result in erroneous (usually too high) morphometrical grades. In spite of this, all HGDs according to... [ABSTRACT FROM AUTHOR]

Background: The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population. Methods: We randomly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Results: From March 2004 through December 2008, we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%) had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large-cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most common major hematologic toxic effects in the chemoradiotherapy–surgery group were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the chemoradiotherapy–surgery group versus 69% in the surgery group (P<0.001). A pathological complete response was achieved in 47 of 161 patients (29%) who underwent resection after chemoradiotherapy. Postoperative complications were similar in the two treatment groups, and in-hospital mortality was 4% in both. Median overall survival was 49.4 months in the chemoradiotherapy–surgery group versus 24.0 months in the surgery group. Overall survival was significantly better in the chemoradiotherapy–surgery group (hazard ratio, 0.657; 95% confidence interval, 0.495 to 0.871; P=0.003). Conclusions: Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer. The regimen was associated with acceptable adverse-event rates. (Funded by the Dutch Cancer Foundation [KWF Kankerbestrijding]; Netherlands Trial Register number, NTR487.) [ABSTRACT FROM PUBLISHER]