Gastric cancer: predictors of recurrence when lymph-node dissection is inadequate

<p>Abstract</p> <p>Background</p> <p>The TNM classification (sixth edition) requires at least 15 lymph nodes to be examined to allow an accurate staging. However, in our environment, only 20% of patients have the recommended minimum of 15 nodes removed.</p> <p>Purpose</p> <p>To evaluate clinicopathological predictors of recurrence in patients with gastric cancer undergoing radical resection with an inadequate number of lymph nodes examined.</p> <p>Methods</p> <p>101 patients were included in this retrospective cohort. We evaluated age, gender, tumoral location, Borrmann type, Lauren histotype, type of gastrectomy, grade, invasion depth of tumor, lymph node involvement, ratio between metastatic and total number of excised lymph nodes keeping 20% as the cutoff value (LNR) and adjuvant treatment. The association between these variables and recurrence was investigated by using univariate methods and multivariate logistic regression analysis.</p> <p>Results</p> <p>Median (range) age was 63 years (44-85). 63% males, 37% females. Median follow-up time for the whole patients population was 36 months (10-104). Median number of lymph nodes retrieved was 6 (0-14). Recurrence: 50 of 101 cases (49,6%); 41 hematogeneus dissemination, 9 locoregional recurrences. The following factors were found to be correlated with the recurrence risk: tumoral location, invasion depth of tumor, lymph node involvement and LNR. A multivariate analysis revealed that depth of invasion [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.03-7.58, P = 0.04] and LNR (OR 2.34, 95% CI 1.05-5.21, P = 0.03) were independent risk factors for recurrences of gastric cancer. Median time to recurrence: 16 months (2-50). 82% of recurrences occurred within the first two years after surgical treatment. The estimated cumulative risk of recurrence at five years: 61% in the whole patients population, with serosal invasion and LNR > and < 20% was 82% and 44%, without serosal invasion 73% and 39% respectively.</p> <p>Conclusion</p> <p>Invasion depth of tumor and LNR were independent predictors of recurrence in gastric cancer after potentially curative resection with an inadequate number of lymph nodes examined.</p

The relationship between quality of life (EORTC QLQ-C30) and survival in patients with gastro-oesopohageal cancer

It remains unclear whether any aspect of quality of life has a role in predicting survival in an unselected cohort of patients with gastro-oesophageal cancer. Therefore the aim of the present study was to examine the relationship between quality of life (EORTC QLQ-C30), clinico-pathological characteristics and survival in patients with gastro-oesophageal cancer. Patients presenting with gastric or oesophageal cancer, staged using the UICC tumour node metastasis (TNM) classification and who received either potentially curative surgery or palliative treatment between November 1997 and December 2002 (n=152) participated in a quality of life study, using the EORTC QLQ-C30 core questionnaire. On univariate analysis, age (P &#60; 0.01), tumour length (P &#60; 0.0001), TNM stage (P&#60;0.0001), weight loss (P&#60;0.0001), dysphagia score (P&#60;0.001), performance status (P&#60;0.1) and treatment (P&#60;0.0001) were significantly associated with cancer-specific survival. EORTC QLQ-C30, physical functioning (P&#60;0.0001), role functioning (P&#60;0.001), cognitive functioning (P&#60;0.01), social functioning (P&#60;0.0001), global quality of life (P&#60;0.0001), fatigue (P&#60;0.0001), nausea/vomiting (P&#60;0.01), pain (P&#60;0.001), dyspnoea (P&#60;0.0001), appetite loss (P&#60;0.0001) and constipation (P&#60;0.05) were also significantly associated with cancer-specific survival. On multivariate survival analysis, tumour stage (P&#60;0.0001), treatment (P&#60;0.001) and appetite loss (P&#60;0.0001) were significant independent predictors of cancer-specific survival. The present study highlights the importance of quality of life (EORTC QLQ-C30) measures, in particular appetite loss, as a prognostic factor in these patients

Analysis of blood transfusion predictors in patients undergoing elective oesophagectomy for cancer

<p>Abstract</p> <p>Background</p> <p>Oesophagectomy for cancers is a major operation with significant blood loss and usage. Concerns exist about the side effects of blood transfusion, cost and availability of donated blood. We are not aware of any previous study that has evaluated predictive factors for perioperative blood transfusion in patients undergoing elective oesophagectomy for cancer.</p> <p>This study aimed to audit the pattern of blood crossmatch and to evaluate factors predictive of transfusion requirements in oesophagectomy patients.</p> <p>Methods</p> <p>Data was collected from the database of all patients who underwent oesophagectomy for cancer over a 2-year period. Clinico-pathological data collected included patients demographics, clinical factors, tumour histopathological data, preoperative and discharge haemoglobin levels, total blood loss, number of units of blood crossmatched pre-, intra- and postoperatively, number of blood units transfused, crossmatched units reused for another patient and number of blood units wasted.</p> <p>Clinico-pathological variables were evaluated and logistic regression analysis was performed to determine which factors were predictive of blood transfusion.</p> <p>Results</p> <p>A total of 145 patients with a male to female ratio of 2.5:1 and median age of 68 (40–85) years were audited. The mean preoperative haemoglobin (Hb) was 13.0 g/dl. 37% of males (Hb < 13.0 g/dl) and 29% of females (Hb < 11.5 g/dl) were anaemic preoperatively. A total of 1241 blood units were crossmatched and 316 units were transfused to 71 patients. Seventy four patients (51%) did not require blood transfusion during their hospital episode. 846 blood units not used for oesophagectomy patients were reused for other patients and 79 units were wasted. The overall crossmatch to transfusion ratio was 4:1 and reuse and wastage rates were 65.2% and 6.3% respectively. The independent predictors of blood transfusion include age >70 years, Hb level <11.0 g/dl, T-stage, presence of postoperative complications and anastomotic leak.</p> <p>Conclusion</p> <p>The cohort of patients audited was over-crossmatched. The identified independent predictors of blood transfusion should be considered in preoperative blood ordering for oesophagectomy patients. This study has directly led to a reduction in the maximum surgical blood-ordering schedule for oesophagectomy to 2 units and a reaudit is underway.</p

Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG): The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

<p>Abstract</p> <p>Background</p> <p>18-Fluorodeoxyglucose-PET (¹⁸F-FDG-PET) can be used for early response assessment in patients with locally advanced adenocarcinomas of the oesophagogastric junction (AEG) undergoing neoadjuvant chemotherapy. It has been recently shown in the MUNICON trials that response-guided treatment algorithms based on early changes of the FDG tumor uptake detected by PET are feasible and that they can be implemented into clinical practice.</p> <p>Only 40%-50% of the patients respond metabolically to therapy. As metabolic non-response is known to be associated with a dismal prognosis, metabolic non-responders are increasingly treated with alternative neoadjuvant chemotherapies or chemoradiation in order to improve their clinical outcome. We plan to investigate whether PET can be used as response assessment during radiochemotherapy given as salvage treatment in early metabolic non-responders to standard chemotherapy.</p> <p>Methods/Design</p> <p>The HICON trial is a prospective, non-randomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders. Patients with resectable AEG type I and II according to Siewerts classification, staged cT3/4 and/or cN+ and cM0 by endoscopic ultrasound, spiral CT or MRI and FDG-PET are eligible. Tumors must be potentially R0 resectable and must have a sufficient FDG-baseline uptake. Only metabolic non-responders, showing a < 35% decrease of SUV two weeks after the start of neoadjuvant chemotherapy are eligible for the study and are taken to intensified taxane-based RCT (chemoradiotherapy (45 Gy) before surgery. ¹⁸FDG-PET scans will be performed before ( = Baseline) and after 14 days of standard neoadjuvant therapy as well as after the first cycle of salvage docetaxel/cisplatin chemotherapy (PET 1) and at the end of radiochemotherapy (PET2). Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV). The percentage difference ΔSUV = 100 (SUV_Baseline- SUV _PET1)/SUV_Baselinewill be calculated and assessed as an early predictor of histopathological response. In a secondary analysis, the association between the difference SUV_PET1- SUV_PET2and histopathological response will be evaluated.</p> <p>Discussion</p> <p>The aim of this study is to investigate the potential of sequential ¹⁸FDG-PET in predicting histopathological response in AEG tumors to salvage neoadjuvant radiochemotherapy in patients who do not show metabolic response to standard neoadjuvant chemotherapy.</p> <p>Trial Registration</p> <p>Clinical trial identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT01271322">NCT01271322</a></p

Coding on countably infinite alphabets

This paper describes universal lossless coding strategies for compressing sources on countably infinite alphabets. Classes of memoryless sources defined by an envelope condition on the marginal distribution provide benchmarks for coding techniques originating from the theory of universal coding over finite alphabets. We prove general upper-bounds on minimax regret and lower-bounds on minimax redundancy for such source classes. The general upper bounds emphasize the role of the Normalized Maximum Likelihood codes with respect to minimax regret in the infinite alphabet context. Lower bounds are derived by tailoring sharp bounds on the redundancy of Krichevsky-Trofimov coders for sources over finite alphabets. Up to logarithmic (resp. constant) factors the bounds are matching for source classes defined by algebraically declining (resp. exponentially vanishing) envelopes. Effective and (almost) adaptive coding techniques are described for the collection of source classes defined by algebraically vanishing envelopes. Those results extend ourknowledge concerning universal coding to contexts where the key tools from parametric inferenceComment: 33 page

Prognostic significance of circumferential resection margin involvement following oesophagectomy for cancer

The factors affecting long-term survival following oesophagectomy for oesophageal cancer are poorly understood. We examined the significance of microscopic tumour involvement at the circumferential resection margin (CRM) on postoperative survival following oesophagectomy. The case notes of 329 patients who underwent a potentially curative oesophagectomy for squamous or adenocarcinoma were reviewed retrospectively. As part of the procedure, all patients underwent an en-bloc resection of their periesophageal tissue. The presence of tumour either at, or within, 1 mm of the CRM was recorded and correlated with their TNM and survival data. A total of 67 patients (20%) were noted to have a positive CRM, of which 40 cases (12%) had tumour at the resection margin and the remainder had tumour within 1 mm of the margin. Univariate analysis showed no statistically significant association between survival and either category of CRM involvement. Multivariate analysis showed that only T-stage, nodal status and tumour grade were prognostic markers. In conclusion, the presence of microscopic tumour at the CRM following an en-bloc oesophagectomy is not a significant prognostic marker

Survival after chemotherapy and/or radiotherapy versus self-expanding metal stent insertion in the setting of inoperable esophageal cancer: a case-control study

<p>Abstract</p> <p>Background</p> <p>Our aim was to compare survival of the various treatment modality groups of chemotherapy and/or radiotherapy in relation to SEMS (self-expanding metal stents) in a retrospective case-control study. We have made the hypothesis that the administration of combined chemoradiotherapy improves survival in inoperable esophageal cancer patients.</p> <p>Methods</p> <p>All patients were confirmed histologically as having surgically non- resectable esophageal carcinoma. Included were patients with squamous cell carcinoma, undifferentiated carcinoma as well as Siewert type I--but not type II - esophagogastric junctional adenocarcinoma. The decision to proceed with palliative treatments was taken within the context of a multidisciplinary team meeting and full expert review based on patient's wish, co-morbid disease, clinical metastases, distant metastases, M1 nodal metastases, T4-tumor airway, aorta, main stem bronchi, cardiac invasion, and peritoneal disease. Patients not fit enough to tolerate a radical course of definitive chemo- and/or radiation therapy were referred for self-expanding metal stent insertion. Our approach to deal with potential confounders was to match subjects according to their clinical characteristics (contraindications for surgery) and tumor stage according to diagnostic work-up in four groups: SEMS group (A), Chemotherapy group (B), Radiotherapy group (C), and Chemoradiotherapy group (D).</p> <p>Results</p> <p>Esophagectomy was contraindicated in 155 (35.5%) out of 437 patients presenting with esophageal cancer to the Department of General and Abdominal Surgery of the University Hospital of Mainz, Germany, between November 1997 and November 2007. There were 133 males and 22 females with a median age of 64.3 (43-88) years. Out of 155 patients, 123 were assigned to four groups: SEMS group (A) n = 26, Chemotherapy group (B) n = 12, Radiotherapy group (C) n = 23 and Chemoradiotherapy group (D) n = 62. Mean patient survival for the 4 groups was as follows: Group A: 6.92 ± 8.4 months; Group B: 7.75 ± 6.6 months; Group C: 8.56 ± 9.5 months, and Group D: 13.53 ± 14.7 months. Significant differences in overall survival were associated with tumor histology (<it>P </it>= 0.027), tumor localization (<it>P </it>= 0.019), and type of therapy (<it>P </it>= 0.005), respectively, in univariate analysis. Treatment modality (<it>P </it>= 0.043) was the only independent predictor of survival in multivariate analysis. The difference in overall survival between Group A and Group D was highly significant (<it>P </it>< 0.01) and in favor of Group D. As concerns Group D versus Group B and Group D versus Group C there was a trend towards a difference in overall survival in favor of Group D (<it>P </it>= 0.069 and <it>P </it>= 0.059, respectively).</p> <p>Conclusions</p> <p>The prognosis of inoperable esophageal cancer seems to be highly dependent on the suitability of the induction of patient-specific therapeutic measures and is significantly better, when chemoradiotherapy is applied.</p

Immunocytochemically detected free peritoneal tumour cells (FPTC) are a strong prognostic factor in gastric carcinoma

We prospectively investigated the prognostic significance of free peritoneal tumour cells (FPTC) in a series of 118 patients with completely resected gastric carcinoma. Immunocytochemistry with the monoclonal antibody Ber-Ep4 was performed on cytospins from intraoperative peritoneal lavage specimens. Twenty-three patients (20%) had FPTC which was significantly correlated with pT and pN categories, stage, tumour size, lymphatic invasion, Laurèn and WHO classifications and perigastric adipose tissue metastases. The median survival time for all FPTC positive compared with negative patients was significantly shorter (11 compared with > 72 months), with estimated 5-year survival rates of 8% vs. 60%. None of the patients with FPTC had an early gastric cancer. In advanced tumour subgroups without and with serosal invasion (n = 59 and 35), there were 19% and 34% with FPTC. Multivariate survival analysis showed nodal status, FPTC, mesenteric lymphangiosis, and lymph node metastasis to the compartment III to be independent prognostic factors with relative risks of 6.6, 4.5, 2.9 and 2.2 respectively. Recurrent disease occurred in 91% of FPTC-positive and in 38% of FPTC-negative patients. FPTC had a positive predictive value of 91% and a specificity of 97% for tumour recurrence. FPTC is a strong negative, independent prognostic indicator for survival in gastric carcinoma. © 1999 Cancer Research Campaig