Potential Predictive Immune and Metabolic Biomarkers of Tumor Microenvironment Regarding Pathological and Clinical Response in Esophageal Cancer After Neoadjuvant Chemoradiotherapy: A Systematic Review.

INTRODUCTION: The tumor microenvironment (TME) plays a crucial role in therapy response and modulation of immunologic surveillance. Adjuvant immunotherapy has recently been introduced in post-surgery treatment of locally advanced esophageal cancer (EC) with residual pathological disease after neoadjuvant chemoradiotherapy (nCRT). F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) remains a valuable imaging tool to assess therapy response and to visualize metabolic TME; however, there is still a paucity in understanding the interaction between the TME and nCRT response. This systematic review investigated the potential of TME biomarkers and 18F-FDG-PET/CT features to predict pathological and clinical response (CR) after nCRT in EC. METHODS: A literature search of the Medline and Embase electronic databases identified 4190 studies. Studies regarding immune and metabolic TME biomarkers and 18F-FDG-PET/CT features were included for predicting pathological response (PR) and/or CR after nCRT. Separate analyses were performed for 18F-FDG-PET/CT markers and these TME biomarkers. RESULTS: The final analysis included 21 studies-10 about immune and metabolic markers alone and 11 with additional 18F-FDG-PET/CT features. High CD8 infiltration before and after nCRT, and CD3 and CD4 infiltration after nCRT, generally correlated with better PR. A high expression of tumoral or stromal programmed death-ligand 1 (PD-L1) after nCRT was generally associated with poor PR. Moreover, total lesion glycolysis (TLG) and metabolic tumor volume (MTV) of the primary tumor were potentially predictive for clinical and PR. CONCLUSION: CD8, CD4, CD3, and PD-L1 are promising immune markers in predicting PR, whereas TLG and MTV are potential 18F-FDG-PET/CT features to predict clinical and PR after nCRT in EC.

Impact of Age and Comorbidity on Choice and Outcome of Two Different Treatment Options for Patients with Potentially Curable Esophageal Cancer.

PURPOSE: This study was designed to assess the impact of age and comorbidity on choice and outcome of definitive chemoradiotherapy (dCRT) or neoadjuvant chemoradiotherapy plus surgery. METHODS: In this population-based study, all patients with potentially curable EC (cT1N+/cT2-3, TX, any cN, cM0) diagnosed in the South East of the Netherlands between 2004 and 2014 were included. Kaplan-Meier method with log-rank tests and multivariable Cox regression analysis were used to compare overall survival (OS). RESULTS: A total of 702 patients was included. Age ≥ 75 years and multiple comorbidities were associated with a higher probability for dCRT (odds ratio [OR] 8.58; 95% confidence interval [CI] 4.72-15.58; and OR 3.09; 95% CI 1.93-4.93). The strongest associations were found for the combination of hypertension plus diabetes (OR 3.80; 95% CI 1.97-7.32) and the combination of cardiovascular with pulmonary comorbidity (OR 3.18; 95% CI 1.57-6.46). Patients with EC who underwent dCRT had a poorer prognosis than those who underwent nCRT plus surgery, irrespective of age, number, and type of comorbidities. In contrast, for patients with squamous cell carcinoma with ≥ 2 comorbidities or age ≥ 75 years, OS was comparable between both groups (hazard ratio [HR] 1.52; 95% CI 0.78-2.97; and HR 0.73; 95% CI 0.13-4.14). CONCLUSIONS: Histological tumor type should be acknowledged in treatment choices for patients with esophageal cancer. Neoadjuvant chemoradiotherapy plus surgery should basically be advised as treatment of choice for operable esophageal adenocarcinoma patients. For patients with esophageal squamous cell carcinoma with ≥ 2 comorbidities or age ≥ 75 years, dCRT may be the preferred strategy.

A meta-analysis on salvage surgery as a potentially curative procedure in patients with isolated local recurrent or persistent esophageal cancer after chemoradiotherapy.

BACKGROUND: Isolated local recurrent or persistent esophageal cancer (EC) after curative intended definitive (dCRT) or neoadjuvant chemoradiotherapy (nCRT) with initially omitted surgery, is a potential indication for salvage surgery. We aimed to evaluate safety and efficacy of salvage surgery in these patients. MATERIAL AND METHODS: A systematic literature search following PRISMA guidelines was performed using databases of PubMed/Medline. All included studies were performed in patients with persistent or recurrent EC after initial treatment with dCRT or nCRT, between 2007 and 2017. Survival analysis was performed with an inverse-variance weighting method. RESULTS: Of the 278 identified studies, 28 were eligible, including a total of 1076 patients. Postoperative complications after salvage esophagectomy were significantly more common among patients with isolated persistent than in those with locoregional recurrent EC, including respiratory (36.6% versus 22.7%; difference in proportion 10.9 with 95% confidence interval (CI) [3.1; 18.7]) and cardiovascular complications (10.4% versus 4.5%; difference in proportion 5.9 with 95% CI [1.5; 10.2]). The pooled estimated 30- and 90-day mortality was 2.6% [1.6; 3.6] and 8.0% [6.3; 9.8], respectively. The pooled estimated 3-year and 5-year overall survival (OS) were 39.0% (95% CI: [35.8; 42.2]) and 19.4% [95% CI:16.5; 22.4], respectively. Patients with isolated persistent or recurrent EC after initial CRT had similar 5-year OS (14.0% versus 19.7%, difference in proportion -5.7, 95% CI [-13.7; 2.3]). CONCLUSIONS: Salvage surgery is a potentially curative procedure in patients with locally recurrent or persistent esophageal cancer and can be performed safely after definitive or neoadjuvant chemoradiotherapy when surgery was initially omitted.

Long-term effects of radioiodine treatment on salivary gland function in adult survivors of pediatric differentiated thyroid carcinoma.

Pediatric differentiated thyroid cancer (DTC) is a rare disease. Initial treatment of DTC consists of a (near) total thyroidectomy and radioactive iodine (131I) therapy. Previous studies in adults showed that 131I treatment may result in a reduced salivary gland function. Studies regarding salivary gland function in children treated for DTC are sparse. Our aim was to assess long-term effects of 131I treatment on salivary gland function in survivors of pediatric DTC. Methods: In a nationwide cross-sectional study, salivary gland function of patients treated for pediatric DTC between 1970 and 2013 (>5 years after diagnosis, ≥18 years old at time of evaluation) was studied. Salivary gland function was assessed by sialometry, sialochemistry and a xerostomia inventory. Salivary gland dysfunction was defined as unstimulated whole saliva flow ≤0.2mL/min and/or a stimulated whole saliva flow ≤0.7 mL/min. Results: Sixty-five patients (median age at evaluation 33 [IQR, 25-40] years, 86.2% female, median follow-up period 11 [IQR, 6-22] years) underwent 131I treatment. Median cumulative 131I activity was 5.88 [IQR, 2.92-12.95] GBq, 47.7% underwent multiple 131I administrations. Salivary gland dysfunction was present in 30 (47.6%) patients. Levels of amylase and total protein in saliva were reduced. Moderate to severe xerostomia was present in 22 (35.5%) patients. Stimulated salivary secretion was lower and severity of xerostomia complaints higher in patients treated with higher cumulative 131I activity. Conclusion: In survivors of pediatric DTC, clinically significant salivary gland dysfunction was found in 35.5% and was related to the cumulative 131I activity of the treatment.

Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study.

BACKGROUND: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSION: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. TRIAL REGISTRATION: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341 .

[Hospital of diagnosis influences the probability of receiving curative treatment for oesophageal and gastric cancer]. / Ziekenhuis van diagnose beïnvloedt kans op curatieve behandeling voor slokdarm- en maagkanker.

OBJECTIVE: The aim of these studies was to examine the influence of hospital of diagnosis on the probability of receiving curative treatment and its impact on survival among oesophageal and gastric cancer. DESIGN: Although oesophageal and gastric cancer surgery is centralised in the Netherlands, the disease is often diagnosed in hospitals that do not perform this procedure. METHOD: Patients with potentially curable oesophageal or gastric cancer tumours diagnosed between 2005 and 2013 were selected from the Netherlands Cancer Registry. The probability to undergo curative treatment was examined for each hospital of diagnosis after adjustment for case-mix. Effects of variation in probability of undergoing curative treatment among these hospitals on survival were investigated Cox regression. RESULTS: All 13,017 patients with potentially curable oesophageal and 5,620 patients with potentially curable gastric cancer, diagnosed in 91 hospitals, were included. After adjustment, the proportion of oesophageal cancer patients receiving curative treatment ranged from 50% to 82% and from 48% to 78% for patients with gastric cancer in 2010-2013, depending on hospital of diagnosis (both P < 0.001). Furthermore, patients diagnosed in hospitals with a low probability of undergoing curative treatment had a worse overall survival in the period 2010-2013 (oesophageal cancer hazard ratio (HR): 1,15; 95%-CI: 1,07-1,24; gastric cancer HR: 1,21; 95%-CI: 1,04-1,41). CONCLUSION: The variation in probability of undergoing potentially curative treatment for oesophageal and gastric cancer between hospitals of diagnosis and its impact on survival indicates that treatment decision-making for these patients may be improved. Regional expert multidisciplinary team meetings in this field may improve the selection of patients for curative treatment.

Esophageal and Gastric Cancer Pearl: a nationwide clinical biobanking project in the Netherlands.

Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers (UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer.

Hospital of diagnosis and probability of having surgical treatment for resectable gastric cancer.

BACKGROUND: Gastric cancer surgery is increasingly being centralized in the Netherlands, whereas the diagnosis is often made in hospitals where gastric cancer surgery is not performed. The aim of this study was to assess whether hospital of diagnosis affects the probability of undergoing surgery and its impact on overall survival. METHODS: All patients with potentially curable gastric cancer according to stage (cT1/1b-4a, cN0-2, cM0) diagnosed between 2005 and 2013 were selected from The Netherlands Cancer Registry. Multilevel logistic regression was used to examine the probability of undergoing surgery according to hospital of diagnosis. The effect of variation in probability of undergoing surgery among hospitals of diagnosis on overall survival during the intervals 2005-2009 and 2010-2013 was examined by using Cox regression analysis. RESULTS: A total of 5620 patients with potentially curable gastric cancer, diagnosed in 91 hospitals, were included. The proportion of patients who underwent surgery ranged from 53.1 to 83.9 per cent according to hospital of diagnosis (P < 0.001); after multivariable adjustment for patient and tumour characteristics it ranged from 57.0 to 78.2 per cent (P < 0.001). Multivariable Cox regression showed that patients diagnosed between 2010 and 2013 in hospitals with a low probability of patients undergoing curative treatment had worse overall survival (hazard ratio 1.21; P < 0.001). CONCLUSION: The large variation in probability of receiving surgery for gastric cancer between hospitals of diagnosis and its impact on overall survival indicates that gastric cancer decision-making is suboptimal.

Radioactive iodine in the treatment of medullary thyroid carcinoma: a controlled multicenter study.

OBJECTIVE: Radioactive iodine (RAI) therapy in medullary thyroid carcinoma (MTC) is applied in some centers, based on the assumption that cross-irradiation from thyroid follicular cells may be beneficial. However, no systematic studies on the effect of RAI treatment in MTC have been performed. The aim of this study was to analyze the effect of RAI treatment on survival in MTC patients. DESIGN: Retrospective multicenter study in eight University Medical Centers in The Netherlands. METHODS: Two hundred and ninety three MTC patients without distant metastases who had undergone a total thyroidectomy were included between 1980 and 2007. Patients were stratified by clinical appearance, hereditary stage, screening status, and localization. All patients underwent regular surgical treatment with additional RAI treatment in 61 patients. Main outcome measures were disease-free survival (DFS) and disease-specific survival (DSS). Cure was defined as biochemical and radiological absence of disease. RESULTS: In multivariate analysis, stratification according to clinical appearance (P=0.72), hereditary stage (P=0.96), localization (P=0.69), and screening status (P=0.31) revealed no significant effects of RAI treatment on DFS. Multivariate analysis showed no significant difference in DSS for the two groups stratified according to clinical appearance (P=0.14). Owing to limited number of events, multivariate analysis was not possible for DSS in the other groups of stratification. CONCLUSIONS: Based on the results of the present analysis, we conclude that RAI has no place in the treatment of MTC.

Preoperative chemoradiotherapy for esophageal or junctional cancer.

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.).

Therapeutic lymph node dissection in melanoma: different prognosis for different macrometastasis sites?

BACKGROUND: The prognostic significance of primary tumor location, especially the poor prognosis for melanomas in the scalp and neck region, is well established. However, the prognosis for different sites of nodal macrometastasis has never been studied. This study investigated the prognostic value of the location of macrometastasis in terms of recurrence and survival rates after therapeutic lymph node dissection (TLND). METHODS: All consecutive FDG-PET-staged melanoma patients with palpable and cytologically proven lymph node metastases operated at our clinic between 2003 and 2011 were included. Disease-free survival and disease-specific survival (DSS) were compared for nodal metastases in the groin, axilla, and neck regions by multivariable analysis. RESULTS: A total of 149 patients underwent TLND; there were 70 groin (47 %), 57 axillary (38 %), and 22 neck (15 %) dissections. During a median follow-up of 18 (range 1-98) months, 102 patients (68 %) developed recurrent disease. Distant recurrence was the first sign of progressive disease in 78, 76, and 55 % of the groin, axilla, and neck groups, respectively (p = 0.26). Low involved/total lymph nodes (L/N) ratio (p < 0.001) and absence of extranodal growth pattern (p = 0.05) were independent predictors of a longer disease-free survival. For DSS, neck site of nodal metastasis (p = 0.02) and low L/N ratio (p < 0.001) were independent predictors of long survival. The estimated 5-year DSS for the groin, axilla, and neck sites was 28, 34, and 66 %, respectively. CONCLUSIONS: There seems significantly longer DSS after TLND for nodal macrometastases in the neck compared to axillary and groin sites, although larger series should confirm this finding.

The value of detectable thyroglobulin in patients with differentiated thyroid cancer after initial ¹³¹I therapy.

OBJECTIVE: To assess the prognostic value of detectable thyroglobulin (Tg) after initial surgery and radioactive iodine (¹³¹I) therapy by comparing patients with a negative post-therapeutic whole body scan (WBS) with either detectable or undetectable Tg. BACKGROUND: Differentiated thyroid cancer has a good prognosis. However, recurrences can occur up to 30 years after initial treatment. Because life-long follow-up is necessary, it is important to explore possible risk factors associated with recurrence and mortality. DESIGN, PATIENTS AND MEASUREMENTS: We studied 539 patients who were treated between 1980 and 2007. After the last therapeutic dosage of 5550 MBq ¹³¹I, 72 patients had negative post-therapeutic WBS and positive Tg levels (Tg+ group) and 399 patients had negative post-therapeutic WBS and negative Tg (Tg- group). The 68 remaining patients had proven residual macroscopic disease. We investigated recurrences and overall mortality in the Tg+ and Tg- group compared with the Dutch population. RESULTS: In the Tg+ group, detectable recurrences occurred significantly earlier and more frequently than in the Tg- group (19%vs 13%, P = 0·024). Survival between these groups was comparable, but shorter than the general Dutch population [Standardised Mortality Rate (SMR) 1·38 (95% CI 1·12;1·63) (P = 0·003)]. Disease-free survival in the Tg groups was comparable and not significantly different from the Dutch population [SMR = 1·09 (95% CI 0·81;1·34) (P = 0·569)]. CONCLUSION: Patients with detectable Tg during the last ¹³¹I treatment and a negative post-therapeutic WBS have significant earlier and more recurrences than patients without detectable Tg. Survival in both groups is comparable. After initial therapy, the combination of a negative high dose post-therapeutic WBS with detectable Tg is a valuable predictor for earlier and more recurrences, but is not associated with survival.

Effect of hospital characteristics on outcome of patients with gastric cancer: a population based study in North-East Netherlands.

BACKGROUND: Surgical resection is an important factor in the curative treatment of gastric cancer. However a variety of aspects of surgical treatment that potentially influence outcome are still not well defined. This study aims to assess the influence of hospital type, referral pattern and proximal or distal location of the tumour on the ultimate survival. METHODS: From January 1994 to January 2007, a total of 5245 patients were diagnosed with gastric adenocarcinoma in the region of the Comprehensive Cancer Centre North-East Netherlands. Hospitals in this region were categorized into three types: teaching university (TU), teaching non-university (TNU), and non-teaching hospitals (NT). The influence of hospital type, referral for surgery and location of the tumour on the relative survival of operated patients was studied. RESULTS: Of the 5245 patients, 2334 patients underwent surgery. For operated patients, the 5-year relative survival was 42.5% for the TU versus 34.0% and 35.5% for respectively TNU and NT hospitals (p = 0.064), with no difference (p = 0.38) in relative survival (25.6-31.9%) in the proximal tumours. A significant difference was found between the hospitals in the 5-year relative survival in the distal tumours; 59.7% in the TU versus 36.4% in the TNU and 36% in the NT (p = 0.03 univariate), however this was not confirmed in the multivariate analysis (p = 0.184). High referral centres did not perform better as far as survival is concerned than low referral hospitals. In conclusion the hospital type in our region did not significantly influence outcome of surgery for gastric cancer.

P-gp and MRP1 expression in parathyroid tumors related to histology, weight and (99m)Tc-sestamibi imaging results.

OBJECTIVE: P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) are membrane efflux pumps that may have a role in the kinetics of (99m)Tc-sestamibi (MIBI) in parathyroid tumors. P-gp and MRP1 expression in parathyroid tumors was studied and related to histology, weight and pre- and intraoperative MIBI imaging results. DESIGN: Patient cohort study SETTING: Tertiary referral center PATIENTS: Thirty-three patients underwent radioguided parathyroidectomy for primary or secondary hyperparathyroidism. MAIN OUTCOME MEASURES: P-gp and MRP1 expression. METHODS: Dual-phase (99m)Tc-MIBI scintigraphy and SPECT results were compared to the surgical findings. Radioactivity and weight of resected parathyroid tumors were measured. Intraoperative radioactivity measurements were decay corrected. After routine histology immunohistochemistry was performed using C494 monoclonal antibodies to P-gp and MRP1r1 to MRP1. P-gp and MRP1 expression were scored covering both distribution of positivity and degree of immunostaining semi quantitatively. RESULTS: P-gp and MRP1 staining was observed in 97% and 43% of the glands respectively. P-gp staining was positive in 91% (21/23) of the adenomas and in all 36 hyperplastic glands. MRP1 staining was positive in 22% (5/23) of the adenomas and in 61% (22/36) of the hyperplastic glands. P-gp or MRP1 expression did not correlate with preoperative (99m)Tc-MIBI imaging or intraoperative radioactivity. Parathyroid weight was associated with preoperative MIBI imaging results and MIBI uptake measured during surgery. CONCLUSION: P-gp and MRP1 expression did not correlate with (99m)Tc-MIBI uptake in parathyroid tumors. Parathyroid weight remains the major known factor influencing (99m)Tc-MIBI uptake.

Intraoperative assessment of microperfusion with visible light spectroscopy in esophageal and colorectal anastomoses.

BACKGROUND: We evaluated the technical feasibility and stability of measurements using visible light spectroscopy to measure microvascular oxygen saturation (StO(2)) in gastrointestinal anastomoses. METHODS: In consecutive esophageal (n = 14) or colorectal (n = 30) resections, during which an uncomplicated anastomosis was performed, measurements of serosal StO(2) were performed during the procedure. RESULTS: In esophageal resections, median (+/- standard error) StO(2) was stable before and after anastomosis in the proximal esophagus (before: 66.0 +/- 4.6, after: 68.3 +/- 6.0%) and the gastric conduit (before: 70.6 +/- 8.6, after: 69.8 +/- 8.0%). Mean colorectal StO(2) before and after anastomosis increased in the proximal part (71.3 +/- 8.4 to 76.6 +/- 8.2%; p < 0.005). Mean StO(2) in the distal part remained stable (72.4 +/- 6.6 to 74.8 +/- 6.7%). CONCLUSIONS: Visible light spectroscopy is a feasible and fast method for intraoperative assessment of microperfusion of the serosa in esophageal and colorectal anastomosis. Future clinical studies will define its role in the prediction of anastomotic leakage.

Importance of fluorodeoxyglucose-positron emission tomography (FDG-PET) and endoscopic ultrasonography parameters in predicting survival following surgery for esophageal cancer.

BACKGROUND AND STUDY AIMS: To assess the prognostic importance of standardized uptake value (SUV) for 18F-fluorodeoxyglucose (FDG) at positron emission tomography (PET) and of EUS parameters, in esophageal cancer patients primarily treated by surgery. PATIENTS AND METHODS: Between October 2002 and August 2004 a prospective cohort study involved 125 patients, with histologically proven cancer of the esophagus, without evidence of distant metastases or locally irresectable disease based on extensive preoperative work-up, and fit to undergo major surgery. Follow-up was complete until October 2006, ensuring a minimal potential follow-up of 25 months. RESULTS: The median SUV was 0.27 (interquartile range 0.13 - 0.45), and was used as cutoff value between high (n = 62) and low (n = 63) SUV. Patients with a high SUV had a significantly worse disease-specific survival compared with patients with a low SUV (P = 0.04). Tumor location (P = 0.005), EUS T stage (P < 0.001), EUS N stage (P = 0.006) and clinical stage (P < 0.006) were also associated with disease-specific survival. However, in multivariate analysis only EUS T stage appeared to be of independent prognostic significance (P = 0.007). CONCLUSION: In esophageal cancer patients, EUS T stage, EUS N stage, location and SUV of the primary tumor are pretreatment factors that are associated with disease-specific survival. However, only EUS T stage is an independent prognostic factor.

Impact of splenectomy on surgical outcome in patients with cancer of the distal esophagus and gastro-esophageal junction.

We aim to determine the effect of splenectomy on clinical outcome in patients with cancer of the distal esophagus and gastro-esophageal junction (GEJ) after a curative intended resection. From January 1991 to July 2004, 210 patients underwent a potentially curative gastroesophageal resection with an extended nodal dissection. The study group was divided into: group I with splenectomy, consisting of 66 patients (31.4%), and group II without splenectomy, of 144 patients. Splenectomy was performed for oncological reasons. Medical records were reviewed retrospectively. Postoperative complications occurred in 27 patients (40.9%) in group I and in 68 patients (47.2%) in group II (P = 0.4). The overall mortality was not significantly different between both groups (P = 0.7). There was a higher administration of red blood cells during surgery (P < or = 0.001), increased operating room (OR) time (P < or = 0.001) and longer intensive care unit (ICU) stay (P = 0.01) in group I. Independent prognostic factors for survival were outcome of surgery, nodal metastases, gender, complications and ICU stay. Sepsis was a strong prognostic factor among the complications. The 1 and 2-year survival was significantly higher in group II; 75% and 67% (P = 0.032) compared to 69% and 56% (P = 0.017) in group I, respectively. However, the 5-year survival was not different in both groups (29% in group I and 60% in group II, P = 0.191). Splenectomy had no marked effect on mortality and morbidity after curative resection of esophageal cancer. Splenectomy had a significant increase in blood transfusions with prolonged OR time and ICU stay and decreased short-term survival.