Extension of resection after positive intraoperative pathology during surgery for gastric and gastroesophageal junction adenocarcinoma: a retrospective cohort study.

BACKGROUND: Residual tumor at the resection margins after surgery for gastric and gastroesophageal junction (GEJ) adenocarcinoma is a known prognostic factor. In this single-center, retrospective cohort study in a tertiary referral center, the authors aimed to evaluate the relevance of intraoperative pathology consultation (IOC) and consecutive extension of surgery on patient survival. STUDY DESIGN: Of 737 consecutive patients undergoing (sub)total gastrectomy for gastric or GEJ adenocarcinoma, 679 cases with curative intent surgery between 05/1996 and 03/2019 were included. Patients were categorized into: R0 without further resection (direct R0), R0 after positive IOC and extension of resection (converted R0), and R1. RESULTS: IOC was performed in 242 (35.6%) patients, in 216 (89.3%) at the proximal resection margin. Direct R0-status was achieved in 598 (88.1%), converted R0 in 26 (3.8%) of 38 (5.6%) patients with positive IOC and R1 in 55 (8.1%) patients. The median follow-up was 29 months for surviving patients. 3-year survival rate (3-YSR) was significantly higher for direct R0 compared to converted R0 with 62.3% compared to 21.8% (hazard ratio=0.298; 95% CI=0.186-0.477, P <0.001). 3-YSR was similar between converted R0 and R1 (21.8 vs. 13.3%; hazard ratio =0.928; 95% CI=0.526-1.636, P =0.792). In multivariate analysis, advanced T ( P <0.001), N ( P <0.001), R ( P =0.003), and M1 status ( P <0.001) were associated with worse overall survival. CONCLUSION: IOC and consecutive extended resection for positive resection margins in gastrectomy for the proximal gastric and GEJ adenocarcinoma does not achieve long-term survival benefits in advanced tumor stages.

Two decades of gastric and gastroesophageal junction cancer surgery.

PURPOSE: Diagnosis and treatment of gastric and gastroesophageal junction cancer have undergone many critical changes during the last two decades. We addressed the question of how clinical reality outside of clinical trials has changed for gastric and gastroesophageal junction cancer patients in a European center for upper gastrointestinal surgery. METHODS: In this retrospective cohort study, patients undergoing (sub)total gastrectomy for gastric or gastroesophageal junction adenocarcinoma between 1996 and 2017 in a tertiary upper gastrointestinal center were included. The time was divided into a) before (1996-2006) (pre-CTx) and b) after (2006-2017) (CTx) the MAGIC trial. Data were comprehensively analyzed for demographics, tumor stage, perioperative treatment, surgery, histopathology, and survival rates (SR). RESULTS: 737 patients (32% female) underwent gastrectomy, 255 patients in the pre-CTx era and 482 patients in the CTx era. The median age was 65 years and the median follow-up was 27.5 months for surviving patients. Around 16.9% of patients received neoadjuvant treatment in the pre-CTx era versus 46.3% in the CTx era. The 3-year survival rate (3-YSR) was 46.4% in the pre-CTx and 60.9% in the CTx era (p < 0.001). For pretreated patients, 3-YSR was 39.0% (pre-CTx) versus 55.3% (CTx) (p = 0.168). Survival rate (SR) for locally advanced tumor stages (cT3/cT4) was higher when neoadjuvant therapy was administered (3-YSR: 56.7% vs 40.6%; p = 0.022). There were no significant differences according to sex (p = 0.357), age (p = 0.379), pT category (p = 0.817), pN stage (p = 0.074), cM stage (p = 0.112), Laurén classification (p = 0.158), and SRs (3-YSR: 60.3% vs 59.4%; p = 0.898) between the MAGIC and FLOT regimens. CONCLUSIONS: Survival rates have dramatically improved for gastric cancer patients during the last two decades. MAGIC and FLOT regimens showed similar results in the postsurgical follow-up.

Does VO2peak Provide a Prognostic Value in Esophagectomy and Gastrectomy for Post-operative Outcomes?

BACKGROUND/AIM: Esophagectomy and gastrectomy are procedures with considerable physical burden and intense post-operative care of which the patient's physical condition seems to be a relevant predictor. The gold standard of the cardiorespiratory fitness is the peak oxygen consumption (VO2peak). This pilot study examined the prognostic value of VO2peak on post-surgery outcomes in esophageal and gastric cancer patients. PATIENTS AND METHODS: In this prospective cross-sectional study, patients scheduled for esophagectomy or gastrectomy were examined 24 h before the surgery regarding their VO2peak. The post-operative complications according to Clavien-Dindo grade IIIb/IV/V, Intensive-Care-Unit days, and overall hospital stay were documented following surgery. In a subset, body weight changes from surgery until hospital discharge and first aftercare visit were recorded. RESULTS: The functional capacity was significantly reduced in 34/35 of the included patients compared to matched norm-values (p<0.01). The only significant correlation was found between VO2peak values and body weight change from surgery to the first aftercare visit. A subgroup comparison of patients with a VO2peak <17 ml/min/kg and ≥17 ml/min/kg suggested small, non-significant differences in post-surgery outcomes and significant differences in the body weight change from surgery to hospital discharge, favoring the higher-VO2peak subgroup. CONCLUSION: The impaired functional capacity following esophagectomy or gastrectomy may strengthen the rational for exercise programs during neoadjuvant and pre-surgery phases. The prognostic value of VO2peak on post-operative outcomes remains uncertain due to noticeable descriptive differences, but no significant correlations, potentially limited by the smallsized population. Nonetheless, a correlation between VO2peak and body weight change post-surgery was observed and indicates a potential prognostic value of VO2peak.

Calcification score versus arterial stenosis grading: comparison of two CT-based methods for risk assessment of anastomotic leakage after esophagectomy and gastric pull-up.

PURPOSE: Anastomotic leakage is a major surgical complication following esophagectomy and gastric pull-up. Specific risk factors such as celiac trunk (TC) stenosis and high calcification score of the aorta have been identified, but no data are available on their relative prognostic values. This retrospective study aimed to compare and evaluate calcification score versus stenosis quantification with regards to prognostic impact on anastomotic leakage. PATIENTS AND METHODS: Preoperative contrast-enhanced computed tomography scans of 164 consecutive patients with primary esophageal cancer were evaluated by two radiologists to apply a calcification score (0-3 scale) assessing the aorta, the celiac axis and the right and left postceliac arteries. Concurrently, the presence and degree of stenosis of TC and superior mesenteric artery were recorded for stenosis quantification. RESULTS: Anastomotic leakage was noted in 14/164 patients and 12/14 showed stenosis of TC (n=11). The presence of TC stenosis was found to have a significant impact on anastomotic healing (p=0.004). The odds ratio for the prediction of anastomotic leakage by the degree of stenosis was 1.04 (95% CI, 1.02-1.07). Ten of 14 patients had aortic calcification scores of 1 or 2, but calcification scores of the aorta, the celiac axis and the right and left postceliac arteries did not correlate with the corresponding TC stenosis values and showed no influence on patient outcome as defined by the occurrence of anastomotic insufficiency (p=0.565, 0.855, 0.518 and 1.000, respectively). Inter-reader reliability of computed tomography analysis and absolute agreement on calcium scoring was mostly over 90%. No significant differences in preoperative comorbidities and patient characteristics were found between those with and without anastomotic leakage. CONCLUSION: Measurement of TC stenosis in preoperative contrast-enhanced computed tomography scans proved to be more reliable than calcification scores in predicting anastomotic leakage and should, therefore, be used in the risk assessment of patients undergoing esophagectomy and gastric pull-up.

Percutaneous Endoscopic Gastrostomy in Direct Puncture Technique: When, Why and How?

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) placed in the pull through (PT) technique is a common procedure to restore enteral feeding in patients with swallowing disorders. Limitations of this technique are patients with obstruction of the pharynx or esophagus or with an esophageal stent. We report our experience with the direct puncture (DP) PEG device. METHODS: We included 154 patients (55 women). One hundred forty patients had cancer. After passing the endoscope into the stomach, 4 gastropexies were performed with a gastropexy device and the PEG was placed with the introducer method. After 1 month, the sutures were removed and a constant gastrocutaneous fistula had been created and the new catheter could be placed safely. RESULTS: The DP PEG was successfully placed in all patients. Overall complication rate was 11% (minor: 6%, major: 5%). The most common event was tube dislocation (40 cases). In 5 cases of dislocation, this resulted in a major complication with injuring the gastric wall and the necessity for surgical treatment. CONCLUSIONS: The DP PEG system is safe, and can be used in cases in which a standard PT PEG is not feasible. To avoid dislocation, strict adherence to a post-interventional protocol is highly recommended.

Incidence and management of chylothorax after Ivor Lewis esophagectomy for cancer of the esophagus.

OBJECTIVE: Chylothorax is a major complication after esophagectomy. As recent studies refer to heterogeneous patient cohorts and surgical procedures, this study was conducted to report the incidence and evaluate the optimal management of chylous fistula in patients treated with transthoracic esophagectomy and 2-field lymphadenectomy for esophageal cancer. METHODS: From January 2005 to December 2013, a total of 906 patients underwent transthoracic esophageal resection for esophageal carcinoma at our institution. En bloc esophagectomy was performed with routine supradiaphragmatic ligation of the thoracic duct. The incidence of chylothorax, and associated morbidity and mortality, were analyzed, and subsequent therapeutic management was reviewed. RESULTS: Chylothorax after Ivor Lewis esophagectomy was observed in 17 (1.9%) patients. Fifteen patients required surgical intervention with rethoracotomy and repeat duct ligation. Thoracic duct ligation was successful in all patients. Two patients died within 90 days after primary esophageal resection. The median time between initial tumor resection and rethoracotomy was 13 days. Average daily chest-tube output at time of reoperation was 1900 mL. In 2 patients, pleural effusion did not exceed 1000 mL per day. In these cases, conservative management with additional thoracic drainage and total parenteral nutrition led to complete resolution of chylous fistula. CONCLUSIONS: Occurrence of chylothorax after prophylactic thoracic duct ligation during transthoracic esophagectomy for esophageal cancer is rare. In patients with high-output chylous fistula, an early rethoracotomy with repeat ligation of the thoracic duct is safe and helps to shorten recovery time. In cases of low-volume drainage, a conservative approach is feasible.

Web-Based Immersive Virtual Patient Simulators: Positive Effect on Clinical Reasoning in Medical Education.

BACKGROUND: Clinical reasoning is based on the declarative and procedural knowledge of workflows in clinical medicine. Educational approaches such as problem-based learning or mannequin simulators support learning of procedural knowledge. Immersive patient simulators (IPSs) go one step further as they allow an illusionary immersion into a synthetic world. Students can freely navigate an avatar through a three-dimensional environment, interact with the virtual surroundings, and treat virtual patients. By playful learning with IPS, medical workflows can be repetitively trained and internalized. As there are only a few university-driven IPS with a profound amount of medical knowledge available, we developed a university-based IPS framework. Our simulator is free to use and combines a high degree of immersion with in-depth medical content. By adding disease-specific content modules, the simulator framework can be expanded depending on the curricular demands. However, these new educational tools compete with the traditional teaching OBJECTIVE: It was our aim to develop an educational content module that teaches clinical and therapeutic workflows in surgical oncology. Furthermore, we wanted to examine how the use of this module affects student performance. METHODS: The new module was based on the declarative and procedural learning targets of the official German medical examination regulations. The module was added to our custom-made IPS named ALICE (Artificial Learning Interface for Clinical Education). ALICE was evaluated on 62 third-year students. RESULTS: Students showed a high degree of motivation when using the simulator as most of them had fun using it. ALICE showed positive impact on clinical reasoning as there was a significant improvement in determining the correct therapy after using the simulator. ALICE positively impacted the rise in declarative knowledge as there was improvement in answering multiple-choice questions before and after simulator use. CONCLUSIONS: ALICE has a positive effect on knowledge gain and raises students' motivation. It is a suitable tool for supporting clinical education in the blended learning context.

Pathohistological classification systems in gastric cancer: diagnostic relevance and prognostic value.

Several pathohistological classification systems exist for the diagnosis of gastric cancer. Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics, disease specific criteria and overall outcome. It is still controversial as to which classification system imparts the most reliable information, and therefore, the choice of system may vary in clinical routine. In addition to the most common classification systems, such as the Laurén and the World Health Organization (WHO) classifications, other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients. In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer, there is no sole classification system that is consistently used worldwide in diagnostics and research. However, several national guidelines for the treatment of gastric cancer refer to the Laurén or the WHO classifications regarding therapeutic decision-making, which underlines the importance of a reliable classification system for gastric cancer. The latest results from gastric cancer studies indicate that it might be useful to integrate DNA- and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance. This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer.

Hereditary esophageal-vulvar syndrome.

This article describes an esophageal leiomyomatosis in mother and daughter. A 33-year-old woman with cardiovascular symptoms was admitted to the hospital. Her mother at a young age had undergone an esophagectomy because of a leiomyosarcoma. The daughter received a diagnosis of diffuse leiomyomatosis of the esophagus and uterus. Because of its size, transthoracic esophagectomy with gastric reconstruction and a hysterectomy were performed. Histopathologic examination of the specimens confirmed the diagnosis of esophageal and uterine leiomyomatosis. These findings are characterized as the esophageal-vulvar syndrome, which is known to occur sporadically.

Evaluation of quality indicators following implementation of total mesorectal excision in primarily resected rectal cancer changed future management.

BACKGROUND AND AIMS: We evaluated the outcome of primarily resected rectal cancer patients immediately after the implementation of total meserectal excision (TME) based on potential quality indicators. PATIENTS AND METHODS: Following initial teaching of two staff surgeons (PMS and AHH) by RJ Heald, 164 consecutive patients were analyzed. The following quality indicators were evaluated: (a) frequency of local recurrence, (b) number of resected lymph nodes, (c) selection of operative technique depending on tumor localization, (d) use of a protective loop ileostomy, and (e) frequency and type of adjuvant therapy. RESULTS: Local recurrence rate was 8.5% after a minimum follow-up of 5 years. An increasing pT category (p < 0.02) and the presence of lymph node metastases (pN+, p < 0.05) were significantly associated with local recurrence rates. The number of resected lymph nodes was significantly associated with nodal metastases rate (p < 0.02). Patients with distal third rectal cancer underwent significantly more often an abdominoperineal amputation (p < 0.0001). Clinical course, but not the rate of anastomotic leakage (9.5%) itself was influenced by using a protective loop ileostomy. Forty-two (29.7%) patients received adjuvant therapy; however, local recurrence rate was higher in patients with adjuvant chemo-/radiotherapy (14.2% vs. 6.1%). CONCLUSIONS: The local recurrence rate of 8.5% demonstrates that through consequent implementation of TME excellent onclogical results can be achieved. The number of resected lymph nodes significantly influenced the pN category. The primary construction of a protective loop ileostomy after TME became standard. Neoadjuvant chemoradiation was systematically introduced in order to improve local tumor control and prevent abdominoperineal amputations. No conclusions can be drawn concerning adjuvant therapy.

Simultaneous occurrence of a hepatocellular carcinoma and a hepatic non-Hodgkin's lymphoma infiltration.

To investigate the simultaneous occurrence of hepatocellular carcinoma and non-Hodgkin's lymphoma, we report the case of a 70 year old patient with a primary diagnosis of non-Hodgkin's lymphoma in 2002. In a routine follow up investigation of his chronic lymphocytic leukemia a newly detected mass in the Couinaud's segments 2 and 3 was found. No hepatitis C virus or hepatitis B virus infection or cirrhosis was evident. After laparoscopic segmentectomy the histological examination revealed a hepatocellular carcinoma. While the relation between liver parenchyma damages and hepatocellular carcinoma or non-Hodgkin's lymphoma is well known, only a few publications have focused on the coexistence of hepatocellular carcinoma and non-Hodgkin's lymphoma. With this case we demonstrate the coexistence of these diseases without having a predamaged liver parenchyma.

CUL2 and STK11 as novel response-predictive genes for neoadjuvant radiochemotherapy in esophageal cancer.

AIMS: Neoadjuvant treatment strategies have been developed to improve the survival of patients with locally advanced esophageal cancer. Since only patients with major histopathological response benefit from multimodality treatment, we profiled the genome of patients with esophageal cancer for markers indicating response or nonresponse. PATIENTS AND METHODS: Pretreatment biopsies of responding and nonresponding patients with locally advanced esophageal cancer, as well as the corresponding normal epithelium, were analyzed by human genome microarrays. Differential gene expression was associated with histomorphological tumor regression. Quantitative real-time reverse transcriptase-PCR was applied for verification of the predictive value of a panel of the identified marker genes, including 66 patients. RESULTS: We detected differentially expressed candidate genes with regard to response and nonresponse to neoadjuvant radiochemotherapy. The response-predictive impact of the novel markers, CUL2 and STK11, was confirmed by the verification study including 66 patients. Whereas CUL2 mRNA expression levels of greater than 1.7 was predictive for major response (p = 0.02) in adeno- and squamous cell carcinoma, STK11 was predominantly response predictive for adenocarcinomas. Downregulation of CUL2 (p = 0.04) and STK11 (p = 0.02) mRNA also correlated with a more favorable prognosis. CONCLUSION: We identified two novel markers, CUL2 and STK11, for response prediction in esophageal cancer. They will be applied to complement our panel of response-predictive markers to further individualize therapy.

Increased platelet counts after transthoracic en bloc resection for esophageal cancer is associated with significantly improved survival.

BACKGROUND: We analyzed perioperative platelet counts as a potential clinical marker for survival after transthoracic en bloc resection for esophageal cancer. Recent data described preoperative thrombocytosis in malignancies to be associated with poor prognosis. METHODS: A retrospective analysis from a prospective database (1997-2006) was performed for 291 consecutive patients with esophageal cancer who underwent transthoracic en bloc esophagectomy and extended lymphadenectomy. Squamous cell cancer was found in 47.0% and adenocarcinoma in 50.9% (2.1% had rare histologies). Neoadjuvant chemoradiation was performed in 152 (52%) patients. Platelet counts before surgery and on postoperative days (PODs) 1, 10, and 30 were evaluated. We used the published cutoff value of 293 × 10(9)/l (mean of 80 healthy controls ± standard deviation) for platelet counts. RESULTS: High platelet counts before surgery missed significance for poorer survival (p = 0.054). Following a perioperative fall in thrombocytes, a significant rise at POD 10 after surgery was evident. Platelet counts of more than 293 × 10(9)/l at this time correlated with a significantly improved survival rate (p = 0.027). Patients with no increase in thrombocytes until POD 10 had significantly poorer survival (p = 0.012). Multivariate analysis confirmed that a thrombocyte increase between the preoperative count and that on POD 10 is an independent prognostic indicator (p = 0.035) for patients with completely (R0) resected tumors. CONCLUSIONS: An increase in platelet counts measured on POD 10 following transthoracic en bloc esophagectomy and extended lymphadenectomy is an independent prognostic indicator for improved survival in patients with esophageal cancer.

Preoperative survivin mRNA detection in peripheral blood is an independent predictor of outcome in esophageal carcinoma.

AIMS: Survivin (SVV) mRNA expression levels in peripheral blood of patients with gastrointestinal malignancies change significantly during the course of treatment. We wanted to scrutinize these findings in patients with esophageal carcinoma and furthermore evaluate whether the detection of mRNA and the change in detecting ability have an association with overall survival. MATERIALS & METHODS: Whole blood was drawn 1 day pre- and 10 days post-operatively from 62 patients with esophageal carcinoma. Tumor cells were enriched from whole blood by density-gradient centrifugation prior to extraction of total cellular RNA and subsequent direct quantitative reverse transcriptase-PCR assays. RESULTS: SVV was detectable in 48 out of 62 patients (77%). Stepwise multivariate Cox linear regression models demonstrated a significant and independent association of measured SVV with overall survival (6.6 exp[b]; 95% CI: 1.97-22.12; p = 0.002). Increased SVV levels after the operation were linked to shorter overall survival (p = 0.04). CONCLUSION: Preoperative SVV expression levels appear to be associated with overall survival in patients with esophageal cancers. Increasing levels could potentially indicate a higher risk for shorter overall survival and therefore demand adapted treatment modalities.

TaqMan low-density arrays and analysis by artificial neuronal networks predict response to neoadjuvant chemoradiation in esophageal cancer.

AIMS: Neoadjuvant radiochemotherapy of locally advanced esophageal cancer is only effective for patients with major histopathological response. A total of 17 genes were selected to predict histopathologic tumor response to chemoradiation (cisplatin, 5-fluorouracil, 36 Gy). MATERIALS & METHODS: For gene-expression analysis quantitative TaqMan low-density arrays were applied. Expression levels in pretreatment biopsies of 41 patients (cT2-4, Nx, M0) were compared with the degree of histopathologic regression in resected specimens applying univariate, multivariate and artificial neuronal network analyses. RESULTS: Dihydropyrimidine dehydrogenase was identified as an independent predictor associated with major response (p < 0.002). Multivariate analysis of the marker combination provided response prediction with 75.0% sensitivity, 81.0% specificity and 78.1% accuracy. Artificial neuronal network analysis was the best predictive model for major histopathologic response (80% sensitivity, 90.5% specificity and 85.4% accuracy), representing a clinically practical system. CONCLUSION: Low-density-array RT-PCR analyzed by artificial neuronal network predicts histopathologic response to neoadjuvant chemoradiation in our patient collective, and could be used to further individualize treatment strategies in esophageal cancer.

Increased human telomerase reverse transcriptase (hTERT) mRNA expression but not telomerase activity is related to survival in curatively resected non-small cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate the significance of human telomerase reverse transcriptase (hTERT) mRNA expression and telomerase activity as prognostic markers in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In a series of 69 curatively resected NSCLC specimens, telomerase activity was analyzed with the telomeric repeat amplification protocol (TRAP) assay and expression of hTERT mRNA by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Partitioning of gene expression levels and protein activities to construct prognostic groups was attempted. RESULTS: Human hTERT mRNA transcripts were detected in 62 (89.9%) cases of NSCLC. Seven (10.1%) tumors were completely negative for hTERT expression. Dichotomized hTERT levels (<0.42 versus > or =0.42) were associated with prognosis and Kaplan-Meier survival curves demonstrated a significant difference (log rank: p<0.01) with 5-year survival rates of 44.3% (+/-7.1%) for low as compared to 80% (+/-8.9%) for high hTERT mRNA expression. Low hTERT expression was also significantly associated with squamous cell histology (p<0.03). Telomerase activity was not associated with survival, stage, pT and pN categories, histological type or grading. Comparison of hTERT mRNA expression and telomerase activity was possible in 66 patients and showed a significant difference (p<0.0001) by Wilcoxon rank test. CONCLUSION: This is the first study which demonstrates that high hTERT mRNA expression is associated with improved 5-year survival rates. Expression patterns are distinct among histopathological subtypes of NSCLC and telomerase activity (TRAP) is significantly higher than hTERT mRNA expression.

Dihydropyrimidine dehydrogenase mRNA expression in peripheral blood of rectal cancer patients is significantly associated with residual tumor and distant metastases following resection.

BACKGROUND: DPD and TS expression have been shown to correlate with response of 5-FU based chemotherapy in colorectal cancer tissue. Little is known about mRNA expression levels of TS and DPD in peripheral blood. The goals of this study were to test the feasibility of DPD and TS detection in blood and their associations to TNM staging and complete surgical resection. METHODS: Whole blood was drawn 1 day pre- and 10 days post-operatively from 23 patients with rectal cancer. Either adjuvant (n = 15) or neoadjuvant (n = 8) treatment was performed. Tumor cells were enriched from whole blood by density gradient centrifugation prior to extraction of total cellular RNA and subsequent direct quantitative reverse transcriptase-PCR assays. RESULTS: DPD was detectable in 21/23 patients (91.3%) and TS in 14/23 (61.7%). Stepwise multiple linear regression models showed a significant association of DPD expression with distant metastases (P = 0.004) and residual tumor categories (P = 0.03). CONCLUSIONS: Quantitative analysis of TS and DPD mRNA expression in peripheral blood of rectal cancer patients is technically feasible. DPD expression levels appear to be associated with residual tumor categories and might serve as a molecular marker for complete tumor resection. Larger studies seem to be warranted to scrutinize our hypothesis.

Leukocyte depletion in allogeneic blood transfusion does not change the negative influence on survival following transthoracic resection for esophageal cancer.

BACKGROUND: Perioperative transfusion of allogeneic blood has been hypothesized to have an immunomodulatory effect and influence survival in several cancer types. This study evaluates the association between receipt of leucocyte-depleted and non-depleted allogeneic blood and survival following esophagectomy for cancer. METHODS: A retrospective analysis was performed including 291 patients with esophageal cancers who underwent transthoracic en bloc esophagectomy and extended mediastinal lymphadenectomy. Neoadjuvant chemoradiation was administered in 152 (52.2%) patients. Perioperative blood transfusions were quantified and the potential prognostic cutoff for transfused units was calculated according to LeBlanc. RESULTS: The median number of perioperative blood transfusions was 2 (0-24), and 106 patients (36.4%) received no transfusions. Patients with one or less blood transfusion showed a significantly improved survival compared to patients receiving more than one unit (p < 0.009). In multivariate analysis, blood transfusion categories showed significance (p < 0.015) next to pT, pN, pM category, and residual tumor categories (R-categories). Separate analysis of 183 patients treated after the mandatory introduction of leukocyte-depleted blood transfusions detected a strong tendency, but no significant difference in survival for patients getting one or less or more than one transfusion (p = 0.056). Receipt of leukocyte-depleted versus non-depleted units, however, had no influence on survival (p = 0.766). CONCLUSIONS: The need for perioperative allogeneic blood transfusions is significantly associated with poorer survival following resection for esophageal cancer by univariate and multivariate analysis. Our data suggest that the reduction of leukocytes in allogeneic transfusions is not sufficient to overcome the negative influence on survival.

Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not accurately predict histopathologic regression after neoadjuvant chemoradiation for esophageal cancer.

OBJECTIVE: To prospectively assess the sensitivity (sens), specificity (spec), positive predictive value (ppv), negative predictive value (npv), and accuracy (acc) for clinical response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound (EUS) to determine histomorphologic regression UICC T-category downstaging after neoadjuvant chemoradiation for esophageal cancer. BACKGROUND: Histomorphologic regression is meanwhile established as objective parameter for response and prognosis after neoadjuvant chemoradiation for esophageal cancer. PATIENTS AND METHODS: Within a prospective observation trial, 80 patients with localized esophageal cancers (cT2-4,Nx,M0) received standardized neoadjuvant chemoradiation (cisplatin, 5-fluorouracil, 36 Gy) and were resected by transthoracic en bloc esophagectomy and two-field lymphadenectomy. Tumor regression was based on the percentage of vital residual tumor cells and classified in 4 categories as reported previously. Evaluation by endoscopy and EUS was performed based on WHO/UICC criteria before starting chemoradiation and before resection and rebiopsies were taken at the time of re-endoscopy. RESULTS: Histomorphologic response was of significant (log rank) prognostic importance (P < 0.001), whereas clinical response evaluation by endoscopy (P = 0.1), rebiopsy (P = 0.34), and EUS (P = 0.35) was not. The results of the 3 diagnostic modalities to assess histomorphologic regression by endoscopy and rebiopsy UICC ypT-category downstaging for EUS are summarized: Endoscopy: sens 60%, spec 34%, ppv 49%, npv 44%, acc 47%. Rebiopsy: sens 36%, spec 100%, ppv 100%, npv 24%, acc 47%. EUS: sens 7%, spec 79%, ppv 18%, npv 57%, acc 50%. CONCLUSIONS: Histomorphologic regression is an objective response parameter of significant prognostic importance. The diagnostic accuracy of endoscopy, rebiopsy, and EUS is inadequate for objective response evaluation after neoadjuvant chemoradiation and can be omitted for this purpose in the clinical practice.

Frequent down-regulation of pim-1 mRNA expression in non-small cell lung cancer is associated with lymph node metastases.

Pim kinases are emerging as important mediators of cytokine signalling pathways in hematopoietic cells, and contribute to the progression of certain leukemias and solid tumors. The mRNA expression of pim-1, a putative oncogenic serine-threonine kinase, was determined in non-small cell lung cancer (NSCLC) patients. Sixty-eight patients with potentially curative resections (R0 resections) for NSCLC in histopathological stages I-IIIA were included. An analysis of pim-1 mRNA expression was performed on paired tumor and normal lung tissue samples by quantitative real-time reverse transcriptase-PCR (RT-PCR) standardized for beta-actin. Pim-1 expression in the tumor (median 0.28) was significantly down-regulated (p<0.0001) compared to the paired normal tissue (median 4.96). Immunohistochemistry showed a strong expression of Pim-1 protein in the normal respiratory epithelium and a lower expression in the tumor cells. A significant association between the pim-1 down-regulation and occurrence of lymph node metastases (p=0.05) was detected. The down-regulation of pim-1 mRNA was demonstrated for 59 out of 68 lung cancer patients (86.8%). Down-regulation occurs already in the early stage of NSCLC and is either directly involved in the lymphatic progression in NSCLC or represents a surrogate marker.