[Prognostic Value of Preoperative Anaemia and Perioperative Blood Transfusion in Surgical Treatment of Rectal Cancer]. / Prognostischer Wert präoperativer Anämie und perioperativer Fremdbluttransfusion in der chirurgischen Therapie des Rektumkarzinoms.

INTRODUCTION: There is evidence for the prognostic value of perioperative blood transfusion in the surgical treatment of patients with rectal cancer in the current literature. Also preoperative anaemia seems to have an impact on the outcome of these patients. The aim of this study was to evaluate the impact of preoperative anaemia and perioperative blood transfusion in patients with rectal cancer treated in our hospital. PATIENTS AND METHODS: 208 patients (81 females, 127 males; median age, 67 years) with rectal cancer were included in this retrospective study. All patients received surgical treatment. In 75 % of the patients an anterior rectum resection was performed while 25 % received an abdominoperineal rectum exstirpation. Patients with neoadjuvant treatment were included and statistical analyses were performed. RESULTS: 107 (51.4 %) patients exhibited preoperative anaemia. Patients with neoadjuvant treatment presented with significantly lower preoperative Hb (haemoglobin) values than patients without neoadjuvant treatment (p = 0.022). Patients with preoperative anaemia received significantly more blood transfusions (p = 0.001), had significantly longer hospital stays (p = 0.023) and significantly lower 5-years overall survival (p = 0.005). Blood transfusion was necessary in 82 patients (39.4 %). These patients presented with a significantly higher rate of perioperative complications (p = 0.01) and a lower 5-years overall survival (p = 0.002). In multivariate analyses neither preoperative anaemia nor perioperative transfusion was a significant prognostic factor. CONCLUSION: In our study preoperative anaemia and perioperative blood transfusion seems to have an impact on outcome of surgical treatment of patients with rectal cancer. However, in multivariate analyses neither preoperative anaemia nor perioperative transfusion was a significant prognostic factor.

[How radical should the surgical therapy for gastric/cardia cancer be?]. / Wie radikal sollte ein Magen- bzw. Kardiakarzinom operiert werden?

With the exception of tumours limited to the mucosa, surgical resection of the primary tumour and its local lymph node metastases still remains the sole option for a curative therapy for potentially resectable gastric cancer, as long as a complete tumour resection (R0 resection) can be performed. In this context, the extent of surgical radicality has been discussed over the last years, especially based on the following aspects: 1. extent of lymphadenectomy/need for splenectomy; 2. subtotal versus total gastrectomy; 3. surgical therapy for cardia cancer; 4. operative approach in cT4-tumours; 5. laparoscopic versus open surgery. Based on the recent study results as well as the current guidelines, this review will discuss these specific issues and gives an insight about the recommended surgical radicality in gastric cancer.

MicroRNA profiling in locally advanced esophageal cancer indicates a high potential of miR-192 in prediction of multimodality therapy response.

To identify possible predictive markers, our study aimed to characterize microRNA (miRNA) profiles of responder and nonresponder in the multimodality therapy of locally advanced esophageal cancer. Initially, a microarray-based approach was performed including eight patients with esophageal cancer. Patients received neoadjuvant chemoradiation followed by surgical resection. Major histopathological response was defined if resected specimens contained less than 10% vital tumor cells (major/minor response: 4/4 patients). Intratumoral RNA was isolated from both, pretherapeutic tissue biopsies in addition to corresponding surgical specimens. The profile of 768 miRNAs was analyzed in 16 specimens (preneoadjuvant and postneoadjuvant therapy). Selected miRNAs were than analyzed on pretherapeutic and post-therapeutic biopsies of 80 patients with esophageal cancer, who underwent multimodality therapy (major/minor response: 30/50 patients). Comprehensive miRNA profiling identified miRNAs in pretherapeutic biopsies that were significantly different between major/minor responders. Based on the microarray results, miR-192, miR-194 and miR-622 were selected and the dysregulated miRNAs were studied on an extended series of esophageal cancer patients. The expression of miR-192, miR-194 and miR-622 was significantly reduced after neoadjuvant therapy confirming the array profiling data. Importantly, the pretherapeutic intratumoral expression of miR-192 and miR-194 was significantly associated with the histopathologic response of esophageal squamous cell carcinoma to multimodal therapeutic treatment. Therefore, in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation followed by esophagectomy, miR-192 and miR-194 in pretherapeutic biopsies are considered as indicators of major histopathologic regression.

Vascular endothelial growth factor expression following ischemic conditioning of the gastric conduit.

The partial devascularization of the stomach, necessary for esophageal reconstruction with a gastric conduit, impairs microcirculation in the anastomotic region of the gastric fundus. Ischemic conditioning of the gastric tube is considered as a possible approach to improve microcirculation in the gastric mucosa. The aim of this study was to investigate whether ischemic conditioning induces neo-angiogenesis in the gastric fundus by expression of vascular endothelial growth factor (VEGF). Twenty patients with an esophageal carcinoma scheduled for esophagectomy and gastric reconstruction were included. To compare VEGF expression before and after ischemic conditioning, preoperative endoscopic biopsies were taken from the gastric fundus. The surgical procedure consisted of two separate steps, the complete gastric mobilization including partial devascularization of the stomach and after a delay of 4-5 days high transthoracic esophagectomy with intrathoracic gastric reconstruction (Ivor-Lewis procedure). The second tissue sample was obtained from the donut of the stapled esophagogastrostomy. For further work-up, preoperative biopsies and the gastric donuts were fixed in liquid nitrogen. Preoperative and intraoperative VEGF expression was measured by quantitative real-time reverse transcription-polymerase chain reaction (VEGF×100/ß-actin) and results were compared using Wilcoxon test for paired samples. In all 40 specimens, a distinct expression of VEGF could be detected. Comparing the level of VEGF expression of the preoperative biopsies and postoperative tissue sample, no significant difference could be demonstrated following ischemic conditioning. In this model of ischemic conditioning with delayed reconstruction of 4-5 days, no induction of neo-angiogenesis could be demonstrated by measurement of VEGF expression.

[Hepatic cholestasis resulting from a long-standing enterothorax: a case report]. / Langjähriger Enterothorax als ungewöhnliche Ursache einer Cholestase: ein Fallbericht.

BACKGROUND: Due to the lack of symptoms an enterothorax frequently remains undetected in adults. Most symptomatic patients complain about bowel obstruction and a surgical repair of the diaphragmatic defect, particularly with a mesh, is mandatory. METHODS: This report presents the case of a 72-year-old female patient with a history of an upside-down stomach presenting with a painless jaundice and signs of liver cirrhosis. CLINICAL COURSE: The preoperative work-up revealed an enterothorax with compression of the main bile duct. Explorative laparotomy showed a liver cirrhosis with distinct intrahepatic cholestasis, a hydropic gallbladder and confirmed a right-sided diaphragmatic defect with an enterothorax. After reposition of the intestine, a cholecystectomy, bile duct revision and the closure of the diaphragmatic defect using a mesh were performed. CONCLUSION: Diaphragmatic defects are the basis for the formation of an enterothorax which may be associated with a complicated clinical course. Therefore, in cases of coincidental diagnosis, even in asymptomatic patients, surgical repair should be performed in order to prevent serious complications as presented in this case.

Radiotherapy in elderly patients with inoperable esophageal cancer. Is there a benefit?

BACKGROUND: Radiation oncologists increasingly face elderly cancer patients impaired by comorbidities and reduced performance status. As less data are available for this particular group of patients, the aim of the study was to assess the prognosis of inoperable esophageal cancer patients ≥ 70 years undergoing definitive radiotherapy or radiochemotherapy. PATIENTS AND TREATMENT PROTOCOL: Patients aged ≥ 70 with inoperable carcinoma of the esophagus undergoing definitive radio(chemo)therapy between 1995 and 2006 at the University of Cologne were included retrospectively. Maximal total dose of radiotherapy administered was 63 Gy (5 × 1.8 Gy/week). Chemotherapy consisted of cisplatin (20 mg/m(2) on days 1-5 and days 29-33) and 5-fluorouracil (650-1,000 mg/m(2) on days 1-5 and days 29-33). Efficacy was compared with a cohort of 152 patients < 70 years treated with the same protocol during the same time period. RESULTS: A total of 51 patients aged ≥ 70 with inoperable cancer of the esophagus undergoing definitive therapy were identified (stage I/II 23.5%, stage III 56.9%, stage IV 9.8%; squamous cell carcinoma 74.5%, adenocarcinoma 25.5%). While 15 patients (29.4%) received combined radiochemotherapy (RCT), 40 patients (70.6%) were treated with radiotherapy alone (RT). Median progression-free survival (PFS) was 9.5 months; median overall survival (OS) was 13.9 months. Patients treated with RCT had a 2-year OS rate of 53.3% compared with 16.7% for RT patients (p = 0.039). The 2-year OS for clinically lymph node negative patients was 38.5% compared with 21.2% for lymph node positive patients (p = 0.072). Median OS was not significantly different between patients ≥ 70 years versus the patient cohort (n = 152) aged < 70 years (13.9 vs. 7.2 months, p = 0.072) but PFS showed a significant difference (4.9 vs. 9.5 months, p = 0.026) in favor of the > 70 years group. CONCLUSION: Prognosis in elderly patients with inoperable esophageal cancer undergoing definitive radiotherapy/radiochemotherapy is limited, although it is not inferior to patients < 70 years.

Evaluation of histological regression grading systems in the neoadjuvant therapy of rectal cancer: do they have prognostic impact?

PURPOSE: Neoadjuvant treatment options have been developed to improve survival of patients with locally advanced rectal cancer. As only patients with a major histopatholocial response benefit from this preoperative therapy, several tumor regression grading systems have been developed. However, currently no accepted comprehensive grading system for clinical use is available. Therefore, we studied the impact of four histological regression grading systems in the neoadjuvant therapy of rectal cancer. METHODS: In this retrospective study, 85 patients with locally advanced rectal cancer were included. All patients received a neoadjuvant radiochemotherapy followed by surgical resection. The histological regression grading was evaluated using four classification systems: (1) grading system by the Japanese society of colorectal cancer, (2) grading system by Junker-Müller, (3) grading system by Dworak, (4) Cologne grading system. The four classification systems were analyzed for their prognostic impact. RESULTS: The following significant correlations were detected between the four classification systems and the ypTNM categories: (1) patients with a ypT3/4 category had significantly more often a worse histopathologic response in all four grading systems (p = 0.001); (2) a ypN0 category was significantly correlated with good histopathologic response only in the Cologne grading system; (3) in the Junker-Müller and Dworak grading systems, a ypM0 category was significantly correlated with a good histopathologic response (p = 0.046; p = 0.03). However, none of the used classification systems had a prognostic impact on survival. CONCLUSIONS: Currently, none of the analyzed histological regression grading systems is effective for clinical use.

Prognostic factors in definitive radiochemotherapy of advanced inoperable esophageal cancer.

The aim of this study was to assess the efficacy and prognostic factors of definitive radiochemotherapy (RCT) for inoperable esophageal cancer. Between 1995 and 2005 all patients with inoperable esophageal cancer that underwent concurrent RCT were included in this retrospective study. Conventional computed tomography-based treatment planning as well as 3D-conformal radiotherapy (RT) was used. Maximum radiotherapy dose was 63 Gy. Chemotherapy consisted of cisplatin (20 mg/m(2) d1-5 and 29-33) and 5-FU (650-1000 mg/m(2) d1-5 and 29-33). Patients not suitable for RCT received radiotherapy alone. Toxicity was measured according to common toxicity criteria (CTC). Two hundred three consecutive patients with inoperable esophageal cancer that received definitive therapy were identified in this time period (160 with squamous cell carcinoma and 43 with adenocarcinoma). The 2-year overall survival probability was 21.2% whereas the progression-free survival at 2 years was 13.8% for all patients. In the univariate analysis, type of histology, T-stage, N-stage, application of chemotherapy, and the radiation dose were significantly correlated with overall/progression-free survival. Moreover, multivariate analysis revealed an independent prognostic impact for N-stage, radiation dose, and concurrent chemotherapy. Definitive RCT is an important palliative treatment option for patients with inoperable esophageal cancer. N-stage, radiation dose, and concurrent chemotherapy are important prognostic factors for survival.

The gene expression profile of cardia intestinal metaplasia is similar to that of Barrett's esophagus, not gastric intestinal metaplasia.

The etiology and significance of cardia intestinal metaplasia (CIM) is disputed. CIM may represent a form of Barrett's esophagus due to reflux or could reflect generalized gastric intestinal metaplasia due to Helicobacter pylori. The aim of this study was to utilize gene expression data to compare CIM to Barrett's and gastric intestinal metaplasia. Endoscopic biopsies were classified by endoscopic and histologic criteria as CIM (n= 33), Barrett's (n= 25), or gastric intestinal metaplasia of the antrum or body (n= 18). The squamocolumnar and gastroesophageal junctions were aligned in CIM patients and patients with diffuse gastric intestinal metaplasia were excluded. H. pylori was tested for in the biopsies of all patients. After laser-capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of a panel of nine genes that has been shown to differentiate Barrett's from other foregut mucosa. Cluster analysis with linear discriminant analysis of the expression data was used to classify each sample into groups based solely on similarity of gene expression. Cluster analysis was performed for three groups (CIM vs. Barrett's vs. gastric intestinal metaplasia) and two groups (CIM + Barrett's vs. gastric intestinal metaplasia). There was no difference in H. pylori infection among groups (P= 0.66). Clustering into three groups resulted in frequent misclassification between CIM and Barrett's while misclassification of gastric intestinal metaplasia was uncommon. The CIM and Barrett's groups were then combined for two group clustering and linear discriminant analysis correctly predicted 95% of CIM and Barrett's samples and 83% of gastric intestinal metaplasia samples based on gene expression alone. In conclusion, the gene expression profiles of CIM and Barrett's esophagus were similar in 95% of biopsies and differed significantly from that of gastric intestinal metaplasia. The indistinguishable gene expression profile of CIM and BE suggests that they may share a common etiology in the majority of patients with a similar biology, and calls into question the perception that CIM is an innocuous process.

[Oesophageal cancer: current status of multimodality therapy]. / Ösophaguskarzinom: Aktueller Stand der multimodalen Therapie.

Multimodality treatment options have been widely promoted in the therapy for locally advanced oesophageal cancer (cT3/4Nx). Generally neoadjuvant chemotherapy and combined radiochemotherapy are frequently used in this setting. The recent meta-analyses evaluating randomised trials of different neoadjuvant therapy protocols prior to surgery for patients with locally advanced oesophageal cancer showed only a modest improvement in survivial of 5-10% survival at 5 years. In contrast, the meta-analyses reveal that patients with excellent histopathological responses seem to highly benefit from neoadjuvant regimens. Patients with poor histopathological responses have no benefit but rather disadvantegeous prognoses. Therefore, predictive markers to allow individualisation of multimodality treatment in locally advanced esophageal cancer are urgently needed.

[Value of distal gastrectomy as a remedial operation for failed fundoplication]. / Stellenwert der distalen Magenresektion mit Rekonstruktion nach Roux-Y zur Behandlung des Refluxrezidivs nach Fundoplikatio.

BACKGROUND: Failure of conventional antireflux surgery is a challenging problem. This study aims at defining the role of distal gastrectomy with Roux-en-Y diversion in the treatment of failed fundoplication. MATERIAL AND METHODS: This report reviews the indications and results of 26 patients who underwent revisional antireflux surgery in our department. Distal gastrectomy and Roux-en-Y reconstruction were performed in 6 patients (group a), refundoplication in 15 (group b), and re-hiatoplasty in 5 patients (group c). RESULTS: Group a patients had the longest history (p = 0.001) and the highest number of previous operative procedures (p = 0.001). In contrast, hospital stay was longer and postoperative morbidity was higher after distal gastrectomy (p = n. s.). At follow-up, symptom improvement was achieved most reliably after distal gastrectomy (groups a-c: 100%, 78.6%, and 60% of patients; p = n. s.). CONCLUSION: Distal gastrectomy with Roux-en-Y diversion is a safe and reliable surgical option for selected patients after failed fundoplication. Distal gastrectomy with Roux-en-Y diversion is a reliable surgical option for selected patients after failed fundoplication. Despite a higher morbidity, this procedure represents an important addition to the surgical armamentarium, particularly in patients with a history of multiple previous interventions.

A multicenter study of survival after neoadjuvant radiotherapy/chemotherapy and esophagectomy for ypT0N0M0R0 esophageal cancer.

OBJECTIVE: To evaluate 5-year survival of patients with locally advanced esophageal cancer (LAEC) who have undergone multimodality treatment with complete histopathologic response. BACKGROUND: Patients with LAEC may obtain excellent local-regional response to multimodality therapy. The overall benefit of a complete histopathologic response, when no viable tumor is present in the surgical specimen, is incompletely understood and existing data are limited to single-center studies with relatively few patients. The aim of this multicenter study was to define the outcome of patients with complete histopathologic response after multimodality therapy for LAEC. METHODS: The study population included 299 patients (229 male, 70 female; median age: 60 years) with LAEC (cT2N1M0, T3-4N0-1M0; 181 adenocarcinomas, 118 squamous carcinomas) who underwent either neoadjuvant radiochemotherapy (n = 284) or chemotherapy (n = 15) followed by esophagectomy at 6 specialized centers: Europe (3) and United States (3). All patients in the study had stage ypT0N0M0R0 after resection. RESULTS: Esophagectomy with thoracotomy (n = 255) was more frequent than with a transhiatal approach (n = 44). The median number of analyzed lymph nodes in the surgical specimens was 20 (minimum-maximum: 1-77). Thirty-day mortality rate was 2.4% and 90-day mortality rate was 5.7%. Overall 5-year survival rate was 55%. The disease-specific 5-year survival rate was 68%, with a recurrence rate of 23.4% (n = 70; local vs distant recurrence: 3.3% vs 20.1%). Cox regression analysis identified age as the only independent predictor of survival, whereas gender, histology, type of esophagectomy, type of neoadjuvant therapy, and the number of resected lymph nodes had no prognostic impact. CONCLUSION: Patients with histopathologic complete response at the time of resection of LAEC achieve excellent survival.

[18F]-fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic response and prognosis after completion of neoadjuvant chemotherapy in gastric cancer.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy is applied to improve the prognosis of patients with advanced gastric cancer. However, only a major histopathological response will provide a benefit. Recent studies suggest that [(18)F]-fluorodeoxyglucose-positron-emission-tomography (FDG-PET) correlates with response and survival in patients with gastroesophageal adenocarcinomas undergoing neoadjuvant chemotherapy. We evaluated the potential of FDG-PET for the assessment of response and prognosis in the multimodality treatment of gastric cancer. METHODS: Study patients were recruited from a prospective observation trial. Forty two patients with advanced gastric cancer received neoadjuvant chemotherapy and subsequently 40 patients underwent standardized gastrectomy (2 patients with tumor progression had therapy limited to palliative chemotherapy without surgery). Histomorphologic regression was defined as major response when resected specimens contained <10% vital tumor cells. FDG-PET was performed before and 2 weeks after the end of neoadjuvant chemotherapy with assessment of the intratumoral FDG-uptake [pre-treatment standardized uptake value (SUV1); post-treatment SUV (SUV2); percentage change (SUVDelta%)]. RESULTS: Histomorphological tumor regression was confirmed as a prognostic factor (P = 0.039). No significant correlations between SUV1, SUV2, or SUVDelta% and response or prognosis were found. CONCLUSION: FDG-PET seems not to be an imaging system that effectively characterizes major/minor response and survival in patients with gastric cancer following multimodality treatment.

Options in the management of esophageal perforation: analysis over a 12-year period.

Controversies exist about the management of esophageal perforation in order to eliminate the septic focus. The aim of this study was to assess the etiology, management, and outcome of esophageal perforation over a 12-year period, in order to characterize optimal treatment options in this severe disease. Between May 1996 and May 2008, 44 patients (30 men, 14 women; median age 67 years) with esophageal perforation were treated in our department. Etiology, diagnostic procedures, time interval between clinical presentation and treatment, therapeutic management, and outcome were analyzed retro- or prospectively for each patient. Iatrogenic injury was the most frequent cause of esophageal perforation (n= 28), followed by spontaneous (n= 9) and traumatic (n= 4) esophageal rupture (in three patients, the reasons were not determinable). Eight patients (18%) underwent conservative treatment with cessation of oral intake, antibiotics, and parenteral nutrition. Twelve (27%) patients received an endoscopic stent implantation. Surgical therapy was performed in 24 (55%) patients with suturing of the lesion in nine patients, esophagectomy with delayed reconstruction in 14 patients, and resection of the distal esophagus and gastrectomy in one patient. In case of iatrogenic perforation, conservative or interventional therapy was performed each in 50% of the patients; 89% of the patients with a Boerhaave syndrome underwent surgery. The hospital mortality rate was 6.8% (3 of 44 patients): one patient with an iatrogenic perforation after conservative treatment, and two patients after surgery (one with Boerhaave syndrome, one with iatrogenic rupture). No death occurred in the 25 patients with a diagnostic interval less than 24 hours, whereas the mortality rate in the group (n= 16 patients) with a diagnostic interval of more than 24 hours was 19% (P= 0.053). In three patients, the diagnostic interval was not determinable retrospectively. An individualized therapy depending on etiology, diagnostic delay, and septic status leads to a low mortality of esophageal perforation.

Histological type of esophageal cancer might affect response to neo-adjuvant radiochemotherapy and subsequent prognosis.

BACKGROUND: This study investigates response and prognosis after neo-adjuvant chemoradiation (CTx/RTx) in patients with advanced esophageal carcinoma, according to histological type. PATIENTS AND METHODS: Patients with uT3 carcinoma of the esophagus treated with curative-intention esophagectomy from 1997 until 2006 were included in this retrospective analysis. Patients receiving preoperative CTx/RTx (5-fluorouracil, cisplatin, 36 Gy) were compared with those with primary surgery for pT3 tumors. Therapy response after CTx/RTx was evaluated using 'Cologne Regression Grade' (minor response: >or=10% vital residual tumor cells (VRTCs), major response: <10% VRTC or pathologic complete response). Prognosis was evaluated for adenocarcinoma (AC) and squamous cell carcinoma (SCC). RESULTS: Of 297 patients, 52% were SCC and 48% AC. In all, 192 patients underwent CTx/RTx, 100 (65%) SCC and 92 (64%) AC (nonsignificant). In SCC group 51% and in AC group 29% achieved major response (P < 0.01). Patients with major response had a 2-year survival rate (2y-SR) of 78% versus those with minor response or without CTx/RTx, with a 2y-SR of 45% (P = 0.001). Examining patients with major response exclusively, the prognosis of AC (2y-SR 85%) is better than that of SCC (2y-SR 54%) (P < 0.01). CONCLUSION: This retrospective study concludes that in esophageal tumors, response to and prognosis after neo-adjuvant CTx/RTx vary according to histology.

GNAS1 T393C polymorphism is associated with histopathological response to neoadjuvant radiochemotherapy in esophageal cancer.

Recent studies have shown an association between the GNAS1 T393C polymorphism and clinical outcome for various solid tumors. In this study, we genotyped 51 patients from an observational trial on cisplatin/5-FU-based neoadjuvant radiochemotherapy of locally advanced esophageal cancer (cT2-4, Nx, M0) and genotyping was correlated with histomorphological tumor regression. The C-allele frequency in esophageal cancer patients was 0.49. Pearson's chi(2)-test showed a significant (P<0.05) association between tumor regression grades and T393C genotypes. Overall, 63% of the patients in the T-allele group (TT+CT) were minor responders with more than 10% residual vital tumor cells in resection specimens, whereas T(-) genotypes (CC) showed a major histopathological response with less than 10% residual vital tumor cells in 80%. The results support the role of the T393C polymorphism as a predictive molecular marker for tumor response to cisplatin/5-FU-based radiochemotherapy in esophageal cancer.

Survivin expression in gastric cancer: Association with histomorphological response to neoadjuvant therapy and prognosis.

BACKGROUND AND OBJECTIVES: Neoadjuvant therapy is applied to improve the prognosis associated with advanced gastric cancer. Only patients with a major response seem to have a survival benefit. Predictive markers to allow individualisation of treatment could be helpful. We examined the association of survivin protein expression with histopathologic response to neoadjuvant chemotherapy and prognosis in patients with gastric cancer. METHODS: Forty patients with gastric cancer received neoadjuvant chemotherapy. Afterwards, 38 patients underwent total gastrectomy, while 2 patients received definitive chemotherapy because of tumour progression. Histomorphologic regression was defined as major response when resected specimens contained <10% tumour cells. Intratumoural survivin expression was determined by immunohistochemistry in pre- and post-therapeutic specimens and correlated with clinicopathologic parameters. RESULTS: The pre- and post-therapeutic intratumoural survivin protein expression was not associated with histomorphologic regression. Post-therapeutic survivin expression did not have prognostic impact. A significant association was detected between pre-therapeutic survivin levels and prognosis: patients with a higher survivin protein expression showed a significant survival benefit. In multivariate analysis pre-therapeutic survivin expression was characterised as an independent prognostic marker, besides pN-status and histopathologic regression. CONCLUSIONS: The pre-therapeutic survivin protein expression seems to be an independent prognostic marker in the multimodality treatment of advanced gastric cancer.

Lack of prognostic significance of serum DNA methylation of DAPK, MGMT, and GSTPI in patients with non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: To further improve the screening, diagnosis and therapy of patients with non-small cell lung cancer (NSCLC) additional diagnostic tools are desperately warranted. Aim of this study was to investigate the potential of the DNA methylation of DAPK, MGMT, and GSTPI in serum of patients with NSCLC as a prognostic molecular marker in this disease. METHODS: Seventy-six patients with NSCLC were included in this study. The analysis of DNA methylation in serum of patients was performed on pre-operative samples. Following DNA isolation and bisulfite-treatment, DNA methylation was analyzed by quantitative-methylation-specific real-time PCR with beta-actin as the internal reference gene. RESULTS: DNA methylation was detectable with following frequencies: DAPK 68.4%, MGMT 7.9%, GSTPI 0%. There were no associations between DNA methylation status and histology, tumor stage, grading or gender detectable. With a mean follow-up of 19.7 months the median survival was 26.3 months. There were no associations between the status of DNA methylation in patient's serum and prognosis detectable. CONCLUSION: The analysis of DNA methylation in serum of patients with NSCLC by quantitative-methylation-specific real-time PCR is technically feasible. Although our results suggest quantification of DNA methylation in serum not of prognostic significance in this disease, further studies are warranted to determine the future potential of this molecular approach.

Reflux esophagitis, high-grade neoplasia, and early Barrett's carcinoma-what is the place of the Merendino procedure?

INTRODUCTION: Because of the increasing frequency of Barrett's cancer in Western industrialized countries, the management of reflux disease with the potential development of Barrett's esophagus, neoplasia, and early carcinoma is very important. In case of established Barrett's esophagus, the malignant degeneration of the specialized epithelium cannot definitely be prevented by antireflux surgery or continuous medication. Mucosal adenocarcinomas nearly never develop lymph node metastasis and can mostly be treated by endoscopic mucosectomy. The deeper the submucosa is infiltrated, the higher is the rate of lymph node metastasis which is, on the average, 30% for submucosal carcinoma. CONCLUSIONS: Therefore, radical subtotal esophagectomy is the treatment of choice for submucosal carcinoma, whereas distal esophageal resection with limited lymph node dissection is only indicated in mucosal carcinoma which cannot be completely removed by interventional endoscopy.

Successful management of esophageal perforation due to an aortic arch aneurysm replacement.

We present the successful management of an esophageal perforation after aortic arch aneurysm replacement in a 64-year-old patient. Four weeks after surgical repair of a perforated aortic arch aneurysm, a contained perforation of the thoracic esophagus on the prosthesis was detected. A subtotal esophagectomy and reconstruction by pull-up of the stomach together with the greater omentum and high intrathoracic esophagogastrostomy was performed. The aortic prosthesis was covered by omentum. After a prolonged postoperative course, the patient was discharged from the hospital on a full oral diet. She is well after 1 year without signs of infection.