Reduced RBM3 expression is associated with aggressive tumor features in esophageal cancer but not significantly linked to patient outcome.

BACKGROUND: RBM3 expression has been suggested as prognostic marker in several cancer types. The purpose of this study was to assess the prevalence and clinical significance of altered RBM3 expression in esophageal cancer. METHODS: RBM3 protein expression was measured by immunohistochemistry using tissue microarrays containing samples from 359 esophageal adenocarcinoma (EAC) and 254 esophageal squamous cell cancer (ESCC) patients with oncological follow-up data. RESULTS: While nuclear RBM3 expression was always high in benign esophageal epithelium, high RBM3 expression was only detectable in 66.4% of interpretable EACs and 59.3% of ESCCs. Decreased RBM3 expression was linked to a subset of EACs with advanced UICC stage and presence of distant metastasis (P = 0.0031 and P = 0.0024). In ESCC, decreased RBM3 expression was associated with advanced UICC stage, high tumor stage, and positive lymph node status (P = 0.0213, P = 0.0061, and P = 0.0192). However, RBM3 expression was largely unrelated to survival of patients with esophageal cancer (EAC: P = 0.212 and ESCC: P = 0.5992). CONCLUSIONS: In summary, the present study shows that decreased RBM3 expression is associated with unfavourable esophageal cancer phenotype, but not significantly linked to patient prognosis.

Expression of ICAM-1, E-cadherin, periostin and midkine in metastases of pancreatic ductal adenocarcinomas.

Development and progression of malignant tumors is in part characterized by the ability of a tumor cell to overcome cell-cell and cell-matrix adhesion and to disseminate in organs distinct from that in which they originated. This study was undertaken to analyze the clinical significance of the expression of the following cell-cell and cell-matrix adhesion molecules in pancreatic ductal adenocarcinomas (PDACs) and synchronous liver metastases: intercellular adhesion molecule 1 (ICAM-1), E-cadherin, periostin, and midkine (MK). ICAM-1, E-cadherin, periostin and MK expression was analyzed by immunohistochemistry on a tissue microarray containing 34 PDACs and 12 liver metastasis specimens. ICAM-1 expression was predominantly localized in the membranes of the cells and was found in weak to moderate intensities in PDACs and liver metastases. E-cadherin expression was absent in the majority of PDACs and corresponding liver metastases. The secreted proteins periostin and MK were expressed in various intensities in primary cancers and liver metastases. Statistical analysis demonstrated that the expression levels of the analyzed markers were neither significantly associated with metastasis in PDACs nor with clinical outcome of patients. Our study shows that the expression of the cell-cell and cell-matrix adhesion molecules ICAM-1, E-cadherin, periostin and MK was not significantly linked to metastatic disease in PDACs. Moreover, our study excludes the analyzed markers as prognostic markers in PDACs.

What should be the gold standard for the surgical component in the treatment of locally advanced esophageal cancer: transthoracic versus transhiatal esophagectomy.

OBJECTIVE: To analyze survival differences between transthoracic esophagectomy (TTE) and limited transhiatal esophagectomy (THE) in clinically (cT3) and pathologically (pT3) staged advanced tumors without neoadjuvant treatment. BACKGROUND: Debate exists whether in the type of resection in locally advanced cancer plays a role in prognosis and whether THE is a valuable alternative to TTE regarding oncological doctrine and overall survival. METHODS: In a retrospective study of 2 high-volume centers, 468 patients with cT3NXM0 esophageal cancer, including 242 (51.7%) squamous cell carcinomas (SCCs) and 226 (48.3%) adenocarcinomas (ACs), were analyzed. A total of 341 (72.9%) TTE and 127 (27.1%) THE were performed. We used the propensity score matching to build comparable groups. Primary endpoint was the overall survival; secondary endpoints included resection status and lymph node yield. RESULTS: TTE achieved a higher rate of R0 resections (86.2% vs 73.2%; P = 0.001) and a higher median lymph node yield (27.0 ± 12.4 vs 17.0 ± 6.4; P < 0.001) than THE. Thirty-day mortality rate was 6.6% (8/121) for TTE and 7.4% (9/121) for THE (P = 0.600). In the matched groups, TTE was beneficial for pT3 SCC (P = 0.004), pT3 AC (P = 0.029), cT3 SCC (P = 0.018), and cT3 AC (P = 0.028) patients. TTE was either beneficial in pN2 disease for cT3 AC + SCC or pT3 SCC but not for pT3 AC patients, without nodal stratification in pT3 and cT3 SCC node-positive patients. On multivariable analysis, TTE remained an independent factor for survival. CONCLUSIONS: Extended TTE achieved a higher rate of R0 resections, a higher lymph node yield, and resulted in a prolonged survival than THE in pT3, cT3, and node-positive patients.

Preoperative Pancreatic Resection (PREPARE) score: a prospective multicenter-based morbidity risk score.

OBJECTIVES: Development of a simple preoperative risk score to predict morbidity related to pancreatic surgery. BACKGROUND: Pancreatic surgery is standardized with little technical diversity among institutions and unchanging morbidity and mortality rates in recent years. Preoperative identification of high-risk patients is potentially one of the rare avenues for improving the clinical course of patients undergoing pancreatic surgery. METHODS: Using a prospectively collected multicenter database of patients undergoing pancreatic surgery (n=703), surgical complications were classified according to the Clavien-Dindo classification. A new scoring system for preoperative identification of high-risk patients that included only objective preoperatively assessable variables was developed using a multivariate regression model. Subsequently, this scoring system was prospectively validated from 2011 to 2013 (n=429) in a multicenter setting. RESULTS: Eight independent preoperatively assessable variables were identified and included in the scoring system: systolic blood pressure, heart rate, hemoglobin level, albumin level, ASA (American Society of Anesthesiologists) score, surgical procedure, elective surgery or not, and disease of pancreatic origin or not. On the basis of 3 subgroups (low risk, intermediate risk, high risk), the proposed scoring system reached an accuracy of 75% for correctly predicting occurrence or nonoccurrence of major surgical complications in 80% of all analyzed patients within the validation cohort (c-statistic index=0.709, P<0.001, 95% confidence interval=0.657-0.760). CONCLUSIONS: We present an easily applied scoring system with convincing accuracy for identifying low-risk and high-risk patients. In contrast to other systems, the score is exclusively based on objective preoperatively assessable characteristics and can be rapidly and easily calculated.

Single versus double Roux-en-Y reconstruction techniques in pancreaticoduodenectomy: a comparative single-center study.

BACKGROUND: The aim of this study was to analyze the impact of single Roux-en-Y reconstruction (RYR) and double Roux-en-Y reconstruction (dRYR) on intraoperative outcome and postoperative morbidity and mortality after pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: All patients who underwent surgery between 2000 and 2005 for dRYR and RYR after PD or PPPD at the study hospital were evaluated for inclusion. Comparison of categorical patient characteristics was performed using the χ (2) test. Data were reported as median and range. Differences were analyzed with the Mann-Whitney U test. Postoperative complications were graded according to the Clavien-Dindo classification scheme and the recommendations of the International Study Group of Pancreatic Surgery (ISGPS). RESULTS: A total of 319 patients were included in final analysis. The median time of surgery was significantly shorter when performing a single Roux-en-Y loop reconstruction (55 min in PD and 50 min in PPPD) (p < 0.001). Saved time had a significant effect on the cost of surgery (p < 0.001). No impact on postoperative outcome according to the Clavien-Dindo classification, the ISGPS definitions of pancreatic fistulas, and delayed gastric emptying was evident. The relaparotomy rate due to severe postoperative hemorrhage was significantly higher in the dRYR PD cohort (2.2 vs. 11.9 %, p < 0.001). CONCLUSIONS: Double Roux-en-Y reconstruction of the alimentary tract is not beneficial in terms of surgical outcome and postoperative morbidity and mortality and should be avoided due to unnecessarily prolonged surgery.

High surgical morbidity following distal pancreatectomy: still an unsolved problem.

BACKGROUND: High surgical morbidity following distal pancreatectomy, especially pancreatic fistula, remains an unsolved problem. The aim of this study was to identify potential risk factors for surgical morbidity with a focus on the development of pancreatic fistula. METHODS: Clinicopathologic parameters were collected for 283 patients who underwent distal pancreatectomy between January 2000 and May 2010. Logistic regression analyses were performed to identify potential risk factors for surgical morbidity and pancreatic fistula. RESULTS: Spleen-preserving pancreatectomy was carried out in 12% of all cases and multivisceral resections were performed in 37.8%. For closure of the pancreatic remnant, three different techniques were used: hand-sewn suture in 44.5%, pancreaticojejunal anastomosis in 24%, and closure by stapler in 31.5%. Overall morbidity and mortality were 53 and 3.5%. Surgical morbidity was observed in 50.2% of all cases and pancreatic fistula in 24%. The stapling group had significantly higher surgical morbidity at 65.2% (p=0.001) and the most pancreatic fistulas, though this did not reach statistical significance (p=0.189). Univariate and multivariate logistic analyses indicated that closure by stapler [odds ratio (OR)=3.61; p<0.001] is a risk factor for surgical morbidity. CONCLUSION: Closure of the pancreatic remnant by using a stapling device was associated with an increased risk of surgical morbidity. With an increasing number of laparoscopic distal pancreatectomies being performed, further studies analyzing the use of stapling devices and newer closure techniques are needed.

How radical should surgery be for early esophageal cancer?

BACKGROUND: We have compared the oncologic effectiveness of limited resection (LR) techniques such as transhiatal (TH) or limited resection of the esophagogastric junction with intestinal interposition (LREGJ) in the treatment of early esophageal carcinoma with that of the extended resection such as the classical thoracoabdominal (TA) en bloc esophagectomy. METHODS: We performed a retrospective analysis of prospectively collected data of 113 patients with T1 esophageal cancer (57 adeno- and 56 squamous cell carcinomas) who had surgical resection with systematic lymphadenectomy. Forty-one underwent extensive (TA) and 72 limited resection (51 TH and 21 LREGJ). RESULTS: Complete resection (R0) was achieved in all cases. Lymphatic metastases were seen in none of the mucosal but in 26.8% of the submucosal T1 cancers. The median lymph node yield was significantly higher in patients with extensive resection (24 vs. 15 lymph nodes; p=0.036), but this did not affect the overall survival (median=88 vs. 102 months, 5-year survival probability=57.8 vs. 67.7%; log rank=0.578). The median hospital stay and ICU stay were significantly shorter in the LR group (p=0.039 and p = 0.044, respectively). CONCLUSION: Limited resection leads to lower lymph node yield but similar oncologic effectiveness as the extensive surgery. It may represent a valuable alternative in the treatment of patients with early (submucosal) esophageal carcinoma.

Multivisceral resections in pancreatic cancer: identification of risk factors.

BACKGROUND: There is an assumption that multivisceral resections (MVRs) in patients with a pancreatic malignancy are associated with higher morbidity. The oncologic benefit, however, remains controversial. METHODS: The aim was to identify risk factors for complications in cases of MVR in patients with pancreatic cancer. Of 1099 patients who underwent major pancreatic resection at our institution between January 1992 and October 2008, a total of 55 were treated with an MVR involving resection of one or more additional organs. This group was compared with 154 patients who had palliative bypass surgery and 303 patients who underwent standard pancreatic head resection. RESULTS: Multivisceral resection patients had an overall higher incidence of major surgical complications (p < 0.001). In-hospital mortality was comparable in all groups. Median survival after MVR was inferior to that after standard resection but was significantly better than that after palliative bypass. Univariate logistic regression analysis identified concomitant colon, kidney, and liver resections and any intraoperative transfusion as predictors of complications; in the multivariate analysis, only kidney resections and any intraoperative transfusion were confirmed predictors. In contrast, T status, kidney resection, resection of four or more organs, any postoperative transfusion, and intensive care unit stay of >2 days were identified as predictors of survival in the univariate Cox regression analysis; in the multivariate analysis, only the T status was confirmed. Median survival after MVR was 16 months, after palliative bypass 6 months, and after standard resection 18 months (p < 0.001). CONCLUSIONS: Multivisceral resections are technically feasible procedures with increased survival when compared to palliative bypass procedures. The incidence of postoperative complications was increased with kidney resection and when intraoperative transfusion was required.

Strong impact of micrometastatic tumor cell load in patients with esophageal carcinoma.

BACKGROUND: To assess the role of immunohistochemically detectable nodal microinvolvement of patients with "curatively" resected esophageal carcinoma. METHODS: In 73 patients with resectable esophageal carcinoma [squamous cell carcinoma (SCC), n = 45 (61.6%); adenocarcinoma (AC), n = 28 (38.4%)] a total of 2174 lymph nodes (LN) were removed. In each of the 1958 LN classified as negative on conventional histopathology, immunohistochemistry was performed using the anticytokeratin antibody AE1/AE3. To determine the role of the amount of residual tumor load, the patients were grouped according to the percentage of LN affected with micrometastasis (0%, <11%, and > or =11%). RESULTS: Tumor cells were immunohistochemically detected in 47 LN (2.4%) from 25 (34.2%) patients. Five-year overall survival probability (5-YSP) of 30% in pN(0 )patients with detected occult tumor cells in LN was significantly worse than that in those without nodal microinvolvement (76%, P = 0.021), hereby resembling that of pN1-patients (24%, P = 0.84). Median overall survival in patients with no (0%), low (<11%), and high (>11%) micrometastatic tumor load was 43, 27, and 11 months, respectively. Substratification according to histological type showed that, in patients with AC, the presence of nodal microinvolvement had a significant impact on 5-YSP (0% versus 65%; P = 0.03), whereas in patients with SCC, differences of 5-YSP were only of borderline significance (24% versus 53%; P = 0.081). CONCLUSION: Minimal tumor cell load as assessed by the ratio of micrometastatically affected LN is a complementary tool for better risk stratification of patients with esophageal carcinoma.

Repeated surgery improves survival in recurrent gastrointestinal stromal tumors: a retrospective analysis of 144 patients.

PURPOSE: Recurrence of a gastrointestinal stromal tumor (GIST) may require multimodal therapy and the role of repeated surgery in this concept is unclear. PATIENTS AND METHODS: A consecutive series of GIST patients treated by surgery, imatinib therapy or both was retrospectively reviewed, and long-term survival was studied by Kaplan-Meier analysis. RESULTS: Institutional primary surgeries before 1999 necessitated reclassification of the histopathological sections and 58/78 patients were classified as having true GIST. In primary surgeries, liver metastases were observed in GIST (6/58) but not in sarcoma/schwannoma patients (0/20), and exulceration of the primary tumor did not correlate with adverse outcome. Additionally, 86 patients were seen on an outpatient basis or were treated for recurrence at our institution, thus a total of 144 GIST patients were seen at our institution between 1994 and 2007 for either primary or secondary tumor manifestation. After 2003, 19/144 GISTs recurred and were treated by targeted therapy with imatinib. The patients showed better overall survival than historic controls. Imatinib therapy enhanced re-resectability due to tumor downsizing, and re-resection (n = 16) improved survival significantly (p = 0.046, log-rank test). CONCLUSION: A multimodal approach including targeted therapy and repeated surgery in the long-term management of recurrent GIST improves survival.

Increase of CD45-positive Immune Cells in Liver Parenchyma Indicates a More Favorable Prognosis for Patients With Barrett's Cancer.

BACKGROUND: Despite advances in perioperative management, the 5-year survival rate of patients with esophageal adenocarcinoma (Barrett's cancer) is poor. Adjuvant immunotherapies are currently the subject of clinical trials. The prognostic role of tumor-infiltrating T-lymphocytes (TILs) expressing CD45 has only been investigated in primary tumors. The significance of TILs in the target organs of distant metastases, in particular the liver, is unclear. This study examined the influence of CD45-positive cells in liver parenchyma and primary tumors on cumulative survival. MATERIALS AND METHODS: The density of CD45-positive cells was analyzed immunohistochemically using tissue microarrays. Sixty-five patients for whom a liver biopsy was available in addition to the primary tumor were included in the study. Liver metastases were found in 21 patients. The results of the immunohistochemical analysis were correlated with patient's outcomes. The Cox proportional hazard model was used to compute mortality hazard ratio in consideration of clinical variables. RESULTS: Elevated density of CD45-positive cells in the liver biopsy corresponded with a better cumulative survival rate (p<0.001), while no significant differences were found for primary tumors. Multivariate Cox regression analysis showed that a high density of CD45-positive cells in the liver parenchyma was an independent prognostic parameter of longer overall survival (hazard ratio(HR)=0.432, p=0.048). CONCLUSION: The density of CD45-positive cells in the liver parenchyma is an easily measured prognostic biomarker that can identify patient subgroups with a better prognosis. In addition, the density of CD45-positive cells in the liver may assist as a criterion for selecting patients with a high potential for response to adjuvant immunotherapy.

FOXO1 overexpression and loss of pSerine256-FOXO1 expression predicts clinical outcome in esophageal adenocarcinomas.

The function of Forkhead box O 1 (FOXO1) and pSerine256-FOXO1 immunostaining in esophageal cancer is unclear. To clarify the prognostic role of nuclear FOXO1 and cytoplasmic pSerine256-FOXO1 immunostaining, a tissue microarray containing more than 600 esophageal cancers was analyzed. In non-neoplastic esophageal mucosae, FOXO1 expression was detectable in low and pSerine256-FOXO1 expression in high intensities. Increased FOXO1 and decreased pSerine256-FOXO1 expression were linked to advanced tumor stage and high UICC stage in esophageal adenocarcinomas (EACs) (tumor stage: p = 0.0209 and p < 0.0001; UICC stage: p = 0.0201 and p < 0.0001) and squamous cell carcinomas (ESCCs) (tumor stage: p = 0.0003 and p = 0.0016; UICC stage: p = 0.0026 and p = 0.0326). Additionally, overexpression of FOXO1 and loss of pSerine256-FOXO1 expression predicted shortened survival of patients with EACs (p = 0.0003 and p = 0.0133) but were unrelated to outcome in patients with ESCCs (p = 0.7785 and p = 0.8426). In summary, our study shows that overexpression of nuclear FOXO1 and loss of cytoplasmic pSerine256-FOXO1 expression are associated with poor prognosis in patients with EACs. Thus, evaluation of FOXO1 and pSerine256-FOXO1 protein expression - either alone or in combination with other markers - might be useful for prediction of clinical outcome in patients with EAC.

Percutaneous transhepatic cholangiodrainage as rescue therapy for symptomatic biliary leakage without biliary tract dilation after major surgery.

Symptomatic biliary leakage following major upper abdominal surgery is a severe complication resulting in increased morbidity and mortality. Treatment options usually include either endoscopic intervention or surgical revision. These options may be burdened by a high perioperative risk for the patient (e.g., patients with severe disease) or simply may not be possible (e.g., nonpreserved gastroduodenal passage). In the past, percutaneous transhepatic cholangiodrainage did only seem to be a viable option for patients with dilated bile ducts. Here, we present our experience in a consecutive series of patients with symptomatic biliary leakage following major upper abdominal surgery and without dilation of the biliary system that underwent percutaneous transhepatic cholangiodrainage. Percutaneous transhepatic cholangiodrainage was feasible in 15 of 18 patients (83.3%). The procedure was technically not possible in three patients (16.7%). In 10 of the 15 patients (66.6%) with feasible percutaneous transhepatic cholangiodrainage, biliary leakage was definitely controlled without the need for surgical revision. Depending on the experience with the interventional procedure, percutaneous transhepatic cholangiodrainage should be considered as an alternative for treatment of symptomatic biliary leakage instead of immediate reoperation.

Association of rare SPINK1 gene mutation with another base substitution in chronic pancreatitis patients.

AIM: To verify and expand the known spectrum of serine protease inhibitor Kazal type 1 (SPINK1) gene mutations in chronic pancreatitis. METHODS: DNA extracted from 172 chronic pancreatitis patients was assayed for SPINK1 gene mutations by PCR and DNA sequencing. A control cohort of 90 unrelated healthy individuals was analysed by the same methods for presence of common populational polymorphisms, and frequency of five-loci haplotypes was calculated. Linkages of gene aberrations in single SPINK1 gene copies were analysed by long-distance PCR followed by allele-specific PCR and DNA sequencing. RESULTS: The most frequent SPINK1 gene mutation N34S was found at a frequency of 6%. Furthermore, we detected the heterozygous intervening sequence (IVS) 3 + 2 T > C mutated gene in 2 German patients and 1 Macedonian chronic pancreatitis patient. In all three SPINK1 gene copies an additional rare base substitution was found: 5'untranslated region (UTR)-215 G > A. Polymorphism analysis revealed that all three affected genes carried the same five-loci haplotype. DNA sequencing of another chronic pancreatitis-related gene PRSS1 (cationic trypsinogen) did not reveal any mutations in these 3 patients. CONCLUSION: We found in 3 (2%) of 172 chronic pancreatitis patients an IVS3 + 2 T > C SPINK1 gene mutation and a base substitution 5'UTR-215 G > A in the same gene copy. Most probably the 5'UTR-215 G > A represents a rare polymorphism and not a mutation as previously concluded. Haplotype analysis suggests a common origin of the IVS3 + 2 T > C mutation in these patients.

Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy.

AIM: To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma. METHODS: Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays. Forty-three (41%) of the 106 patients were staged as pT((1/2)), 63 (59%) as pT((3/4)), 51 (48%) as pN(0), and 55 (52%) as pN(1). The study population included 59 (56%) patients exhibiting G((1/2)), and 47 (44%) patients with G(3) tumors. Patients received no adjuvant chemo- or radiation therapy and were followed up for a median of 12 (range: 3.5 to 139) mo. RESULTS: Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as "tumor free" by conventional histopathology in 73 (69%) out of the 106 patients. Twenty-nine (57%) of 51 patients staged histopathologically as pN(0) had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free (relative risk 2.92, P=0.005) and overall (relative risk 2.49, P=0.009) survival. CONCLUSION: The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports may help to improve risk stratification of patients with pancreatic cancer.

Glasgow Prognostic Score may be a prognostic index for overall and perioperative survival in gastric cancer without perioperative treatment.

BACKGROUND: Systemic inflammation is a key factor in tumor growth. C-reactive protein and albumin are parameters of systemic inflammation from the Glasgow Prognostic Score (GPS). The purpose was to evaluate the prognostic role of GPS in a homogeneous population of gastric cancer patients undergoing surgical treatment only. METHODS: Patients underwent operations between 2009 and 2014. Those who had received perioperative treatment or had other malignancies or inflammatory diseases were excluded. Eighty-eight patients met all inclusion criteria (age >18 years, documented preoperative serum levels of albumin and C-reactive protein, histologically proven gastric cancer, curative operation, including lymphadenectomy). C-reactive protein and albumin levels were retrieved from our prospective database. GPS was correlated with clinicopathologic characteristics and outcome. RESULTS: Increasing GPS was linked to aggressive tumor biology in terms of tumor size (GPS 0: 51.2% T1 and T2, 48.8% T3 and T4; GPS 1: 23.8% T1 and T2, 76.2% T3 and T4; GPS 2: 23.1% T1 and T2, 76.9% T3 and T4; P = .026), synchronous distant metastases (GPS 0: 47.1% M0, 0.0% M1; GPS 1: 25.9% M0, 0.0% M1; GPS 2: 27.1% M0, 100.0% M1; P = .030), venous vessel invasion (GPS 0: 91.2% V0, 8.8% V1; GPS 1: 66.7% V0, 33.3% V1; GPS 2: 55.0% V0, 45.0% V1; P = .008), resection margin status (GPS 0: 97.4% R0, 2.6% R1; GPS 1: 90.0% R0, 10.0% R1; GPS 2: 77.3% R0, 22.7% R1; P = .044), reduced overall survival (GPS 0: median 25.2 months [range 0.4-106.0]; GPS 1: 15.3 [0.2-59.5]; GPS 2: 5.8 [0.1-55.3]; P = .016) with median overall survival in the whole cohort being 16.2 months (range 0.1-106.0) and perioperative mortality (GPS 0: 0.0% of perioperative deaths, GPS 1: 20.0%, GPS 2: 80.0%; P = .036). Furthermore, GPS was identified as an independent prognosticator of overall survival (P = .033). A gradual decrease in survival between GPS subgroups was evident. CONCLUSION: GPS represents an independent prognostic factor for long-term outcome in resected gastric cancer patients without perioperative treatment and is strongly associated with perioperative mortality.

Locally advanced esophageal carcinoma: is there still a role of surgery alone without neoadjuvant treatment?

OBJECTIVE: The aim of this study is to evaluate the impact of upfront surgery without neoadjuvant pretreatment on survival in patients with clinically staged locally advanced esophageal carcinoma before the new era of neoadjuvant therapy regimes. MATERIAL AND METHODS: This is a retrospective analysis of prospectively collected data of patients with clinically advanced esophageal cancer (cT3) and without neoadjuvant treatment who underwent transthoracic esophagectomy (TTE) in curative intent between 1992 and 2009. Locally advanced esophageal cancer was defined based on presurgical computertomography, endoscopy, and endosonography findings as a tumor infiltrating the paraesophageal tissue or the adjacent structures, with or without lymph node affection. RESULTS: Histological subtypes included 131 squamous cell carcinomas (SCC) and 81 adenocarcinomas (AC). Complete resection (R0) was achieved in 84.0% of all 212 patients. Thirty-day mortality rate was 7.1%. Final pathology revealed 50 patients (23.5%) with pT1 or pT2 carcinomas which were preoperatively overstaged. Median overall survival following TTE for SCC was 13.7 months (95% CI; 10.1-17.2 months) and 24.8 months (95% CI; 14.5-35.1 months) for AC, respectively (p = 0.007). The 5-year survival rates were 14% for SCC and 26% for AC, respectively. In median, 27 lymph nodes were resected. On multivariable analyses, histological type, tumor localization, tumor grading, and resection status remained independent factors influencing overall survival. CONCLUSION: Our results in the treatment of patients with locally advanced esophageal carcinoma undergoing primary TTE are comparable to the results reported for patients undergoing neoadjuvant chemo-radio-therapy followed by surgery in the pre-CROSS-study era. Histological subtypes show different survival rates and should therefore be separately examined in future trials.

Prognostic impact of neoadjuvant chemoradiation in cT3 oesophageal cancer - A propensity score matched analysis.

BACKGROUND: The prognostic effect of neoadjuvant treatment in advanced oesophageal cancer is still debated because most studies included undefined T-stages, different radio/chemotherapies or different types of surgery. OBJECTIVES: To analyse the prognostic impact of neoadjuvant chemoradiation in patients with clinical T3 oesophageal cancer and oesophagectomy. METHODS: In a retrospective study 768 patients from two centres with cT3/Nx/M0 oesophageal cancer and transthoracic en-bloc oesophagectomy were selected. Clinical staging was based on endoscopy, endosonography and spiral-CT scan. Propensity score matching using histology, location of tumour, age, gender and ASA-classification identified 648 patients (n=302 adenocarcinoma (AC), n=346 squamous cell carcinoma (SCC)) for the intention-to-treat analysis comparing group-I (n=324) patients with planned oesophagectomy and group-II (n=324) patients with planned neoadjuvant chemoradiation (40Gy, 5-FU, cisplatin) followed by oesophagectomy. The prognosis was analysed by univariate and multivariate analyses. RESULTS: In the intention-to-treat analysis group-I had a 17% and group-II a 28% 5-year survival rate (5-YSR) (p<0.001). After excluding patients without oesophagectomy the 5-YSR of group-II increased to 30%. The results were more favourable for patients with AC (5y-SR of 38%) compared to SCC (22%) (p=0.060). In group-II patients with major response (n=128) had a 41% 5-YSR compared to 20% for those with minor response (n=155, p<0,001). In multivariate analysis neoadjuvant chemoradiation was a favourable independent prognostic factor. CONCLUSION: Neoadjuvant chemoradiation followed by oesophagectomy results in 11% higher 5-YSR than surgery alone for patients with cT3/Nx/M0 oesophageal cancer. This effect is due to the substantial prognostic benefit of the major responders.

Depth of submucosal tumor infiltration and its relevance in lymphatic metastasis formation for T1b squamous cell and adenocarcinomas of the esophagus.

BACKGROUND: Surgery for early esophageal carcinoma has been challenged by less invasive endoscopic approaches. Selecting patients in need for surgical intervention according to their risk of lymphatic spread is mandatory. OBJECTIVE: The aim of this study was to evaluate risk factors for lymphatic metastasis formation in T1b esophageal carcinomas. METHODS: Histopathological specimens following surgical resection for T1b esophageal carcinomas were reevaluated for overall submucosal layer thickness, depth of submucosal tumor infiltration, tumor length as well as lymphatic and vascular infiltration. Depth of tumor infiltration to overall submucosal thickness was divided in thirds (SM1, SM2, and SM3) and factors influencing lymphatic metastasis formation were assessed. RESULTS: A total of 67 patients with pT1b tumors were analyzed, including 36 adenocarcinomas (53.7 %) and 31 squamous cell carcinomas (46.3 %). Lymph node involvement was seen in 22.4 % (15/67) patients without significant differences between SM1 3/11 (27.3 %), SM2, 4/18 (22.2 %), and SM3 (8/38) (21.8 %) (p = 0.909) carcinomas. On binomial log-regression models, only lymphangioinvasion and tumor length >2 cm was significantly associated with lymph node involvement. CONCLUSION: As depth of submucosal tumor infiltration did not correlate with the formation of lymph node metastases and in regard of the risk of lymphatic spread in these cases, surgical resection is warranted in pT1b carcinomas.

LigaSure™ vs. conventional dissection techniques in pancreatic surgery--a prospective randomised single-centre trial.

BACKGROUND: Surgical procedures in pancreatic surgery are well established, but still involve time-consuming manual dissection. We compared the use of LigaSure with conventional dissection techniques in pancreatic surgery in a prospective randomised single-centre trial (registration number: NCT00850291). METHODS: Patients with tumours of the pancreatic head that were assumed to be technically resectable were randomised to LigaSure or conventional surgery. The primary endpoint of this study was overall operation time. Secondary endpoints were preparation time until tumour resection, intraoperative blood loss, number of given units of packed red blood cells, costs of surgery, postoperative morbidity, length of hospital stay and mortality. RESULTS: There was no difference in overall operation time between the two groups (P = 0.227). Median costs for pancreatic surgery were significantly less in the conventional group with €3,047 (range 2,004-5,543) vs. €3,527 (range 2,516-5,056, P = 0.009). Preparation time, intraoperative blood loss, number of units of packed red blood cells, postoperative morbidity, length of hospital stay and mortality did not differ between the two groups. CONCLUSION: Our data indicate that the LigaSure device is equivalent to conventional dissection modalities in pancreatic surgery.