Plasma Expression Levels of Circulating miR-21 are not Useful for Diagnosing and Monitoring Colorectal Cancer.

BACKGROUND: Recent evidence suggests that microRNAs play an important role in cancer diagnostics. We assessed plasma microRNA-21 levels in patients with colorectal cancer (CRC) at different stages and in patients with benign polyps. METHODS: Plasma levels of miR-21 were assessed by quantitative reverse transcription polymerase chain reaction assay in plasma samples of 76 CRC patients and in 20 patients with benign polyps. Differences between groups were evaluated with Mann-Whitney and Kruskal-Wallis tests. RESULTS: No significant differences of miR-21 plasma levels were observed between CRC patients and subjects with benign polyps (p > 0.05). Also, no significant differences were found between CRC patients with advanced (III-IV) or early cancer stages (I-II) (p > 0.05). CONCLUSIONS: These results do not support the hypothesis that circulating miR-21 expression is increased in adenoma-carcinoma-advanced carcinoma sequence. Accordingly, plasma miR-21 assessment does not appear to be a useful biomarker for diagnosing and staging CRC.

Lack of an association between circulating adiponectin levels and risk of colorectal adenoma.

BACKGROUND: The putative association between serum adiponectin levels and colorectal adenomas is actually under debate. The aim of this study was to investigate this association in relation to factors known to influence the levels of adiponectin such as anthropometric, metabolic, inflammatory parameters as well as lifestyle individual characteristics. METHODS: 40 patients with adenomas and 40 controls were enrolled. Body weight, height, waist circumference, and blood pressure were recorded. Fasting plasma glucose, lipids, C-reactive protein, and adiponectin levels were measured. Metabolic Syndrome was defined and lifestyle characteristics assessed. RESULTS: No differences were found in adiponectin values between patients and controls (p = 0.101). Adiponectin levels were significantly higher in females than in males (p = 0.004). Adiponectin levels did not result in significant association with colorectal adenomas even after adjustment for metabolic and life style parameters. CONCLUSIONS: This study did not confirm the hypothesis that high levels of adiponectin confer decreased risk of colorectal adenomas.

Tumor site and perigastric nodal status are the most important predictors of para-aortic nodal involvement in advanced gastric cancer.

BACKGROUND: This study was designed to identify pathological predictors of para-aortic nodal invasion in advanced gastric cancer. METHODS: Between 1990 and 2007, 294 patients with advanced gastric cancer underwent gastrectomy with D2 lymphadenectomy + para-aortic nodal dissection in Siena and Verona, Italy. RESULTS: Forty-seven (16%) patients had para-aortic node metastases. Of these, 91%, 88%, and 74%, respectively, also had metastases at stations No. 3, No. 1, and No. 7. Para-aortic node metastases were never observed when stations No. 1 and No. 3 were both negative. Patients were divided into three groups, according to the risk of para-aortic node invasion: (1) high-risk group (n = 24, 8.2%), presenting a 42% risk and comprising T3/T4 cancers with mixed/nonintestinal histology, arising from the upper third; (2) low-risk group (n = 138, 46.9%), presenting a 0-10% risk and including middle-lower third tumors-either T2 irrespective of histology, or T3/T4 with intestinal histology; (3) intermediate-risk group, comprising all other patients (n = 132, 44.9%). Their risk ranged between 16% and 30%, but increased up to 21-37.5% after excluding 33 patients with negative No. 1 and No. 3 stations. CONCLUSIONS: The combination of tumor site, histology, and T stage with perigastric nodal status allowed identification of patients at higher risk of para-aortic nodal invasion who could benefit from para-aortic nodal dissection.

A multicentric Western analysis of prognostic factors in advanced, node-negative gastric cancer patients.

BACKGROUND: The presence of lymph node metastasis is one of the most important prognostic factors in patients with gastric carcinoma. Node-negative patients have a better outcome, nevertheless a subgroup of them experience disease recurrence. AIM: To analyze the clinicopathological characteristics of lymph node-negative advanced gastric carcinoma patients submitted to gastrectomy and D2 lymphadenectomy with a retrieved number of nodes greater than 15, after an actual follow-up of almost 5 years, and to evaluate outcome indicators. STUDY DESIGN: The records of 301 patients who underwent curative gastrectomy for gastric carcinoma and were adequately staged as N0 between 1992 and 2002 were retrospectively analyzed from the prospectively collected database of 7 centers participating to the Italian Research Group for Gastric Cancer. RESULTS: Disease-specific and disease-free survival after 3, 5, and 10 years were 90.4%, 86.1%, 75.9%, and 72.1%, 57.3%, 57.3%, respectively. Mortality was 1.7%. The factors associated with a better disease-free survival at univariate analysis were age <60, T2 tumors, distal location, intestinal histotype, and number of retrieved nodes >25; depth of infiltration and histotype were the only 2 independent predictors of 5-year recurrence-free survival at multivariate analysis. CONCLUSION: These parameters must be considered to stratify node-negative gastric cancer patients for an adjuvant treatment and follow-up scheduling. Survival was similar to that previously reported by Eastern Centers. Lymphadenectomy is suggested to be effective, and retrieval of more than 25 nodes may be warranted.

Real-time polymerase chain reaction quantification of free DNA in serum of patients with polyps and colorectal cancers.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent causes of cancer related deaths worldwide. Recently, the use of cell-free DNA as diagnostic tools to identify cancer has been investigated. The aim of this work was to assess whether circulating DNA could be considered a useful marker for detection of early stage CRC and polyps. METHODS: A total of 118 patients with CRC were included in the study along with 49 patients with colorectal polyps and 26 control subjects. Cell-free DNA was quantified using a real-time TaqMan-polymerase chain reaction assay. Non-parametric tests (Mann-Whitney test and Spearman correlation) were utilized for statistical analysis. RESULTS: Serum DNA concentrations were significantly higher in CRC patients and patients with polyps (median value 105.0 ng/mL and 40.0 ng/mL) compared with controls (median value 14.0 ng/mL; p<0.05). Although carcinoembryonic antigen was above the cut-off in only 13/66 (19.7%) patients with early stage CRC, serum free DNA showed values above the threshold identified using receiver operator characteristic (ROC) curve analysis in 53/66 (80.3%) patients. CONCLUSIONS: Our data confirm that serum DNA concentrations are significantly increased in CRC patients with early stage disease and in patients with polyps. This marker might be useful for identifying high-risk individuals.

Postoperative variation of C-reactive protein and procalcitonin in patients with gastrointestinal cancer.

BACKGROUND: Despite substantial advances in radiotherapy, chemotherapy and immunotherapy, surgical management remains the standard of care, especially in patients with no evidence of distant metastases and who are fit for surgery. It is traditionally known, however, that patients undergoing surgery for gastrointestinal malignancies suffer from a high rate of infective complications and there is little information on the behavior of C-Reactive Protein (CRP) and procalcitonin (PCT) in these patients. METHODS: The study population included 18 consecutive patients with untreated gastric (n = 6) or colorectal (n = 12) carcinoma and 18 control subjects. Blood samples were collected from cancer patients the day before surgery and on the following 1, 7, 30 postoperative days. Results of PCT and CRP were corrected for plasma volume changes. RESULTS: Pre-surgery values of CRP, but not of PCT, were significantly higher in cancer patients than in controls. Both markers in patients without postoperative infections reached peak-levels on day 1. On day seven, CRP values were still significantly increased, while those of PCT were non statistically different from pre-surgery. By receiver operating characteristic (ROC) analysis, both PCT and CRP discriminated patients with or without pneumonia on the day 7 post-surgery, but not between patients with or without surgical wound infection. CONCLUSIONS: Taken together, our findings are consistent with the hypothesis that PCT might be a more useful marker than CRP for monitoring the postoperative course and diagnose severe perioperative bacterial infections in patients undergoing surgery for gastrointestinal malignancies after the 7th postoperative day.

[Spontaneous rupture of the femoral artery after radiotherapy: a case report]. / Rottura spontanea dell'arteria femorale dopo radioterapia: presentazione di un caso clinico.

Radiation-induced arteriopathy is a well-known disease whose incidence is not known and which usually arises chronically many years after radiation therapy. When it arises acutely, spontaneous rupture or, more rarely, thrombosis of the involved vessel may occur. Spontaneous rupture can occur within 4 to 32 weeks of radiotherapy, and usually affects the carotid artery involved in radiotherapy of the neck and head. Spontaneous rupture of the femoral artery is a very rare event and only a few cases have been reported in the literature. In this paper we report a case of spontaneous rupture of the left femoral superficial artery after adjuvant radiotherapy following surgery for a liposarcoma of the spermatic cord with multiple local recurrences, successfully treated with an extra-anatomic bypass through the obturator canal and rectal muscle flap.

Mesenteric revascularisation in a young patient with antiphospholipid syndrome and fibromuscular dysplasia: report of a case and review of the literature.

Fibromuscular dysplasia or fibromuscular hyperplasia is a rare non-atherosclerotic and non-inflammatory vascular disease that primarily involves medium-size and small arteries, most commonly the renal and carotid arteries, and less frequently the vertebral, iliac, subclavian or visceral arteries (mesenteric, hepatic, splenic). Antiphospholipid syndrome is one of the most commonly acquired hypercoagulable states, defined by the association of laboratory evidence of anti-phospholipid antibodies with arterial or venous thrombosis or recurrent pregnancy losses. The presence of these antibodies is associated with an increased risk of thromboembolic phenomena, including peripheral thrombophlebitis, pulmonary thromboembolism, stroke, retinal artery occlusion, myocardial infarction, placental thrombosis and Budd-Chiari syndrome. In this report we discuss the uncommon case of a young male patient with both antiphospholipid syndrome and fibromuscular dysplasia that came to our attention for pulmonary embolism and "angina abdominis" due to occlusion of three mesenteric vessels. The possible relationship between antiphospholipid syndrome and fibromuscular dysplasia encountered in our patient still remains unclear. We treated the patient as if he had the two different diseases. After partial failure of endovascular surgery, the patient underwent surgery with reimplantation of three visceral arteries to the aorta. Subsequently he was treated with stent placement after development of a re-stenosis of one of the three reimplanted visceral arteries. The patient was treated conservatively for antiphospholipid syndrome with anticoagulant oral therapy for life.

Laparoscopic cholecystectomy for severe acute cholecystitis. A meta-analysis of results.

OBJECTIVE: The aim of this review was to evaluate surgical outcomes of laparoscopic cholecystectomy for gangrenous and empyematous acute cholecystitis defined as severe acute cholecystitis. BACKGROUND: It is not known to what extent surgical outcomes of laparoscopic cholecystectomy for severe acute cholecystitis differ from those for the nonsevere acute form, making it questionable whether urgent laparoscopic cholecystectomy is the best approach even in severe acute cases. METHODS: Literature searches were conducted to identify: (1) comparative studies which reported laparoscopic surgical outcomes separately for severe acute and nonsevere acute cholecystitis; (2) studies comparing such an approach with open cholecystectomy, subtotal laparoscopic cholecystectomy or cholecystostomy in severe acute cholecystitis. Results were pooled by standard meta-analytic techniques. RESULTS: Seven studies with a total of 1,408 patients undergoing laparoscopic cholecystectomy were found. The risks of conversion (RR 3.2, 95% CI 2.5 to 4.2) and overall postoperative complications (RR 1.6, 95% CI 1.2-2.2) were significantly higher in severe acute cholecystitis with respect to the nonsevere acute forms. However, no difference was detected as regards to local postoperative complications. No studies comparing open cholecystectomy or cholecystostomy with urgent laparoscopy were found. CONCLUSION: A lower feasibility of laparoscopic cholecystectomy has been found for severe cholecystitis. A lower threshold of conversion is recommended since this may allow to reduce local postoperative complications. Literature data lack valuable comparative studies with other treatment modalities, which therefore need to be investigated.

Primary aortoduodenal fistula: a challenge to the vascular surgeon.

Primary aortoduodenal fistula is a serious and rare complication of abdominal aortic aneurysms. This life-threatening disease results most commonly from an abdominal aortic aneurysm, with the fistula forming between the aorta and the third or the fourth portions of the duodenum. Diagnosis is often difficult and urgent adequate surgical treatment as soon as possible is the only therapeutic option to save the lives of these patients. In this paper we report the case of a 76-year-old female admitted to our institution for massive haematemesis, melaena, severe hypotension and violent back pain. The urgent diagnostic work-up revealed an abdominal aortic aneurysm with a strong suspicion of duodenal fistulisation. The diagnosis was confirmed in the operating room, where the patient was immediately submitted to closure of the fistula and in situ aortic reconstruction using an aortic homograft. The postoperative course was uneventful and after 6 months the patient is doing well without any recurrence of infection.

Intra-thoracic desmoid tumour in a patient with a previous aortocoronary bypass.

BACKGROUND: Intra-thoracic desmoid tumours with mediastinal invasion are very rare. Although rare they have to be taken into account in the differential diagnosis of a thoracic mass and therapeutic options have to be weighted since surgical treatment may require wide excision. CASE PRESENTATION: A 48-year-old male diabetic, dyslipidaemic, former heavy smoker with psychiatric illness was operated by sternotomy for a triple aorto-coronary bypass 4 years before, presented with complains of recent onset such as constant and oppressive chest pain. At surgery a mass extending from the aortic arch into the entire anterior mediastinum and to most of the right pleural cavity was found. The mass was separated from sternal periosteum and vessels of aorto-coronary by pass were isolated starting from the aortic arch up to the pericardium. The histological examination revealed aggressive fibromatosis. CONCLUSION: Although technically demanding, radical surgical excision is actually the most indicated therapeutic approach for intra-thoracic desmoid tumours.

Comparison of genetic and epigenetic alterations of primary tumors and matched plasma samples in patients with colorectal cancer.

BACKGROUND: Although recent advances in circulating DNA analysis allow the prediction of tumor genomes by noninvasive means, some challenges remain, which limit the widespread introduction of cfDNA in cancer diagnostics. We analyzed the status of the two best characterized colorectal cancer (CRC) genetic and epigenetic alterations in a cohort of CRC patients, and then compared the degree to which the two patterns move from tissue to plasma in order to improve our understanding of biology modulating the concordance between tissues and plasma methylation and mutation profiles. METHODS: Plasma and tumor tissues were collected from 85 patients (69±14 years, 56 males). KRAS and SEPT9 status was assessed by allele refractory mutation system quantitative PCR and quantitative methylation-specific PCR, respectively. Six of the most common point mutations at codon 12 and 13 were investigated for KRAS analysis. RESULTS: KRAS mutations and SEPT9 promoter methylation were present in 34% (29/85) and in 82% (70/85) of primary tumor tissue samples. Both genetic and epigenetic analyses of cfDNA revealed a high overall concordance and specificity compared with tumor-tissue analyses. Patients presenting with both genetic and epigenetic alterations in tissue specimens (31.8%, 27/85) were considered for further analyses. The median methylation rates in tumour tissues and plasma samples were 64.5% (12.2-99.8%) and 14.5% (0-45.5%), respectively. The median KRAS mutation load (for matched mutations) was 33.6% (1.8-86.3%) in tissues and 2.9% (0-17.3) in plasma samples. The plasma/tissue (p/t) ratio of SEPT9 methylation rate was significantly higher than the p/t ratio of KRAS mutation load, especially in early stage cancers (p=0.0108). CONCLUSION: The results of this study show a discrepant rate of epigenetic vs. genetic alterations moving from tissue to plasma. Many factors could affect mutation cfDNA analysis, including both presence of tumor clonal heterogeneity and strict compartmentalization of KRAS mutation profile. The present study highlights the importance of considering the nature of the alteration when analyzing tumor-derived cfDNA.

The role of resistin in colorectal cancer.

BACKGROUND: To date the role of resistin in colorectal cancer (CRC) is far from being elucidated. The aim of this study was to investigate the association between serum resistin levels and CRC in relation to known risk/protective factors including anthropometric, metabolic, inflammatory parameters as well as lifestyle individual characteristics. METHODS: 40 CRC patients and 40 controls were enrolled. Body weight, height, waist circumference and blood pressure were recorded. Fasting plasma glucose, lipids, C-reactive protein (CRP) and resistin levels were measured. Metabolic Syndrome (MS) was defined according to the harmonized definition. RESULTS: Resistin levels were significantly higher in CRC patients than in controls (p=0.028) and gradually increased with tumor stage progression (p=0.042). A high resistin level was statistically significant determinant of CRC after adjusting for age, sex, body mass index and lifestyle parameters (p=0.029). Resistin showed a strong association with CRP levels (p ≤ 0.0001). In stepwise regression analysis CRP remained the only independent predictor of both resistin levels (p=0.001) and CRC risk (p=0.021). CONCLUSIONS: These results clarify the nature of the association between resistin and CRC risk suggesting that the proinflammatory state of cancer, rather than the clinical diagnosis of CRC itself or its link with obesity and MS, may govern this association.

18F-FDG-PET/CT in patients with breast cancer and rising Ca 15-3 with negative conventional imaging: a multicentre study.

OBJECTIVES: Breast cancer is the second cause of death in women in Europe and North America. The mortality of this disease can be reduced with effective therapy and regular follow up to detect early recurrence. Tumor markers are sensitive in detecting recurrent or residual disease but imaging is required to customize the therapeutic option. Rising tumor markers and negative conventional imaging (US, X-mammography, CT and MR) poses a management problem. Our aim is to assess the role of 18F-FDG-PET/CT in the management of post-therapy patients with rising markers but negative conventional imaging. MATERIALS AND METHODS: In the period from January 2008 to September 2009, 89 female patients with breast cancer who developed post-therapy rising markers (serum Ca 15-3 levels=64.8±16.3 U/mL) but negative clinical examination and conventional imaging were investigated with 18F-FDG-PET/CT. RESULTS: Tumor deposits were detected in 40/89 patients in chest wall, internal mammary nodes, lungs, liver and skeleton. The mean SUVmax value calculated in these lesions was 6.6±1.7 (range 3.1-12.8). In 23/40 patients solitary small lesion were amenable to radical therapy. In 7 out of these 23 patients a complete disease remission lasting more than 1 year was observed. CONCLUSIONS: 18F-FDG-PET/CT may have a potential role in asymptomatic patients with rising markers and negative conventional imaging. Our findings agree with other studies in promoting regular investigations such as tumor markers and 18F-FDG-PET/CT rather than awaiting the developments of physical symptoms as suggested by current guidelines since the timely detection of early recurrence may have a major impact on therapy and survival.

Additional value of FDG-PET/CT in management of "solitary" liver metastases: preliminary results of a prospective multicenter study.

BACKGROUND AND AIM: The most common malignancy affecting the liver is metastasis from a wide variety of tumors, particularly those of gastrointestinal origin. Successful surgical removal of a solitary liver metastasis may significantly extend survival and optimal preoperative assessment in this regard is a mandatory prerequisite for proper patient selection. The addition of positron emission tomography/computed tomography (PET/CT) to other more conventional imaging procedures (e.g., ultrasound (US), CT, and magnetic resonance) has the potential to greatly improve the selection process by the combination of high-resolution anatomy afforded by CT directly combined with the functional scintigraphic map of intra- and extrahepatic lesions depicted by 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET. In this study, we assess the additional value of PET/CT in the management strategy of patients with solitary liver metastasis from colorectal and other cancers identified by conventional imaging methods. METHODS: We evaluated 43 consecutive patients (17 males, 26 females, mean age 53 +/- 6 years) with known solitary liver metastasis. This sample consisted of 18 patients with colorectal cancer, 15 with nonsmall cell lung cancer, six with breast carcinoma, and four ovarian cancers. In addition to contrast-enhanced CT and US, all patients were studied with FDG-PET/CT before surgery. PET/CT was performed within 3 weeks of the initial diagnosis and the scans were read by two experienced radiologists/nuclear medicine specialists blinded to the clinical data. A final diagnosis was obtained at surgery in 31 patients, by fine needle biopsy in five, and long-term clinical, biochemical, and follow-up imaging in seven patients. RESULTS: In 12 out of 43 patients (28%), PET/CT resulted in restaging disease and a change in therapy. Twenty-two of 31 patients with confirmed solitary liver lesions (71%) were disease-free, eight of 31 (26%) developed a new recurrence, and one of 31 (3%) died from disease progression over a 17 +/- 6-month follow-up interval. Nine of 12 patients (75%) with multiple metastases demonstrated by FDG-PET/CT were alive with disease and three of 12 (25%) deceased due to disease progression (p < 0.01) over a 17 +/- 6-month follow-up interval. CONCLUSION: The addition of FDG-PET/CT to the routine assessment of patients with liver metastasis has a significant impact on disease staging and selection of suitable candidates for solitary liver metastasis resection and outcome.

Concomitant pulmonary carcinoma and abdominal aortic aneurysm: therapeutic strategies.

PURPOSE: A diagnosis of concomitant pulmonary carcinoma and abdominal aortic aneurysm is rare (<1% of treated cases). However, such an association makes the therapeutic decisions critical, especially regarding the priority and timing of treatment. This article reports on our experience of 14 cases of concomitant pulmonary carcinoma and abdominal aortic aneurysm. METHODS: From April 1987 to June 2006 we observed 14 cases of concomitant pulmonary carcinoma and abdominal aortic aneurysm. In patients for whom simultaneous treatment was not indicated due to a poor general condition, priority was given to lung cancer except for cases in which the aneurysm needed an urgent approach. Patients observed after 2000 and scheduled for a two-stage treatment were treated with endovascular procedures whenever possible. RESULTS: Only one patient was treated by a simultaneous aneurysmectomy and a left lower lobectomy, while in the other 13 patients two-stage treatment was performed. Lung carcinoma was operated on first in 7 cases but one patient underwent an urgent aneurysmectomy after chest surgery due to a rupture of the aneurysm. Priority was given to an aneurysmectomy in 2 patients. An endovascular approach was performed in 4 patients, thus allowing a pulmonary resection during the same period of hospitalization, 2 days after 2 uneventful endovascular procedures and on the 6th and 7th postoperative days in 2 cases due to an intraoperative rupture of right iliac artery and type I postoperative endoleak, respectively. CONCLUSION: An endovascular exclusion of the aneurysm may therefore be proposed in order to achieve a concomitant treatment of both diseases. Such an approach excludes complications due to a postoperative rupture of the aneurysm when a pulmonary resection would be first performed; moreover, it does not delay the performance of a pulmonary resection when treatment of the aneurysm is considered to have priority.

Lymph node involvement in advanced gastroesophageal junction adenocarcinoma.

OBJECTIVE: The prognosis of gastroesophageal junction adenocarcinoma is unquestionably related to the extent of nodal involvement; nonetheless, few studies deal with the pattern of lymph node spread and specifically analyze the prognostic value of the site of metastasis. The present study was aimed at evaluating these key aspects in advanced gastroesophageal junction adenocarcinoma. METHODS: Of 219 patients consecutively operated on for gastroesophageal junction adenocarcinoma at the Department of General Surgery and Surgical Oncology, University of Siena, and at the Department of General Surgery, University of Verona, 143 pT2-4 tumors not submitted to prior chemoradiation were analyzed according to the Japanese Gastric Cancer Association pN staging system. RESULTS: The majority of patients were given diagnoses of nodal metastases (77.6%). The mean number (P = .076) and the percentage of patients with pN+ disease (P = .022) progressively increased from Siewert type I to type III tumors. Abdominal nodes were involved in all but 1 of the patients with pN+ disease; conversely, nodal metastases into the chest were 46.2% for type I, 29.5% for type II, and 9.3% for type III tumors. Survival analysis showed virtually no chance of recovery for patients with more than 6 metastatic nodes or lymph nodes located beyond the first tier. CONCLUSIONS: In advanced gastroesophageal junction adenocarcinoma, the high frequency of nodal metastases and the related unfavorable long-term outcome achieved by means of surgical intervention alone are indicative of the need for aggressive multimodal treatment along with surgical intervention to improve long-term results.

Chemoradiotherapy followed by surgery for squamous cell carcinoma of the thoracic esophagus with clinical evidence of adjacent organ invasion.

BACKGROUND: The role of surgery for esophageal squamous cell carcinoma (SCC) with clinical evidence of adjacent organ invasion (cT4) is a debated issue. This study was aimed at analyzing our experience with chemoradiotherapy (CRT) followed by surgery as treatment for non-metastatic cT4 SCC of the thoracic esophagus. METHODS: The results of 51 patients consecutively treated at the First Department of General Surgery, University of Verona, from January 1987 to December 2004 were analyzed. RESULTS: The most frequently clinically involved structures were the trachea (43.1%), the main left bronchus (17.6%), and the thoracic aorta (15.7%). CRT was completed in all but one of the patients (98.0%) without toxicity-related deaths. After completion of induction treatment 49 patients underwent surgery (96.1%), and resection was possible in 40 patients (78.4%) but R0 surgery was rarely obtained (39.2%). Pathologic downstaging was achieved in 18 cases (35.3%) while a major response (responders) was observed in 10 patients (19.6%) and a complete response (pT0N0) in 7 (13.7%). The overall median survival time was 11.1 months with a 3-year survival rate of 8.8%. A significantly better survival (P < 0.001) was observed after a R0 resection (median: 22.3 months; 3-year survival: 25.4%; P < 0.001) and for responders (median: 33.1 months; 3-year survival: 25.7%; P = 0.019). CONCLUSIONS: Aggressive multi-modal therapy with CRT followed by surgery in cT4 SCC of the thoracic esophagus is feasible. Surgery should be limited to patients with significant response to induction treatment and a high probability of R0 resection.