LM02 trial Perioperative treatment with panitumumab and FOLFIRI in patients with wild-type RAS, potentially resectable colorectal cancer liver metastases-a phase II study.

Background: Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM. Methods: Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS. Results: We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively. Conclusions: Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed-mutation rate of the marker higher than expected.

BACKGROUND: In operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The • Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies. METHOD: Biomarker analysis was conducted using the mark53 analysis. Calculation of patient number needed was based on a 60% rate of marker positivity, deduced from the results of a phase II pilot study. RESULTS: From 2007-2012, the • Pancho trial recruited 235 patients with operable esophageal cancer in Austria. A total of 181 patients were eligible and could be subjected to mark53 analysis and randomization. After randomizing 74 patients, the overall TP53 mutation rate was 79%. However, due to the high prevalence of marker positivity, the number of projected patients was increased to 181 patients in order to ensure a sufficient number of marker-negative patients. After completion of the trial, the overall TP53 mutation rate was 77.9%. CONCLUSION: Due to high medical need, the recruitment for the academic trial was excellent. Mark53 analysis clearly detected more mutations in the TP53 gene as compared to the cancer-specific p53 literature. Final analysis examining the interaction between the mark53 status and the effect of chemotherapies applied in the • Pancho trial is now awaited.

Fast Early Recovery After Transabdominal Preperitoneal Repair in Athletes with Sportsman's Groin: A Prospective Clinical Cohort Study.

BACKGROUND: Current literature on chronic groin pain suggests that laparoscopic mesh repair on athletes enables a faster recovery and subsequent return to unrestricted athletic activities. The aim of this study was to evaluate the role of transabdominal preperitoneal (TAPP) mesh repair in athletes resistant to conservative therapy. METHODS: A multidisciplinary approach with tailored physiotherapy. Thirty-nine professional athletes with chronic groin pain were referred to surgery at a single clinic. A full assessment was carried out on each, including medical history, physical examination, dynamic ultrasound, and pelvic magnetic resonance imaging. TAPP repair was performed using a polypropylene mesh and fibrin glue fixation on 30 athletes who had exhibited typical symptoms, shown resistance to conservative therapy, not benefited from accompanying physiotherapy, and had ceased training in the 3 to 6 months prior. The outcome measures were early postoperative recovery of 6 weeks and full resumption of athletic activities. RESULTS: Mean duration of symptoms from onset to surgical repair was 7 months. Conservative treatment had improved symptoms temporarily or to some extent in 7 athletes, while 2 ceased competing altogether. Twenty-three athletes exhibited unilateral and 16 bilateral groin pain. Laparoscopy confirmed posterior wall deficiency in 24 and true inguinal hernia in 6 athletes. Mild scrotal hematoma occurred in 2 athletes postoperatively; all were discharged within 24 hours of surgery. Twenty-one (70%) returned to sports activities after 6 weeks of convalescence. Persistent mild pain was experienced by 5 athletes postoperatively for up to 1 year, yet did not interfere with normal daily activity. Twenty-five participants (85%) reported full satisfaction with the procedure 1 year after treatment; all returned to the same or even higher level of athletic performance. CONCLUSION: The study confirms that the endoscopic placement of retropubic mesh is an efficient, safe, and minimally invasive treatment that enables fast early recovery.

Preparing for prospective clinical trials: a national initiative of an excellence registry for consecutive pancreatic cancer resections.

BACKGROUND: Despite significant improvements in perioperative mortality as well as response rates to multimodality treatment, results after surgical resection of pancreatic adenocarcinoma with respect to long-term outcomes remain disappointing. Patient recruitment for prospective international trials on adjuvant and neoadjuvant regimens is challenging for various reasons. We set out to assess the preconditions and potential to perform perioperative trials for pancreatic cancer within a well-established Austrian nationwide network of surgical and medical oncologists (Austrian Breast & Colorectal Cancer Study Group). METHODS: From 2005 to 2010 five high-volume centers and one medium-volume center completed standardized data entry forms with 33 parameters (history and patient related data, preoperative clinical staging and work-up, surgical details and intraoperative findings, postoperative complications, reinterventions, reoperations, 30-day mortality, histology, and timing of multimodality treatment). Outside of the study group, in Austria pancreatic resections are performed in three "high-volume" centers (>10 pancreatic resections per year), three "medium-volume" centers (5­10 pancreatic resections per year), and the rest in various low-volume centers (<5 pancreatic resections per year) in Austria. Nationwide data for prevalence of and surgical resections for pancreatic adenocarcinoma were contributed by the National Cancer Registry of Statistics of Austria and the Austrian Health Institute. RESULTS: In total, 492 consecutive patients underwent pancreatic resection for ductal adenocarcinoma. All postoperative complications leading to hospital readmission were treated at the primary surgical department and documented in the database. Overall morbidity and pancreatic fistula rate were 45.5 % and 10.1 %, respectively. Within the entire cohort there were 9.8 % radiological reinterventions and 10.4 % reoperations. Length of stay was 16 days in median (0­209); 12 of 492 patients died within 30 days after operation, resulting in a 30-day mortality rate of 2.4 %. Seven of the total 19 deaths (36.8 %) occurred after 30 days, during hospitalization at the surgical department, resulting in a hospital mortality rate of 3.9 % (19/492). With a standardized histopathological protocol, there were 70 % (21/30) R0 resections, 30 % (9/30) R1 resections, and no R2 resections in Vienna and 62.7 % (32/51) R0 resections, 35.3 % (18/51) R1 resections, and 2 % (1/51) R2 resections in Salzburg. Resection margin status with nonstandardized protocols was classified as R0 in 82 % (339/411), R1 in 16 % (16/411), and R2 in 1.2 % (5/411). Perioperative chemotherapy was administered in 81.1 % of patients (8.3 % neoadjuvant; 68.5 % adjuvant; 4.3 % palliative); chemoradiotherapy (1.6 % neoadjuvant; 3 % adjuvant; 0.2 % palliative), in 4.9 % of patients. The six centers that contributed to this registry initiative provided surgical treatment to 40 % of all Austrian patients, resulting in a median annual recruitment of 85 (51­104) patients for the entire ABCSG-group and a median of 11.8 (0­38) surgeries for each individual department. CONCLUSIONS: Surgical quality data of the ABCSG core pancreatic group are in line with international standards. With continuing centralization the essential potential to perform prospective clinical trials for pancreatic adenocarcinoma is given in Austria. Several protocol proposals aiming at surgical and multimodality research questions are currently being discussed

Gastrointestinal stromal tumors: diagnosis, therapy and follow-up care in Austria.

Optimal treatment for patients suffering from gastrointestinal stromal tumors (GIST) is based on an interdisciplinary treatment approach. Austrian representatives of Medical and Surgical Oncology, Pathology, Radiology, Nuclear Medicine, Gastroenterology, and Laboratory Medicine issued this manuscript on a consensual base within the context of currently available and published literature. This paper contains guidelines and recommendations for diagnosis, therapy, and follow-up of GIST patients in Austria.

Palmar metastasis of an adenocarcinoma of the esophago-gastric-junction: First case report.

INTRODUCTION: Hand metastasis represents only approximately 0.007-0.2% of all metastatic lesions. The most common origin of hand metastasis is the lung, which is approximately 50% of all cases, followed by breast and kidney. Hand metastasis from gastric or esophagic cancer is even much more rare. PRESENTATION OF CASE: This is the first case report of a metastasis to the palm of hand (tendon) due to an adenocarcinoma of esophago-gastric-junction. DISCUSSION: While most of the esophagic and gastric carcinomas metastasizes to liver, lungs and brain, the rare possibility of encountering metastasis to the hand either to the bone, but also to the tendon exists. Therefore, we recommend obtaining a thorough history and a detailed clinical examination, plain radiographs, followed by axial imaging techniques like MRI and a histopathologic evaluation. CONCLUSION: Even if metastatic lesions to the hand are really rare, the surgeon should always be suspicious of a metastatic lesion, when presented with a patient older than 40 years who has a history of cancer.

Comparison of lymphangiogenesis between primary colorectal cancer and corresponding liver metastases.

BACKGROUND: Liver metastasis (LM) is the determining factor of poor prognosis in colorectal cancer (CRC). Peripheral lymphatico-venous communications have been discussed as a potential pathway of tumor cell dissemination for the development of LMs. In the current study, we investigated the clinical impact of the lymphangiogenic activity in CRCs and their corresponding LMs. PATIENTS AND METHODS: In 47 patients with CRC, the primary tumors and the corresponding LMs were investigated. Lymphangiogenesis (LMVD), lymphovascular invasion (LVI), lymphatic vascular endothelial growth factor C expression (VEGF-C) were investigated RESULTS: A significant correlation was observed between LMVD and LVI in CRCs (p=0.001) as well as in LMs (p=0.0001). LMVD in CRC correlated significantly with that in LMVD-LMs (p=0.026) and LVI in LMs (p=0.036). Survival analysis reveilled a significant difference in disease free and overall survival between patients with and without VEGF-C expression in LMs (p=0.0019 and p=0.0101, respectively). CONCLUSION: Our data provide evidence for an important role of lymphangiogenesis in liver metastasis of CRC and provide further support for a possible role of a lymphatico-venous metastatic pathway.

Current perioperative practice in rectal surgery in Austria and Germany.

OBJECTIVE: 'Fast-track' rehabilitation is able to accelerate recovery, reduce general morbidity, and decrease hospital stay. This is widely accepted for colonic resections. Despite recent evidence that fast track concepts are safe and feasible in rectal resection, there is no information on the acceptance and utilization of these concepts among Austrian and German surgeons. METHOD: A questionnaire concerning perioperative routines in elective, open rectal resection was sent to the chief surgeons of 1,270 German and 120 Austrian surgical centers. RESULTS: The response rate was 63% in Austria (76 centers) and 30% in Germany (385 centers). Mechanical bowel preparation is only abandoned by 2% of the Germany and 7% of the Austrian surgeons. Nasogastric decompression tubes are rarely used; four of five of the questioned surgeons in both countries use intra-abdominal drains. Half of the surgical centers allow the intake of clear fluids on the day of surgery. Mobilization starts in half of the centers on the day of surgery. Epidural analgesia is used in three-fourths of the institutions. Institutions which have implemented fast track rehabilitation for rectal resections discharge the patients earlier then hospitals that adhere to traditional care. CONCLUSION: In many perioperative procedures, Austrian and German Surgeons rely on their traditional approaches. Recent evidence-based adaptations of perioperative routines in rectal resections are only slowly introduced into daily routine; therefore, further efforts have to be done to optimizing patients' care.

[Gastrointestinal stromal tumors: recommendations for diagnosis, treatment and aftercare in Austria]. / Klinische Empfehlungen. Gastrointestinale Stromatumore: Empfehlungen zu Diagnose, Behandlung und Nachsorge in Osterreich.

Diagnosis and treatment of gastrointestinal stromal tumors (GIST) requires an interdisciplinary treatment approach. This strategy should be reflected by the content of this article. Austrian representatives of 'GIST relevant' specialties authored this publication on a consensual base. This manuscript should be regarded as a guideline for 'GIST involved' colleagues in Austria.

[Surgical treatment of gastrointestinal stromal tumors]. / Chirurgie des gastrointestinalen Stromatumors.

Interdisciplinary management is required in the therapy of gastrointestinal stromal tumors, in consideration of complex strategies in the treatment of patients with GIST. Endoscopy, histopathology - mutation analysis included - but also radio diagnostic, surgery and oncology are topics in treating patients suffering from GIST. Especially in cases of advanced gastrointestinal stromal tumor or metastatic disease our multidisciplinary knowledge is required, because information about these entities are rather rare.

Gastrointestinal stromal tumors: Recommendations on diagnosis, therapy and follow-up care in Austria.

Adequate treatment of gastrointestinal stromal tumors (GISTs) is linked to an interdisciplinary treatment approach. Austrian representatives of medical oncology, surgery, pathology, radiology and gastroenterology have issued this consensus manuscript within the context of currently available and published literature. The paper contains guidelines and recommendations for diagnosis, therapy and follow-up of GIST patients in Austria.

Genetic detection of lymph node micrometastases: a selection criterion for liver transplantation in patients with liver metastases after colorectal cancer.

BACKGROUND: Liver transplantation for nonresectable liver metastases from colorectal cancer was abandoned in 1994 on account of high recurrence rates. The aim of this study was to investigate whether the genetic detection of micrometastases in histologically negative lymph nodes of the primary colon cancer could be applied to select patients for liver transplantation. METHODS: We analyzed 21 patients with colorectal cancer who had undergone liver transplantation between 1983 and 1994 for liver metastases. Eleven patients were histologically lymph node negative at the time of surgery; ten patients with lymph node metastases served as control group. DNA sequencing was used to screen tumor material for p53 and K-ras mutations. Mutant allele-specific amplification (MASA) was then used to search for micrometastases in DNA from regional lymph nodes of the primary colorectal cancer. RESULTS: p53 and K-ras mutations were detected in 12 (57%) and 3 (14%) of 21 patients in the colorectal cancer, respectively. The mutations were confirmed in the corresponding liver metastases. Of 11 patients with histologically negative lymph nodes, nine were eligible for MASA due to presence of p53 or K-ras mutation. MASA revealed six of nine patients to be genetically positive for micrometastases. Three patients were both genetically and histologically negative. These three patients showed a significantly longer overall survival (P = 0.011) of 4, 5, and 20 years, respectively. CONCLUSIONS: We conclude that the genetic detection of micrometastases by MASA could be a powerful prognostic indicator for selecting patients with colorectal liver metastases who could benefit from liver transplantation.

Analysis of hepatic resection of metastasis originating from gastric adenocarcinoma.

Few patients with metastatic gastric cancer have disease that is amenable to curative surgery. Thus far, little is known about liver surgery for metastases arising from gastric adenocarcinoma and prognostic factors. Of 73 patients operated on between 1980 and 1999 for noncolorectal, non-neuroendocrine hepatic metastases, 15 underwent liver resection for gastric adenocarcinoma metastasis. Ten patients underwent synchronous hepatic resection and five underwent metachronous hepatic surgery after a median disease-free interval of 10 months (range 6.1 to 47.3 months). None of the patients died within the first 30 days after surgery, and the in-hospital mortality rate was 6.7%. Among patients in the synchronous group, 26.7% experienced major complications mainly associated with gastric surgery. Overall median survival was 8.8 months (range 4 to 51 months); two patients survived more than 3 years. Univariate analysis revealed that the appearance of liver metastasis (synchronous vs. metachronous), the distribution of liver metastases (unilobar vs. bilobar), and the primary tumor site (proximal vs. distal) were marginally significant predictive factors regarding overall survival. Because of its high morbidity, synchronous liver resection for metastases originating from gastric adenocarcinoma is rarely followed by survival longer than 2 years. Primary tumor localization within the proximal third of the stomach and bilobar liver involvement appear to be predictive of poor outcome. On the other hand, curative resection of metachronous liver metastases may allow long-term survival in selected patients.

Current value of intraoperative sonography during surgery for hepatic neoplasms.

Noninvasive liver imaging has developed rapidly resulting in increased accuracy for detecting primary and secondary hepatic tumors. Intraoperative ultrasonography (IOUS) was commonly considered to be the gold standard for liver staging, but the current value of IOUS is unknown in view of more sophisticated radiologic tools. The purpose of this prospective study was to evaluate the impact of IOUS on the treatment of 149 patients undergoing liver surgery for malignant disease (colorectal metastasis, 61 patients; hepatoma, 52 patients; other hepatic malignant tumors, 36 patients). The sensitivities of computed tomography (CT), helical CT, magnetic resonance imaging, and IOUS in patients with colorectal metastases were 69.2%, 82.5%, 84.9%, and 95.2% in a segment-by-segment analysis; in patients with hepatoma their sensitivities were 76.9%, 90.9%, 93.0%, and 99.3%; and in patients with other hepatic malignancies they were 66.7%, 89.6%, 93.3%, and 98.9%, respectively. Additional malignant lesions (AMLs) were first detected by inspection and palpation in 20 patients (13.4%). In another 18 patients (12.1%) IOUS revealed at least one AML. Overall, the findings obtained only by IOUS changed the surgical strategy in 34 cases (22.8%). It was concluded that IOUS, having undergone some refinement as well, still has immense diagnostic value in hepatectomy candidates. Frequently avoiding palliative liver resection and occasionally disproving unresectability as assessed by preoperative imaging, IOUS still has a significant impact on surgical decision making and should still be considered the gold standard.

Accuracy of multiphasic helical computed tomography and intraoperative sonography in patients undergoing orthotopic liver transplantation for hepatoma: what is the truth?

OBJECTIVE: To determine the real value of liver imaging in cirrhosis by macro- and histomorphologic examination of the entire organ after orthotopic liver transplantation for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: In comparative studies, a virtual sensitivity of up to 94% is described for helical computed tomography in HCC staging. The tumor detection rate of intraoperative ultrasonography (IOUS) is reported to be almost 100%. METHODS: This prospective observational study comprised 23 patients with HCC in cirrhosis admitted for orthotopic liver transplantation. Results of preoperative triphasic helical computed tomography (HCT) and IOUS were correlated with histopathologic results after 3-mm-slicing of the explanted liver. RESULTS: Overall, 179 liver segments were examined by HCT, IOUS, and MHM. Fifty-two malignant lesions and 10 dysplastic nodules were revealed by MHM. Using HCT, 13 HCCs could not be identified in 8 patients and 15 results were falsely positive in 10 patients. The detection rate of dysplastic nodes was 40% for HCT and 60% for IOUS. IOUS missed four HCCs in four patients and had six false-positive results in six patients. In a segment-based analysis, the overall accuracy of IOUS was significantly higher for IOUS (95.5%) versus HCT (89.9%). In the lesion-by-lesion analysis, the sensitivity was 92.3% for IOUS and 75.0% for HCT, with a significant difference. CONCLUSIONS: Correlation of explanted liver pathologic results offers precise evaluation of imaging modalities. The data of this histopathologically based study confirm that IOUS is significantly superior in staging HCC in cirrhosis versus CT, even after technical refinements through enhanced multiphasic high-velocity helical scanning.