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Cellular responses induced by surgical procedure or ischemia-reperfusion injury (IRI) may severely alter transcriptome profiles and complicate molecular diagnostics. To investigate this effect, we characterized such pre-analytical effects in 143 non-malignant liver samples obtained from 30 patients at different time points of ischemia during surgery from two individual cohorts treated either with the Pringle manoeuvre or total vascular exclusion. Transcriptomics profiles were analyzed by Affymetrix microarrays and expression of selected mRNAs was validated by RT-PCR. We found 179 mutually deregulated genes which point to elevated cytokine signaling with NFκB as a dominant pathway in ischemia responses. In contrast to ischemia, reperfusion induced pro-apoptotic and pro-inflammatory cascades involving TNF, NFκB and MAPK pathways. FOS and JUN were down-regulated in steatosis compared to their up-regulation in normal livers. Surprisingly, molecular signatures of underlying primary and secondary cancers were present in non-tumor tissue. The reported inter-patient variability might reflect differences in individual stress responses and impact of underlying disease conditions. Furthermore, we provide a set of 230 pre-analytically highly robust genes identified from histologically normal livers (<2% covariation across both cohorts) that might serve as reference genes and could be particularly suited for future diagnostic applications., Competing Interests: Declaration of Competing Interest KZ is founder and CEO of Zatloukal Innovations GmbH. RS is employed by TATAA Biocenter AB. MK is employed by BioXpedia A/S, which has no commercial interest in the results of the present publication., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In locally advanced breast cancer, axillary lymph node dissection remains a pivotal component of surgical therapy. Apart from this, it has been mostly replaced by sentinel node biopsy. Complications after axillary dissection include wound infection, neuropathy, lymphedema and-most frequently-seroma. In this retrospective multi-centre study, we compared the use of LigaSure TM with monopolar electrocautery regarding perioperative outcome., Methods: A retrospective data analysis from female breast cancer patients who underwent axillary dissection at two breast centres in Austria that are using two different surgical techniques was performed for this study. We compared the rate of complications and re-operations, length of hospital stay, time to drain removal, total drain fluid, seroma formation after drain removal, number of seroma aspirations and total seroma fluid., Results: Seventy one female patients with a median age of 63 (30-83) were included in this study. In 35 patients LigaSure TM and in 36 monopolar cautery was used for axillary dissection. There was no significant difference regarding intraoperative complications and rate of re-operations between the two groups (2.9 vs. 5.6%; p = 1 and 2.9 vs. 13.9%; p = 0.199). The time to drain removal and the length of hospital stay was similar in both groups. A significant difference in the occurence of postoperative wound infection could also not be shown. However, we found a significantly smaller total drain fluid in the LigaSure TM -group compared to the cautery-group (364.6 ml vs. 643.4 ml; p = 0.004). Seroma formation after drain removal was more frequent in the LigaSure TM -group (68.6 vs. 41.7%; p = 0.032) with a higher number of outpatient seroma aspirations (2.0 vs. 0.9; p = 0.005)., Conclusion: LigaSure TM and monopolar cautery provide equivalent techniques in axillary lymph node dissection with comparable postoperative outcomes., (© 2022. The Author(s).)

Background: The incidence of diaphragmatic rupture is low; however, it may be life threatening. Normally caused by blunt trauma, some cases are reported after pulmonary infections with extensive coughing. Covid 19 causes pulmonary infections and pneumonia and has been associated with weakening of the diaphragm after prolonged ventilation. We present a patient who suffered from diaphragmatic rupture 2 months after recovering from a severe Covid 19 pneumonia., Case: A 71 years old male patient presented with massive thoraco-abdominal pain and severe dyspnea. At the time of admission, the patient was diagnosed with rupture of the diaphragm and developed cardiogenic shock. Intraoperatively there was a 4 cm diameter large rupture of the diaphragm with enterothorax (transverse colon, stomach, spleen, parts of the jejunum). Avulsion of the mesenteric arteries made a segmental resection of the jejunum together with the spleen necessary. A jejuno-jejunostomy was performed and organs were replaced into the abdomen. The rupture of the diaphragm underwent primary closure with non-resorbable suture material. The patient has shown an uneventful post-operative course, fully recovered and was discharged on day 11 after surgery., Conclusion: Covid 19 is a disease that is known to have various effects on different organs. The diaphragm is only paid heed in case of dysfunction. Also in the setting of Covid 19 it is not known as prominent effector organ. Nevertheless its affection by coughing caused by Covid 19 can lead to life threatening complications., (© 2022. The Author(s).)

Background/aim: Prognostic factors like the CRP-to-albumin ratio (CAR) represent potential predictors for survival of pancreatic cancer patients. We aimed to investigate the prognostic strength of the CAR for overall survival of patients with pancreatic cancer undergoing pancreatic resection., Patients and Methods: Data from a total of 202 patients with pancreatic adenocarcinoma who had undergone curative pancreatic resection were subjected to a retrospective review. Overall survival was calculated according to the Kaplan-Meier method, and multivariate Cox regression analysis was used for calculating the prognostic strength of CAR., Results: CAR was an independent prognostic factor of overall survival in univariate and multivariate Cox regression analysis. Elevated CAR was associated with a higher median value of Charlson Index, higher Union for International Cancer Control (UICC) classification and increased carcinoembryonic antigen (CEA) levels., Conclusion: CAR is a useful prognostic factor for the prediction of overall survival for patients undergoing pancreatic surgery. The impact of CAR in individual risk assessment should be evaluated in further studies., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Diagnosis and management of non-obstetric abdominal pathologies during pregnancy are clinically challenging for both obstetricians and general surgeons. Our aim was to evaluate the outcome of pregnant patients who had undergone non-obstetric abdominal surgery., Methods: We retrospectively reviewed 76 pregnant patients who had required surgery for non-obstetric abdominal pathologies during pregnancy at our department from January 2005 to December 2015. Data were collected retrospectively from medical records as well as from our institutional perinatal database. We evaluated data for clinical presentation, perioperative management, preterm labor, and maternal and fetal outcomes., Results: The patients' mean age was 29 (interquartile range IQR 25-33) years. Indications for surgery were acute appendicitis in 63%, adnexal pathology in 11%, cholecystolithiasis in 5% and other indications in 21%; surgery was performed in an elective setting in 18% and in an emergent/urgent setting in 82%. In five cases, complications, three of them oncological, called for further surgery. Ninety-seven percent of operations were conducted under general anesthesia. Median skin-to-skin time was 50 (37-80) minutes, median in-hospital stay was 4 (3.5-6) days, and 5 % required postoperative intensive care. Preterm labor occurred in 15%, miscarriage in 7% (none of them directly related to abdominal surgery)., Conclusion: Abdominal surgery for non-obstetric pathology during pregnancy can be performed safely, if mandatory, without increases in maternal and fetal pathology, miscarriage, and preterm birth rates.

Background/aim: The liver is a frequent site for metastases of colorectal cancer. Approximately 15% of patients have hepatic metastases at the time of diagnosis and another 50% develop them over the course of their disease. Only 10-25% of patients are candidates for liver resection. The aim of this study was to assess the benefit of preoperative computed tomography (CT)-guided wire marking of disappearing colorectal liver metastases (CRLMs) (radiological disappearance of metastases) before surgical resection., Patients and Methods: Between January 2011 and January 2014, 20 patients with potentially disappearing CRLMs were selected for CT-guided wire marking. Following treatment with neoadjuvant chemotherapy, disappearing CRLMs were marked via CT guidance. Afterwards, the marked sites were resected., Results: Complete histological response to neoadjuvant chemotherapy was only in 10 resected sites (18%), and 46 (82%) resected liver metastases showed metastatic tissue present. Both overall survival and the disease-free rates in patients after using our method were 55%., Conclusion: This study demonstrated the usefulness of CT-guided wire marking to mark disappearing CRLMs in order to improve long-term effectiveness of surgical treatment., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Gastrointestinal complications following on-pump cardiac surgery are orphan but serious risk factors for postoperative morbidity and mortality. We aimed to assess incidence, perioperative risk factors, treatment modalities and outcomes., Material and Methods: A university medical center audit comprised 4883 consecutive patients (median age 69 [interquartile range IQR 60-76] years, 33% female, median logistic EuroScore 5 [IQR 3-11]) undergoing all types of cardiac surgery including surgery on the thoracic aorta; patients undergoing repair of congenital heart disease, implantation of assist devices or cardiac transplantation were excluded. Coronary artery disease was the leading indication for on-pump cardiac surgery (60%), patients undergoing cardiac surgery under urgency or emergency setting were included in analysis. We identified a total of 142 patients with gastrointestinal complications. To identify intra- and postoperative predictors for gastrointestinal complications, we applied a 1:1 propensity score matching procedure based on a logistic regression model., Results: Overall, 30-day mortality for the entire cohort was 5.4%; the incidence of gastrointestinal complications was 2.9% and median time to complication 8 days (IQR 4-12). Acute pancreatitis (n = 41), paralytic ileus (n = 14) and acute cholecystitis (n = 18) were the leading pathologies. Mesenteric ischemia and gastrointestinal bleeding accounted for 16 vs. 18 cases, respectively. While 72 patients (51%) could be managed conservatively, 27 patients required endoscopic/radiological (19%) or surgical intervention (43/142 patients, 30%); overall 30-day mortality was 12.1% (p<0.001). Propensity score matching identified prolonged skin-to-skin times (p = 0.026; Odds Ratio OR 1.003, 95% Confidence Interval CI 1.000-1.007) and extended on-pump periods (p = 0.010; OR 1.006, 95%CI 1.001-1.011) as significant perioperative risk factors., Comment: Prolonged skin-to-skin times and extended on-pump periods are important perioperative risk factors regardless of preoperative risk factors., Competing Interests: The authors have declared that no competing interests exist.

Background & Aim: Primary hepatic angiosarcoma is a rare tumor with poor prognosis. The aim of this study was to generate a new angiosarcoma model to improve research on hepatic angiosarcoma., Methods: Pigs sus scrofa were treated with different regimens of diethylnitrosamine (DENA). Tissues were analyzed by histology and immunohistochemistry. Serum parameters were determined. Angiosarcoma tissue was investigated for chromosomal aberrations by aCGH analysis., Results: Animals of almost all different treatment regimens developed a multitude of variable liver lesions. Different tumor types such as granulation tissue type, cellular-like, hyalinization necrosis-like, angiosarcoma-like, dysplastic nodule-like, hepatocellular-like, glandular structure-like, and leiomyoma-like lesions were observed. Weekly treatment with 15 mg/kg for up to 52 weeks or a single shot of 200 mg/kg DENA led to the development of hepatic angiosarcomas. aCGH analysis of angiosarcoma tissue revealed increased alterations in tumors compared to non-tumorous tissue. Most of the chromosomal alterations were found on chromosomes 6, 7, 12, and 14., Conclusion: In this preliminary study treatment of sus scrofa with weekly injections of 15 mg/kg DENA results in a new model for primary hepatic angiosarcoma. This model may help to shed light on the pathomechanisms of primary hepatic angiosarcoma and might therefore open new treatment options., Competing Interests: The authors have declared that no competing interests exist.

Background: Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphoma with or without involvement of extranodal sites. Rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy represents the current standard therapy, achieving a rather dissatisfying outcome in approximately 30-40% of all cases., Case Presentation: We present the case of a 43-year-old Austrian woman with an incidentally detected large pelvic mass which was diagnosed as diffuse large B-cell lymphoma. Initially, the lymphoma intraoperatively appeared to be an inoperable conglomerate tumor. Soon, intestinal perforation induced by tumor infiltration occurred, which initiated a closure of the small intestine and application of a jejunal probe and a percutaneous endoscopic gastrotomy tube. Treatment utilizing the gold standard rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) was performed, partly resulting in remission according to radiological follow-up. In view of diagnosis and primary treatment development, the predictive outcome appeared unsound. However, within the procedure of the latest surgical intervention, which was intended to at least reconstruct the intestinal passage in order to improve quality of life, a surgical R0 resection of the residual tumor mass was achieved., Conclusions: The case presented here reports an unanticipated process of diffuse large B-cell lymphoma, underlining the importance of interdisciplinary cooperation and surgical intervention within the realms of state-of-the-art treatment.

Background: While previously believed to be mutually exclusive, concomitant mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS)- and V-raf murine sarcoma b-viral oncogene homolog B1 (BRAF)-mutated colorectal carcinoma (CRC), has been described in rare instances and been associated with advanced-stage disease. The present case series is the first to report on the implications of concurrent KRAS/BRAF mutations among surgically treated patients, and the largest set of patients with surgically treated colorectal liver metastasis (CRLM) and data on KRAS/BRAF mutational status thus far described., Case Series: We present cases from an international, multi-institutional cohort of patients that underwent hepatic resection for CRLM between 2000-2015 at seven tertiary centers. The incidence of KRAS/BRAF mutation in patients with CRLM was 0.5% (4/820). Of these cases, patient 1 (T2N1 primary, G13D/V600E), patient 2 (T3N1 primary, G12V/V600E) and patient 3 (T4N2 primary, G13D/D594N) succumbed to their disease within 485, 236 and 79 days respectively, post-hepatic resection. Patient 4 (T4 primary, G12S/G469S) was alive 416 days after hepatic resection., Conclusion: The present case series suggests that the incidence of concomitant KRAS/BRAF mutations in surgical cohorts may be higher than previously hypothesized, and associated with more variable survival outcomes than expected., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Plexiform fibromyxoma is a very rare mesenchymal tumor of the stomach, found almost exclusively in the antrum/pylorus region. The most common presenting symptoms are anemia, hematemesis, nausea and unintentional weight loss, without sex or age predilection. We describe here two cases of plexiform fibromyxoma, involving a 16-year-old female and a 34-year-old male. Both patients underwent complete resection (R0) by distal gastrectomy and retrocolic gastrojejunostomy (according to Billroth 2); for both, the postoperative course was uneventful. Histology showed multiple intramural and subserosal nodules with characteristic plexiform growth, featuring bland spindle cells situated in an abundant myxoid stroma with low mitotic activity. Immunohistochemistry showed α-smooth muscle actin-positive spindle cells, focal positivity for CD10, and negative staining for KIT, DOG1, CD34, S100, β-catenin, STAT-6 and anaplastic lymphoma kinase. One of the cases showed focal positivity for h-caldesmon and desmin. Upon follow-up, no sign of disease was found. In the differential diagnosis of plexiform fibromyxoma, it is important to exclude the more common gastrointestinal stromal tumors as they have greater potential for aggressive behavior. Other lesions, like neuronal and vascular tumors, inflammatory fibroid polyps, abdominal desmoid-type fibromatosis, solitary fibrous tumors and smooth muscle tumors, must also be excluded., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest.

Background: The purpose of this study is to review our results for pancreatic resection in patients with intraductal papillary mucinous neoplasm (IPMN) with and without associated carcinoma., Methods: A total of 54 patients undergoing pancreatic resection for IPMN in a single university surgical center (Medical University of Graz) were reviewed retrospectively. Their survival rates were compared to those of patients with pancreatic ductal adenocarcinoma., Results: Twenty-four patients exhibit non-invasive IPMN and thirty patients invasive IPMN with associated carcinoma. The mean age is 67 (+/-11) years, 43 % female. Surgical strategies include classical or pylorus-preserving Whipple procedure (n = 30), distal (n = 13) or total pancreatectomy (n = 11), and additional portal venous resection in three patients (n = 3). Median intensive care stay is three days (range 1 - 87), median in hospital stay is 23 days (range 7 - 87). Thirty-day mortality is 3.7 %. Median follow up is 42 months (range 0 - 127). One-, five- and ten-year overall actuarial survival is 87 %; 84 % and 51 % respectively. Median overall survival is 120 months. Patients with non-invasive IPMN have significantly better survival than patients with invasive IPMN and IPMN-associated carcinoma (p < 0.008). In the subgroup of invasive IPMN with associated carcinoma, a positive nodal state, perineural invasion as well as lymphovascular infiltration are associated with poor outcome (p < 0.0001; <0.0001 and =0.001, respectively). Elevated CA 19-9(>37 U/l) as well as elevated lipase (>60 U/l) serum levels are associated with unfavorable outcome (p = 0.009 and 0.018; respectively). Patients operated for pancreatic ductal adenocarcinoma show significantly shorter long-term survival than patients with IPMN associated carcinoma (p = 0.001)., Conclusions: Long-term outcome after pancreatic resection for non-invasive IPMN is excellent. Outcome after resection for invasive IPMN with invasive carcinoma is significantly better than for pancreatic ductal adenocarcinoma. In low- and intermediate risk IPMN with no clear indication for immediate surgical resection, a watchful waiting strategy should be evaluated carefully against surgical treatment individually for each patient.

Background/aim: Liver resection is the best treatment for metastatic colorectal cancer (CRC). Hepatic lymph node metastases are considered as extrahepatic disease and represent an unfavorable prognostic factor. However, extrahepatic disease, when resectable, provides no contraindication for surgical therapy. The aim of this study was to evaluate the prevalence of hepatic lymph node involvement in our patients' cohort., Patients and Methods: Twenty patients submitted to resection for colorectal liver metastases were studied prospectively. Three areas for lymph node dissection were defined and analyzed separately. Lymph nodes were examined by hematoxylin and eosin staining and immunohistochemistry for Pan-Keratin., Results: In average, 5 lymph nodes were harvested per patient. Macroscopic enlargement was not a definite sign for metastatic involvement. No morbidity or mortality was associated with lymphadenectomy. In our patients' collective, no cases of lymph node metastases occurred., Conclusion: There is no evidence of a survival benefit after lymph node dissection in patients with CRC liver metastases in the literature. Systematic lymphadenectomy can, however, provide a prognostic tool to better plan further treatment., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: In this study we aimed to determine if advanced age represents a risk factor for negative perioperative and long-term outcome in patients undergoing curative surgery ductal pancreatic adenocarcinoma surgery., Patients and Methods: Two-hundred-twenty-one consecutive patients, twelve (6%) patients ≥80 years were included in the study. We assessed perioperative and long-term outcome and independent predictors for in-hospital mortality with Cox regression analysis., Results: Advanced age was not a predictor for in-hospital mortality (6.3% in non-octogenarian versus 8.3% in octogenarians; p=0.55) nor for morbidity (31% vs. 32%; p=0.69). An ASA score >II was the only predictor for in-hospital mortality (odds ratio (OR)=10.10, 95%CI=1.28-79.60; Hosmer-Lemeshow: p=0.86). No significant difference was observed in one- and five-year survival rates (68 and 58% vs. 16 and 14%; log-rank p=0.61)., Conclusion: Advanced age is not a risk factor for negative outcome in curative pancreatic cancer surgery. Therefore, this single curative option should be considered in octogenarians at risk., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal tumor entity of the gastrointestinal tract. In fewer than 5% of cases, primary GISTs are located in the duodenum. Surgery represents the treatment of choice for localized tumor disease and remains challenging in GISTs located at the duodenum. The optimal surgical approach is currently discussed controversially in the literature due to the fact that extended resections in terms of pancreaticoduodenectomy may cause significant postoperative morbidity and mortality compared to limited resection. We report on a rare case of GIST located in the upper part of the duodenum treated by limited surgical resection. Avoidance of postoperative complications may lead to optimal oncological outcome in selected patients., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Gastroenteropancreatic neuroendocrine tumors are known for their aggressiveness. Diagnosis of various bile duct pathologies, like biliar intraepithelial neoplasm, mixed adenoneuroendocrine carcinomas or small cell carcinomas, is challenging. This case report focuses on a rare case of a focal primary minute small cell carcinoma in the vicinity of the extrahepatic bile duct, presenting itself next to an extensive biliar intraepithelial neoplasm. This finding led to adjuvant chemotherapy, followed by major surgery. Therapeutic approach was based on CT and MRI scans but most importantly on immunohistochemistry and histological evaluation. Initially CR seemed achievable, but metastases were to be found rapidly. The authors want to underline the fact that major clinical decisions are based on sometimes tiny specimens; as literature shows it is absolutely advisable to use markers to differentiate the dignity of investigated areas. The authors call for keeping collision of tumors in mind and adding KOC staining and using it in a routine manner examining biliary duct lesions., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Incisional hernias (IHs) occur universally after orthotopic liver transplantation (OLT). This study aimed to investigate the effectiveness of porcine dermal collagen (PDC) as a closing aid in giant hernias after OLT in a prospective trial. If direct closure (DC) was not feasible due to the hernia size and abdominal wall constitution, a PDC mesh was implanted. All patients from the PDC and DC groups were followed prospectively for 24 months. IH recurrence rates served as the primary endpoint, and the development of infections and wound healing disorders served as the secondary endpoints. Recurrence rate was 21% (4/19) in DC patients and 12% (2/16) in PDC patients (P = 0.045). Implant site infections occurred in five of PDC and one of DC patients (P < 0.05). All of them were managed with antibiotics; two of the PDC patients required surgical drainage. Histological analysis of PDC mesh biopsies indicated good angiogenesis and integration of the PDC into the abdominal wall. PDC was effective in our study for incisional hernia repair, and our results compared favourably with those of patients in whom direct hernia closure was feasible., (© 2014 Steunstichting ESOT.)

Due to ameliorated surgery as well as better immunosuppression, the recipient age after liver transplantation has been extended over the past years. This study aimed to investigate the health related quality of life after liver transplantation in recipients beyond 60 years of age. The SF-36 was used to evaluate the recipients' health-related quality of life as standardized tool. It comprises 36 items that are attributed to 8 subscales attributed to 2 components: the physical component score and the mental component score. Differences in the health-related quality of life between the included aged recipients and age-matched general population as well as among female and male recipients. Aged recipients showed significantly lower scores in physical functioning (29 vs. 76, p = 0.001), role physical (42 vs. 73, p = 0.003), bodily pain (34 vs. 71, p = 0.003), general health (28 vs. 59, p = 0.001), vitality (25 vs. 61, p = 0.001), social functioning (36 vs. 87, p =0.001), role emotional (46 vs. 89, p = 0.001) as well as the physical component score (28 vs. 76, p = 0.001). Aged female recipients showed lower results as compared to males in social functioning, physical functioning, role physical, and social functioning (p = 0.03 respectively) but comparable results in the remaining. Quality of life seems to be an issue among aged recipients and should be assessed on a regular basis.

Aim: We present a case of a new mesenchymal tumor entity named 'distinctive microcystic and pseudopapillary spindle and round cell neoplasm', of which only 30 cases have been reported worldwide., Case Report: A fifty-two-year-old woman presented in January 2012 with epigastric pain of changing character and weight loss. Examinations revealed a tumor 10×6.8×9.8 cm in diameter showing infiltration in the surrounding organs. A Whipple procedure and a right hemicolectomy were necessary to achieve free resection margins. At the last follow-up in November 2012 the patient was well and there were no signs of recurrence or metastatic spread. Intra-abdominal mesenchymal tumors cause unspecific abdominal symptoms. Local recurrence and metastatic spread can occur. The main prognostic factors for survival are a free margin after resection and the histological subtype of the tumor. Behavioral prediction is not possible in every case and the treatment has to be individualized for every patient., Conclusion: This case represents a new entity of mesenchymal tumor. It was treated according to the guidelines for intra-abdominal sarcomas. Further investigation of this kind of tumor is necessary to define therapeutic guidelines.

The purpose of this trial was to examine the efficacy of the addition of levamisole (LEV) or interferon alfa (IFN) to an adjuvant chemotherapy with 5-fluorouracil (5-FU) in patients with stage III colon cancer. According to a 2 x 2 factorial study design, 598 patients were randomly assigned to one of four adjuvant treatment arms. Patients in arm one received 5-FU weekly for 1 year, patients in arm two 5-FU plus LEV, in arm three 5-FU plus IFN and patients in arm four 5-FU, LEV and IFN. The relative risk of relapse and the relative risk of death were significantly higher for patients treated with LEV compared with those without LEV treatment (HR 1.452, 95% CI 1.135-1.856, P=0.0028; HR 1.506, 95% CI 1.150-1.973, P=0.0027, respectively). No significant impact on survival was observed for therapy with IFN in the univariate analysis. The addition of LEV to adjuvant 5-FU significantly worsened the prognosis of patients with stage III colon cancer. Interferon alfa had no significant influence on survival when combined with adjuvant 5-FU, but increased the toxicity of therapy substantially.

Objective: To confirm evidence that breast-conserving treatment (BCT) does not impair the prognosis in breast cancer patients as compared to mastectomy and to argue that it be regarded as the treatment of choice in stage I and II disease., Summary Background Data: Scientifically, survival rates in breast cancer have been shown to be stage-dependent, but independent of the extent of surgical breast tissue removal, as long as the resection margins are free of tumor infiltration., Methods: Between 1984 and 1997, six different trials conducted by the Austrian Breast & Colorectal Cancer Study Group accrued a total of 4,259 women with hormone-responsive disease. The authors selected and compared three patient groups (n = 3,316) according to pathologic stage, age, and the surgical procedure applied., Results: Over this interval, the BCT rate in the premenopausal node-positive subgroup experienced a highly significant increase from 27.2% to 73.2% overall. In the group of postmenopausal node-negative patients, the BCT rate grew significantly by 37.3% to 77.3% in total. With an overall BCT rate growing from 22.5% to 56.8% in postmenopausal node-positive women, those presenting with T1 tumors saw a significant increase from 35.1% to 65.9%. Mortality and local recurrence rates proved stable or even decreased considerably over time and in all subgroups., Conclusions: The presented outcome of BCT rates, significantly improved over this 16-year period and in no way counterbalanced by higher local recurrence or death rates, reflects an excellent example of surgical quality control. BCT can safely be regarded as the standard of therapy for T1 and increasingly for T2 disease. Especially in multi-institutional adjuvant breast cancer trials, the highest priority should be given to breast-conserving procedures.

Intracytoplasmic hyaline bodies (IHBs) resemble inclusions in hepatocellular carcinoma cells, which so far have escaped further characterization. A relationship to Mallory bodies was suggested on the basis of light microscopy and filamentous ultrastructure. A hepatocellular carcinoma containing numerous IHBs was studied. Our studies revealed immunoreactivity of IHBs with the monoclonal antibodies SMI 31 and MPM-2, which recognize hyperphosphorylated epitopes present on paired helical filaments in Alzheimer's disease brains (SMI 31) or on diverse proteins hyperphosphorylated by mitotic kinases in the M-phase of the cell cycle (MPM-2). One- and two-dimensional gel electrophoresis of tumor extracts followed by immunoblotting with SMI 31 and MPM-2 antibodies revealed a major immunoreactive protein with an apparent molecular weight between 62 and 65 kd, which was resolved into several highly acidic (pH 4.5) protein components in two-dimensional gels. This protein was undetectable in non-neoplastic liver tissue. Sequence analysis identified the SMI 31 and MPM-2 immunoreactive material as p62, indicating that p62 is a major constituent of IHBs. p62 is an only recently discovered protein that is a phosphotyrosine-independent ligand of the SH2 domain of p56(lck), a member of the c-src family of cytoplasmic kinases. Moreover, p62 binds ubiquitin and may act as an adapter linking ubiquitinated species to other proteins. These features suggest a role of p62 in signal transduction and possibly also carcinogenesis. IHBs observed in the hepatocellular carcinoma cells presented are the first indications of a role of p62 in disease.