[Prognostic value of lacrimal duct diagnostics after tube removal : Retrospective analysis of risk of relapse during the first postoperative year after transcanalicular lacrimal duct surgery with silicone tubing]. / Prognostische Aussagekraft der Tränenwegsdiagnostik nach Intubatentfernung : Retrospektive Analyse des Rezidivrisikos im ersten postoperativen Jahr nach transkanalikulärer Tränenwegschirurgie mit Silikonschlauchintubation.

BACKGROUND: Transcanalicular lacrimal duct surgery has become more important over the past two decades. OBJECTIVES: The aim of the study was to prove the prognostic value of postoperative lacrimal syringing and the testing of spontaneous drainage of lacrimal fluid immediately after tube removal. METHODS: A total of 110 cases with postoperative lacrimal syringing and 183 cases with verification of the postoperative lacrimal fluid drainage performed between January 2001 and August 2008 were retrospectively evaluated. The indication for postoperative diagnostics was set by the investigator. The prognostic value of these two procedures was determined by using prognostic parameters (positive predictive value, PPV; negative predictive value, NPV) and analyzing recurrence nonexistence via Cox regression and Kaplan-Meier estimator. The observation period was limited to 12 months. Predominantly, recurrence was defined on the patient's satisfaction and absence of symptoms, which was determined with the help of a questionnaire. RESULTS: Postoperative verification of the lacrimal syringing is a suitable instrument to estimate surgical success within the first year after lacrimal surgery with a PPV of 92.31%. Testing of the spontaneous drainage of lacrimal fluid after tube removal reached a PPV of 63.33%. CONCLUSION: The proven prognostic value shows that syringing of the lacrimal duct and verification of spontaneous drainage should be integrated into postoperative care in a standardized manner. Hereby, early information for the patient about the expected result of the surgical procedure is enabled.

[Implementation of a thermal management concept to prevent perioperative hypothermia : Results of a 6­month period in clinical practice]. / Umsetzung eines Wärmemanagementkonzeptes zur Vermeidung von perioperativer Hypothermie : Ergebnisse eines Sechsmonatszeitraums in der klinischen Praxis.

BACKGROUND: Perioperative hypothermia is defined as a core temperature below 36 °C. The literature shows that perioperative hypothermia is a frequent but potentially preventable complication of the surgical process. The risk of experiencing perioperative hypothermia is inherent for all anesthetized patients, independent of the type of surgery. Unless preventative measures are taken, perioperative hypothermia occurs in 50 to 70 % of all surgical patients. In Germany and Austria the guideline "Preventing inadvertent perioperative hypothermia" has been published. In Wolfsburg we started already in 2012 with a standard operating procedure to prevent perioperative hypothermia in all surgical patients. In two clinical departments we established an additional prewarming-protocol starting prior to induction of anaesthesia on the normal ward on the day of surgery. MATERIAL AND METHODS: For a period of 6 months we analyzed all temperature data of patients having undergone surgery, beginning before the start of general anaesthesia until the end of the operation. RESULTS: In total 3228 patients were enrolled into the study. Prewarming was performed in 1329 patients. In 1902 patients active warming was limited to the intraoperative period. The total rate of hypothermia in all patients was 32.6 %, whereas the rate of hypothermia at the end of the operation was 19.3 %. In the group of patients without prewarming the overall rate was 39.1 vs. 25 % at the end of the operation. In the groups of patients with prewarming the total rates of hypothermia were 25.2 and 24.7 % overall and 14.4 and 12.5 % at the end of the operation. In multifactorial regression it could be shown that patients without prewarming had a 1.8-fold increased risk of perioperative hypothermia compared to patients with intraoperative warming only. CONCLUSION: We conclude that temperature management is a challenge in the clinical situation, and that it is difficult to achieve rates of hypothermia close to zero. The addition of prewarming was very effective in improving the results in our patients.

[Balloon dilatation of the Eustachian tube during middle ear surgery : Study planning and first experiences during recruitment]. / Ballondilatation der Tuba auditiva bei Mittelohroperationen : Studienplanung und erste Erfahrungen bei der Rekrutierung.

BACKGROUND: Eustachian tube dysfunction is considered a major contributor to chronic middle ear disease. In clinical case series, the results of balloon dilation (balloon Eustachian tuboplasty, BET) as a treatment for Eustachian tube dysfunction have been reported. OBJECTIVE: This study aims to analyze whether patients undergoing planned surgery for chronic middle ear disease would benefit from additional BET. METHODS: In a randomized controlled, patient and observer (not surgeon)-blind clinical study, 100 adult patients with planned surgery for chronic middle ear disease will be investigated. Patients will be randomized into two groups, one of which (50%) will receive additional BET of the affected side during the planned surgery. Eustachian tube function will be evaluated using the Valsalva maneuver and tubomanometry according to Estève, as well as on the basis of patient reports. Various scores will be used as outcome measures, including ETS-5 (Eustachian Tube Score 5), the extended version ETS-7, and the ETDQ-7 (Seven-Item Eustachian Tube Dysfunction Questionnaire). Follow-up is at 3, 6, and 12 months. RESULTS: From June to December 2015, 162 patients underwent microscopic ear surgery. Inclusion criteria were not fulfilled by 90 patients. Of the remaining 72 patients with chronic middle ear disease, 12 patients (17%) have been randomized so far, 28 (39%) did not exhibit Eustachian tube dysfunction, and 32 (44%) patients could not be included for other reasons. CONCLUSION: The rate of recruitment was lower than expected. Depending on the case number calculations for the patient groups identified in the study for whom BET might be particularly beneficial, multicenter studies in specific disease groups may follow.

Expression of microRNA 210 associates with poor survival and age of tumor onset of soft-tissue sarcoma patients.

Expression of microRNAs can affect age of tumor onset and prognosis of cancer patients. However, nothing is known about the effects of microRNAs on altered age of cancer onset and disease-specific survival of soft-tissue sarcoma (STS) patients. The levels of miR-210, also known as hypoxia-regulated microRNA, were analyzed by quantitative real-time (RT)-PCR in the tumors of 78 STS patients. The patients were stratified according to their microRNA levels with low, intermediate and high expression levels and the association of microRNA expression and patients' survival was analyzed using multivariate Cox's regression hazard analyses. A significant correlation between an intermediate miR-210 expression and disease-specific death of STS patients [relative risk (RR) = 3.19; p = 0.018] was observed compared with patients with high expression levels in their tumors. Interestingly, the association between an intermediate expression of miR-210 and a poor prognosis was only significant in female STS patients (RR = 11.28; p = 0.010), but not observed in male individuals. Furthermore, the expression of miR-210 showed a significant association with the age of tumor onset in a gender-specific manner. Specifically, male patients with an intermediate expression of miR-210 associated with a 9.6-year later age of tumor onset (p = 0.017) compared with males with a low expression of miR-210 in their tumors. However, no significant differences in the female patients were observed. This study provides the first evidence of a correlation of expression levels of a single microRNA (miR-210) with the prognosis and age of tumor onset in a gender-specific manner in STS patients.

Expression and distribution of tenascin in rat submandibular glands following irradiation.

UNLABELLED: The aim of this study was to investigate the late changes in the expression of tenascin-C (TN-C) in salivary glands (SG) following irradiation (IRR). MATERIALS AND METHODS: In 124 submandibular SG from 62 Wistar rats, the effect of IRR dose (fractionated IRR, 2 Gy per day, total dose of 20, 40, or 60 Gy), time since IRR (6 months vs. 12 months), and animal age (1 year vs. 1.5 years) on TN-C expression profile and its distribution pattern was investigated. RESULTS: Expression of TN-C showed slight to moderate alterations in the irradiated specimens. The expression differed in frequency and degree among various tissue structures. The most striking finding was pronounced dose-dependent heterogeneity, with increases, decreases and fluctuations in staining. CONCLUSION: The staining of TN-C predominantly showed notable dose-dependent heterogeneity, persisting for up to 1 year after completion of IRR. Thus, these findings can be attributed to late radiation effects. The altered expression of tenascin-C may play at least a partial role in late radiogenic dysfunction of the submandibular SG.

Co-detection of members of the urokinase plasminogen activator system in tumour tissue and serum correlates with a poor prognosis for soft-tissue sarcoma patients.

BACKGROUND: The urokinase plasminogen activator (uPA) system is one of the best-investigated protease systems, both under physiological and pathological conditions, including various types of cancer. However, effects of co-expression of members of the uPA system in soft-tissue sarcoma (STS) patients at the protein level in both tumour tissue and serum have not been investigated yet. METHODS: We examined 82 STS patients for protein levels of uPA, PAI-1and uPAR in tumour tissue and serum by ELISA. RESULTS: A significant correlation between high antigen levels of uPA, PAI-1 or uPAR in tumour tissue, and of uPAR in serum, with poor outcome of STS patients was found for the first time. Most strikingly, we observed an additive effect of combined uPA, PAI-1 or uPAR levels in tumour tissue extracts with uPAR levels in serum on patients' prognosis. High uPA/uPAR, PAI-1/uPAR and uPAR/uPAR antigen levels in tumour tissue/serum were associated with a 5.9-fold, 5.8-fold and 6.2-fold increased risk of tumour-related death (P=0.003, 0.001 and 0.002, respectively) compared with those patients who displayed low levels of the respective marker combination. CONCLUSION: As expression of members of the uPA system in tumour tissue and serum is additively correlated with prognosis of STS patients, our results suggest that combinations of these biomarkers can identify STS patients with a higher risk of tumour-related death.

Impact of quality of life parameters and coping strategies on postchemotherapy nausea and vomiting.

To assess whether prechemotherapy quality of life (QoL) factors and certain coping strategies are associated with postchemotherapy nausea and vomiting (PCNV). A total of 43 chemotherapy-naïve patients scheduled to receive anti-emetic prophylaxis were enrolled in this study. QoL parameters were measured by a modified EORTC Quality of Life Questionnaire (QLQ-30). In addition, questions regarding active or passive coping strategies were asked 1 day before chemotherapy. Prechemotherapy QoL factors, coping strategies as well as other patient, disease and treatment variables were compared between the groups of patients with or without PCNV. The univariate analysis identified four QoL parameters, 'tiredness', 'impairment of daily life by pain', 'sensation of abdominal pressure and fullness' and 'impairment of social activities' as associated with PCNV. No association was found between coping strategies and PCNV. In the multivariate analysis, the factors 'impairment of social activities' and 'sensation of abdominal pressure and fullness' remained significant. Specific pretreatment QoL parameters are associated with the risk to develop PCNV. Thus, in addition to other established risk factors for PCNV, patients should be screened for these QoL factors in order to improve the control of PCNV and facilitate the selection of appropriate, individualised anti-emetic prophylaxes.

Expression and distribution of cytokeratins and vimentin in rat larynx and trachea following irradiation.

BACKGROUND: External irradiation (IRR) of advanced head and neck tumors often includes tissues of the larynx and trachea unaffected by cancer. In these normal tissues, both single-cell damage (necrosis, apoptosis, functional cell death) and interstitial damage (edema, fibrosis, vascular alterations, cellular infiltrations) resulting in tissue remodeling can occur, depending on various IRR parameters. However, reports on radiogenic intermediate filament protein alterations in laryngeal-tracheal tissues are very rare. In this study, we investigated the phenotypic characterization of the normal integrity-supporting cytokeratins (CK) and vimentin following a clinically relevant IRR protocol in laryngeal-tracheal tissues. MATERIALS AND METHODS: In 61 laryngo-tracheal specimens from Wistar rats the expression profile and distribution pattern of CK (CK13, CK17/19, CK18) and vimentin were investigated according to IRR dose (fractionated IRR, 2 Gy per day, total dose of 20, 40 or 60 Gy), time from IRR (6 months vs. 12 months) and animal age (1 year vs. 1.5 years) using immunohistochemical methods, semiquantitative assessment and multivariate analysis. RESULTS: In irradiated specimens, expression of both CK and vimentin showed slight to moderate dose-dependent alterations. The expression differed in frequency and level among the various tissue structures and showed remarkable heterogeneity, with increases, decreases and fluctuations in staining. In the glottic mucosal layer (non-keratinizing squamous epithelium), CK13 expression decreased with increasing dose. The CK17/19 expression of supra- and subglottic respiratory epithelia following 20 and 60 Gy exposure was significantly lower than in controls. The respiratory epithelia and, in part, the cuboidal epithelia of the indifferent type at the inner side of the aryepiglottic fold revealed increasing CK17/19 immunoreactions up to 40 Gy IRR, but a distinct decrease in expression at 60 Gy. In subglottic gland structures, CK18 was detected at significantly higher levels than in controls. There was increasing expression with increasing dose. CK18 reactions of supra- and subglottic respiratory mucosal layer, supraglottic gland structures and thyrocytes tended towards increasing expression with increasing dose and in older animals. Tracheal mucosal epithelia, tracheal glands, and respiratory epithelia of the inner side of the aryepiglottic fold tended towards decreasing expression of CK18 with increasing dose and in older animals. In part, these tissues showed dose-dependent fluctuations. Furthermore, the vimentin reactions showed dose-dependent, heterogeneous patterns, with increases, decreases, and fluctuations in staining. Moreover, there were differences in frequency and intensity of expression among the various tissue structures. Age and time from IRR had no significant effect on immunoreaction. CONCLUSION: The staining of CK and vimentin predominantly showed a notable dose-dependent heterogeneity, with increases, decreases and fluctuations in expression. The expression pattern persisted for up to 1 year after the completion of irradiation. Thus, these findings must reflect late radiation effects. The altered expression of CK and vimentin may play at least a partial role in structural (e.g. edema) and functional (e.g. voice disorders) changes associated with irradiation of the head and neck.

Stem cell-associated genes are extremely poor prognostic factors for soft-tissue sarcoma patients.

Cancer stem cells can play an important role in tumorigenesis and tumor progression. However, it is still difficult to detect and isolate cancer stem cells. An alternative approach is to analyse stem cell-associated gene expression. We investigated the coexpression of three stem cell-associated genes, Hiwi, hTERT and survivin, by quantitative real-time-PCR in 104 primary soft-tissue sarcomas (STS). Multivariate Cox's proportional hazards regression analyses allowed correlating gene expression with overall survival for STS patients. Coexpression of all three stem cell-associated genes resulted in a significantly increased risk of tumor-related death. Importantly, tumors of patients with the poorest prognosis were of all four tumor stages, suggesting that their risk is based upon coexpression of stem cell-associated genes rather than on tumor stage.

Expression of the stem cell self-renewal gene Hiwi and risk of tumour-related death in patients with soft-tissue sarcoma.

Self-renewal is considered as a common property of stem cells. Dysregulation of stem cell self-renewal is likely a requirement for the development of cancer. Hiwi, the human Piwi gene, encodes a protein responsible for stem cell self-renewal. In this study, we investigated the expression of Hiwi at the RNA level by real-time quantitative PCR in 65 primary soft-tissue sarcomas (STS) and ascertained its impact on prognosis for STS patients. In a multivariate Cox's proportional hazards regression model, we found that an increased expression of Hiwi mRNA is a significant negative prognostic factor for patients with STS (P=0.017; relative risk 4.6, 95% confidence interval (CI) 1.3-16.1) compared to medium expression of Hiwi transcript. However, a low expression of Hiwi transcript is correlated with a 2.4-fold (CI 0.7-8.0) increased risk, but this effect was not significant (P=0.17). Altogether, high-level expression of Hiwi mRNA identifies STS patients at high risk of tumour-related death. This is the first report showing a correlation between expression of a gene involved in stem cell self-renewal and prognosis of cancer patients.

DNA-flow cytometry, DNA-image cytometry and proliferation index (MIB-5) in irradiated rat salivary glands and salivary gland tumors.

AIM: Salivary glands (SG) can become atrophic following radiation exposure. Malignant transformation of SG in a radiation field is another known sequela of patients who have been treated by radiotherapy for a malignant tumor in the head and neck region. The aim of this study was to investigate cytogenetic alterations and to determine the proliferation index (PI) of SG of rats subjected to various total dosages of fractionated X-rays. MATERIALS AND METHODS: We investigated rat SG, subjected to 20, 40, or 60 Gy exposure by X-rays to the left neck and skull base. Non-irradiated rats served as a control group. Tumors originating from the SG were histologically-diagnosed following the descriptions for human SG tumors. The MIB-5 antibody was used to determine the PI. The ploidy was determined by flow and image cytometry (FCM, ICM). RESULTS: We consistently recorded diploid histograms in the FCM in irradiated glands. ICM revealed aneuploid histograms in 6/22 tumors, 3 of them were Auer Type III or IV. The PI showed a dose- and time-dependent course, indicative of variable regeneration properties of the parenchyma. Statistically significant differences were found for the PI within the irradiation groups and comparing irradiated SG and tumors. CONCLUSION: Irradiation of rat SG can cause almost complete loss of function. On the other hand, the PI remained in animals subjected to 40 Gy and investigated 1 year after completion of radiation at a level up to 10-fold higher than in untreated controls. The PI in carcinoma is higher in this species than in irradiated SG. Constantly elevated PI could support the development of cancer in SG.

Expression and distribution of basement membrane proteins in rat larynx and trachea following irradiation.

OBJECTIVE: Basement membranes-(BM) influence polarization, differentiation, migration and proliferation of cell and play an important role in maintaining structural and functional tissue integrity. While BM alterations have been reported in various lesions (e.g. inflammation, tumors) of laryngeal-tracheal tissues, reports on radiogenic BM alterations are rare. External irradiation (IRR) of advanced head and neck tumors often includes "normal tissues" (tissues without cancer) of the larynx. In these normal tissues both single-cell damage (necrosis, apoptosis, functional cell death) and interstitial damage (edema, fibrosis, vascular alterations, cellular infiltrations) resulting in tissue remodeling can occur, depending on various IRR parameters. In this study, we set out to add to our knowledge on the phenotypic characterization of the radiogenic BM expression pattern in laryngo-tracheal tissues. MATERIALS AND METHODS: In 63 laryngo-tracheal specimens from Wistar rats, we investigated the laminin (LA) and collagen IV (CIV) expression profile and distribution pattern depending on the IRR dose (fractionated IRR, 2 Gy/day, up to a total dose of 20, 40, or 60 Gy), the time since IRR (6 months vs 12 months) and animal age (1 year vs 1.5 years) using immunohistochemical methods, semiquantitative assessment, and multivariate analysis. RESULTS: In specimens irradiated with more than 20 Gy, both BM constituents predominantly showed dose-dependent increases and sometimes fluctuations in staining at slight to moderate levels. The expression differed in frequency and level among the various tissue structures. In some structures there was decreased expression. In the vocalis muscle, laryngeal and esophageal nerve endings, recurrent laryngeal nerve and laryngeal and tracheal muscles, LA was detected at levels significantly stronger than in controls. BM surrounding gland structures, nerve endings of the piriform sinus and esophageal muscles showed a marked tendency towards increased LA expression. However, the BM underlying the mucosal layer of the supra- and subglottic region revealed decreasing LA immunoreaction up to 40 Gy IRR, but a distinct increase in expression at 60 Gy. In the esophageal and tracheal muscles, tracheal perichondrium, recurrent laryngeal nerve and capillaries, CIV was detected at significantly stronger levels than in the controls. The vocal ligament exhibited positive CIV immunoreactions adjacent to interstitial and infiltrate cells and CIV-positive BM condensations, resulting in increased staining of these structures. CIV reactions of laryngeal and hypopharyngeal nerve endings tended towards increased expression. In contrast, BM staining surrounding vocal muscle cells revealed significantly decreased expression. In addition, there was a tendency towards decreased expression for supraglottic, subglottic and hypopharyngeal muscle cells. Age and time since irradiation had no significant effect on staining. CONCLUSION: The BM constituents laminin and collagen IV showed prominent dose-dependent increases and sometimes fluctuations in expression. This expression pattern persisted up to one year after completion of the irradiation. Thus, these findings must be related to late radiation effects. The altered BM expression may play a role, at least in part, in structural (e.g. laryngeal edema) and functional (voice disorders) changes associated with irradiation of the head and neck area.

The expression pattern of collagen I in irradiated mandibular salivary glands of rats.

UNLABELLED: Irradiation damage to salivary glands leads to loss of function and fibrosis. Immunohistochemical analysis of extracellular matrix proteins might give a more precise insight into the irradiation damage of glands. Collagen I (C-I) is a major component of the extracellular space. The aim of this study was to analyse the effects of irradiation on the distribution pattern of C-I in the salivary glands of rats. MATERIALS AND METHODS: Sixty female Wistar rats were fractionated irradiated up to 60 Gy (left side of the neck; 2 Gy/d, 5d/week; total dosage either 20, 40 or 60 Gy). The glands were explanted after 6 or 12 months following supravital anesthesia, the shielded right gland serving as internal control. C-I was detected immunohistochemically. RESULTS: In non-irradiated animals the immunoreaction was mainly homogeneous and slight around the ductal epithelia, in the area of the capsule and septae and the peri- and epineurium of nerves. A statistically significant difference was identified in the irradiated rats vs control animals and comparing in-the-radiation field (left side) vs outside-the-radiation field (right side) situated glands. Multivariate analysis revealed a statistically significant increase in staining of irradiated rats concerning the excretory ducts, the area of the capsule and septae, the nerves and striated ducts and adventitia of vessels [p = 0.0001]. The increase of immunoreaction in irradiated glands started above 20 Gy total dosage and was at its maximum after 60 Gy. However, the expression profile was inhomogenous following 20 Gy exposure and did not differ statistically from glands of control animals. Neither the age of the animals nor the latency period following exposure to the radiation source yielded a statistically significant effect on the immunoreaction. CONCLUSION: Studies on irradiation damage to the salivary glands require a more detailed description of the proteins accumulating in the extracellular space, thereby forming the so-called "fibrosis". These accumulations of proteins, e.g. C-I, may both support apoptosis and support a hypoxic environment giving rise to transformed cells.

SCC antigen in the serum as an independent prognostic factor in operable squamous cell carcinoma of the cervix.

The aim of this study was to retrospectively examine whether the occurrence of squamous cell carcinoma (SCC) antigen tumour marker in the serum has prognostic significance in operable SCC of the cervix at the International Federation of Gynaecology and Obstetrics (FIGO) stages IA2-IIB. A total of 129 patients who had undergone a radical hysterectomy for SCC of the uterine cervix at the Department of Gynecology of the Martin-Luther University, Halle-Wittenberg in 1991-2000 were included. SCC antigen (Ag) was measured by IMx SCC-Ag microparticle enzyme immunoassay (Abbott Laboratories, Abbott Park, IL, USA). To assess the prognostic value of SCC antigen in the serum, we used a step-by-step multivariate analysis based on the Cox proportional hazard regression model. Using a cut-off value of 3.0 ng/ml, we detected preoperative SCC antigen in the serum as an independent prognostic factor in SCC of the cervix, both for recurrence-free and overall survival (P=0.003 and 0.0078). In this retrospective analysis the value of the SCC antigen tumour marker correlates with prognosis in operable SCC of the cervix, independent of tumour size, pelvic nodal status, cervical stroma infiltration, parametrial spread and tumour grading.

[Origin of shoulder pain after "neck dissection". Importance of the cervical plexus]. / Entstehung von Schulterschmerzen nach "neck dissection". Wertigkeit des Plexus cervicalis.

BACKGROUND: The role of sensitive parts of the cervical plexus for the development of neuropathic pain is not yet clear. Our study investigated the correlation between shoulder pain and cervical plexus damage after different types of neck dissection (ND). MATERIAL AND METHODS: The sensitivity for warm/cold and sharp/blunt was tested in the dermatomes of C2, C3, C4, and the minor occipital nerve. Shoulder pain was measured semiquantitatively by a rating scale. RESULTS: Motion-dependent shoulder pain was observed 6 months postoperatively in 50% after resection and in 29.2% after preservation of these structures. Pain occurred more frequently following radical ND than after modified radical types 1 and 3 ND. DISCUSSION: Our investigations showed that the superficial cervical plexus function is assessable by cutaneous sensitivity tests. The minor occipital nerve seemed to be less affected. Fewer pain symptoms in cases with preserved cervical plexus could be demonstrated. We can conclude that preservation of the superficial cervical plexus is important to diminish postoperative shoulder pain.

Microscopic (R1) and macroscopic (R2) residual disease in patients with resected non-small cell lung cancer.

OBJECTIVES: This retrospective study evaluates the probability of survival in patients who had undergone resection for non-small cell lung cancer (NSCLC) and in whom residual disease at the resection margins was found. METHODS: During a period of 6 years, 596 patients with NSCLC were operated upon with curative intention. Residual disease at the resection margin was divided into microscopic (R1) and macroscopic (R2). RESULTS: Twenty-six patients (4.4%) showed R1 and 12 (2%) R2 residual disease. An extrabronchial (thoracic wall, vessels) R1 situation was found in five patients and a bronchial R1 infiltration in 21 cases. The bronchial resection margin was subject to peribronchial infiltration in most cases (16/21). A total of 17/21 (65%) patients with bronchial infiltration had N2 disease. Thirty day lethality was 3.8% in the R1 group. Fifteen patients had postoperative irradiation. The 5-year survival rate for patients with R1 resection was 14%. The differences in survival between patients with extrabronchial vs. bronchial infiltration and N0/N1 vs. N2 were significant using univariate analysis. Adjuvant radiation did not result (especially in N2 disease) in a survival benefit. Among 12 patients with macroscopic residual disease (R2), 3/12 (25%) died within the first 30 days after the operation, and none of the R2 patients survived the first year after the operation. CONCLUSIONS: Patients with an R1 situation have a survival rate of 14% comparable to curative resected patients (RO) in stage III. Adjuvant radiation had no clear effect on survival. Patients with macroscopic tumor (R2) should receive palliative treatment after the operation depending on their condition.

Increased survivin transcript levels: an independent negative predictor of survival in soft tissue sarcoma patients.

Survivin, a recently identified inhibitor of apoptosis protein (IAP), is expressed in diverse embryonic tissues and in various human cancers. We have investigated the quantitative expression of survivin mRNA by a sensitive TaqMan-based RT-PCR assay in tissue samples from 94 patients with soft tissue sarcomas (STS). Survivin transcript levels were measured and normalized to GAPDH transcripts. By using a multivariate Cox regression analysis, we found an inverse correlation between the level of survivin mRNA (ratio >2 zmol survivin/amol GAPDH) and the rate of overall survival (p = 0.009, RR = 2.7). Survivin transcript variants as detected by qualitative RT-PCR analysis were revealed in 36 of 56 STS patients (64%). Only survivin DeltaEx3 and/or full-length survivin variants but not survivin 2B were identified. Our results suggest that a higher level of survivin mRNA is an independent predictor of survival for STS patients.

Prognostic significance of local recurrence in breast cancer after postmastectomy radiotherapy.

PURPOSE: We have retrospectively analyzed the impact of local recurrence in patients with adjuvant radiation therapy after mastectomy for breast cancer. PATIENTS AND METHODS: From January 1985 through December 1993, 959 patients were irradiated after mastectomy for breast cancer. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3-12.2 years). 368 (38%) were pre- and 591 (62%) postmenopausal. 35% had T3-4 tumors, 62% had axillary lymph node involvement, and 66% received additional systemic hormonal and/or cytotoxic therapy. Postmastectomy radiotherapy was administered in case of positive axillary nodes and in high-risk pN0-patients. The chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field with 50 Gy and the chest wall with an electron field with 44 Gy in 2-Gy fractions. RESULTS: The overall survival was 70.5% after 5 and 59.8% after 10 years. 53 patients (5.5%) developed a locoregional recurrence 2-96 months after treatment (median 26 months). The local control rate was 92.7% after 5 and 86.4% after 10 years. Axillary lymph node involvement was the most important and (in a multivariate analysis the only) risk factor for local recurrence (p = 0.0001). Patients with local control had a significantly better 10-year distant-disease-free survival and overall survival as compared to patients with local recurrence (44.5% vs 15.4%, p = 0.002 and 62.1% vs 34.8%, p = 0.004). Local recurrence increased the risk of death by a factor of 1.7 and in a Cox regression model, axillary lymph node status, T-category and local recurrence were significant prognostic factors for overall survival. In patients with local recurrence, the initial axillary lymph node status was the most important prognostic factor for survival after local recurrence. The 3-year survival after local relapse was 86% for patients with pN0 status vs 27% in with positive axillary nodes (p = 0.025). CONCLUSIONS: Local recurrence after treatment of breast cancer with mastectomy + radiotherapy +/- systemic therapy is associated with a significantly higher risk of distant metastases and death. In this analysis, local recurrence was a strong and, besides lymph node status and T category, an independent risk factor for survival. Minimizing the risk of local recurrence is therefore an essential goal of a curative treatment concept.

Tumor hypoxia and systemic levels of vascular endothelial growth factor (VEGF) in head and neck cancers.

BACKGROUND: Hypoxia is the most important stimulus for the up-regulation of vascular endothelial growth factor (VEGF), one of the key cytokines for angiogenesis. We have investigated the possible relationship between tumor hypoxia and systemic levels of VEGF. PATIENTS AND METHODS: 56 patients with head and neck cancers underwent measurement of tumor volume (pretreatment CT scans), tumor oxygenation (pO2 histography) and serum levels of VEGF. The hemoglobin level ranged from 9.1 to 16 g/dl. The absolute amount of hypoxic tumor (hypoxic tumor volume) was determined as the product of the absolute tumor volume and the relative frequency of hypoxic (< 5 mm Hg) measurements in the pO2 histography. RESULTS: The serum VEGF levels in the 56 head and neck cancer patients ranged from 102 to 1699 pg/ml (median 405 pg/ml, mean 527 +/- 396 pg/ml). Elevated serum-VEGF levels (> 700 pg/ml) were found in 14/56 patients (25%). Serum-levels of VEGF were significantly and independently correlated with hypoxic tumor volume (R2 = 0.63, p < 0.001), but also with total tumor volume, hemoglobin levels, platelet counts and tumor hypoxia. There was no correlation with T and N category, histological grading, and age. CONCLUSIONS: The strong and independent impact of the hypoxic tumor volume on systemic VEGF levels suggests that the absolute amount of hypoxia within a tumor represents the most important stimulus for up-regulation of angiogenesis. Anemia acts as a co-factor via worsening of tumor tissue oxygenation.