Serious Failure Modes After EVAR Are Device Specific.

OBJECTIVES: Type I and III endoleaks following endovascular aneurysm repair (EVAR) can lead to catastrophic events that require major re-interventions. We reviewed our experience with aortic endograft re-interventions for type I and III endoleaks and other serious failures among different devices. METHODS: We retrospectively reviewed patients with a prior EVAR who underwent open conversion (OC) or major endovascular intervention (MEI) (re-lining, cuff/limb extension, parallel graft) for type I/III endoleaks at our institution from 2002 to 2019. Baseline characteristics, procedural details, re-interventions, and outcomes were collected. RESULTS: A total of 229 patients (194 men) underwent re-interventions for type I and III endoleaks after EVAR (90 OC, 139 MEI) for devices implanted between 1997 and 2019. Average age at re-intervention was 78±8.5 years. A total of 135 (59%) were implanted at our institution, whereas 93 (41%) were referred. Median time to re-intervention was 4 years with 25% to 75% interquartile range (IQR) of 2.2-6.6 years. There was no significant difference in baseline demographics or type of re-interventions (OC/MEI) between device types. 42/229 (18%) presented with ruptured aneurysms, 20/229 (9%) were symptomatic, whereas the rest presented with asymptomatic radiographic findings. Type 1A endoleak was present in 146/229 (63.8%-72 with proximal migration), type IB in 46/229 (20.1%), type IIIA in 37/229 (16.6%), type IIIB in 15/229 (6.5%), and persistent aneurysm sac growth with no radiographic evidence of an endoleak in 6/229 (2.6%). Devices included most commercial products: AFX, Excluder, AneuRx, Ancure, Endurant, and Zenith. A smaller number of investigational devices accounted for the rest. Type 1A endoleak was the most common indication for re-intervention among all devices except for AFX and ancure devices, proximal migration was a frequent presentation with AneuRx. AFX devices more frequently presented with a type III and ancure devices more frequently presented with a type IB endoleak. CONCLUSIONS: Serious failure modes after EVAR differ between endografts and occur throughout the follow-up period. This is important to guide targeted interrogation of surveillance studies and follow-up schedules, even for discontinued devices, as well as comparisons between various series and estimation of EVAR failure rates. CLINICAL IMPACT: Surveillance after EVAR is critical for long term success of the repair, understanding of the differential modes of failure of every graft available is important in the longitudinal evaluation of these endografts. Equally important is the understanding of the modes of failure of legacy endografts that are no longer on the market but still being followed, in order to be able to tailor a surveillance regiemn and the evntual repair if needed.

Unique expatriate factors associated with job dissatisfaction among nurses.

AIM: To assess whether expatriate-specific factors were associated with nurses' overall job dissatisfaction after controlling for known factors. BACKGROUND: Current evidence about job dissatisfaction among nurses in Saudi Arabia is not specific to expatriate nurses. Specific aspects such as job insecurity, fear of litigation, and language barriers have not been assessed in the context of job dissatisfaction. INTRODUCTION: The majority of nurses in the Arab Gulf countries are expatriate. The motive for employment here is purely financial because there is no path to permanent residency. METHODS: This was a cross-sectional electronic survey of 977 expatriate nurses in Al-Qassim, Saudi Arabia. The survey included questions on demography, job dissatisfaction (overall and related to salary, workload, and teamwork), job characteristics, job duration as an expatriate, communication issues with patients and doctors, fear of litigation, and job insecurity. We used a hierarchical logistic regression to evaluate whether unique factors were associated with overall job dissatisfaction either as a group, or individually. RESULTS: The mean age of the nurses was 32 years, and 19% reported overall job dissatisfaction. The unique expatriate factors as a group contributed significantly to the model. Job insecurity, patient communication problems, and shorter job duration were significantly associated with higher overall job dissatisfaction. CONCLUSIONS: Job insecurity, job duration, and patient communication were significant correlates of overall job dissatisfaction among expatriate nurses. IMPLICATIONS FOR NURSING POLICY: A longer job contract and organizational initiatives to help new expatriate nurses acculturate will likely decrease feelings of job insecurity and increase job satisfaction.

Adjuvant and Neoadjuvant Radiation Therapy for Locally Advanced Bladder Cancer.

Local-regional failure for patients with ≥pT3 urothelial carcinoma after radical cystectomy is a significant clinical challenge. Prospective randomised trials have failed to show that chemotherapy reduces the risk of local-regional recurrences. Salvage treatment for local failures is difficult and often unsuccessful. There is promising evidence, particularly from a recent Egyptian National Cancer Institute trial, that radiation therapy plus chemotherapy can significantly reduce local recurrences compared with chemotherapy alone, and that this improvement in local-regional control may translate to meaningful improvements in disease-free and overall survival with acceptable toxicity. In light of the high rates of local failure following cystectomy for locally advanced disease and the progress that has been made in identifying patients at high risk of failure and the patterns of failure in the pelvis, the National Comprehensive Cancer Network guidelines were revised to include postoperative radiotherapy as an option to consider for patients with ≥pT3 disease. Here we review the problem of local-regional failure after cystectomy, identify patients who would probably benefit from adjuvant radiotherapy, review the patterns of pelvic failure after cystectomy, discuss technical details of radiation treatment and review the modern literature on this topic. Adjuvant radiotherapy should be considered as a treatment option for patients with locally advanced disease, especially those with positive margins or squamous cell carcinoma.

Unilateral retinoblastoma; natural history and an age-based protocol in 248 patients.

OBJECTIVES: We aimed to study the clinical state and prognosis of patients with unilateral retinoblastoma who were being treated at a paediatric comprehensive cancer centre in a limited-resource country, to assess the different phases of treatment and the success of different, more complex real-life models. SUBJECTS: In this retrospective study, we created a snapshot of our retinoblastoma database for the period between 2007 and 2015. Patients whose data were included in the study were followed up until 2016. Out of a total of 744 screened patients, we included data of 248 patients who had been diagnosed with unilateral retinoblastoma. RESULTS: As classified as per the International Retinoblastoma Classification, 1 patient presented with group A, 21 with group B, 39 with group C, 104 with group D and 83 with group E retinoblastoma. Chemotherapy was the initial line of treatment in 115 patients and enucleation in 133 others. Later, 141 patients (56.9%) required further management. Patients had a mean ocular survival time of 20.8 months. Nine patients developed extraocular disease at a later stage of management: five after upfront enucleation and four after neoadjuvant chemotherapy. Mean overall survival time stood at 90.2 months. Four and three deaths were recorded in groups D and E, respectively. A single patient died in the initial chemotherapy arm, while six passed away in the initial enucleation arm. CONCLUSION: Our study highlights the importance of initial chemotherapy and close follow-up after enucleation of classes D and E affected eyes even in absence of germline mutations.

The Practice of Paediatric Radiation Oncology in Low- and Middle-income Countries: Outcomes of an International Atomic Energy Agency Study.

AIMS: Childhood cancer survival is suboptimal in most low- and middle-income countries (LMICs). Radiotherapy plays a significant role in the standard care of many patients. To assess the current status of paediatric radiotherapy, the International Atomic Energy Agency (IAEA) undertook a global survey and a review of practice in eight leading treatment centres in middle-income countries (MICs) under Coordinated Research Project E3.30.31; 'Paediatric radiation oncology practice in low and middle income countries: a patterns-of-care study by the International Atomic Energy Agency.' MATERIALS AND METHODS: A survey of paediatric radiotherapy practices was distributed to 189 centres worldwide. Eight leading radiotherapy centres in MICs treating a significant number of children were selected and developed a database of individual patients treated in their centres comprising 46 variables related to radiotherapy technique. RESULTS: Data were received from 134 radiotherapy centres in 42 countries. The percentage of children treated with curative intent fell sequentially from high-income countries (HICs; 82%) to low-income countries (53%). Increasing deficiencies were identified in diagnostic imaging, radiation staff numbers, radiotherapy technology and supportive care. More than 92.3% of centres in HICs practice multidisciplinary tumour board decision making, whereas only 65.5% of centres in LMICs use this process. Clinical guidelines were used in most centres. Practice in the eight specialist centres in MICs approximated more closely to that in HICs, but only 52% of patients were treated according to national/international protocols whereas institution-based protocols were used in 41%. CONCLUSIONS: Quality levels in paediatric radiotherapy differ among countries but also between centres within countries. In many LMICs, resources are scarce, coordination with paediatric oncology is poor or non-existent and access to supportive care is limited. Multidisciplinary treatment planning enhances care and development may represent an area where external partners can help. Commitment to the use of protocols is evident, but current international guidelines may lack relevance; the development of resources that reflect the capacity and needs of LMICs is required. In some LMICs, there are already leading centres experienced in paediatric radiotherapy where patient care approximates to that in HICs. These centres have the potential to drive improvements in service, training, mentorship and research in their regions and ultimately to improve the care and outcomes for paediatric cancer patients.

α-Lipoic acid and amlodipine/perindopril combination potentiate the therapeutic effect of mesenchymal stem cells on isoproterenol induced cardiac injury in rats.

Cardiac injury is a dangerous disease and become a greater issue in the forthcoming decades. The ultimate goal is to prevent the progression of heart failure and apoptotic processes. Cardiac tissue may regenerate itself but to certain extent depending on the number of resident stem cells that is limited. Thus, research had been focused on bone marrow derived stem cells (BM-MSCs) as a promising therapy in different types of tissues, including the heart. This study is designed not only to assess the therapeutic effect of BM-MSCs but also to improve their therapeutic effect in combination with antioxidant α-lipoic acid (ALA) and antihypertensive therapeutic drug form (AP) against isoproterenol-induced cardiac injury and compared with that of BM-MSCs alone. Cardiac injury was induced in 70 male rats by Isoproterenol (ISO was injected s.c. for four consecutive days). Experimental animals were divided into six ISO-treated groups beside a control non treated one. The six ISO-treated groups were divided into: ISO group, ISO+BM-MSCs group, ISO+ALA group, ISO+AP group, ISO+ALA+AP group and ISO+ALA+AP+BM-MSCs group, the last five groups were treated with the examined materials after one week of ISO injection. Isoproterenol significantly increased serum CK-MB, LDH activities, Troponin1 and TNF-α. Oxidative stress is evidenced by the increased MDA, NO and Caspase-3 activity associated with significant reduction of GSH content and SOD activity in cardiac tissue. Furthermore, mRNA expression of NFκB and iNOS were significantly up regulated and eNOS mRNA expression was down regulated. Administration of BM-MSCs, ALA and AP alone significantly mitigated the induced cardiac injury. Concomitant administration of ALA and AP after BM-MSCs induced a more pronounced improving effect on cardiac functions. In conclusion, the concomitant administration of ALA and AP after BM-MSCs infusion increases the cellular antioxidant levels of cardiac tissue that improves the repairing function of BM-MSCs.

Gelfoam haemostatic agent with or without autologous bone marrow-derived stem cells for the regeneration of critical-size mandibular defects in the rabbit.

This study evaluated the effect of Gelfoam sponge with and without autologous bone marrow-derived stem cells (BMSCs) on bone regeneration in critical-size mandibular defects. The study involved 56 New Zealand rabbits assigned to four groups (14 in each). The osseous defects in group I were irrigated with normal saline, those in group II were grafted with autogenous tibial bone, and those in group III were filled with Gelfoam sponge. Group IV defects were treated as for group III, but the interface between the Gelfoam sponge and bone surface was injected with BMSCs. At the end of 4weeks, seven rabbits in each group were euthanized; the remaining animals were euthanized at the end of the experiment, at 8 weeks postoperative. The percentage area of newly formed bone was significantly higher in group IV at week 4 (0.030±0.01%) and week 8 (0.060±0.03%) than in group I (0.01±0.00% and 0.02±0.00%, respectively) and group III (0.08±0.01% and 0.015±0.02%, respectively), but was lower than that in group II (0.038±0.02% and 0.082±0.01%, respectively). Thus, the combination of Gelfoam and autologous BMSCs promoted the regeneration of mandibular critical-size defects better than the use of Gelfoam alone. However, the amount of newly generated bone was lower than in defects grafted with autogenous bone.

A multidisciplinary approach to improving the care and outcomes of patients with retinoblastoma at a pediatric cancer hospital in Egypt.

BACKGROUND: Retinoblastoma poses a substantial burden in developing countries. We conducted this study to assess the effect of implementing a multidisciplinary approach and standardized protocols for treating pediatric patients with retinoblastoma at the Children's Cancer Hospital Egypt (CCHE). MATERIALS AND METHODS: In January 2011, the CCHE implemented standardized protocols for the diagnosis, treatment, and reporting of retinoblastoma cases. The hospital also introduced a new retinoblastoma management algorithm and data analysis system. In this study, we compared the pathologic features, tumor invasiveness, reporting, and survival of 276 pediatric patients who underwent enucleations of 290 eyes before or after the implementation of the retinoblastoma protocols. RESULTS: Time to enucleation (indicating time needed for decision taking) decreased significantly within the neoadjuvant chemotherapy group for intraocular disease after January 2011 (68.7 ± 48 weeks vs. 47.3 ± 28.3 weeks; p < 0.05). Mean optic nerve stump length increased from 5.6 mm in the earlier period to 7.2 mm in the later period (p = 0.004). The overall quality of pathology reporting also improved during the later period. The probability of 3-year survival was significantly higher for patients during the later period (94.2% vs. 79.2%; p = 0.018). CONCLUSIONS: The implementation of standardized protocols and a multidisciplinary approach improved reporting; discrepancies in disease classification and the amount of missing data were reduced; and quality measures and prognostic capabilities of the team were substantially improved. Such established data-driven practice supports faster decision making to enucleate diseased eyes and save patients' lives through providing measurable indicators.

Effect of agmatine on experimental vascular endothelial dysfunction.

This study was designed to investigate the effect of agmatine sulfate (AG, CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in rabbits. NIC was administered to produce VED in rabbits with or without AG for 6 weeks. Serum lipid profile, serum thiobarbituric acid reactive substances, reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate, serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor κB (NF-κB) levels were analyzed.Treatment with AG markedly improves lipid profile and prevented NIC-induced VED and oxidative stress. The mechanism of AG in improving NIC-induced VED may be due to the significant reduction in serum VCAM-1 levels and aortic NF-κB. Thus, it may be concluded that AG reduces the oxidative stress, nitric oxide production, VCAM-1 levels, and aortic NF-κB expression, thereby consequently improving the integrity of vascular endothelium.

A phase II study of gemcitabine plus cisplatin chemotherapy in advanced bilharzial bladder carcinoma.

Bilharzial bladder cancer represents a distinct clinicopathological entity. To investigate whether gemcitabine-cisplatin is also active against bladder cancer of bilharzial origin, we performed a phase II study of previously untreated patients with stage III/IV disease. Standard eligibility criteria were used. Patients received gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 and cisplatin (70 mg/m(2)) on day 2 of every 28-day cycle. The 32 males and 5 females had a median age of 59 years (range: 29-81 years). Of 33 evaluable patients, 8 (24%) achieved complete responses, and 10 (30%) partial responses, for an overall response rate of 55%. 3 patients had minor responses. Responses were observed at all disease sites including lung and liver lesions. Myelosuppression was significant but manageable. Non-haematological toxicity was limited mainly to nausea and vomiting and raised liver enzymes. Thus, these data suggest that gemcitabine plus cisplatin induces high response rates in patients with bilharzial bladder cancer with a moderate toxicity profile.

Dysgerminoma of the ovary: good prognosis even in advanced stages.

Dysgerminoma is a rare germ cell tumor of the ovary. It constitutes about 0.5% of all ovarian malignancies. During a 12-year period (1978-1989), 22 patients were treated at the National Cancer Institute, Cairo, Egypt. According to the FIGO classification system, 4 patients were allocated to Stage I, 2 were Stage II, 13 were Stage III, and 3 were Stage IV. The 5-year actuarial survival rate for all patients was 76%. Conservative treatment in addition to retrieval therapy upon recurrence could achieve 100% survival rate in Stage I patients. Surgery followed by irradiation resulted in a 66% 5-year actuarial survival rate in Stage III and 67% in Stage IV. Retroperitoneal lymph nodes seemed to have a better survival than peritoneal tumor extension. The adoption of an elective irradiation policy to the mediastinum and supraclavicular area seemed to have a good influence on prognosis. However, the extent of surgery performed could not be shown to affect survival.

Schedule-dependent therapeutic gain from the combination of fractionated irradiation plus c-DDP and 5-FU or plus c-DDP and cyclophosphamide in C3H/Km mouse model systems.

Cytotoxic drugs were administered either in single or fractionated doses before, during, or after a standard course of 5 daily X ray exposures. SCCVII and RIF-1 tumors were grown from cells implanted in the gastrocnemius muscles of syngeneic C3H/Km mice, and treatments were evaluated by regrowth delay (GD). Non-tumor-bearing mice were irradiated locally to the upper abdomen for analysis of intestinal crypt cell survival, an acute normal tissue effect; other non-tumor-bearing mice were irradiated locally to the thorax for analysis of early (pneumonitis) and late (fibrosis) effects on the lungs, as reflected in changes in breathing rates. In a series of experiments to test the combination of i.p. 5-FU, cis-DDP, and X ray, dose effect factors (DEF's) were compared so that therapeutic gain factors (TGF's) could be calculated from the ratio, DEF (tumor)/DEF (normal tissue). The highest TGF, 6.7 (tumor/duodenum), was obtained for the schedule in which 100 mg/kg 5-FU was given 24 hr before the simultaneous administration of 1.6 mg/kg cis-DDP and X ray for 5 consecutive days. The following summary refers only to tumor growth delay data. In confirmation of previous extensive experiments, the combination of cis-DDP + X ray showed supra-additivity, whether the drug was given in a single dose (abbreviated P) or simultaneously with X ray (abbreviated px), that is, P x x x x x or px px px px px. For CY + X ray, the greatest supra-additivity was obtained for either C x x x x x or x x x x x C. 5-FU alone did not act supra-additively with fractionated irradiation, but the addition of 5-FU to cis-DDP + X ray was supra-additive for certain schedules, maximally for F px px px px px. CY combined to give greater than additivity with either cis-DDP or X ray alone, and the combination of CY + cis-DDP + X ray appeared to be supra-additive for five different schedules, maximally for C x x x x x P. Normal tissue effects are being evaluated for these same schedules so that TGF's might soon be obtained.

Interleukin 1 increases thymidine labeling index of normal tissues of mice but not the tumor.

PURPOSE: This study was conducted to investigate the action of human recombinant interleukin 1 as a radioprotector for different mouse normal cells other than bone marrow cells. METHODS AND MATERIALS: Semi-continuous injections of tritiated thymidine were administered every 6 h, over 24 h to determine thymidine labeling index. Mice were injected with recombinant human interleukin 1 24 h prior to tritiated thymidine and were compared to control animals that did not receive interleukin 1. Mice were killed 1 h after the last thymidine injection. The 24 h thymidine labeling index for normal tissues and RIF-1 tumor was determined. Labeling indices were also determined 1-14 days after a series of fractionated irradiations with or without pretreatment with a single dose of interleukin 1 administered 24 h prior to the first radiation. RESULTS: The thymidine labeling index of normal tissues was higher following the injection of recombinant human interleukin 1 24 h before radiolabeling. This was found in all normal tissues tested, including the lip and tongue mucosal basal cell layers, crypt cells of the duodenum, alveolar cells of the lung, hepatocytes, and basal skin cells. The thymidine labeling index of RIF-1 fibrosarcoma was not affected by interleukin 1 injection. A single interleukin 1 injection 24 h before the first radiation fraction also increased the thymidine labeling indices of normal tissues after localized fractionated irradiation. The thymidine labeling index of RIF-1 tumor was not increased by interleukin 1 administration except after relatively high radiation doses (20 Gy in five fractions). The ability of interleukin 1 to enhance the thymidine labeling index declined after the first day following the completion of fractionated irradiation. CONCLUSION: Recombinant human interleukin 1 increased the 24 h thymidine labeling index in normal tissues in mice, but not in RIF-1 tumor. Fractionated irradiation could maintain the effect of a single dose of interleukin 1, administered 24 h prior to the first fraction, up to 24 h after the end of radiation.

Interleukin-1 modulatory effect on the action of chemotherapeutic drugs and localized irradiation of the lip, duodenum, and tumor.

PURPOSE: This study was conducted to examine the radioprotective and radiochemoprotective capabilities of interleukin 1 beta (IL-1) on two acute-reacting normal tissues of the C3H mouse, the mucosa of the lip and the duodenum. Also assessed was the modulating effect of IL-1 on tumor growth in the same strain of mice. METHODS AND MATERIALS: IL-1 was administered to C3H/Km mice in combination with fractionated irradiation, or with cyclophosphamide, cisplatin, or 5-fluorouracil (5FU) followed by irradiation. Normal tissue damage was evaluated in the mouse lip, using a subjective scoring system for tissue reaction, and in the duodenum, using the crypt cell survival assay. RIF-1 fibrosarcoma tumor response was assayed with the regrowth delay method. RESULTS: IL-1 protected against the acute reaction produced by fractionated irradiation in the lip mucosa, shifting the dose-response curve by 3.8 Gy. IL-1 was protective when injected intraperitoneally 24 hr before CY or c-DDP, which were given immediately before the first of five daily radiation dose fractions. The dose-response curves for cyclophosphamide and cisplatin were shifted 4.0 Gy and 1.6 Gy, respectively. IL-1 did not protect against 5FU toxicity when treatments were administered in that same sequence; however, when 5FU was given 4 or 8 hr before IL-1 and the first radiation dose fraction followed 20 or 16 hr later, there was significant protection and the curves were separated by 1.5 Gy or 3.5 Gy. IL-1 also protected duodenal crypt cells against the cytocidal effect of fractionated irradiation, with a dose difference of 1.5 Gy and an improvement of crypt survival of 11.7%. It was even more protective for these cells against the enhanced drug toxicity when cyclophosphamide or 5FU were administered immediately before the first of five daily radiation doses, with the dose differences of 4.4 and 5.3 Gy, respectively, and improvements of crypt survival of 33.8 and 29.9%, respectively. There was no modification by IL-1 of the effect of irradiation alone on the RIF-1 tumor. CONCLUSION: This study demonstrates the potential for use of IL-1 as an auxiliary in combinations with chemotherapeutic agents and radiation. It also indicates that for some drugs, such as 5FU, IL-1 effects may be sequence dependent.

Prognostic implication of apoptosis and angiogenesis in cervical uteri cancer.

PURPOSE: A retrospective study was performed to investigate the relationship between spontaneous apoptosis and angiogenesis uterine cervix squamous cell carcinoma patients. The prognostic value of each (and both) of these biologic parameters was also tested. METHODS AND MATERIALS: The pathologic materials of 40 cervical uteri squamous cell carcinoma patients were examined and immunohistochemically stained to determine the tumor angiogenesis (tumor microvascular score), using factor VIII-related antigen, and their tumor apoptotic index (AI), using the TdT-mediated dUTP nick end-labeling (TUNEL) method. Three patients were Stage I, 18 were Stage II, 15 were Stage III, and 4 were Stage IV (FIGO classification). All patients were treated with radical radiotherapy and all had follow-up for more than 2 years. RESULTS: The mean AI was 15.1 +/- 12.8, with a median of 8.3. The mean tumor microvascular score was 39.7 +/- 14.4, with a median of 3 8. The patients' age and tumor grade did not seem to significantly affect the prognosis. On the other hand, AI and angiogenesis (tumor microvascular score) were of high prognostic significance. The 3-year disease-free survival (DFS) rate for the patients having AI above the median was 78% (confidence interval [CI] 69-87%), compared to 32% (CI 22-42%) for those having AI below the median. The DFS was 18% (CI 9-27%) for patients having an angiogenesis score above the median, while it was 86% (CI 78-94%) for those patients having a score below the median. CONCLUSION: Determination of both tumor microvascular score and AI can identify patients with the best prognosis of 100% DFS (with low angiogenesis score and high AI). Women with a high score and low AI had the worst prognosis (DFS = 3%, CI 1-5%). Moreover, high AI can compensate partially for the aggressive behavior of tumors showing a high rate of angiogenesis.

Postoperative radiotherapy of carcinoma in bilharzial bladder: improved disease free survival through improving local control.

Two hundred thirty-six patients with T3 bladder cancer who survived radical surgery and proved to have P3a, P3b, or P4a tumors were randomized in two phases into three groups: (a) no further treatment (83 patients); (b) postoperative radiotherapy multiple daily fractionation (MDF), using 3 daily fractions of 1.25 Gy each, with 3 hr between fractions, up to a total dose of 37.5 Gy in 12 days (75 patients); and (c) postoperative radiotherapy conventional fractionation (CF), for a total dose of 50 Gy/5 weeks (78 patients). The tolerance of the patients to postoperative radiotherapy was quite acceptable, with equal acute reactions in MDF and CF groups. The 5-year disease-free survival (DFS) rates amounted to 49 and 44% in MDF and CF postoperative radiotherapy groups, respectively, compared to 25% in the cystectomy-alone group. The 5-year local control rates were 87% and 93% for those treated with multiple daily fractionation and conventional fractionation while it was 50% in the surgery-alone group. The therapeutic benefit of postoperative irradiation was consistent for all tumor types, histological grades, and pathological stages for both the disease-free survival and local control. Patients with nodal metastases demonstrated lower recurrence rates in the postoperative radiotherapy groups, but this was not associated with improved disease-free survival. Multivariate analysis using the Cox Model confirmed these results. The independent prognostic factors affecting both disease-free survival and local control were the addition of postoperative radiotherapy, the nodal status, the pathological stage, and the tumor grade. Late complications of radiotherapy in the skin, small intestine, rectum, and the anastomotic site of the urinary division were lower with MDF than with conventional fractionation.

Pharmacokinetics of etanidazole (SR-2508) in bladder and cervical cancer: evidence of diffusion from urine.

Following an IV infusion of 2.0 g/m2 of Etanidazole, the mean tumor concentration 40 min after injection was 126 micrograms/g in bladder cancer and 65 micrograms/g in cervical cancer. The tumor/plasma concentration ratio was 1.88 in bladder and 0.85 in cervical cancer. This high tumor concentration in bladder cancer could be accounted for by diffusion from a highly concentrated urine. This renders bladder cancer a suitable clinical model for testing this sensitizer.

Postoperative radiotherapy of carcinoma in bilharzial bladder using a three-fractions per day regimen.

Patients with T3 bladder cancer who survived surgery and proved to have P3a, P3b or P4a tumors were randomized to either no further treatment (61 patients) or postoperative total pelvic irradiation (55 patients). A three-fraction per day regime was adopted with a dose per fraction of 125 cGy and an interval of 3 h between fractions. The total dose amounted to 3750 cGy divided into 30 fractions over 12 days. Patients of the postoperative radiotherapy group were re-randomized to radiotherapy alone or radiotherapy plus misonidazole (MISO) in a daily dose of 1 g/m2 given orally 2 h before the first daily fraction. The 2-year disease-free survival rate in the cystectomy alone group was 33 +/- 6% compared to 65 +/- 6% in the postoperative radiotherapy group. The therapeutic benefit applied to the two cell types, all histological grades and stages and to patients with or without nodal metastases. The benefit of postoperative irradiation was also verified by the Cox's multivariant analysis which adjusts for the relative representation of the important prognostic factors particularly pathological stage and nodal involvement. MISO did not seem to add to the therapeutic gain. No late complications were encountered in the wall of the rectum, small bowel or uretero-intestinal anastomotic sites. This is suggested to be due to the small dose per fraction used. However, early small bowel reactions were dose-limiting.

Accelerated versus conventional fractionation in the postoperative irradiation of locally advanced head and neck cancer: influence of tumour proliferation.

Fifty-six patients with locally advanced head and neck squamous cell carcinoma were subjected to adjuvant radiotherapy after radical surgery with randomisation to either conventional fractionation (CF), comprising 50 Gy/25 F/5 weeks, or to accelerated hyperfractionation (AHF) to a dose of 42 Gy/30 F/11 days (3 F/day), a dose/F of 1.4 Gy and an interfraction interval of 4 h. The in vitro [3H]thymidine labelling index (TLI) was determined as an indicator of tumour proliferation. Early mucosal reactions were somewhat more severe after AHF than after CF and the peak was attained earlier. The actuarial 3-year complication rate was significantly lower in the AHF (64%) than in the CF group (87%). This is probably related to a smaller fraction size and a lower total dose. The overall 3-year disease-free survival amounted to 46 +/- 7%. Sex, the anatomical site, the nodal status, the performance status and TLI have been shown to be significant prognostic factors, but only the latter two proved to be independent covariates. Overall, the type of fractionation did not seem to influence survival. However, AHF seemed to offer higher survival probabilities in fast growing tumours and this attained a significant level for tumours with TLI > 10.4% (Tpot < 4.5 days). However, CF and AHF were associated with similar survival rates in slowly growing tumours. The relative effectiveness of the CF and AHF schedules is predictable on the basis of the linear-quadratic system. In the case of tumour response, a time factor has to be included assuming that accelerated repopulation of microscopic residues occurs from the outset.(ABSTRACT TRUNCATED AT 250 WORDS)

A new surgical strategy for breast conservation in locally advanced breast cancer that achieves a good locoregional control rate: preliminary report.

The scope of breast conserving surgery has recently expanded to include locally advanced breast cancer (LABC) patients who are downstaged following neoadjuvant chemotherapy (NACT). However, the efficacy of this approach in achieving adequate locoregional control of disease is in doubt. Some reports have attributed the failure to the association of NACT-induced tumour downstaging which can leave multifocal in situ and invasive lesions around the main tumour mass. In the present study, in order to eradicate all possible tumour satellites, a very wide local excision that included the whole original tumour-bearing area was performed regardless of the expected wide defect. This defect was then immediately reconstructed by an ipsilateral pedicled latissimus dorsi myocutaneous (LDM) flap. The study included 26 patients with LABC without evidence of primary tumour-multicentricity. Tumours were downstaged following NACT. The early cosmetic outcome was good in the majority of cases. Early complications were minimal. Twenty-two patients had a mean follow up period of 30.2 (range 7-50) months. In those evaluable cases, locoregional control of the disease was excellent (100%) but distant metastases occurred in seven cases (31.8%).