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Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia. Results of a phase II trial.

AIM: The disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia. PATIENTS AND METHODS: From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherapy and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4 x 5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions. RESULTS: The acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One patient did not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7 degrees C (range 40.3 to 43.2 degrees C), 41.1 degrees C (range 39.2 to 42.5 degrees C) and 39.9 degrees C (range 37.7 to 41.9 degrees C), respectively. Cumulative minutes of T90 > 40 degrees C (Cum40T90) and cumulative minutes, which were isoeffective to 43 degrees C, were calculated (CEM43T90, CEM43T50, CEM43T20). CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments (p = 0.019). CONCLUSIONS: This treatment modality has proved to be feasible and well tolerable. The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix.

Adult↗

Role of intraoperative neurophysiology in primary surgery for obstetrical brachial plexus palsy (OBPP).

OBJECTIVE: Management of conducting neuroma-in-continuity in primary surgery for obstetrical brachial plexus palsy (OBPP) is still discussed controversially. We present our experience with intraoperative neurophysiological recordings in the management of lesions in continuity in OBPP. METHODS: A series of ten children with lesions in continuity of the upper brachial plexus is presented. Due to recordable compound nerve action potentials (CNAPs) and muscle response to motor stimulation across the neuroma, five children underwent external neurolysis of neuroma only (neurolysis group). Due to lack of recordable CNAPs or muscle response, resection of neuroma and interpositional nerve grafting were performed in another five children (resection and grafting group). Functional recovery after at least 30 months of follow-up was assessed. RESULTS: There was a marked difference in functional recovery between the neurolysis and the resection and grafting group. Especially, recovery of shoulder function was disappointing after external neurolysis of conducting neuroma-in-continuity. At the end of follow-up, results of shoulder and elbow function after resection of neuroma followed by interpositional nerve grafting were better without exception. CONCLUSION: Intraoperative neurophysiological recordings face certain difficulties when used in small children with OBPP. Due to overoptimistic assessment of prognosis after intraoperative CNAP recordings and motor stimulation, the functional results after neurolysis of conducting neuroma-in-continuity are disappointing. Resection of neuroma-in-continuity, conducting or not, offers the best opportunity for maximal functional recovery of the compromised upper limb in OBPP. The role of intraoperative neurophysiological techniques should be confined to the diagnosis of root avulsions.

Adolescent↗

Torsion of the adnexa in children: the value of laparoscopy.

Experience with adnexal torsion in neonates and children is often disappointing. Delay between the first symptoms and operation is important, and adnexal loss the rule. The authors reviewed their experience and the literature to assess the appropriate diagnostic and therapeutic approach. Diagnostic procedures (standard ultrasonography [US], color Doppler US, computed tomography, magnetic resonance imaging, endorectal US, and diagnostic laparoscopy) are discussed; for neonates and premenarcheal girls a specific surgical approach is proposed. Twenty-seven adnexal torsions treated between 1985 and 1995 in the same institution were retrospectively reviewed. Neonatal (7) and premenarcheal cases (20) were separated. The neonatal cases (7) were all operated upon: 4 adnexectomies, 2 oophorectomies, and 1 detorsion with cystectomy were performed. In the premenarcheal group (20) 8 adnexectomies, 6 oophorectomies, 5 detorsions with cystectomy, and 1 salpingectomy were performed. There were only 6 salvaged adnexa in this series. In the neonatal group, US seemed accurate in predicting complicated cases. Prenatal puncture of large (>40 mm) ovarian cysts is possible. The authors advocate a laparoscopic approach in the first days of life of all uncomplicated cysts independent of size in order to increase the percentage salvaged. In ultrasonic complicated cases a delayed operation is proposed in the premenarcheal group, endorectal US will probably become the diagnostic method of choice for complicated ovaries; other methods were disappointing. In order to increase adnexal salvage, the authors recommend a laparoscopic approach in the emergency situation if a clinical examination is positive as well as better medical (pediatricians, gynecologists) and general (girls, parents) information. They suggest controlateral oophoropexy in cases of torsion of a normal adnexum.

Adnexal Diseases↗

The effect of adverse life events on glycaemic control in children with insulin dependent diabetes mellitus.

Forty-five children aged 6 to 14 years with insulin-dependent diabetes mellitus were recruited from a paediatric diabetic clinic. Glycaemic control, child emotional and behavioural problems, and maternal mental state were assessed at recruitment and after 12 months. Life events were measured at 12 months using a standardised semi-structured interview schedule. A between-groups comparison design was used to explore the effect of life events, child emotional and behavioural problems, and maternal mental state on glycaemic control. The children had relatively high rates of emotional and behavioural problems. Overall, the children had a similar number of life events to healthy children in the general population, but proportionally, experienced fewer desirable events. Children who had experienced at least one event in a family setting, or a disappointing event, were more likely to have high glycated haemoglobin levels afterwards than were children who had not experienced such events. Linear regression models showed that only disappointments, family events and glycated haemoglobin at the start of the study made important independent contributions to glycated haemoglobin at 12 months. Child age, emotional and behavioural problems, and maternal mental state, had no effect on glycaemic control.

Anxiety Disorders↗

Banking of the human heart valves and the arteries at the European homograft bank (EHB)--overview of a 14-year activity in this International Association in Brussels.

Processing of the human heart valves and arteries has been carried out at the European Homograft Bank (EHB) in Brussels since 1989 and 1991, respectively. Heart valve donors of 0-65 years were classified in (1) Beating heart donors (BHD), of which recipients of heart transplantation (RHT) and multiorgan donors (MOD) after brain death, and (2) non-beating heart donors (NBHD) with warm ischaemic time (WIT) of less then 6 h. Past history of the donors has been checked for malignant and chronic diseases, as well as biology for transmissible and infectious diseases. Perfect collaboration has been established with the transplant coordinators and transplant teams of the implanting centres. Dissection, decontamination, cryopreservation and storing in fluid nitrogen has been carried out in accordance with the Belgian and European Standards of cardiovascular allografts. During this period, a total of 2.828 hearts, 28 predissected valves and 616 batches of arteries arrived in the EHB. 3.537 valves and 1.137 different arteries were accepted for implantation. The main reasons for tissue rejection were morphology, contamination and cuts during the tissue retrieval or dissection. A huge network of different hospitals in Belgium and elsewhere in Europe and Switzerland were included in this process. Pulmonary allografts were not sent for implantation in the left ventricular outflow tract after 1998, since the early and mid-term results after 76 implantations were disappointing. The number of implanted aortic and pulmonary allografts remains stable from year to year, however the number of the allografts used for Ross operation is still increasing. Since the results of the follow up were disappointing, we still only require the implantation and immediate postoperative results, whereas the follow-up information only for specific study purposes.

Arteries↗

Melanoma: adjuvant therapy and other treatment options.

Melanoma, diagnosed and treated at its earliest stages, can be successfully cured by surgery alone. However, when metastatic beyond the regional nodes, it is almost uniformly deadly. Adjuvant therapy targeted toward the treatment of microscopic residual disease after surgical resection is the subject of intense scientific investigation because this is the stage at which it is possible to have the greatest impact on disease-free and overall survival. However, standard therapies commonly used for other solid tumors have had disappointing results in the treatment of melanoma in the adjuvant setting. These disappointing results have led researchers and clinicians to work to develop innovative treatment strategies for this disease, most of which center on the use of immunotherapy. The realm of cancer immunotherapy is broad and rapidly expanding; it encompasses strategies using immunomodulating agents, such as interferon and interleukin-2, in addition to a wide range of novel vaccination strategies for the induction of active antitumor immune responses. Although clinical trials continue to be conducted to sort out the safety and efficacy of a myriad of new treatment modalities and novel combinations of the old and the new, data indicate that high-dose interferon-alfa-2b should be offered to appropriately selected intermediate- and high-risk patients with melanoma not involved in an experimental protocol.

Antineoplastic Agents↗

The surgical treatment of microtia: a long-term review of 17 patients.

Fourteen children were reviewed approximately 3 1/2 years after surgical reconstruction of the pinna had been completed. Seven had unilateral microtia and seven bilateral microtia, including four caused by thalidomide. Using objective criteria the cosmetic results were disappointing. Treatment entailed protracted hospitalisation, numerous operations and produced adverse emotional and educational sequelae. Nearly all the children covered their ears by growing their hair long. Attempts by the ENT department to improve hearing in the children with bilateral microtia had been disappointing. Three other children who were not treated although they had been referred for surgery were also reviewed. The problems of reconstructive surgery for microtia and the indications for treatment are discussed. It is suggested that reconstruction may be inadvisable for children who have bilateral anotia or associated deformities and who have an unstable family background.

Abnormalities, Multiple↗

Long-term follow-up in patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) for transitional cell carcinoma of urinary bladder: cause for concern.

Twenty-one patients with high-stage transitional cell carcinoma (TCC) of the bladder were treated with a combination of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (M-VAC). There was a minimum follow-up of thirty-six months (range 36-45) in all patients. Patients were divided into three groups: 10 patients with recurrent TCC post radical cystectomy, 6 patients staged as T3/T4 or N1 treated in a neo-adjuvant setting, and 5 patients who received adjuvant M-VAC four weeks post radical cystectomy. The overall initial response rate in patients with measurable disease was 68 percent (11 of 14), complete response rate 31 percent, and partial response rate 37 percent. There was no response in 31 percent. The durability of response in this series was very disappointing with all complete responders having recurrence of disease, with duration of responses ranging from eight to twenty-one months. Of the 5 patients who received M-VAC as adjunctive therapy, only 1 remains disease-free; the other 4 patients experienced disease progression four to seventeen months postoperative, and all have died. There was one drug-associated death due to nadir sepsis, and myelosuppression occurred in 12 patients. While M-VAC seems to be the best protocol currently available, the real durability of response is most disappointing.

Aged↗

Anesthesia for intracranial aneurysm surgery.

Aneurysmal rupture represents the most common cause of subarachnoid hemorrhage. Approximately two-thirds of persons who experience a subarachnoid hemorrhage will die or become disabled. Although advances in neurosurgical techniques, neuroanesthetic management, and neuroradiology have resulted in great progress in reducing the operative risk for patients with intracranial aneurysms, the overall outcome following subarachnoid hemorrhage remains disappointing. This article provides an overview of some current concepts related to the perioperative management of patients with intracranial aneurysms, such as the risk and management of rebleeding and vasospasm, and considerations related to the timing of surgery. The anesthetic management of these patients is reviewed, emphasizing principles relating to the facilitation of surgery--by optimizing operative conditions and minimizing the risks of intraoperative aneurysmal rupture or the aggravation of neurologic deficits--and to the provision of a smooth, stable recovery. Despite the disappointing overall prognosis following subarachnoid hemorrhage, adherence to these principles can optimize the outcome for those patients who reach the operating room.

Anesthesia, General↗

New endocrine therapies for breast cancer.

How do the new endocrine therapies stand up to the aims of modern endocrine therapy outlined in Table 1? We wish to see increased efficacy, decreased toxicity and improved general health in women taking a new agent. None of the new non-steroidal anti-oestrogens have shown unequivocal evidence of improved efficacy in the clinic to mirror their improved profiles over tamoxifen in preclinical studies. We know that toremifene is equivalent to tamoxifen, but we do not have any phase III data from the other four compounds in development. The specific steroidal antioestrogen, ICI 182,780, looks very promising, but is early in its developmental programme. The new aromatase inhibitors are likely to prove equal to tamoxifen or progestagens, but it is disappointing that improved oestrogen suppression has not led, to date, to improved efficacy. No comment can be made about adjuvant or preventative therapy for any of the new agents, although trials are planned for the new aromatase inhibitors in this clinical situation. Currently, the antiprogestins are disappointing and we will need to wait a considerable time for new agents in preclinical testing to reach the clinic. Many of the new agents are associated with decreased toxicity. It is likely that the NSAEs will be equitoxic with tamoxifen. The steroidal antioestrogen looks particularly non-toxic as do the new aromatase inhibitors, and thus we have an advance in terms of reduced toxicity. The effects of the new agents on the uterus, lipids and bone are in the early stages of testing. Raloxifene, ICI 182,780 and the new aromatase inhibitors are expected to have no proliferative effects on the endometrium, but only the new NSAEs are expected to have beneficial cardiovascular and skeletal effects. If the steroidal anti-oestrogens and new aromatase inhibitors become adjuvant therapies of choice, other agents to prevent osteoporosis and cardiovascular events may also have to be administered.

Animals↗

Advances in medical therapy of inflammatory bowel disease.

The past few years have seen increased knowledge and optimism on the use of biological therapy in Crohn's disease. Important lessons have been learned from the expanding clinical experience with infliximab, fuelling belief that current treatment will continue to evolve as therapy is aimed at specific targets within the immune cascade. Several other studies of agents that target tumour necrosis factor-alpha revealed mixed and sometimes disappointing results. However, this was balanced by encouraging results with agents that inhibit lymphocyte trafficking, as well as with other biological agents. Previous disappointing results of biological therapy in ulcerative colitis have been overcome with recent positive clinical trials with infliximab and the anti-CD3 antibody visilizumab. There now appears to be an expanding array of treatment options available to clinicians; however, as the number of potential molecular targets expands, unanswered questions remain regarding optimal treatment strategies, the long-term safety of biologicals and the ability of these novel and often expensive therapies to alter the natural history of the disease.

Adalimumab↗

Assessment of quality of life outcomes in the treatment of advanced colorectal malignancies.

QOL assessment in oncology has made great strides in recent years. There was a difficult time initially, during which QOL tools were "thrown in" to many clinical trials as an afterthought, without a pre-specified scientific question. As expected from such a scattershot approach, the results were underwhelming and disappointing. The disappointing results from this period led many practitioners to question the value added by QOL assessment in oncology clinical trials. This healthy skepticism has led to a renaissance period, in which situation-specific and disease-specific QOL assessments have been developed and have contributed substantial information to the cause of the disease, the effects of treatments, and the experiences of cancer patients. Today, there is a dawning recognition that asking the patient directly about their QOL using the same scientific rigor required of other clinical outcomes can provide valuable data for prognosis, treatment, symptom management, and supportive care. With time and further successful experiences like those cited in this article, QOL assessment may eventually become as routinely collected and integrated into oncology clinical practice as pain and blood pressure assessments are today.

Colorectal Neoplasms↗

Relationships between income, subjective health and caregiver burden in caregivers of people with dementia in group living care: a cross-sectional community-based study.

BACKGROUND: Family caregivers of relatives with dementia report higher level of psychological distress than other caregivers and report their self-related health as poorer than that of comparison groups. AIMS AND OBJECTIVES: The purpose of the study was to examine characteristics of family caregivers and to assess whether income, subjective health, age and relationship were associated with the burden of care they experienced. SETTING: Group living units in southern Sweden. PARTICIPANTS: Fifty caregivers who served as informal caregivers of relatives with dementia in group living care. DESIGN: Interviews regarding economic and social conditions and well-evaluated scales for health and caregiver burden (CB) were used. RESULTS: The majority of the family caregivers were adult children, and twice as many were female than were males. The investigation showed that total burden, strain and disappointment, adjusted for health and age, were related to income. Disappointment showed a relation to subjective health. The adult children showed a significantly higher degree of total burden, irrespective of age, compared to other family caregivers. Low income was associated with a higher degree of burden among adult children. However, elderly participants experienced less of burden than younger ones. CONCLUSION: Our findings indicate that caregivers with low health profile and low income, especially adult children, are associated with higher CB. RELEVANCE TO CLINICAL PRACTICE: People with coexisting risk factors (low income, low perceived health) are the ones who may benefit most from health-oriented interventions.

Adaptation, Psychological↗

Adolescent girls with negative pregnancy tests.

UNLABELLED: STUDY OBJECTIVES AND DESIGN: This descriptive study assessed background characteristics and attitudes about pregnancy held by adolescent girls presenting for pregnancy tests and receiving negative results. An additional aim was to determine types of health care services that would be of perceived benefit to them to reduce their risk of subsequent pregnancy. SETTING: Two health care sites in an urban community included a hospital-based adolescent clinic and a hospital-based women's health care clinic. PARTICIPANTS: Sixty-five adolescent, low-income, single women with negative pregnancy test results in a consecutive sample were included in the study. Participants had a mean age of 16.9 (+/-1.3) years and described themselves as 64.1% African American, 26.6% Latina and 9.4% white, with 81.5% enrolled or recently graduated from high school. MAIN OUTCOME MEASURES: The following variables were included: demographic characteristics, reproductive health history, personal and perceived partner attitude about the negative pregnancy test result, perceived parental influences, and teens' suggestions for health care services to prevent unintended pregnancy. RESULTS: Health history data revealed high risk status for unintended pregnancy and sexually transmitted infections (STI); 28.5% of participants were ambivalent or disappointed with their negative result, 71.4% were pleased and the majority felt that their partners would be more disappointed with the negative result than they were. Health care services that teens felt would be most helpful were one-on-one contraceptive education and discussion sessions with their own health care provider. CONCLUSIONS: Sexually active teen women with negative pregnancy test results are at high risk of subsequent pregnancy and STIs, and present important opportunities for preventive reproductive health care during visits with health care providers.

Adolescent↗

Management of metastatic melanoma 2005.

The management of metastatic melanoma in 2005 remains a major clinical challenge. Multidisciplinary treatment planning and careful attention to sites of metastases, tumor biology, and comorbid conditions are critical to making the best clinical decisions for individual patients. No standard of care exists because no systemic therapies have yet shown efficacy in phase III trials. Single-agent or combination chemotherapy has not impacted over-all survival, and response rates are of short duration. High-dose IL-2 produces durable responses in a small subset (7%) of highly selected patients and has considerable toxicity and quality-of-life trade-offs. Biochemotherapy results in overall higher responses, but its impact on overall survival has been disappointing and its toxicity and expense are considerable. Re-searchers are further investigating biochemotherapy modifications with maintenance biotherapy and CNS consolidation in effort to increase durability of responses and prevent or delay the devastating sequela of CNS metastases. Despite a disappointing past, the advancement of science and a better understanding of critical cellular targets and pathways make the future of melanoma research encouraging. Clinical trials are actively studying novel immune potentiators, cytotoxics, and targeted therapies. Combinations of these new agents will likely be necessary to advance the treatment of the dis-ease. All patients should be encouraged to participate in clinical trials.

Antineoplastic Agents↗

The demise of primary profundaplasty.

Although the importance of the profunda femoris artery in maintenance of lower extremity integrity was recognized in the earliest days of modern vascular surgery, disappointment with the performance of primary profundaplasty has emerged fully only in recent years. During the 10 year period from 1977 to 1987, only 17 patients were subjected to this procedure at Northwestern Memorial Hospital. The nine men and eight women averaged 65.6 years in age and exhibited the usual precursors of arterial insufficiency: a history of smoking in 12 patients (71 percent), clinical coronary artery disease in 8 patients (47 percent), hypertension in 7 patients, diabetes mellitus in 6 patients, hyperlipidemia in 2 patients, and uremia in 1 patient. Four patients exhibited hemodynamic improvement after profundaplasty (ankle-brachial index increase of greater than 0.15). Four required amputation postoperatively, and a fifth exhibited hemodynamic failure 9 months postoperatively and required amputation. Two patients required subsequent femoral-to-peroneal bypass to improve distal arterial perfusion. One patient died after the procedure, for a 5.9 percent mortality rate. Thus, the fact that profundaplasty has proved disappointing in the treatment of severe arterial insufficiency deserves emphasis at this time.

Adult↗

Vesicointestinal fissure revisited.

This complicated anomaly of bladder exstrophy, intestinal fistula, and various degrees of colonic atresia with imperforate anus is readily recognizable. The long-term result of conventional management has been disappointing. Fecal and urinary incontinence have been unavoidable and a source of disappointment to patients and parents. An alternative method of total management is detailed. This variation of management may result in earlier and more complete social acceptability of the child so afflicted. At as young an age as possible, the vesicointestinal connection is detached and the bladder defect as well as the intestinal opening closed. The short colon is freed and transected at its midpoint. The right half of the colon is brought out through a separate wound as a colostomy. The distal half of the divided colon is brought out as mucous fistula on the left. This distal colonic segment is the proposed future colonic loop for urinary diversion to be fashioned in the first year of life. The exstrophied bladder is removed at a later date. Epispadias in the male may be repaired later. A Pediatric Ostomy Club has been organized to include a pediatric stomal therapist and involved nurses and physicians. The group gives the parents advice and moral support. We believe that this approach will permit the child to go to school and carry on relatively normal activity and to be socially acceptable. An overview of our total experience in the management of 25 patients with vesicointestinal fistula details the result in 9 surviving patients.

Anus, Imperforate↗

[Orthopedic treatment of spinal deformities in infancy and early childhood].

Surgical treatment of spinal deformities in infancy and early childhood (before age 6) is often very useful if the lesion is localized and curable by one unique surgery, such as hemivertebra resection and fusion. On the contrary, if the lesion, whether idiopathic or paralytic, is extended to a large part of the spine, early surgical treatment in infancy gives very disappointing results and often worsens the status of the child, especially respiratory function if the lesion is mainly thoracic. The goal of this paper is to explain in detail indications and management of non-surgical treatment of such lesions. These are variable according to localization, etiology, and associated anomalies, and are mainly based on proper casting (often repeated), bracing (often intermittent between casting) and proper respiratory equipment. From time to time, a surgical treatment is locally indicated, but most of the time results are disappointing and the best is to repeat non-surgical treatment until proper definitive arthrodesis can be performed. This approach is not very rewarding for the child and family, but is clearly better than sudden extensive surgery in early childhood with very severe and disastrous results in adulthood. It is our hope that the recommendations and thoughts presented in this paper will help readers to manage young children using the most efficient, non-aggressive, but long-lasting therapy.

Age Factors↗