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A well-maintained modern machine can typically be expected to deliver the intended dose with an accuracy of 2% symptoms kidney failure cheap zyprexa 2.5 mg line, and have a total mechanical accuracy of about 1 mm. Radiation protection While the irradiation of the patient is intentional, specific, and intended to be beneficial, any dose to others is undesirable and should be maintained as low as reasonably achievable. Limits on the permitted dose to the public and staff in a radiotherapy facility are specified nationally; however, most countries apply limits based on recommendations of the International Commission on Radiation Protection (44). Grays, the unit of absorbed dose, and sieverts are numerically equivalent for whole-body exposure to X-rays (where the weighting factors are both equal to 1. In this formalism, occupational exposure is limited to 20 mSv/year (using a 5-year average) and 1 mSv/year for the public. These limits are achieved through well-educated qualified staff and stringent facility design. The walls, door, ceiling, and floors of the room containing a linac are constructed considering the materials to be used, occupancy of adjacent spaces by staff or the public, and machine features such as maximum energy and anticipated workload. The shielding required can be substantial, and a common treatment room design that satisfies International Commission on Radiation Protection requirements uses walls constructed of 2. Image guidance the correct placement of the brachytherapy applicator relative to the targeted disease area is critical to the success of the treatment. A poorly placed applicator is problematic because not only will the tumour receive less dose than required, but the normal healthy tissues will receive an unnecessary dose. Imaging is an important component of the brachytherapy applicator placement procedure, which verifies correct placement of the device. Originally, 2D planar X-ray imaging was used to define the applicator placement in relation to the target area, which could be defined using radio-opaque clips inserted into the cervix; and contrast used to define the bladder and rectal dose points. However, recent evidence (41) has shown that magnetic resonance-based imaging is the current standard for the definition of tumour volumes, including areas of suspected clinical extension. Also, the modern method of reporting doses to both the target and normal tissues is to report the integrated dose to a volume of tissue, as opposed to point doses. Cervix cancer Introduction In many developing countries, cancer of the cervix is the second most common cancer and cause of cancer deaths in women, in part due to limited access to cervical cancer screening and prevention programmes. Physics/biology Radiation dosimetry Modern linacs deliver a specified amount of X-ray energy with high accuracy and precision. The clinical target volume includes the primary cervical tumour, upper vagina, parametria, and pelvic lymph nodes including the external and internal iliac and presacral lymph nodes. In patients with involved pelvic nodes, the clinical target volume may be expanded to include common iliac nodes, and those with common iliac involvement may require treatment of the next echelon para-aortic lymph nodes. An important component includes shields to reduce the bowel, bladder, and femoral head dose. Role for concurrent chemotherapy and radiation Based on a series of five randomized trials reported in 1999, which demonstrated improved survival and acceptable toxicity, concurrent weekly cisplatin in five courses (at a dose of 40 mg/m2) and radiotherapy has become the standard of care in cervix cancer (45). Role for radiotherapy by stage Decisions regarding optimal treatment for early-stage disease are critically dependent on a multidisciplinary discussion between gynaecological, radiation, and medical oncologists, with input from gynaecological imaging and pathology. Definitive chemoradiotherapy is curative in women with cervix cancer, in part due to the combination of external bean radiation with intracavitary brachytherapy, delivering a high local dose to the tumour while sparing normal tissues (46); and in part due to the increased radiosensitivity and better outcomes associated with human papillomavirus-related tumours, including other human papillomavirus-related sites such as oropharynx (47, 48). Typical treatment includes external beam pelvic radiotherapy (45 Gy in 25 daily fractions over 5 weeks) plus concurrent weekly cisplatin chemotherapy, followed by intracavitary brachytherapy. External beam pelvic radiotherapy (45­50 Gy) plus concurrent cisplatin chemotherapy, followed by intracavitary brachytherapy results in progression-free and overall survival in 65­70%, depending on stage (52). Locally advanced/metastatic cervix cancer Patients with locally advanced or metastatic disease are assessed for suitable palliative treatment, which may include combinations of chemotherapy, radiation, or no active treatment until symptoms arise. Locally recurrent tumours may be suitable for retreatment with radiation to deal with pain and bleeding (53). Postoperative radiotherapy External beam chemoradiation therapy is recommended for highrisk features following modified radical hysterectomy and pelvic lymph node dissection including close or positive surgical resection margins, the presence of capillary lymphatic invasion, and positive pelvic lymph nodes. Randomized studies have shown improved outcomes, particularly with adenocarcinomas, with low rates of serious toxicity (54). Brachytherapy Intrauterine tandem applicator with vaginal colpostats or ring using high-dose rate afterloading brachytherapy is used during or following external radiotherapy. Typical doses are 28­30 Gy in four to five fractions (36­40 Gy low-dose rate equivalent) of high-dose rate brachytherapy in the third to fifth week of external beam radiotherapy, depending on tumour response. Follow-up care this involves clinic visits for assessment including pelvic exam every 3­4 months for 2 years after completing treatment, then every 6 months to 5 years. Cervical/vaginal cytology is performed at the discretion of the oncologist beginning 1 year after completing radiotherapy in order to avoid false-positive results due to radiation effects. Hormone replacement therapy may be considered for patients who were premenopausal prior to treatment. Uterine cancer Role for radiotherapy by stage Despite decades of study, the role of adjuvant therapy in the treatment of endometrial cancer has been difficult to define. Radiotherapy has been shown to reduce the risk of local recurrence but its effects on survival remains unclear. Several factors contribute to the uncertainty of the role of radiotherapy, including the overall failure rate which is only 15% in all newly diagnosed endometrial cancer confined to the uterus treated with surgery, resulting in a very small improvement in prognosis with the addition of any further therapy. Additional factors include biased retrospective studies and randomized studies that included many low-risk patients who would not benefit from any further therapy. Therefore, the decision to treat with adjuvant therapy, including radiotherapy, is based on the understanding of the risk factors of recurrence, natural history of disease, the interpretation of data, and the risk of complications in each individual case. These patients have a 90% cure rate with surgery alone and do not need further adjuvant therapy.

Just under 40% of women underwent screening and treatment on the same day and nearly two-thirds received treatment (cryotherapy) within a week of being screened medicine xalatan purchase zyprexa visa. Of the 326 women who had cervices suspicious for cancer, there was no information on 230 women and only 96 women were known to be investigated, of whom 79 had cancer and 17 either had no cancer or the outcome was unknown. Overall, 77 or the 326 women with possible cancer (24%) were known to have undergone treatment. By contrast, in the Shastri trial (26), compliance with treatment for invasive cancer was 86. Five-year survival from colon, rectal, and breast cancers had increased steadily in most developed countries. For example, for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remained lethal in all nations with 5-year survivals ranging from 15% (North America) to 7% (Mongolia and Thailand). The global range in 5-year net survival was very wide, particularly in Africa, Central and South America, and Asia. National estimates of 5-year survival ranged from less than 50% to greater than 70% with marked regional variations and very little improvement in the time periods of 1995­1999 and 2005­2009. Research in the past years has focused on evaluating alternative approaches to screening, particularly approaches that use low technology and that can give a result if not immediately, then within a short time period, to enable women to be treated at or shortly after the screening visit. Detection of cervical cancer was similar between the screening methods during the first 2. The cumulative incidence of cervical cancer in women who had negative tests at entry was 4. This approach may enable larger numbers of women to be reached and enable a significant impact on cervical cancer incidence and mortality, particularly if the option of self-testing is included in the screening algorithm (36, 37). Besides cost, other challenges facing developing countries include the fact that an adolescent health platform does not exist (immunization is included in the care of young children only) and reaching the target population is not easy, the necessity for a cold chain and medical waste management, 760 SeCtIon 12 Gynaecological Oncology cultural issues, and reticence to discuss a sexually transmitted infection among others. School-based health clinicbased models predicted high coverage as was management by a non-governmental organization. Further, Gavi plans to reach 30 million by 2020 by introducing the vaccine into 40 countries. In the relapse setting, patients carrying mutations more frequently responded to both platin and non-platin regimens than mutation-negative patients, even those with early relapse post primary treatment. Epithelial ovarian cancers have been traditionally divided according to morphological appearance but it now clear that they are a heterogeneous groups of cancers primarily classified by cell type into serous, mucinous, endometrioid, clear cell, transitional, and squamous cell tumours. They are further subdivided into benign, borderline, and malignant carcinomas depending on the degree of cell proliferation, nuclear atypia, and stromal invasion (49). Recently, based on histopathology, immunohistochemistry, and molecular genetic analysis, at least five main types of ovarian cancer are identified: high-grade serous carcinoma (70%), endometrioid carcinoma (10%), clear cell carcinomas (10%), mucinous carcinomas (3%), and low-grade serous carcinoma (<5%) (50). These tumours account for 98% of ovarian carcinomas, can be reproducibly diagnosed on light microscopy, and are inherently different diseases as indicated by differences in epidemiological and genetic risk factors, precursor lesions, patterns of spread, molecular events during oncogenesis, response to chemotherapy, and prognosis (50, 51). Most studies, however, produced disappointing results- even with a specificity of 99% it was evident that as many as 25 surgeries would need to be performed to uncover one case of ovarian cancer (52). Unfortunately, at this moment, there is no reliable early detection test that can detect ovarian cancer in its early stages. There is no convincing evidence to support the introduction of organized screening programmes for ovarian cancer in public health services. In 2015, 255,700 women were expected to be diagnosed with ovarian cancer and 163,800 women were estimated to die of it in the world; the corresponding figures for less developed regions were 150,300 and 93,800 respectively. Neither early detection nor screening has been able to reduce mortality from the disease, and the only possible means of reducing mortality is prevention. Two-thirds of women diagnosed with ovarian cancer are over the age of 55 years and a family history of ovarian or breast cancer in a first-degree relative triples the risk (41). An Australian study recruited 1001 women with non-mucinous ovarian cancer into a population-based case­control study and women were screened for point mutations and large deletions in both genes (47). They contend that it is necessary to wait for 10­ 12 years from diagnosis to conclude that an ovarian cancer patient is cured and there are many factors that delay the time from diagnosis to death but do not reduce the absolute numbers of deaths. Whether screening will prevent death from ovarian cancer or delay it by a few years is still too early to tell. Based on all deaths from ovarian/peritoneal cancers over the entire period, the hazard ratio was 0. Prevention of ovarian cancer There are several ways that the risk of epithelial ovarian cancer may be reduced both in high- and average-risk women; however, much less is known about the means to prevent germ cell and stromal tumours. Of the eight cancers in the surgical group, six were stage one ovarian cancers diagnosed at the time of surgery. Neither breast nor ovarian cancer developed in 185 out of 259 subjects who underwent prophylactic oophorectomy. The first accepts that Mullerian epithelium is established in the ovary over time in the form of endosalpingiosis, cortical inclusions, or endometriosis. These cells could evolve through metaplasia, or exfoliation of tubal epithelial cells, among other routes, into cancer. Over the last decade, ovarian cancer has been divided into two basic categories that have different aetiologies, molecular pathogenesis, and clinical behaviour. Type 1 tumours are less common, present at a lower stage, and usually arise from a precursor lesion (57). Type 2 tumours present with advanced stage disease and account for the majority of deaths from ovarian cancer (58). There is now evidence to support the proposal that most type 2 ovarian cancers develop from epithelial cells of the fallopian tube, making prophylactic salpingectomy a mode of primary prevention. It is the most common invasive gynaecological cancer in developed countries and its incidence in developing countries is increasing.

Erectile function after posterior urethroplasty for pelvic fracture-urethral distraction defect injuries medicine 751 buy cheap zyprexa 7.5 mg on line. Mundy Introduction to genital trauma Genital trauma accounts for one to two-thirds of all genitourinary trauma. Eighty per cent (80%) of it is blunt trauma but 35% of all penetrating urological injuries are genital injuries. The commonest type of significant blunt trauma is penile fracture due to sexual intercourse or masturbation. Penetrating trauma can occur as a result of animal or human bites, or as a result of amputation, other sharp injury, or as a result of gunshot wounds or other military injuries. This incision gives the best exposure to both the corpora cavernosa and the corpus spongiosum, which are repaired with absorbable sutures. Ruptured suspensory ligament this occurs from a similar mechanism during sexual intercourse as for penile rupture. It is less common and typically is associated with pain without, necessarily, detumescence. There is a palpable defect on physical examination where the suspensory ligament should be. In the longer term, this is associated with chronic pain and instability of the penis on erection and is best treated by repair of the ligament. The characteristic clinical features are a cracking or popping sound associated with pain and detumescence during the sexual act. The rupture of the tunica albuginea is generally on the ventral or the lateral aspect of the penis. Urethral injury occurs in 10­25% of these patients, usually at the same site as the cavernosal tear. Even when circumstances allow the testis to be crushed against the pubis, it takes a considerable force to do so. Prompt treatment almost always gives a satisfactory result, whereas delayed treatment reduces the chance of salvage and increases the need for orchidectomy. Haematocele If an ultrasound scan after scrotal injury shows a large haematocele then it is usually best drained, even if there is no sign of testicular rupture, to facilitate recovery. In short, after any blunt trauma to the scrotum, the safest approach is to explore it. High-flow priapism One of the consequences of perineal or genital trauma is high-flow priapism. This is uncommon and is usually distinguishable from low-flow priapism because of its gradual onset and because it is not painful. It typically follows perineal trauma and rupture of the perineal artery causing an arteriolacunar (the equivalent of an arteriovenous) fistula. Typically, on aspiration of the penis, the blood is bright red and has a normal pH-unlike the colour and pH of lowflow priapism. Ice packs to the penis may reduce or eliminate the priapism; otherwise, arteriography should be performed with a view to embolization (see also Chapter 7. Stab wounds, gunshot wounds, and other penetrating injuries Penetrating injuries should always be explored, debrided if necessary, and repaired if possible. In civilian practice, debridement and repair are usually straightforward2,20-quite the reverse in a military setting. Antibiotic cover and a tetanus booster or vaccination should be given to all patients. The risk to healthcare personnel of contracting hepatitis B and particularly C appears to be higher than usual in treating patients with penetrating genital trauma, in whom the incidence of these conditions has been reported to be as high as 38%. Whatever the timing of presentation, co-amoxiclav, for the commonest type of infection, Pasteurella multicida, should be given. When an animal bite is the cause, one should consider rabies vaccination and a tetanus booster, or vaccination should be given to all patients. For some reason or another, women in Thailand in the 1970s started to perform amputation of the penis on their unfaithful husbands. As a result of this, Thai surgeons developed some experience of the management of penile amputation, whether by the patients themselves or by their partners. Fifty per cent (50%) are schizophrenic, 20% are psychotically depressed, and a significant number of the remainder have personality or transsexual disorders. In the meantime, amputations should be treated, if possible, by replanting the penis. The amputated penis, pending replantation, should be wrapped in clean saline gauze and kept on ice. Microsurgical treatment is first to anastomose the dorsal arteries (the cavernosal arteries are much smaller and much more difficult to reanastomose). Attention is then directed to the dorsal veins and the tunica albuginea, and then to the urethra and finally the skin. Anastomosis of the dorsal nerves is usually attempted but whether this leads to an improvement in postoperative erectile function is debatable. If the amputated penis has been lost or if it is too late after the injury, then a phalloplasty should be considered as described elsewhere in this volume. Civilian gunshot wounds to the genitoruiary tract: incidence, anatomic distribution, associated injuries, and outcomes. Urethral fistulae and urethral strictures and the difficulties of providing a penile implant are a significant problem in the phalloplasty group, making replantation a better option when possible. Accidental damage to the penis occurs from time to time for other reasons whether as a result of penetrating trauma, such as military trauma, or mundane causes such as damage to the glans during circumcision.