Laurence S. Baskin, MD

• Chief of Pediatric Urology
• University of California?an Francisco
• Benioff Children? Hospital San Francisco, California

Overall the lack of enthusiasm for brachytherapy coupled with concerns regarding delayed healing and a reduced commercial interest has led to extremely limited use of this treatment modality insomnia heart palpitations buy unisom 25 mg on line. On the other hand insomnia 7 year old child order generic unisom canada, if structural discontinuity is present then repeat stenting may be advantageous sleep aid rain sound buy unisom with visa. Importantly f51 0 insomnia non organica discount unisom 25mg visa, however insomnia tips on falling asleep cheap unisom 25 mg on line, subgroup analyses of patients with large vessels and edge restenosis suggested benefit with additional stent placement insomnia zoloft withdrawal purchase cheap unisom on line, which intuitively makes sense. By splinting balloon-disrupted plaque and sealing iatrogenic dissection planes acute results are more stable after stent implantation. In addition, the scaffold properties of stent backbones deliver mechanical advantage and oppose early vessel recoil. In addition the radial strength of the stent prevents later-occurring constrictive vessel remodeling. Concerns about long-term adverse effects of bare-metal stents as permanent endovascular prostheses remain poorly defined. The longitudinal view (B) shows focal severe stent underexpansion with evidence of multiple layers of metallic stents-so-called onion skin phenomenon-in the cross-sectional view (A). In terms of restenosis within bare-metal stents, early experience with drug-eluting stent implantation from registry reports was encouraging. The hypothesis in favor of a switch strategy is that although restenosis is undoubtedly multifactorial hyporesponsiveness or resistance to the eluted drug may play some role in the pathogenesis. Drug release is facilitated by a coating that consists of a mixture of lipophilic drug and a hydrophilic spacer or excipient that facilitates faster uptake into the vessel wall. The spacer or excipient combines with the active drug to form a matrix coating that remains on the surface of the balloon catheter. Exipient 13 Treatment of In-Stent Restenosis Washington Hospital Center with clinical follow-up. Moreover, all of these data are limited by the nonrandomized nature of the treatment comparisons; accordingly it is difficult to fully adjust for treatment selection bias on the part of the operator. The balloon coating is typically comprised of two elements: a lipophilic active drug (to date all commercially available devices use paclitaxel) and a spacer or excipient (which increases the solubility of the active drug and facilitates its transfer from the balloon surface to the vessel wall). Preclinical studies have documented effective drug transfer with evidence of local fibrin deposition in the vessel wall as a signature of therapeutic efficacy. This might be simply a manifestation of more assiduous lesion preparation or could also reflect diverging neointimal behaviors after dilation; for example, paclitaxel application might in theory attenuate the acute neointimal recoil reported in some patients after balloon angioplasty by freezing the disrupted neointimal. Subsequently published 5-year results confirmed durability of efficacy over the medium to long term. The restenotic lesion was predilated with a noncompliant balloon (C) and treated with a 60-second drugcoated balloon inflation (D) with good acute angiographic result (E; Video 13-21). However, in trials comparing angioplasty with stenting, late loss is not a suitable endpoint: modalities with higher acute gain tend to have higher late loss per se ("the more you gain, the more you lose"). Early generation paclitaxel-eluting stents have largely fallen out of use due to more effective next generation platforms. However, binary restenosis and clinical events at 1 year were low and similar in both groups. In addition, intravascular imaging may permit more accurate sizing of the reference vessel, which may guide choice of balloon diameter. The main limitation is the requirement for additional contrast agent administration to ensure a bloodfree field for image acquisition. In addition, lower tissue penetration means that the external elastic lamina cannot always be well imaged and this makes accurate vessel sizing more difficult. Considerable variation exists in the use of intravascular imaging to guide re-intervention for restenosis. Some centers recommend systemic adjunct imaging, whereas others restrict intravascular imaging to selected cases with challenging diagnostic characteristics. Local factors such as operator experience and reimbursement play an important role. However, these novel devices may present specific challenges in case of stent failure. To date, restenosis after bioresorbable stent implantation remains poorly characterized. Management of this condition remains challenging and optimal treatment algorithms have not been defined. Due to high recurrence rates the use of plain balloon angioplasty has a limited role. In addition atherectomy techniques and vascular brachytherapy have largely fallen out of use. Further studies are required to identify patient-specific characteristics that may help to tailor treatment selection in order to improve clinical outcomes. The longitudinal view (D) shows some stent underexpansion with reduced lumen caliber in comparison with both the proximal (C) and distal stent (A) and the distal native vessel segment. Kastrati A, Byrne R: New roads, new ruts: lessons from drug-eluting stent restenosis. Latib A, Mussardo M, Ielasi A, et al: Long-term outcomes following the percutaneous treatment of drug-eluting stent restenosis. Nakazawa G, Otsuka F Nakano M, et al: the pathology of neoatherosclerosis in human coronary, implants bare-metal and drug-eluting stents. Nakano M, Otsuka F Yahagi K, et al: Human autopsy study of drug-eluting stents restenosis:, histomorphological predictors and neointimal characteristics. Alfonso F Zueco J, Cequier A, et al: A randomized comparison of repeat stenting with balloon, angioplasty in patients with in-stent restenosis. Kastrati A, Mehilli J, von Beckerath N, et al: Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial. Scheller B, Hehrlein C, Bocksch W, et al: Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. Unverdorben M, Vallbracht C, Cremers B, et al: Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Habara S, Mitsudo K, Kadota K, et al: Effectiveness of paclitaxel-eluting balloon catheter in patients with sirolimus-eluting stent restenosis. Wiemer M, Konig A, Rieber J, et al: Sirolimus-eluting stent implantation versus beta-irradiation for the treatment of in-stent restenotic lesions: clinical and ultrasound results from a randomised trial. Habara S, Iwabuchi M, Inoue N, et al: A multicenter randomized comparison of paclitaxelcoated balloon catheter with conventional balloon angioplasty in patients with bare-metal stent restenosis and drug-eluting stent restenosis. Alfonso F Garcia P Fleites H, et al: Repeat stenting for the prevention of the early lumen loss, phenomenon in patients with in-stent restenosis. Kobayashi Y, Teirstein P Linnemeier T, et al: Rotational atherectomy (stentablation) in a lesion, with stent underexpansion due to heavily calcified plaque. Vales L, Coppola J, Kwan T: Successful expansion of an underexpanded stent by rotational atherectomy. Adamian M, Colombo A, Briguori C, et al: Cutting balloon angioplasty for the treatment of in-stent restenosis: a matched comparison with rotational atherectomy, additional stent implantation and balloon angioplasty. Torguson R, Sabate M, Deible R, et al: Intravascular brachytherapy versus drug-eluting stents for the treatment of patients with drug-eluting stent restenosis. Alfonso F Cequier A, Zueco J, et al: Stenting the stent: initial results and long-term clinical and, angiographic outcome of coronary stenting for patients with in-stent restenosis. Elezi S, Kastrati A, Hadamitzky M, et al: Clinical and angiographic follow-up after balloon angioplasty with provisional stenting for coronary in-stent restenosis. Alfonso F Melgares R, Mainar V, et al: Therapeutic implications of in-stent restenosis located at, the stent edge. Degertekin M, Regar E, Tanabe K, et al: Sirolimus-eluting stent for treatment of complex in-stent restenosis: the first clinical experience. Dibra A, Kastrati A, Alfonso F et al: Effectiveness of drug-eluting stents in patients with bare, metal in-stent restenosis: meta-analysis of randomized trials. Byrne R, Iijima R, Mehilli J, et al: [Treatment of paclitaxel-eluting stent restenosis with sirolimuseluting stent implantation: angiographic and clinical outcomes]. Cosgrave J, Melzi G, Corbett S, et al: Repeated drug-eluting stent implantation for drug-eluting stent restenosis: the same or a different stent. Garg S, Smith K,Torguson R, et al: Treatment of drug-eluting stent restenosis with the same versus different drug-eluting stent. Li Y, Li L, Su Q, et al: Same versus different types of drug-eluting stents in the treatment of in-stent restenosis: a meta analysis. Naganuma T, Costopoulos C, Latib A, et al: Feasibility and efficacy of bioresorbable vascular scaffolds use for the treatment of in-stent restenosis and a bifurcation lesion in a heavily calcified diffusely diseased vessel. Ielasi A, Latib A, Naganuma T, et al: Early results following everolimus-eluting bioresorbable vascular scaffold implantation for the treatment of in-stent restenosis. Iqbal J, Onuma Y, Ormiston J, et al: Bioresorbable scaffolds: rationale, current status, challenges, and future. Acute myocardial infarction can also occur as a result of thrombotic occlusion of a saphenous vein graft. Saphenous vein graft occlusion may be associated with larger thrombus burden than native coronary artery occlusion and therefore may require different strategies for management. Stent thrombosis is becoming increasingly recognized as a distinct cause of acute myocardial infarction. Unfortunately, such disruption of thrombus likely results in macro- and micro-embolization into the downstream coronary bed. This can also be observed during coronary angiography by assessment of myocardial blush grade, which represents flow in the microcirculation (0 = no blush, 1 = minimal blush, 2 = moderate blush, and 3 = normal blush). Despite successful epicardial coronary flow, impaired myocardial flow (blush grade 0 to 2) has been observed in over 70% of patients. This review will principally center on the current pharmacological and mechanical approaches to manage thrombotic lesions. Inadequate antiplatelet therapy might be the result of poor patient compliance, but is also seen among patients undergoing noncardiac surgical procedures who have been instructed to minimize or stop their antiplatelet therapy. With this approach it was hoped that improvement in preprocedure coronary flow could reduce infarct size and improve survival. When the stopcock is turned, the catheter aspirates blood/thrombotic debris from the catheter tip. The catheter is slowly advanced through the site of occlusion and returned to the guide catheter when the syringe is filled with blood and thus no longer aspirating. Normally one to two or more passes with the aspiration catheter are performed to restore epicardial blood flow. One can continue passes until there is no more debris noted in the aspirate when run through a mesh filter or gauze. Many catheters now come preloaded with a stylet that can facilitate deliverability of the device to the site of occlusion. There is no clear advantage of one device over another; however, most of the clinical trial data support the Export device. The catheter is attached to a stopcock and syringe that is prepped with negative pressure and advanced over Fr, French. The Pronto V4 has an embedded wire for additional deliverability and kink resistance. This is also to potentially discharge retained thrombus as above Caution if the guide catheter pressure is severely damped, since opening the hemostatic valve can entrain air rather than bleed back With poor coronary flow, intracoronary administration of medications through the guide catheter may end up in the systemic rather than coronary circulation the sylet stiffens the catheter and enhances deliverability Similarly, a guide extender may provide enough support to allow the thrombectomy catheter to track into position Slow down during advancement of catheter into the body Once device is removed from body, back bleed from hemostatic valve Aspiration thrombectomy catheters can also be used to infuse medications into the myocardial bed Angiojet distaflex catheters. Some patients will require a temporary pacemaker, especially when thrombectomy is performed in the right coronary artery. Some operators recommend theophylline infusion to prevent bradyarrhythmias, although there are few data to support this. The Angiojet Distaflex is intended for small vessels (tip is 4 Fr and body of catheter is 5 Fr). This creates a low-pressure zone through which the thrombus can be withdrawn into the catheter through entry ports and externalized to a collection bag. Rheolytic thrombectomy catheters create -600 mm Hg at the catheter tip compared with -10 mm Hg for aspiration thrombectomy catheters. The patient was an 83-year-old man with prior coronary artery bypass grafting and percutaneous coronary intervention who presented to the hospital with an acute myocardial infarction. Next, rheolytic thrombectomy was performed with the Angiojet Spiroflex device (Video 14-4). Potentially Useful Devices An alternative approach is to trap the thrombus within the coronary artery rather than retrieve it. The console energizes the 3 2 Saline jets travel backwards to create a low pressure zone causing a vacuum effect. This trial was unable to document a mortality benefit from aspiration thrombectomy. The ClearWay catheter (Atrium Medical; Hudson, New Hampshire) is a device that was designed to infuse drug. Data are not as robust or as supportive regarding the use of rheolytic thrombectomy. No local delivery of abciximab and no aspiration thrombectomy Aspiration thrombectomy did not reduce final infarct size at 30 days, although local delivery of abciximab was associated with a modest reduction in infarct size (p = 0. The devices have been studied in native coronary artery occlusion; however, they are not used due to lack of efficacy. Although not powered for clinical endpoints, patients with good myocardial blood flow had improved clinical outcomes. Stent thrombosis is an important and increasing cause of acute myocardial infarction. The current standard of care for mechanical management of thrombus is manual aspiration thrombectomy; however, important questions remain with this strategy and further data will be forthcoming. Its integration into the catheterization procedure as an adjunct to coronary angiography has made a significant impact on clinical decision making and outcomes for patients with a variety of angiographic presentations including intermediately severe single-vessel disease, multivessel disease, left main stenosis, diffuse disease, and bifurcation or ostial branch stenoses. The interpretation of this image as representing an ischemia-producing lesion is both difficult and unreliable as evidenced from the poor correlation between noninvasive testing with angiographic percent diameter stenosis. Angiography does not provide vascular wall detail sufficient to characterize plaque size, length, or eccentricity.

Diseases

• Bronchogenic cyst
• Harlequin type ichthyosis
• Aplastic anemia
• Hereditary hyperuricemia
• AIDS dementia complex
• Cystinuria
• Endometrial stromal sarcoma
• Dermatitis herpetiformis

It is more To Confirm Malignancy Cytologic examination for detection of malignant cells is carried out from the fluid collected by abdominal paracentesis or "cul-de-sac"aspiration sleep aid devices purchase unisom 25mg online. To Identify the Extent of Lesion Straight X-ray chest to exclude pleural effusion and chest metastasis sleep aid pill cheap unisom online mastercard. Ultrasound imaging: Features suggestive of malig-nancy are: multiloculation with thick-walled septa sleep aid and alcohol order cheapest unisom and unisom, nodular areas (> 6 cm) insomnia 40 weeks pregnant discount unisom online, papillary surface projections or neovascularisation (on Doppler study) sleep aid magnesium purchase unisom 25mg overnight delivery. Operative Findings x Nature of peritoneal fluid: While hemorrhagic fluid is very much suggestive but a clear or straw color fluid cannot rule out malignancy insomnia night club purchase cheap unisom online. Histological Diagnosis All ovarian tumors irrespective of their nature must be subjected to histologic examination. This not only confirms the diagnosis but also identifies the type and grade of malignancy. Clinical Clinical diagnosis in early stage is very much deceptive because of: No age specificity: Although more prevalent beyond the age of 45 (40% of ovarian neoplasms are malignant), no age is immune to ovarian cancer. All physicians must be aware of the possible significance of persistent gastrointestinal symptoms in women over the age of 40 with a history of ovarian dysfunction. No specific symptom: It may remain asymptomatic in about 15% when first diagnosed. Unrelated to duration of symptoms: Even with symptoms of short duration may have extensive spread, conversely a long-standing tumor may remain benign. Unrelated to the size of the tumor: A big tumor may remain benign for a long time whereas, a small enlarged ovary may be found malignant. The cumulative effects of such vagaries explain the fact that at the time of diagnosis, about 70% of patients with epithelial carcinomas have metastases outside the pelvis. The most common sites of metastases are-peritoneum (85%), omentum (70%), contralateral ovary (70%), liver (35%), lung (25%) and uterus (20%). In established and/or advanced cases of malignancy, the clinical features as mentioned earlier are enough to arrive at a diagnosis. Annual mammographic screening for women with strong family history of breast cancer. Bilateral salpingectomy with delayed oophorectomy may be an option for premenapauseal women. Guidelines for management of an enlarged ovary An ovarian enlargement of > 8 cm during childbearing period deserves careful follow up. Examination under anesthesia may be useful in doubtful cases, specially in an obese patient. As such, screening aims at detecting early ovarian malignancy in asymptomatic women. Till date no specific method of screening for early detection of epithelial ovarian cancer is available. Elevated level indicates bulky residual disease or tumor recurrence or resistant clones to chemotherapy. Ultrasound imaging: Transvaginal color Doppler imaging has been able to differentiate benign from malignant tumors by assessment of its vascular supply and intratumoral blood flow. Opportunistic bilateral salpingectomy at the time of surgery for benign adenexal disease or hysterectomy. The aims are: x To stage the disease (staging laparotomy) accurately, thereby allowing better choice of adjuvant therapy and a better assessment of prognosis. Practical Guidelines Liberal vertical incision to minimize chance of rupture of the tumor and to facilitate better exploration. To note the character of the ascitic fluid, if any, and to collect sample for cytology. If appreciable fluid is not available, then a sample of peritoneal wash with 100 mL saline in the subdiaphragmatic area is to be collected. A systematic (visual and manual) exploration- palpation of liver, gastrointestinal tract, subdiaphragmatic area, omentum, and paraaortic lymph nodes. Any metastatic deposit over the peritoneal surfaces, under surface of the diaphragm should be biopsied. In the absence of any metastatic disease, multiple peritoneal biopsy, scraping from the diaphragm for cytology should be taken. Primary Surgery Early stage disease (Stage Ia, G1, G2): Young woman o Unilateral oophorectomy (fertility sparing surgery) o Routine follow up and monitoring o Completion of family o Removal of the uterus and the other ovary. In Stage Ia, G3 disease and others stage I diseases: Staging laparotomy o Hysterectomy and bilateral salpingo-oophorectomy. Advanced stage disease: Exploratory laparotomy o Cytoreductive or debulking surgery. Lesser the residual tumor (optimally debulked) volume (< 1 cm), better is the survival. Maximum cytoreductive surgery may need resection of a segment of bowel, bladder or the lymph nodes. Removal of omental cake by cytoreductive surgery improves the result of subsequent chemotherapy or radiotherapy. Large tumor masses have huge number of poorly oxygenated cells in the "resting" phase (Go) (see p. In all other stage I disease o Adjuvant chemotherapy with carboplatin and paclitaxel for six cycles. Chemotherapy: Chemotherapy is used widely following surgery to improve the result in terms of survival. Combination chemotherapy: Paclitaxel (175 mg/ m2) and carboplatin (400 mg/m2) are commonly used Table 24. Patients who are hypersensitive to paclitaxel, topotecan 1 mg/m2 for 5 days, every 3 weeks or Gemcitabine 800 mg/ m2, every 3 weeks is given (see p. Platinum compounds (cisplatin, carboplatin) are the most effective drugs in terms of tumor response and survival rate (see p. Taxane derivatives (paclitaxel, docetaxel) are found to be very effective in ovarian cancer (see p. Taxane derivatives prevent cell division by polymerization of microtubules and making them excessively stable. Paclitaxel is recommended as the primary treatment of all epithelial ovarian cancer following optimal cytoreductive surgery. Combination chemotherapy: Drugs acting in different ways on the cell cycle (see p. Currently paclitaxel and carboplatin combination chemotherapy is found to have better survival rate in advanced ovarian cancer Tables 24. Single agent: Alkylating agents (melphalan, cyclophosphamide, ifosfamide) are commonly used (see Table 24. Intraperitoneal chemotherapy is used only for minimal (< 2 cm) or microscopic residual disease. Postoperative chemotherapy may be needed in a few without an adverse effect to these child bearing. There is distinct benefit of intraperitoneal cisplatin and docetaxel over their intravenous use. Maintenance chemotherapy including bevacizumab could not establish any survival benefit. Subsequent surgery is easier and morbidity is reduced, Optimum cytoreduction with minimal residual disease may be possible. Herceptin, an antibody, when used along with chemotherapy improves the response rate (see p. Secondary Surgery Secondary cytoreductive surgery may be done in some selected cases: 1. It is done in patient with no evidence of persistent tumor after an interval of chemotherapy. The findings of second look surgery may be: x Negative (both clinically and microscopically) x Microscopically positive but clinically negative x Positive (both clinically and microscopically). Histological type-endometrioid tumor has got a higher survival rate than serous type because the former tumor is highly well-differentiated. Karyotyping is needed (presence of Y chromosome) specially when a premenarcheal girl presents with a pelvic mass. Presence of metastatic disease before cytoreductive surgery-poor the prognosis and shorter the survival. Ploidy status-diploid tumors are prognostically better compared to aneuploid tumors. Microscopic appearance reveals uniform large round cells (monotonous pattern), arranged in cords or clumps with abundant clear cytoplasm. Microscopically the ovaries are either not involved or exhibit cortical implants < 5 mm in depth. Mature cystic teratoma (dermoid cyst) is the most common germ cell ovarian tumor (95%) and it is benign. Germ cell tumors have the following feature: (1) Occur predominantly in children and young adults. Recurrent disease is treated either with combination chemotherapy or radiation therapy. Radiation therapy is considered for patients who had been treated with combination chemotherapy earlier. Overall survival following unilateral oophorectomy in early stage (stage Ia) disease 100% and following cisplatin-based combination chemotherapy in advanced disease is 75%. It is commonly (50%) seen in women between the ages of 10 and 20 years and rarely seen after menopause. The prognosis of immature teratoma depends mainly on the tumor grade and the stage of the disease. In a young patient where preservation of fertility is desired, laparotomy for surgical staging including lymphoderectomy should be done. Conservative surgery, unilateral salpingo-oophosrctomy may done in early stage disease. If there is any suspicion of involvement to the other ovary, bisection of the contralateral ovary and excisional biopsy should be done. Systemic chemotherapy is the treatment of choice, where fertility is to be preserved, even in the presence of metastatic disease. Different chemotherapeutic agents are used either singly or in combination (see Ch 31) Table 24. Patient with Y chromosome as detected on karyotyping should have both the ovaries (gonads) removed. Treatment Unilateral oophorectomy with surgical staging is the optimum treatment when the tumor is confined to one ovary. Yolk sac tumors are unilateral and are usually solid, more than 10 cm in diameter. Characteristic histological feature is the presence of cystic spaces lined by flattened epithelium. Eosinophilic, hyaline bodies containing alphafetoprotein and other proteins are also constant microscopic features. Menstrual function, fertility and other endocrine functions have been found to be normal following use of these drugs. Treatment Surgical staging and unilateral salpingo-oophorectomy is generally the treatment of choice. Total hysterectomy and contralateral salpingo-oophorectomy do not improve the prognosis in any way. Chemotherapy: Routine use of combination chemotherapy has improved the survival significantly. Combinations containing platinumbased compounds are associated with better response and survival. The tumor produces alphafetoprotein which is an useful marker (serum level above 20 g/mL) to monitor regression and detect recurrence. Patients with these tumors often present with features of excess estrogen or androgen. Patients often present with primary amenorrhea, virilism or genital abnormalities. The tumor cell nuclei are variable in size but they are pale, usually grooved or folded and are called "Coffee bean" nuclei. The cells are arranged in a number of architectural pattern but commonly in folliculoid type. These structures are called Call-Exner bodies and are pathognomonic of granulosa cell tumor. The juvenile tumor has less number of Call-Exner bodies and less number of "Coffee bean" nuclei compared to the adult Chemotherapy in Germ cell Tumor Combination chemotherapy has improved the survival following conservative surgery in advanced malignant germ cell tumors of the ovary. The tumor cells secrete inhibin (inhibin B) and it is an useful marker for the disease (see p. As the tumor produces estrogen, there may be associated endometrial hyperplasia (50%). Presence of Call-Exner bodies (microfollicular pattern) are diagnostic Clinical Features It occurs in all ages, 10% prior to puberty, 40% during child-bearing period, and 50% in postmenopausal women. Apart from the nonspecific features due to tumor mass, it produces effects caused by hyperestrinism which differs with ages.

Clinical diagnosis is by the classic symptoms of progressively increasing dysmenorrhea insomnia hillsboro order discount unisom, dyspareunia insomnia during pregnancy unisom 25 mg sale, infertility and feel of nodules in the pouch of Douglas insomnia home remedies best unisom 25 mg. Microscopic diagnostic features are: presence of endometrial glands 8dp3dt insomnia cheap 25 mg unisom with mastercard, stroma and hemosiderin-laden macrophages sleep aid comparison generic unisom 25mg fast delivery. However insomnia norwegian movie buy 25 mg unisom free shipping, the association of minimal to mild endometriosis and infertility is controversial. Other complications of endometriosis are acute abdomen due to rupture of chocolate cyst, infection of the cyst, colorectal obstruction and ureteral obstruction. The short-term goals of treatment for endometriosis are: (i) relief of pain and (ii) improvement of fertility. Expectant treatment is extended to unmarried or young married with no abnormal pelvic findings. The mechanism of atrophy can be explained by pseudopregnancy or by pseudomenopause or by medical hypophysectomy (see p. Conservative surgery in endometriosis includes removal of all macroscopic endometriosis, lysis of adhesions and restoration of normal pelvic anatomy. Endoscopic laser surgery is the best in selected cases for the treatment of pain and to prevent the disease progress. Large ovarian endometrioma (> 3 cm) is treated by laparoscopic ovarian cystectomy. Definitive surgery includes total hysterectomy with bilateral salpingo-oophorectomy. Laparotomy is done for advanced stage disease or in women who has completed her family. Postoperative estrogen replacement therapy after total hysterectomy and bilateral oophorectomy may be given 3 months after surgery. Women with adenomysis presents with: menorrhagia, dysmenorrhea, dyspareunia or infertility. Regression frequently occurs in young woman, during pregnancy or when it is caused by viral infection. To exclude vaginal or cervical neoplasia, cytologic evaluation has to be performed. Chapter 23 x Premalignant Lesions Biopsy: Confirmation of diagnosis is done by biopsy. The characteristic histologic picture is presence of Paget cells in the epidermis. Associated adenocarcinoma of apocrine gland (adenocarcinoma in situ) is present in about 10% of the cases. There is hyperkeratosis, acanthosis (hyperplasia of epidermis) and chronic inflammatory cell infiltration. Symptoms Medical Topical therapy: Commonly used agents are: Imiquimod 5% cream, cidofovir emulsion, or 5% fluorouracil cream. Local examination reveals-labia majora appear red, scaling, with elevated lesion. Multiple biopsies are to be taken to exclude associated adenocarcinoma of the apocrine glands. If it is found positive, bilateral lymph node dissection should be done at a second stage. Presence of invasive carcinoma must be excluded beforehand as no specimen is available for histological evaluation following laser ablation. Simple vulvectomy: It is employed in diffuse type specially in postmenopausal women. However, there is considerable degree of overlapping regarding the precise definition of each category of intraepithelial neoplasia. Two mechanisms are involved in the process of replacement of endocervical columnar epithelium by squamous epithelium. Squamous epidermidization by ingrowth of the squamous epithelium of the ectocervix under the columnar epithelium. Initially, the squamous cells are immature but ultimately become mature and indistinguishable to the adjacent squamous epithelium. This metaplastic process is very active at the time of menarche and during and after first pregnancy. This metaplastic cells have got the potentiality to undergo atypical transformation by trauma or infection (scheme-1). The prolonged effect of carcinogens can produce continuous changes in the immature cells which may lead to malignancy. Early age sexual activity and multiple sexual partners are the most consistent risk factors. Thus, it is apparent that some of these epithelial atypia either remain stationary, regress or even progress to invasive carcinoma. Hightened estrogenic activity exposes the columnar epithelium onto the ectocervix; C. New squamocolumnar junction is situated at or slightly outside the external os during reproductive period. This squamocolumlar junction is a dynamic point and it changes with phases of life; D. The nuclei are hyperchromatic, irregular with multinucleate forms Infectious agents: the causative agents appear to be transmitted to the susceptible women during intercourse. Cytologic screening (Scheme-3): Exfoliative cytology (Papanicolaou and Traut, 1943) has become the gold standard for screening. Activated p53 causes cell apoptosis (cell death) and thus stop the viral multiplication. Cytology is the laboratory method while colposcopy is the clinical method of detection. Colposcopy evaluates mainly the changes in the terminal vascular network of the cervix which reflect the biochemical and metabolic changes of the tissue. In fact, cytology identifies the patient having cervical neoplasm, colposcopy identifies the site where from biopsies are to be taken. Indications of colposcopy Repeated abnormal cytology (moderate to severe dyskaryotic smear). Punctuation-dilated capillaries which appear on the surface as dots (end on view of vessels). Positive test result in elderly women (> 30 years) suggests colposcopic examination. Those women with acetowhite lesions are considered for colposcopic examination and/or biopsy. Alternatively, ring biopsy is taken from the squamocolumnar junction and subjected to serial sections. Colposcopic view of the posterior tip of the cervix showing typical mosaic pattern. The impact of vaccines is greatest when it is given to females who are not already infected. Vaccine induced neutralizing antibodies (IgG, IgA) works locally (cervix) by preventing the attachment of the virus to the cervical epithelium. Immune defense is type specific and is effective only when given prophylactically. Ablation of the local lesion the following criteria should be fulfilled: the entire lesion is visualized within the transformation zone. Double freeze technique (freeze-thaw-freeze) increases the effectiveness of cryotherapy (see p. Carbon dioxide laser through colposcopic guidance- can destroy the epithelium by vaporization up to a depth of 7 mm. Advantages of laser vaporization: (a) preservation of transformation zone for subsequent follow up, (b) precision control technique in depth and breadth, and (c) rapid healing. Complications such as hemorrhage, infection, cervical stenosis or incompetence depend on the length of cone excised. As such, complete destruction of the lesion is considered to be a satisfactory treatment. Pretreatment accurate evaluation about the extent of lesion and exclusion of invasive carcinoma with the available gadgets (cytology, colposcopy, and directed biopsy) is a sine-qua-non to get a good result. Tissue up to a depth of 10 mm or more can be removed and sent for histological examination. Follow up protocol includes an initial post-treatment cytology at 6 months and then repeated at 12 months. Longterm unopposed estrogen, particularly around the time of menopause, often leads to various types of endometrial hyperplasia. In the postmenopausal women with obesity, peripheral conversion of androgens into estrogen is a risk factor. Long-term estrogen stimulation in condition of polycystic ovarian syndrome or feminizing ovarian tumor may predispose to endometrial cancer (Flowchart 23. But the constant feature is abnormal perimenopausal uterine bleeding and ultimate diagnosis is ideally by hysteroscopy and endometrial biopsy (see p. Vaginal pool smear, endometrial aspiration (pipelle endometrial Chapter 23 x Premalignant Lesions Flowchart 23. The nuclei of the glands show enlargement, irregular size and shape, hyperchromasia, and coarse chromatin. Management Preventive Definitive treatment Preventive To maintain ideal body weight. The combined estrogen-progestogen preparations reduce the risks than estrogen alone. Follow-up at interval of 6 months by endometrial sampling is essential to note whether its regression is there or not. The glands are dilated, mitosis is present in stroma also 272 Textbook of Gynecology Moderate to severe atypical hyperplasia and also those women who fail to respond with progestin therapy should be considered for hysterectomy. Atypical hyperplasia: During hysterectomy, in such cases, peritoneal washings are collected for cytology and surgical staging. Perimenopausal and postmenopausal women Hyperplasia without atypia: Continuous progestin therapy may be considered. However, hysterectomy with bilateral salpingo-oophorectomy is done as an alternative as the risk of carcinoma increases with age. Alternatively, colposcopic examination and biopsy may be done after application of 5 percent acetic acid. Pap smear (cytology) is the gold standard for screening and has reduced the incidence of invasive carcinoma of cervix by about 80% and the mortality by 70%. It moves further down during pregnancy and recedes up into the endocervical canal after menopause. This metaplastic cells can undergo atypical transformation by trauma or infection, if the host response is poor. Cytologic and colposcopic findings are aids to the diagnosis but biopsy is only confirmatory. This strategy eliminates the need for unnecessary colposcopic examinations and also frequently repeated Pap smears, when it is negative. Cone excision should be done to detect cervical glandular disease when cytology and colposcopy are not reliable. The disadvantages are: risk of postoperative hemorrhage, specimen margins are lost due to thermal damage, may have adverse effects on future pregnancy (miscarriage, preterm labor). The disadvantages are: increased risk of hemorrhage, large volume of tissue removed, increased risk of subsequent pregnancy complications (cervical incompetence). If regression fails to occur or in perimenopausal women, hysterectomy with bilateral salpingo-oophorectomy should be done. Atypical hyperplasia in peri or postmenopausal women is considered for hysterectomy. In most of the developed countries, cancer of the breast tops the list in female malignancies; whereas in the developing countries, including India, genital malignancies top the list. There is also not only wide variation in the incidence but also in the distribution and lifetime risk of the major genital malignancies Tables 24. Naked Eye x Ulcerative: the features are raised everted edges, sloughing base with surrounding induration.

Diagnosis Most often accidentally discovered on laparotomy and histologic examination of the excised tube insomnia jason derulo buy generic unisom line. Suspected features are: Persistent postmenopausal bleeding with uterine pathology being excluded by curettage insomnia css discount 25 mg unisom with mastercard. Persistent positive Papanicolaou smear with a negative cervical and endometrial pathology insomnia zoloft order unisom online now. Laparoscopy: In cases of persistent postmenopausal bleeding with a negative uterine pathology insomnia 2 hours a night cost of unisom. Depending on mitotic activity endometrial stromal tumors are of three types: (i) endometrial stromal nodule (mostly benign) insomnia vs sleep apnea purchase unisom canada, (ii) endolymphatic stromal myosis (low grade malignancy) insomnia icd-9 order unisom, and (iii) endometrial stromal sarcoma (high grade malignancy). Leiomyomatosis peritonealis disseminata-where benign smooth muscle nodules grow over the peritoneal surfaces. It is thought to arise from the metaplasia of subperitoneal mesenchymal stem cells to smooth muscle, fibroblasts, myofibroblasts under the influence of estrogen and progesterone. The cut section shows yellowish appearance with hemorrhage and cystic degeneration. The tumor is termed homologous when the tissue elements are native (smooth muscle) or heterologous when tissue elements are not native (cartilage, striated muscle, bones). Histologically, three types of cells are seen-spindle, round or combination of the two along with giant cells. There may be history of pelvic irradiation either for induction of menopause or malignancy. Abnormal vaginal discharge-offensive, watery foul smelling discharge associated at times with expulsion of fleshy necrotic mass. Suspected sarcomatous change in a fibroid is evidenced by: Postmenopausal bleeding Rapid enlargement of fibroid Recurrence following myomectomy or polypectomy. Speculum examination may reveal a polypoidal mass protruding out through the external os. Chapter 24 x Genital Malignancy x Diagnostic uterine curettage and endometrial biopsy may reveal the mucosal form of sarcoma. It may also present as a solitary solid nodular or as a cystic pedunculated growth. Clinical Features the presenting features are: Blood stained watery vaginal discharge. Vaginal examination reveals pinkish, grape-like polypoidal soft growth arising from the cervix. Diagnosis is confirmed by histologic appearances of loose myxomatous stroma, pleomorphic malignant cells with striated rhabdomyoblasts. Treatment Primary chemotherapy followed by conservative surgery to excise the residual tumor have been done. However the subtype sarcoma botryoides has been best chance to cure following treatment. Classic traid of adnexal mass, intermittent profuse watery discharge (hydrops tubae profluens) and vaginal bleeding is considered pathognomonic for tubal carcinoma. Persistent postmenopausal bleeding and/or positive vaginal cytology for adenocarcinoma, in the absence of endometrial carcinoma, the diagnosis of tubal carcinoma should be considered. Total hysterectomy with bilateral salpingo-oophorectomy along with omentectomy is done. This is followed by platinum based combination chemotherapy as the adjuvant treatment. Secondary carcinoma (metastatic) is common (90%), the primary sites are from ovary, uterus, breast or gastrointestinal tract. Mitotic figure is an important prognostic factor for leiomyosarcoma of the uterus. Sarcoma botryoides is a special type of mixed mesodermal tumor arising from the cervix. Multimodality approach (multiagent chemotherapy with surgical removal and occasionally radiation) gives better result. Though the two organs are anatomically separate entities but integrated with complex functional interplay. The descriptive anatomy of the urinary bladder and urethra has been described in Chapter 1. The anatomic and physiologic peculiarities involved in storage and voiding of urine are to be discussed here. With this arrangement, it forms an active and dominant role in both storage and voiding. Inner longitudinal: It courses downwards from the fundus of the bladder and continues in the form of spirals upto the midurethra. Recent studies, however, suggest that there is frequent interchange of fibers between the bundles and the separate layers are not distinctly defined. From a functional point of view, the detrusor appears to contract as a single syncytial mass. The detrusor muscles are shown to contain significant amount of acetylcholinesterase. This part has got an additional support by the intrinsic striated muscle (rhabdosphincter urethrae). This muscle encircles the whole urethra and is composed predominantly of skeletal muscle with nerve supply from parasympathetic division of autonomic nerves. This rhabdosphincter is further enforced in the upper part by levator ani muscles (extrinsic muscles) being separated from it by a distinct connective tissue septum. The extrinsic periurethral muscle (levator ani) is supplied by the perineal branch of pudendal nerve. The intrinsic striated muscles (slow twitch fibers) is responsible for urethral closure at rest. The extrinsic periurethral striated muscles (first twitch fibers) provide additional support to urethra on stress. Distal urethra: this part is a passive conduit and is surrounded by collagen tissue. Pubourethral ligaments and condensed endopelvic fascia are found to contain smooth muscle fibers. They work together to maintain the normal anatomic support and prevent hypermobility of bladder neck and urethra. Parasympathetic division acts through acetylcholine binding to muscarinic or nicotinic receptors. On stimulation D-receptors cause uretheral contraction and urine storage and continence. D-receptors are located mainly in the bladder base urethra and are responsible for urethral contraction and continence of urine. E-receptors are located mainly on the fundus of the bladder and cause detrusor relaxation. The sympathetic is concerned mainly with the filling and storage phase of micturition. Parasympathetic supply (acetylcholine) is responsible for detrusor contraction and normal voiding. Submucous Layer of the Urethra Submucous layer is the vascular layer which by its plasticity helps in urethral compression. A distal one which varies little with age and a proximal one beneath the bladder neck which undergoes marked changes with age. In the reproductive period, these vessels give a cavernous appearance to the submucosa which disappears in the postmenopausal period. This urethral vascular system plays a significant role in the maintenance of resting urethral pressure. Somatic the somatic supply to the striated muscle of urethra is through the pudendal nerve. The rhabdosphincter is supplied by pelvic splanchnic nerves traveling with the parasympathetic fibers. Extrinsic periurethral striated muscle is supplied by the motor fibers of the pudendal nerves. The intravesical pressure is raised to remain at almost steady level of about 10 cm of water even with a volume of about 500 mL. The intravesical pressure is kept lower than that of the urethra by delicately coordinated relaxation of detrusor muscle. The bladder fundus is rich in parasympathetic (muscarinic) receptors (M) and sympathetic E-adrenergic receptors (E). The bladder neck contains higher number of sympathetic D-adnergic receptors (D) Proximal urethral musculature acts like a sphincter by maintaining tonic contraction. Stretching of the detrusor reflexly contracts the sphincteric muscles of the bladder neck. Inhibition of the cholinergic system responsible for detrusor contraction operating from the spinal centers. Stimulation of E-adrenergic receptors results in further relaxation of the detrusor and D-adrenergic dominance leads to contraction of smooth muscles round the bladder neck (internal sphincter). The external sphincter mechanism contributes the second line guard assisting the first line guard provided by the internal sphincter of the bladder neck. A desire to void is reached, not by increased intravesical pressure but by stimulation of stretch receptors in the bladder wall. The sensation passes up the spinal roots S2, S3 and S4 and in untrained bladder (children), there sets in motion a reflex which automatically contracts the detrusor and results in voiding. But in the trained adults, this urge can be suppressed specially if the time or place is not convenient. Because in adults, the reflex spinal arc is under control of the hypothalamus and higher areas of the brain (anterior part of the frontal lobes). Cerebral control of micturition is complex but is predominantly controlled by pontine center. When the time or the place is convenient, the higher centers via the hypothalamus no longer inhibit the detrusor and the bladder changes from its passive to active role. The pressure is further raised to about 100 cm of water by voluntary contraction of the abdominal muscles. The intraurethral pressure at rest is maintained by the following: Apposition of the longitudinal mucosal folds. Abundant deposition of collagen and elastic tissues throughout the circumference of the urethra. Approximately, one-third of the resting urethral pressure is due to rhabdosphincter effects, one-third to smooth muscle effects and one-third to its vascular plexus. Reflex contraction of the urethral striated sphincter and periurethral striated musculature during stress. Bladder neck is pulled upward and forward behind the symphysis pubis due to preferential better support to the posterior wall of the urethra than to the base of the bladder given by the pubocervical fascia. It may be due to mechanical injury to the supports of the bladder neck following childbirth, trauma (surgery), or due to aging. Urethral sphincter incompetence is principally due to: Hypermobility of urethra due to distortion of the normal urethrovesical anatomy. Lowered urethral pressure-lowered intraurethral pressure at rest below the intravesical pressure. There may be genetic variations in collagen and other connective tissues which normally maintain anatomic and physiologic aspect of the vesicourethral unit. Denervation of the smooth and striated components of the sphincter mechanism also operates. Pregnancy: It is probably functional in nature and related to high level of progesterone. Postmenopausal: Estrogen deficiency leads to atrophy of the supporting structures along with diminished periurethral vascular resistance. Incidence the reported incidence in the Western countries is as high as 40% in association with prolapse. Bladder base becomes flat and lies in line with the posterior wall of the proximal urethra. Thus, even a small rise of intravesical pressure during stress, allows the urine to escape out. Differential Diagnosis Sometimes, there may be clinical confusion with other forms of incontinence such as urge or detrusor instability. Clinical Features Patient Profile the patients are usually parous, may be postmenopausal. Often the complaints date back to the last childbirth or some vaginal plastic operation. Midstream urine examination: this should be a routine prior to urodynamic studies to avoid risk of flaring up the infection during invasive procedures. Any woman with a urine dipstick test positive for both leucocytes and nitrites should have a midstream urine specimen for culture and sensitivity. Pad test: An one hour extended pad test is recommended in cases when the clinical stress test is negative. The patient wears a preweighed sanitary pad, drinks about 500 mL of water and rests for 15 minutes, then performs exercises like walking or climbing stairs for 30 minutes. This is to be followed by provocative exercises such as bending, jumping, coughing, etc. Some degree of pelvic relaxation with cystocele or cystourethrocele is usually evident.

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