Andrew Chan, MD

• Resident, Neurological Surgery, University of California, San Francisco, San Francisco, CA

https://profiles.ucsf.edu/andrew.chan

Patients complain of nasal blockage that often switches from side to side, sneezing and rhinorrhoea menstrual kotex cheap 20 mg tamoxifen with visa. In severe cases with nasal obstruction, reduction of the inferior or middle turbinates may provide relief menstrual underpants buy 20mg tamoxifen fast delivery. The narrow maxillary ostia and uncinate processes are seen on this cut (arrow), lateral to the middle turbinate menstruation 6 weeks after giving birth cheap 20 mg tamoxifen mastercard. Nasal polyps the best means of imaging the paranasal sinuses and the middle meatus of the nose, where the sinus ostia are situated women's health issues 2012 buy tamoxifen 20 mg cheap. Oedematous paranasal sinus mucosa extrudes through sinus ostia to produce nasal polyps breast cancer pictorial order tamoxifen american express. Rarely, there is a single posterior protrusion from the maxillary sinus (antrochoanal polyp) pregnancy kit discount tamoxifen online visa. Temporary improvement in the resulting nasal obstruction can be produced by topical or systemic steroids. Thus, many patients opt for periodic courses of oral steroid therapy, and only resort to surgery for uncontrollably severe symptoms. Diseases of the nose Trauma this may result in fracture and displacement of the nasal bones. If the fracture is not reduced within 14 days, it is usually fixed and hard to mobilise. There may also be displacement and fracture of the septal cartilage and bone (deviated nasal septum;. Corrective septoplasty surgery requires a posttrauma interval of 3 months to allow for soft tissue repair before surgery. Bleeding into the septum causes a septal haematoma, Epistaxis Nose bleeds may be associated with a number of disease processes (Table 26. Severe bleeding not controlled by a pack can be arrested by clipping either the sphenopalatine, anterior ethmoid or maxillary artery. The frontal sinus is an ethmoid air cell that has migrated into the frontal bone, and it is connected to the middle meatus of the nose via the frontonasal duct. The sphenoid sinus is posterior to the ethmoid labyrinth, inferior to the pituitary fossa. Pain arising from the maxillary sinus is felt in the cheek, that from the ethmoid labyrinth is felt over the nasal bridge, and frontal sinus pain is felt in the forehead. Chronic sinusitis may result from failure of resolution of acute infection or may arise insidiously. Surgical treatment is frequently required and includes enlargement of the natural ostium of the maxillary sinus, often with clearance of infected ethmoid cells. Infection may spread from the sinuses, usually the ethmoid or frontal sinuses, to involve other areas such as the cranial cavity or orbit. The ethmoid labyrinth Tumours the most common malignant neoplasm found in the paranasal sinuses is squamous carcinoma. The skull base lies superiorly and the Eustachian tubes open into its lateral walls. Diseases of the nasopharynx Adenoids the adenoids consist of B-cell predominant lymphoid tissue and in young children they occupy a significant proportion of the space within the nasopharynx. They increase in size until the age of 5 years and then become relatively smaller as the nasopharynx continues to grow. They also have a role in the pathogenesis of childhood middle ear effusion and, increasingly in the West, sleep apnoea syndrome. Surgical removal may be indicated to improve the outcomes of glue ear treatment and in sleep apnoea. Tumours A Carcinoma of the nasopharynx is very common in certain areas of the Far East such as South China. Male adolescents may rarely develop a benign but locally invasive angiofibroma of the nasopharynx. Juvenile nasopharyngeal angiofibroma presents with obstruction and epistaxis, and is treated by embolisation plus surgical excision. Endoscopic resection has lower intraoperative blood loss without increase in recurrence rate compared with open approaches. It extends posteriorly to the junction of the anterior two-thirds and posterior onethird of the tongue. The ducts of the submandibular salivary glands open anteriorly into the floor of mouth under cover of the tongue. These relatively uncommon tumours are managed by a combination of surgery and radiotherapy, or by local surgery and topical chemotherapy. A minority relate to food allergy, smoking cessation, stress, or deficiency of iron, folate or vitamin B12. This may progress to dysplasia and cellular atypia, and is therefore a premalignant condition. The anterior two-thirds of tongue and the floor of mouth are the most common sites. Carcinogenesis involves irritants like cigarette smoking and alcohol, and overexpression of oncogenes. In South Asia, chewing tobacco along with betel leaves, betel nuts and slaked lime (paan or khaini), which is retained in the oral cavity for long periods of time, is a major risk factor. Occasionally, a large ranula may push its way through the mylohyoid muscle to present in the upper neck (plunging ranula). Leukoplakia Leukoplakia (white patch) develops on the oral mucosa as a response to chronic irritation-e. Different intraoral sites have different considerations, as outlined in the following summaries. Carcinoma of the tongue Clinically and anatomically, the tongue is divided into the anterior two-thirds or the oral tongue, and the posterior one-third, which lies in the oropharynx. The anterior lateral border is the most common source of oral cancer due to dental trauma. Nodal metastasis is related to poor differentiation, depth of invasion, involvement of extrinsic muscles of the tongue, tumour thickness >4 mm, lymphovascular invasion and perineural invasion. Retromolar trigone the retromolar trigone is the area of the mucosa overlying the ascending ramus of the mandible from the posterior surface of the last molar tooth to the apex superiorly. Tumours here are extensive, and often involve the posterior floor of mouth and the maxillary tuberosity. Lymph from the buccal mucosa drains into the parotid, submental, and submandibular lymph nodes, and from there to the upper deep cervical nodes. Floor of the mouth It is a horseshoe-shaped space extending from the inner surface of the lower alveolar ridge undersurface of the tongue. The floor of the mouth contains the openings of the submandibular and sublingual salivary gland ducts. Sore throat with exudate over the tonsils is a common manifestation of infectious mononucleosis (glandular fever). Liver function should be tested, and patients with abnormal tests advised to refrain from alcohol for a period of time. The hard palate the hard palate is a concave semicircular area that extends from the inner surface of the superior alveolar ridge to the posterior edge of the palatine bone. Tonsillitis this is due to bacterial infection of the tonsils, usually with Strep. Patients present with episodic sore throat associated with dysphagia, lymph node enlargement, fever and malaise. Tonsillitis must be differentiated from viral sore throats, which are not usually associated with pyrexia and often form part of a more generalised upper respiratory tract infection. Tonsillitis may be complicated by the development of a peritonsillar abscess (quinsy). Recurrent tonsillitis whose frequency and severity fulfil consensus-based guidance can be treated successfully by tonsillectomy. At the junction of the mouth and oropharynx are the tonsils, which consist of lymphoid tissue. Together with the adenoids (see earlier) and the lingual tonsil in the base of the tongue, they form a ring of lymphoid tissue. This ring is important in the development of immunity during early infancy, but subsequently can be removed without ill effect. The pharynx itself is surrounded by three constrictor muscles arranged one inside the other like a stack of bottomless beakers. Apnoeic individuals tend to sleep poorly, wake unrefreshed and become drowsy during the day. Simple snoring can be improved by weight loss and reduction of nocturnal alcohol intake. When excision of the primary site is recommended, this is often a conservation transoral approach: either transoral laser or transoral robotic intervention. The entire sequence takes half a second, at the end of which respiration, which must pause during the swallow sequence, can resume. A much slower, smooth muscle peristaltic wave then carries the bolus down the tubular oesophagus to the stomach. Assessment Hypopharynx Anatomy Below the oropharynx, the aerodigestive tract divides into an air passage (larynx/trachea) and an alimentary passage (oesophagus). The entrance to the air passage is protected by a purse-string mechanism formed when the mobile cartilage of the epiglottis is drawn down over the laryngeal inlet as the aryepiglottic folds shorten. Closure of the false cords forms a second sphincteric layer to protect against aspiration. Glottic closure, conversely, serves chiefly to stop air escaping from the chest, as when sustaining a long note in phonation, straining or lifting (fixing the chest volume). The entry of material into the oesophagus is controlled by the cricopharyngeus ring of muscle. Lateral to the larynx, the pharynx continues inferiorly on both sides into a pair of blind-ended pits known as the pyriform fossae. Clinical features Obstruction of the oesophagus and disorders that interfere with the muscle activity involved in swallowing cause dysphagia. Physical obstruction causes dysphagia that is worse for solids, whereas neurological disorders cause more difficulty with liquids. Hypopharyngeal pain may be felt locally or retrosternally, or may be referred to the ear (see Table 26. The level of obstructive dysphagia is always below the level at which the symptom is experienced. Hence, dysphagia localised by the patient in the pharynx requires an assessment down to the gastro-oesophageal junction. Examination the pharynx can be assessed in the clinic using a flexible rhinolaryngoscope. An ultra-thin, transnasal, digital video-oesophagoscope can be used to visualise the oesophagus and gastro-oesophageal junction under topical anaesthesia. More detailed images are obtained by the gastroenterology team using a wider bore flexible scope passed transorally, if required, as far as the duodenum. Physiology of swallowing Swallowing is achieved by the coordinated contraction and relaxation of muscles. A solid bolus will then gather at the tongue base, until the tongue propels it off through the pharynx when the swallow reflex fires. As the laryngeal inlet closes, the Imaging A barium swallow has a relatively limited part to play in swallow dysfunction. Video recording of small-volume contrast swallows (videofluoroscopy) can be used to provide additional information about the biomechanics of the oropharyngeal phase, and about bolus transit. It is the examination of choice where there is a suspicion of aspiration or misdirected swallow. Epiglottis Supraglottis Diseases of the hypopharynx Pharyngeal pouch this is formed by mucosal herniation through the weakest part of the pharyngeal musculature, the posterior midline between the two portions of the inferior constrictor of the pharynx. The hallmark symptom is dysphagia for solids, as the pouch tends to fill and compress the tubular oesophagus; but there may also be regurgitation of food, sometimes hours or even days after it was swallowed. In most cases, it is possible to divide the wall between the pouch and the oesophagus anterior to it. A specially designed disposable staple gun is passed transorally via an adjustable endoscope (diverticuloscope). Once the bar is divided, there is usually only a low shelf between the pouch and the oesophagus, and food no longer builds up under pressure. An alternative is laser division of the cricopharyngeal bar, especially if the pouch is too small to admit the staple gun. Endoscopic techniques may not be possible where transoral access is limited or the pouch is a very large pouch, and excision via an external neck incision may be indicated.

Dapsone Dapsone women's health clinic baulkham hills buy tamoxifen 20mg with amex, used among other indications against leprosis women's health clinic amarillo tx order tamoxifen online, apparently has no teratogenic potential women's health issues journal abbreviation order tamoxifen paypal. As dapsone bears a structural similarity to the sulfonamides women's health promotion issues purchase discount tamoxifen, it has been argued that it might compete with bilirubin for protein binding pregnancy videos generic tamoxifen 20 mg without a prescription, and thus could lead to hyperbilirubinemia in the newborn women's health center upper east side order tamoxifen 20mg without prescription. Fidaxomicin Fidaxomicin is a macrocyclic antibiotic which is approved for the treatment of infections with Clostridium difficile. If treatment took place in the first trimester, a detailed ultrasound examination should be offered to ascertain the normal development of the fetus. Linezolid Linezolid is a member of the oxazolidinone class, a new group of antibiotics. It acts bactericidally by inhibiting bacterial protein synthesis and is indicated in the treatment of multi-resistant pathogens. After intrauterine exposure from gestational weeks 14 to 18 a healthy infant was delivered at term (Mercieri 2010). With the lack of experience, linezolid should only be used for severe infections with problematic germs. Pentamidine the antiprotozoal agent pentamidine, among others effective in Pneumocystis pneumonia, has not been evaluated sufficiently in pregnancy to 2. Pentamidine is to be reserved in pregnancy for special situations when better tested antibiotics are not effective. Minimal enteral resorption and negative animal testing suggest that a high embryotoxic risk is unlikely. Streptogramins Streptogramins are a group of cyclic peptide antibiotics that inhibit, like macrolides and lincosamides, the synthesis of bacterial proteins. The later developed derivatives quinupristin and dalfopristin are used in a fixed combination. Streptogramins should only be applied as reserve antibiotics for infections with highly resistant Gram-positive germs. Their children were smaller and had lower birth weights than the control group of children of healthy mothers. These standard medications have not shown teratogenic or fetotoxic effects in humans. An increasing development of resistance makes it harder to choose the right medication in pregnancy. It can cross the placenta, but the risk of congenital malformations when used during pregnancy appears to be low. There are no reports indicating that ethambutol can cause ocular toxicity in the fetus, as it does in adults, when given in higher doses. The older literature contains case reports of different malformations and neurological damages in prenatally exposed children. As its structure resembles nicotinamide, it is assumed that it intervenes with the nucleic acid metabolism of the bacterial cell. In animal experiments, teratogenic effects were seen with doses 5­10 times higher than in human treatment. A long-term therapy of the mother could result in inhibition of vitamin K synthesis, and result in a higher bleeding tendency in neonates. When used near term the newborn should receive an extended vitamin K prophylaxis (Chapter 2. It is bactericidal, particularly affecting germs that proliferate extracellularly. Streptomycin is contraindicated during pregnancy because of its ototoxic properties. Inadvertent exposure does not require risk-based termination of pregnancy or invasive diagnostic procedures, but hearing tests should be performed after birth (Chapter 1. The extent of documented experiences in pregnancy is limited, and insufficient for a differentiated risk assessment. The reserve drugs discussed here should only be used for multi-resistant tuberculosis when standard therapy is not indicated. An inadvertent exposure during pregnancy does not require a risk-based termination or invasive diagnostic, but a detailed ultrasound examination should be carried out (Chapter 1. Further, with topical therapy, sensitization and resistance development need to be considered. Fusafungine has bacteriostatic and anti-inflammatory effects and is used as a spray for the treatment of infections of the nose and throat area. Fusidic acid is an antibiotic that is almost exclusively used externally; its prenatal tolerance has not been examined systematically, although the medication has been available for a long time. It has a narrow spectrum of effectiveness against Gram-positive bacteria (staphylococci) and is not recommended for an untargeted treatment. Mupirocin is primarily bacteriostatic, affecting staphylococci and streptococci by inhibiting bacterial protein synthesis. Mupirocin has not been examined systematically, but there is no evidence of undesirable effects in pregnancy. Retapamulin is the first representative of the pleuromutilins that is approved for human treatment. It is applied as an ointment for short-term treatment of superficial skin infections. Retapamulin inhibits bacterial protein synthesis and is bacteriostatic, primarily for Gram-positive germs. Systemic resorption is minimal with topical use, but nevertheless, as experience in pregnancy has been limited, its application needs to be critically examined. Taurolidine is an antimicrobial solution that can be used for lavage in peritonitis and for the prevention of infections with catheters. Nevertheless, the application of local antibiotics needs to be critically assessed. Increased resistance of malaria pathogens make it more difficult to suggest a general recommendation. Especially difficult is the management of malaria tropica caused by Plasmodium falciparum. Pregnancy enhances the clinical severity of falciparum malaria, especially in the primiparous and non-immune woman. Maternal malaria increases the risk of spontaneous abortion, stillbirth, prematurity, and low birth weight, and thus results in excess infant mortality. Therefore, mosquito-bite prevention, prophylaxis, and treatment of malaria should not be shortened or omitted in an ongoing pregnancy. Traveling to areas with multidrug-resistant malaria should be avoided if possible. The choice of drug for malaria prophylaxis and treatment during pregnancy depends on the local pattern of antimalarial drug resistance, the severity of the malaria, and the degree of pre-existing immunity. It is important to be well informed about the current recommendations for prophylaxis and treatment of malaria in the area to be visited. For travelers to malaria-endemic areas, a general recommendation is difficult because of increasing resistances. Depending on the drug, the chemoprophylaxis must be continued for up to 4 weeks after leaving the malarial region. Although data from prospective studies are limited quinine, chloroquine, proguanil, and clindamycin (Section 2. For the second and third trimester the World Health Organization recommends artemisinin derivatives. Reserve medications include the following: amodiaquine, atovaquone, dapsone (Section 2. During gestation plasma concentrations of many antimalaria agents are lower and their elimination is enhanced. Generally, the physician should discuss with a patient if the trip to a tropical region could be postponed (Section 2. The risk of exposure can be reduced by long clothes, mosquito netting, and repellents. In no case should medications be denied for prophylaxis or treatment on behalf of a pregnancy, as the potential risk for the unborn child predominates. If medications with inadequate pregnancy experience are used in the first trimester, a detailed ultrasound examination should be offered. A risk-based termination is not justified when the above-described medications have been used in pregnancy (Chapter 1. It can cause severe side effects such as liver damage and agranulocytosis, and for this reason, is unsuitable for prophylaxis. There has been no evidence of tetatogenicity (review by Thomas 2004), but experiences are limited. One study found only mild maternal side effects in 450 pregnant women who had been treated in the second or third trimester. An increase in miscarriages, prematurity, stillbirth, or malformations was not observed (Tagbor 2006). Artemisinin derivatives Artemisinin and its derivatives artemether, artemotil, artesunate, and dihydroartemisinin, are increasingly used against malaria as Plasmodium falciparum has developed resistance to other drugs. These compounds combine rapid blood schizonticide activity with a wide therapeutic index. Artemisinins should be given as combination therapy to protect them from resistance. Manyando (2010) more commonly found umbilical hernias in an additional 140 children whose mothers had been treated with artemether and lumefantrine. There are experiences with more than 1,500 pregnant women who used artemisinin derivatives in the second and third trimester. In summary, these studies did not find an increased risk in miscarriages, stillbirths, and malformations. To some degree the artemisisin derivatives were better tolerated by pregnant women, and were more effective than treatments of the control group. As plasma levels of artemether are decreased during pregnancy, it has been suggested that the dose and the dose interval may have to be adjusted. Monotherapy quickly leads to resistance, thus it is combined with proguanil when used for malaria prophylaxis and treatment. A Danish cohort study based on a prescription register with 149 women exposed during their first trimester to atovaquone, 93 of them exposed at any time in weeks 3 through 8 after conception, found no increased risk for birth defects (Pasternak 2011). When used in the second and third trimester, small studies observed no adverse effects (McGready 2005, Na-Bangchang 2005). Available data are insufficient for a differentiated risk assessment, but do not suggest a teratogenic risk. McGready (2003) discusses the need of a dose adjustment as clearance increases and levels decrease during pregnancy. Chloroquine Chloroquine, an antimalaria drug of the group of 4-aminoquinolines, works well and effectively as a schizonticidal drug against the erythrocytic forms of all types of plasmodia. Today though, almost all pathogens of the potentially lethal malaria tropica have become resistant to this rather well tolerated, and for many decades, useful medication. Resistance has also been noted for Plasmodium vivax, the pathogen of the less severe malaria tertiana. Plasmodium ovale and plasmodium malariae still remain mainly sensitive to chloroquine. Chloroquine is not embryo- and fetotoxic when used at the usual dose for malaria prophylaxis or for a three-day treatment of a typical malaria attack (McGready 2002, Phillips-Howard 1996). Current evidence does not suggest fetal ocular toxicity when chloroquine was used as antimalarian medication during pregnancy (review by Osadchy 2011). Lee (2008) examined 12 pregnant women and nonpregnant controls, and did not find any changes in the pharmacokinetics or the serum level of chloroquine. The anti-inflammatory properties of chloroquine are used also for antirheumatic therapy (Section 2. Antirheumatic doses of chloroquine are higher than those used for malaria prevention. Chloroquine may be used throughout pregnancy for the prophylaxis and treatment of malaria. If chloroquine resistance of the parasite is likely or has been demonstrated, other drugs must be used. Becauses it can provoke life-threatening cardiac arrhythmias in patients with heart disease, or in conjunction with other arrhythmogenic medications, halofantrine is no longer recommended. Halofantrine is only to be used in cases of acutely threatening malaria that cannot be managed with better tested and less toxic drugs. Lumefantrine Lumefantrine belongs to the group of arylamine alcohols like quinine, mefloquine, and halofantrine. Artemether plus lumefantrine is currently a popular artemisinin-based combination therapy. Few experiences are available regarding its application in the first trimester without showing evidence of a teratogenic risk. For the second and third trimester, studies with several hundred patients have been reported and do not indicate a major risk (Piola 2010, McGready 2008). Manyando (2010) found only a mild increase in umbilical hernias in 140 children whose mothers took artemether and lumefantrine during the first trimester. Most of these had disappeared when follow-up examination was conducted 12 months later. In summary, current experiences do not suggest a major embryo- or fetotoxic risk of lumefantrine. During pregnancy, the plasma concentration is lower and the elimination enhanced, thus increasing the risk of treatment failure. Mefloquine Mefloquine displays an effective and rapid activity against the erythrocytic forms of all plasmodia. Current experiences with more than 2,000 treated pregnant women, several hundred of them in the first trimester, do not suggest a teratogenic or fetotoxic potential in humans.

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Patients present with symptoms of low blood glucose (hypoglycaemia), which may be improved by eating or with vague neurological symptoms breast cancer breakthrough purchase 20 mg tamoxifen visa. Further controlled testing includes the 72-hour fast, which is the criterion standard for establishing the diagnosis of insulinoma, as 98% of patients with insulinomas will develop symptomatic hypoglycaemia within 72 hours menopause estrogen discount tamoxifen 20 mg overnight delivery. These tumours are generally malignant and may present as large tumours with 70% having evidence of tumour spread at the time of diagnosis breast cancer volleyball socks buy tamoxifen with american express. Aggressive surgical removal of as much tumour as possible is often indicated to relieve the severe symptoms associated with excessive hormone secretion pregnancy gender prediction tamoxifen 20 mg for sale. Some patients do not present with all these tumours, so it has been agreed that diagnosis is made when a patient presents with two of these concomitantly breast cancer 3 day san diego buy tamoxifen cheap. Hyperparathyroidism occurs in about 90% of patients, endocrine pancreatic tumours in 60% of patients; usually they are small and nonfunctional, and the most common hormonally active ones are insulinomas or gastrinomas pregnancy 8 weeks 1 day order tamoxifen with paypal. Pituitary adenomas are present in 40% of patients, and in 60% of the patients skin manifestations can also be present. On percussion, an enlarged spleen causes dullness over the ninth rib in the midaxillary line. Physiology Circulatory filtration the cut surface of the spleen reveals areas of red and white pulp surrounded by fibrous trabeculae. The red pulp is a loose honeycomb of reticular tissue that contains the splenic sinusoids, lined by macrophages, and blood vessels pass into the pulp along the trabeculae. As erythrocytes age, the normal lifespan being about 120 days, the cell membrane becomes less flexible and because erythrocytes are required to deform to pass through the sinusoids, senescent cells are trapped within the spleen and therefore removed from the circulating population of cells. Following phagocytosis iron is split from the haem portion, and stored as haemosiderin before being transported to the bone marrow bound to transferrin to be incorporated into a new population of erythrocytes. Unlike in some mammals, the spleen is not a site of significant blood pooling except in pathological conditions with splenomegaly, where the spleen may contain more than a litre of blood. Following splenectomy, there is an increased number of misshapen red cells in the peripheral blood, some containing nuclear remnants (Howell-Jolly bodies) and others containing clumps of iron (siderocytes). The spleen Surgical anatomy the spleen is a vascular organ lying in the left upper quadrant of the abdomen alongside the 9th, 10th and 11th ribs, and is usually impalpable. The convex outer surface and superior pole lies against the diaphragm, the concave inner surface is related to the fundus of the stomach, the pancreatic tail and the upper pole of the right kidney, and its lower pole rests on the splenic flexure of the colon below. The phrenicocolic ligament, which runs between the splenic flexure of the colon and the undersurface of the diaphragm, provides additional support. Arterial inflow is primarily through the tortuous splenic artery arising from the coeliac axis, which carries 40% of the splanchnic blood flow into the spleen. The splenic vessels are closely related to, and may run within, the pancreas entering the spleen at the splenic hilum. The spleen has a secondary vascular inflow and outflow via the short gastric vessels that run within the lienogastric ligament to the upper part of the greater curvature of the stomach, which assume importance when the main splenic vessels are occluded through surgical division, radiological embolisation or spontaneous thrombosis. It is then best palpated bimanually, with the patient lying on the right side with the left side turned slightly forward. The distinctive notch on the anteroinferior border of the spleen may Immunological function the spleen is an important site for promoting both cell-mediated and humoral immunity. Antigens entering the spleen are engulfed by macrophages, promoting antigen presentation, with subsequent antibody production in the germinal centres. Haemopoiesis In utero in the second and third trimester the spleen is an important source of erythrocyte and granulocyte production for the foetus. Although at birth this function usually ceases, in some disease processes with a high turnover of erythrocytes the spleen may continue to contribute to this process (extramedullary haemopoiesis). Indications for splenectomy (nontraumatic) Although the recommendation to remove the spleen often comes from the haematologist, the surgeon must be aware of the indications for splenectomy and the criteria that should be fulfilled before accepting a patient for operation. Splenectomy is indicated if treatment fails from the outset or if there is a fall in the haemoglobin following the reduction or cessation of steroids. Immunoglobulin G (IgG) antibody develops against platelet membrane antigen, resulting in the premature destruction of platelets. The low platelet count is associated with reactive megakaryocytosis within the bone marrow. Epistaxis, bleeding from the gastrointestinal tract and other sites is associated with petechiae and ecchymoses. The spleen is usually not overly enlarged, making it particularly suitable for laparoscopic removal. Hypersplenism this syndrome consists of splenomegaly and pancytopenia in the presence of an apparently normal bone marrow and the absence of an autoimmune disorder. There is sequestration and destruction of blood cells in the spleen, affecting predominantly white cells and platelets. In portal hypertension, splenic congestion frequently leads to splenomegaly and hypersplenism. The enlarged spleen results in an expansion of the total blood volume to fill the increased vascular spaces of the enlarged spleen with pooling of cells and increased destruction within the sinusoids. This results in anaemia, leucopenia and thrombocytopenia, with reticulocytosis and leucoerythroblastosis in the marrow. Increased haemoglobin turnover results in increased amounts of urobilinogen in the urine. Splenectomy may be appropriate but the potential morbidity, the risks of late septic complications and the prognosis of the underlying cause of the hypersplenism require to be balanced with the potential alleviation of the pancytopenia. Splenectomy is in general contraindicated in secondary purpuras, although it may be advised if hypersplenism is associated with symptomatic secondary thrombocytopenia. Thrombosis may result from acute or chronic pancreatitis, or the vessel may become compromised by direct invasion from a carcinoma of the pancreas. Gastric varices are particularly prominent in this condition and often communicate directly with short gastric veins. Acute variceal haemorrhage in this situation is, however, relatively rare but may be best managed by splenectomy with ligation of the vessels on the greater curvature of the stomach, as endoscopic control can be difficult. Recurrent haemorrhage is unusual following surgery and the prognosis is favourable, given that there is often no associated liver disease. Haemolytic anaemias Hereditary spherocytosis In this autosomal dominant disorder, red blood cells are spherical rather than biconcave, are fragile, and are destroyed when trapped within the splenic sinusoids. Mild hereditary spherocytosis can be managed without folate supplements and does not require splenectomy. Moderately and severely affected individuals are likely to benefit from splenectomy, which Proliferative disorders Myelofibrosis It is recognised that this condition is due to an abnormal proliferation of mesenchymal elements in the bone marrow, spleen, liver and lymph nodes, and that extramedullary haemopoiesis occurs at many sites. Splenectomy decreases transfusion requirements and, by relieving the discomfort of a grossly enlarged spleen, also improves symptoms. Other tumours Of the other rare tumours, haemangiomas (capillary or cavernous) may reach sufficient size to cause splenic enlargement, with a consumptive coagulopathy and haemorrhagic tendency. Miscellaneous conditions Cysts of the spleen Cysts of the spleen are uncommon and are usually single. Congenital cysts are due to an embryonic defect and result in a dermoid-like lesion. The wall is fibrous and often calcified, and the cyst is filled with brownish fluid or paste-like material. Pancreatic pseudocysts may extend to involve the spleen and parasitic cysts may occur due to infection with Echinococcus granulosus (hydatid disease). Symptomatic cysts may present with left upper quadrant pain radiating to the back or left shoulder. In addition, in patients with splenic enlargement, the mechanism may be relatively trivial. The cardinal features are those of significant blood loss, and local signs of peritoneal irritation (peritonitis or left shoulder tip pain). Patients that do not respond to initial resuscitation require an emergency laparotomy and usually a splenectomy along with a careful exploratory laparotomy to exclude injury to other structures. Approximately 80% of splenic injuries may be managed conservatively, and of these the requirement for intervention is apparent within 72 hours in 95%. In the unstable patient, control of haemorrhage and restoration of circulating volume are paramount and consideration regarding organ preservation is of secondary importance. Unlike an elective splenectomy, a midline laparotomy is usually performed with packing of the left upper quadrant, which will normally control the splenic haemorrhage to allow the remainder of the abdomen to be examined. If examination of the spleen reveals bleeding from the splenic hilum, preservation is not appropriate and a splenectomy should be performed. Splenic infarct Splenic infarct may present with acute onset of left upper quadrant pain in a patient with known hypersplenism. Asymptomatic infarcts may be observed in patients following a severe attack of pancreatitis or following a spleen-preserving distal pancreatectomy. These may resolve with the formation of a splenic cyst, but do not require surgical intervention. It should be suspected when progressive splenic enlargement is associated with bacteraemia and abscess formation at other sites. Image guided drainage may be appropriate in select cases but splenectomy is often required to achieve resolution. Splenic artery aneurysm this may occur primarily as a complication of atherosclerosis in elderly patients where the calcified wall of the aneurysm may be visible on x-ray or secondary to acute or chronic pancreatitis. The presence of a small, uncomplicated primary aneurysm is not necessarily an indication for intervention, particularly as they often affect elderly, frail patients. Bleeding can occur, however, and mesenteric angiography with embolisation is the treatment of choice. Bleeding is more common in secondary aneurysms, and again the treatment of choice is radiological if possible as surgery in an actively bleeding patient is associated with a high mortality rate. Splenic conservation Because of the immunologic function of the spleen, interest over the last century has turned to salvage of the spleen rather than splenectomy. As the majority of patients can be managed conservatively without embolisation, care needs to be taken that in striving to avoid laparotomy inappropriate delay in haemostasis does not occur in those with ongoing bleeding. For example, the patient with blunt polytrauma with competing priorities, such as a closed head injury, will not tolerate the haemodynamic compromise from a delayed bleed following an attempt at splenic preservation. Similarly, physiological instability including coagulopathy may necessitate splenectomy as part of a damage-control approach, even in the context of a spleen that was otherwise suitable for preservation. An increase in platelet adhesiveness is also seen, leading to an increased risk of thrombosis. The immunological defects seen after splenectomy include a poor response to immunisation with particulate antigens, decreased levels of phagocyte-promoting peptide, deficiency of serum IgM levels and decreased properdin levels. Postsplenectomy immunisation Loss of lymphoid tissue reduces immune activity and impairs the response to bacteraemia. The risk of overwhelming postsplenectomy sepsis is greatest when splenectomy is performed in childhood. The British Committee for Standards in Haematology recommends that all splenectomised patients should receive pneumococcal polysaccharide vaccine, Haemophilus influenzae type B vaccine, and meningococcal C conjugate vaccine. Lifelong prophylactic antibiotics are still recommended (oral phenoxymethylpenicillin or erythromycin). Other indications for splenectomy Removal of the spleen may be required as part of other surgical procedures, such as distal pancreatectomy and radical gastrectomy for carcinoma and, less frequently, for proximal splenorenal shunt. Effects of splenectomy Following splenectomy changes occur in the blood cell composition and immunological status of the patient. Absence of pitting 15 the small and large intestine Chapter contents Introduction 252 Surgical anatomy and physiology 252 Clinical assessment of the small and large intestine 253 Principles of operative intestinal surgery 254 Disorders of the appendix 255 Inflammatory bowel disease 255 Disorders of the small intestine 261 Small and large bowel obstruction 264 Non-neoplastic disorders of the large intestine 266 Intestinal stoma and fistula 272 Polyps and polyposis syndromes of the large intestine 272 Malignant tumours of the large intestine 275 16 Malcolm G. Most disorders are self-limiting, benign conditions but serious pathology can have enigmatic, or even, no symptoms until a late stage in the natural history of the disease. Infective diarrhoea most commonly affects the young; inflammatory conditions those in early and middle adulthood; cancer and diverticular disease in middle and old age. There are similarities in presenting symptoms despite varied underlying disorders and it is usually not possible to differentiate underlying causes from clinical assessment alone (see Box 16. Thus, self-resolving disorders, in which watchful waiting is appropriate, may be indistinguishable from those requiring timely investigation and active management. Investigation can be potentially harmful, since it frequently involves invasive investigations such as colonoscopy and radiation exposure. Careful history and examination, informed by knowledge of the hierarchy of likely age-related diagnoses is essential when assessing patients with intestinal problems. Surgical anatomy and physiology Anatomy and function of the small intestine the small bowel extends from the pylorus to the ileocaecal valve and ranges in length from 3 to 7 metres. The jejunum comprises two-fifths of the small intestine and is of wider calibre than the ileum.

Bonapace and Fisher (1998) did not find an increased risk of malformations when docusate was used during pregnancy breast cancer kills 20mg tamoxifen fast delivery. An osmotic effect leads to the secretion of water into the intestinal lumen resulting in a softening of the stool women's health center vashon cheap tamoxifen 20mg visa. As a mono-preparation glycerol is harmless and to be preferred to its combination with docusate menstrual android generic 20 mg tamoxifen overnight delivery. After the sugar part has been cleaved off in the intestine it is absorbed to some degree and eliminated through urine (discoloration! If the conversion to a diet rich in fiber is not sufficiently effective breast cancer options safe 20mg tamoxifen, bulking agents may be used women's health subscription buy tamoxifen 20mg line. Sodium picosulfate pregnancy x category drugs buy genuine tamoxifen line, sodium sulfate, and mannitol and sorbitol rectally are acceptable. Anthraquinone derivatives, paraffin, and, if possible, castor oil are not to be used. If infectious enteritis has an invasive course (bloody stools, high fever), diagnostic clarification is mandatory and antibiotic treatment may be necessary. It is a pethidine derivative, which reacts with opiate receptors, but it does not have analgesic properties. In a prospective study of 105 pregnant women who took loperamide (89 of them exposed in the first trimester), no evidence of teratogenic effects was seen. Notable, however, was that the birth weight of newborns was on average 200 g lower than controls when mother were continuously treated (Einarson 2000). An analysis of data of the Swedish Birth Registry with 638 loperamide-treated pregnant women noted a slightly increased risk of malformation, but, as the author admits, exposure time, duration and application dosage were not, or were only partially, known. The statistically elevated risk for hypospadia, placenta previa, high birth weight and caesarean section was considered to be a random event due to multitesting (Kдllйn 2008). Racecadotril, a prodrug of tiorphan, works by inhibiting a cell membrane peptidase (enkephalinase) as an antisecretory agent in the intestine. Regarding tannin and albumin tannate, agents that are not appreciably absorbed, there are no indications of specific embryotoxic effects, but also hardly any documented pregnancy experiences. Medical charcoal, apple pectin and similar agents do not present a danger for the pregnancy. Oral ethacridine lactate is effective primarily locally in the intestine at a local level, and almost none of it is absorbed. As little of it becomes biologically available, an increased risk for malformation appears to be unlikely. It is rare that acute diarrhea requires a treatment that would exceed dietetic measures. If it really becomes necessary to impede intestinal motility any further, loperamide may be used, preferably after the first trimester. An active disease increases the risk of miscarriage, premature birth, low birth weight, and perinatal complications. Naturally, exacerbations need to be treated during pregnancy in order to improve the pregnancy outcome. In view of the risk-benefit ratio the therapy has to be determined for each patient based on the individual course (Pedersen 2013, Bortoli 2011, Mowat 2011, Dignass 2010, van der Woude 2010, Cassina 2009, Travis 2008). This applies also for a therapy during the remission phase of an unplanned pregnancy. The antibiotics metronidazole, ciprofloxacin and clarithromycin may be used during pregnancy if necessary (see Chapter 2. Probiotics derived from, for example, Escherichia coli, Lactobacillus and Bifidobacterium spp. Concerns that the sulfonamide, when given prenatally, might favor kernicterus in the newborn are theoretically plausible, but practically insignificant. Sulfasalazine and mesalazine have been well investigated; fewer data are available for olsalazine and balsalazide. Up to now, no animal and human studies have demonstrated a consistent teratogenic effect of these drugs. Many varied experiences support that sulfasalazine and mesalazine are well tolerated by mother and fetus throughout 104 2. Studies on 157, 165, and 123 pregnant women (Nшrgеrd 2007, Diav-Citrin 1998, Marteau 1998) failed to detect an increased developmental risk. There was no increase in miscarriages, premature births, and low birth weights (Rahimi 2008). A case report of a newborn with renal functional disturbances whose mother had taken 2­4 g/d mesalazine from the third to the fifth month has been published (Colombel 1994). While up to 50% of orally given mesalazine is adsorbed, only small amounts cross the placenta and reach the fetus. This may also explain why so far no cases of premature closure of the ductus arteriosus have been observed when treatment took place after the 30th gestational week. On the other side, a publication described similar concentrations of mesalazine in maternal and umbilical blood (Christensen 1994). Paternal exposure: Sulfasalazine may lead to a reversible reduction in the number and motility of sperm. An Inflammatory bowel disease requires treatment accordingly with its degree of intensity in the pregnancy. Flare-ups of the disease activity should be treated appropriately since they have been associated with fetal and maternal adverse effects. Corticosteroids may be used during pregnancy, locally or systemically, when indicated (see Chapter 2. The same holds for 6-mercaptopurine and, in a more limited way, for 6-thioguanine. Biological agents such as infliximab and adalimumab are only to be used when the aforementioned agents have failed (see Chapter 2. The formation of gallstones with cholesterol is favored during pregnancy presumably due to a lessened contractility of the gall bladder. This effect is apparently not due to the also observed increase on the cholesterol concentration in the biliary fluid (Braverman 1980). So far, only four cases have been published with exposure during the first trimester (Zamah 2008, Korkut 2005). Malformations and liver damage have been observed in animal experiments when these medications were administered; a corresponding finding has not been observed in humans. It decreased itching more effectively, resulted in less prematurity, and brought liver values to lower levels (Kondrackiene 2005). There is no documented experience with the use of chenodeoxycholic acid in pregnancy. If a patient conceives during therapy, the medication should be discontinued, if possible. After exposure during the first trimester, a follow-up sonogram may be offered to verify normal fetal development. In the treatment of hypercholesterolemia fibrates represent an outdated treatment approach; the superiority of statins has been documented. Treatment with fibrates is further compromised by suspected carcinogenicity, hepatotoxicity, and immune reactions. Moreover, as the fetus has a diminished ability to conjugate glucuronides, it is possible that toward the end of pregnancy fibrates accumulate in the fetus. Pharmacologically and toxicologically bezafibrate, etofibrate, fenofibrate, ciprofibrate and gemfibrozil appear similar to clofibrate that has been withdrawn from the market in several countries because of severe side effects. Gemfibrozil is useful (as a back-up medication) for the management of severe hypertriglyceridemia and combined hypertriglyceridemia and hypercholesterolemia, more so when there is a high risk for pancreatitis. Experiences with the above-mentioned medications are inadequate for a risk assessment. Atorvastatin, fluvastatin, lovastatin, simvastatin, and pitavastatin are lipophilic drugs, while pravastatin and rosuvastatin are hydrophilic. Cerivastatin was removed from the market in 2001 as it leads to severe rhabdomyolysis, sometimes with lethal outcome. Indisputably, statins have a beneficial effect in secondary prevention in patients who have manifested a cardiovascular disease. Thus, a recent meta-analysis failed to find a reduction in the mortality when statins were used in patients without preexisting cardiovascular disease (Ray 2010). There are theoretical concerns about the use of these medications in pregnancy, when an undisturbed cholesterol synthesis is important. Moreover, there is some suspicion that statins can influence the development of the embryo and fetus by blocking the synthesis of cholesterol. Gibb 2005) ­ there are no other studies suggesting a risk of embryonic/fetal development. Positive experiences with the use of statins during pregnancy covers more than 600 women exposed to them. One manufacturer reports about 225 prospectively ascertained pregnancies where simvastatin or lovastatin was used. They did not reveal an increased risk of malformations, nor did two prospective studies with 64 (Taguchi 2008) and 249 (Winterfeld 2013) pregnant women exposed in the first trimester. An investigation with registry data of 64 pregnancies with exposure to statins did not find an increased risk when compared to a fibrate group and a control group with affected women not taking any medication (Ofori 2007). Evaluation of the data of the National Birth Defect Prevention Study and the Slone Epidemiology Center 2. Statins used for primary prevention should be discontinued when planning a pregnancy, or at the very latest when a (unplanned) pregnancy is diagnosed, as the therapeutic benefit still has not been proven, and harm for the mother is not to be expected when therapy is withheld during the duration of her pregnancy. However, for women with severe metabolic disease an individual decision should be made weighting risks and benefits. If statins were prescribed for secondary prophylaxis after a cardiovascular event, they may be continued in pregnancy as well, if this is deemed necessary. After statin exposure during the first trimester, a detailed fetal ultrasound should be offered to ascertain normal fetal development. Colestyramine, also cholestyramine, is an anion exchange resin that is not adsorbed by the gastrointestinal tract. It binds with bile acids forming an insoluble complex that is eliminated with the feces. Colestyramine is used in the treatment of dyslipidemia, chronic cholestatic liver diseases and intrahepatic cholestasis of pregnancy. Ursodeoxycholic acid, however, is more effective in the treatment of hitching due to gestational cholestasis (Kondrackiene 2005). Case reports with colestyramine do not show any signs of teratogenicity (Landon 1987). This is further supported by a recommendation of the manufacturer to use colestyramine as a washout therapy (3Ч daily 8 g over 11 days) when there had been an accidental leflunomide treatment during pregnancy. In the largest prospective study assessing the compatibility of leflunomide in the first trimester, 61 pregnant women had received colestyramine (Cassina 2012, Chambers 2010). Moreover, there is a theoretical risk for fetuses because colestyramine binds not only to bile acids but also to other lipophilic agents such as fat-soluble vitamins and medications. Two case reports describe severe brain hemorrhage in fetuses after exposure to colestyramine and discuss a vitamin K deficiency due to the pharmacologic therapy of the mother (Sadler 1995, and from unpublished own data). Other bile acid sequestrants that are not adsorbed by the gastrointestinal tract are colestipol and colesevelam. These medications have not been sufficiently studied for pregnancy effects, but there have not, as yet, been indications of specific teratogenic effects. As with the related agent cholestyramine, they can bind and impede the absorption of a variety of nutrients. The methods applied to collect the data in different studies and their low case numbers do not allow a reliable assessment of risk. When interpreting these data it should be recognized that the mothers have significant comorbidity, such as obesity, diabetes mellitus, hypertension, and preeclampsia. When absolutely necessary, colestyramine may also be used to lower a high lipid level. If given for a longer time, the need for the supply of fat-soluble vitamins has to be considered, although these have to be taken at a different time from colestyramine. Other lipid-lowering drugs Fish oil contains the omega-3 fatty acids (eicosapentaenoic, docosahexaenoic and linoleic acids) that are thought to reduce triglyceride levels. The mechanism of action remains unclear and the effectiveness in terms of any reduction of vascular problems is unproven. Nicotinic acid, a water-soluble B-vitamin, and its derivative acipimox are used in the treatment of hypertriglyceridemia but their mechanism of action has not been fully explained. Nicotinic acid often triggers a flush, and to control this side effect, a combination drug with Laropiprant and nicotinic acid has been released. Laropiprant is a prostaglandin D2 receptor 1 antagonist that has its own side effect profile. It has not yet been tested whether this therapy has a positive effect upon cardiovascular endpoints. Ezetimibe selectively inhibits the intestinal resorption of cholesterol from food and bile. There is some concern that the combination of these two cholesterol-lowering drugs could lead to a higher incidence of myopathy and hepatitis with elevations of transaminases. The other lipid-lowering agents mentioned here should not be prescribed as they lack safety data. Most anorectics have been taken off the market in Europe, even dexfenfluramine worldwide, because of cardiac side effects.