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Copious bilateral milky discharge (galator- index nger and thumb and a ne needle attached to rhoea) may indicate a prolactinoma (see page 421) hence asyringe (often in a holder) is inserted into the lesion aserum prolactin level should be sent discount 3mg stromectol with visa antibiotics for sinus infection dose. Aspiration is performed by exerting gentle negative Management pressure through the syringe cheap stromectol 3 mg without prescription antibiotic heat rash. A number of passes are If thereisnomass order stromectol 3 mg mastercard bacteria zombie,anon-bloodydischargeandtheinves- made through the lesion at differing angles whilst neg- tigations have proved negative, management is conser- ative pressure is maintained. Surgical intervention is indicated if the discharge is profuse and embarrassing or if malignancy cannot be the area. One or Investigations/procedures two passes are usually sufcient to obtain diagnostic material. Imaging in breast disease Cytology from either procedure is graded into ve cate- gories (see Table 10. There are two main modalities of imaging used in as- sessment of breast disease depending on the age of the patient: r Breast reconstruction Ultrasound is the imaging method of choice for estab- lishing the nature of a breast mass in younger women Following a mastectomy breast reconstruction can be (less than 35 years). Mammograms can be difcult to performed at the same time or as a delayed procedure. Mammography alone has C2 B2 Benign a 10% false negative rate, hence it is used as part of C3 B3 Probably benign C4 B4 Probably malignant the triple assessment (clinical examination, imaging, C5 B5 Malignant breast tissue sampling). Breast development Fibroadenoma, juvenile r Previous irradiation does not rule out breast recon- hypertrophy struction but may affect the choice of surgical tech- Cyclical activity Cyclical mastalgia, cyclical niques. The mammary dysplasia) these have now been classied skin may need to be gradually stretched rst using as aberrations of normal development and involution atissue expander. A free ap requires its blood vessels to be surgically re- Aetiology anastomosed such as a latissimus dorsi ap. It may be used Some women develop generalised breast nodularity and as a pedicle or free ap. Complications of myocuta- others present with more localised nodularity (see also neous aps include necrosis of the ap and scarring section Breast Lumps, page 409). Nipple prostheses offer an alternative to ination, imaging and tissue sampling) is required for further surgical treatment. Benign breast disease Fibroadenoma Denition Denition Abnormalities that occur during the normal cycle of Previously broadenomas were considered to be benign breast proliferation and involution. Larger lesions and those with equivocal his- theyarebestconsideredasanaberrationofnormalbreast tology should be excised. Prognosis Incidence Untreated only 10% of broademonas increase in size Most common cause of a discrete breast lump in young over a 2-year period most of which occur in teenage women. Breast cysts Denition Pathophysiology Acommon uid lled epithelial lined space in the breast Fibroadenomas are usually solitary lesions that result presenting as a mass. Fibroadenomas are under hormonal Incidence control,theymayenlargeduringpregnancyandinvolute Palpable cysts occur in 7% of women in Western coun- at menopause. Clinical features Aetiology/pathophysiology Patients (normally young women) present with a Breast cysts are a very common nding in the years lead- smooth, rm, painless nodule that is well-demarcated ing up to the menopause and are thought to arise due to and freely mobile (breast mouse). Juvenile broadenoma is a rare subtype that occurs in femaleadolescentsandgrowsrapidly. Macroscopy/microscopy An encapsulated rubbery white lesion with a glisten- Investigations ing cut surface. It consists of a brous connective tissue Patients require a triple assessment consisting of clinical component and abnormally proliferated ducts and acini examination (see page 409), imaging using ultrasound (adenoma) in varying proportions. Investigations Investigation of any breast lump involves a triple assess- Management ment consisting of clinical examination (see page 409), Patients with a single cyst do not need to be reviewed fol- imaging normally by ultrasound as patients are young lowing an otherwise normal ultrasound and successful and sampling by core biopsy or ne needle aspiration neneedleaspiration. Indications for surgical biopsy in- Management clude bloody uid detected on ne needle aspiration, If conrmed as a broadenoma on triple assessment, aresidual mass following aspiration, or multiple recur- small lesions may be left unless the patient requests rence at the same site. This is Denition associated with an increased risk of developing breast Abenign breast disorder with dilation (ectasia) of the cancer. Clinical features Most patients present with a bloody or serous nipple Age discharge. It is often possible to identify the discharge Most common in women approaching the menopause. There may be a small Aetiology/Pathophysiology swelling at the areolar margin (30%), which if pressed The dilated ducts are lled with inspissated secretions may produce discharge. Macroscopy/microscopy One to two centimetres sized papilloma within a di- Clinical features lated duct with secretions collected behind it. The le- Duct ectasia may be asymptomatic or may cause nipple sion usually consists of fronds of vascular tissue covered discharge (often green) and localised tenderness around byadouble layer of cells resembling ductal epithelium. Investigations Macroscopy/microsopy Mammography and/or ductography show the dilated The ducts may be dilated as much as 1 cm in diam- duct and lling defect. Awire is often passed into the responsible duct, which is excised as a microdochectomy with the breast segment Investigations that drains into it. Although ductography or duc- toscopy are possible, they are not routine investigations. Fat necrosis Denition Management An uncommon condition in which there is death of fat Once the diagnosis is conrmed surgery may be required cellswithin the breast. Treatment is by subareolar excision Aetiology/pathophysiology of the affected ducts. The aetiology is unclear, it is suggested that the death of fat cells may result from trauma. There is an acute inammatory response, which in some cases progresses Duct papilloma to chronic inammation and organisation with brous Denition tissue. The result may be a hard, irregular mass, which Abenign proliferation of the epithelium within large can mimic carcinoma. Clinical features Aetiology pathophysiology Patients present with a hard mass, which may also have Papillomas usually arise less than 1 cm from the nipple skin tethering; often in an obese patient with large and obstruct the natural secretions from the gland. Breast-feeding should be encouraged as this aids drainage of the affected segment of the breast. Lipid-laden macrophages breast-feeding, the baby should be fed from the non- (foam cells/lipophages) may form multinucleate giant infected breast and expression of milk used to drain cells. An alternative is daily ultrasound-guided aspiration with antibiotics until the infection has resolved. Infections of the breast Acute mastitis Breast cancer Denition Acute bacterial inammation of the breast is related to Denition lactation in most cases. Aetiology/pathophysiology r Incidence Breast-feeding predisposes to infection by the devel- Approximately 2/1000 p. Peak 5060 years Periductal non-lactating mastitis is associated with smoking in 90%. It has been suggested that smok- ing may damage the subareolar ducts, predisposing Sex to infection. Clinical features Patients present with painful tender enlargement of the Aetiology breast, often with a history of a cracked nipple. If left In most cases it appears to be multifactorial with a strong untreated an abscess may form after a few days.

Rates of hypoglycaemia 3 mg stromectol otc antibiotics zone of inhibition chart, however generic 3 mg stromectol visa antibiotic resistance experts, were very low overall and the study only followed up patients for 12 weeks order 3 mg stromectol amex antibiotic bone cement. Extrapolation from the evidence would suggest that specific subgroups of patients may benefit. These include those who are at increased risk of hypoglycaemia or its consequences, and those who are supported by health professionals in acting on glucose readings to change health behaviours including appropriate alterations in insulin dose. Further research is needed to define more clearly which subgroups are most likely to benefit. B Routine self monitoring of blood glucose in people with type 2 diabetes who are using oral glucose-lowering drugs (with the exception of sulphonylureas) is not recommended. Studies suggest that urine testing is equivalent to blood testing but these studies were generally carried out in an era when HbA1c levels were higher than would now be considered acceptable, limiting the applicability of these data to current practice. The meta-analysis suggests that a very modest improvement in glycaemic control is associated with urine testing versus placebo (HbA1c -0. B Routine self monitoring of urine glucose is not recommended in patients with type 2 diabetes. In the emergency department setting, a cross-sectional study suggested that blood ketone measurement may be a more accurate predictor of ketosis/acidosis than urine ketone measurement. There is insufficient evidence to make a recommendation on the routine measurement of ketones in patients with type 1 or type 2 diabetes. Smoking cessation reduces these risks substantially, although the decrease is 61, 62 4 dependent on the duration of cessation. Men who smoke are three times more likely to die 55 aged 45-64 years, and twice as likely to die aged 65-84 years than non-smokers. Studies done among women during the 1950s and 1960s reported relative risks for total mortality ranging from 1. A pack year is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years an individual has smoked. There is a suggestion that smoking may be a risk factor for retinopathy in type 1 diabetes64, 65 2+ but not in people with type 2 diabetes. A Healthcare professionals involved in caring for people with diabetes should advise them not to smoke. B Intensive management plus pharmacological therapies should be offered to patients with diabetes who wish to stop smoking. There is no clear evidence suggesting that pharmacological intervention or counselling strategies to aid smoking cessation in patients with diabetes should differ to those used in the general 4 population. B Healthcare professionals should continue to monitor smoking status in all patient groups. Health-enhancing physical activity is physical activity conducted at a sufficient level to bring about measureable health improvements. This normally equates to a moderate intensity level or above and can generally be described as activity that slightly raises heart rate, breathing rate and core temperature but in which the patient is still able to hold a conversation. Exercise is a subset of physical activity which is done with the goal of enhancing or maintaining an aspect of fitness (eg aerobic, strength, flexibility, balance). It is often supervised (eg in a class), systematic and regular (eg jogging, swimming, attending exercise classes). There is no gold standard and techniques range from heart rate monitoring to motion counters and self reports. Self report is the easiest format but there is often an over reporting of minutes spent in activity. The Scottish Physical Activity Questionnaire 4 is an example of one self report format that has known validity and reliability for assessing moderate activity. A rate of perceived exertion scale is useful for estimating exercise intensity, particularly in people with autonomic neuropathy who have reduced maximal heart rate. This risk reduction is consistent over a range of intensity and frequency of activity, with a dose- 2+ related effect. Greater frequency of activity confers greater protection from development of 2++ type 2 diabetes and this is valid for both vigorous- and moderate-intensity activity. All of these studies have shown a relative risk reduction varying from 46 to 58% in the development of type 2 diabetes. Programmes lasting from eight weeks to one year improve glycaemic control as indicated by a decrease in HbA1c levels of 0. No significant difference was found between groups in quality of life, plasma cholesterol or blood pressure. A People with type 2 diabetes should be encouraged to participate in physical activity or structured exercise to improve glycaemic control and cardiovascular risk factors. Limited research has addressed the economic impact of physical activity and exercise programmes. A systematic review of randomised and observational studies reported that exercise and physical activity programmes in people with type 1 diabetes do not improve glycaemic control but + 1 improve cardiovascular risk factors. B People with type 1 diabetes should be encouraged to participate in physical activity or structured exercise to improve cardiovascular risk factors. Greater amounts of activity should provide greater health benefits, particularly for weight management. Adults should also do moderate- or high-intensity muscle-strengthening activities that involve all major muscle groups on two or more days per week. If this is not possible due to limiting chronic conditions, older adults should be as physically active as their abilities allow. Older adults should also try to do exercises that maintain or improve balance if they are at risk of falling. In people with type 2 diabetes physical activity or exercise should be performed at least every second or third day to maintain improvements in glycaemic control. In view of insulin 4 adjustments it may be easier for people with type 1 diabetes to perform physical activity or exercise every day. A combination of both aerobic and resistance 1++ exercise appears to provide greater improvement in glycaemic control than either type of exercise alone. Expert opinion suggests using social-cognitive models and making advice 4 person-centred and diabetes specific. An evidence based public health guidance document reported that there was insufficient evidence to recommend the use of exercise referral schemes to promote physical activity other 4 than as part of research studies where their effectiveness is being evaluated. If exercise can be anticipated, a reduction + 2 of the normal insulin dose will significantly reduce the risk of hypoglycaemia and delayed hypoglycaemia. If exercise cannot be anticipated and insulin dose has already been taken, extra carbohydrate before exercise will reduce the risk of hypoglycaemia. Injection of insulin into exercising areas increases the absorption of insulin and the risk of + 96-98 2 hypoglycaemia and should therefore be avoided. C Individualised advice on avoiding hypoglycaemia when exercising by adjustment of carbohydrate intake, reduction of insulin dose, and choice of injection site, should be given to patients taking insulin. Patients using glucose-lowering drugs, such as sulphonylureas, may also be at risk of hypoglycaemia during exercise.

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Patients and their families should be instructed to recognize signs and symptoms of hypoglycemia and its management cheap stromectol 3 mg fast delivery antimicrobial jobs. Metformin + sulfonylurea is the preferred oral combination for patients who no longer have adequate glycemic control on monotherapy with either drug order 3mg stromectol mastercard treatment for upper uti. Use regular insulin or short-acting insulin analogues for patients who require mealtime coverage cheap 3 mg stromectol visa bacteria database. Recurrent nocturnal hypoglycemia despite optimized regimen using glargine or detemir. Therefore, the frequency of monitoring should be based upon clinical judgment taking into account the management of diabetes, the reason for admission, and the stability of the patient. Due to safety concerns related to potential adverse events with oral anti-hyperglycemic medications, it is prudent to thoughtfully review these agents in the majority of hospitalized patients. It may be reasonable to continue oral agents in patients who are medically stable and have good glycemic control on oral agents at home. It is appropriate to continue pre-hospitalization insulin regimens, but reasonable to reduce the dose in order to minimize the risk of hypoglycemia. A supplementary correction (sliding) scale is also recommended but correction scale insulin regimens as sole therapy are discouraged. Evidence is lacking to support a lower limit of target blood glucose but based on a recent trial suggesting that blood glucose < 110 mg/dl may be harmful, we do not recommend blood glucose levels < 110 mg/dl. Insulin therapy should be guided by local protocols and preferably dynamic protocols that account for varied and changing insulin requirements. A nurse-driven protocol for the treatment of hypoglycemia is highly recommended to ensure prompt and effective correction of hypoglycemia. The patient with recurrent or severe hypoglycemia should be evaluated for precipitating factors that may be easily correctable (e. If the patient does not achieve his/her target range, the provider should identify barriers to patient adherence to the treatment regimen (e. If barriers are identified referral to a case manager or behavioral/financial counselor should be considered as appropriate. Set a target range after discussion with patient [E] 4 5 Consider referral for Is patient high-risk? Intensification of therapy should be undertaken based upon individual clinical circumstances and treatment option. Clinicians should recognize that any HbA1c value from any laboratory has measurement error associated with it (the intra-assay coefficient of variation). This has implications for the way HbA1c levels are interpreted as to whether a patient has or has not achieved their glycemic control target. Target values for glycemic control do not have to be a whole number since HbA1c is a continuous risk factor. It should be understood that achieving the goals must not occur at the expense of safety; that small differences from goal may not have significant impact upon absolute risk reduction of complications. Also, goals can and should be modified (upward or downward) as clinical circumstances or patient preferences warrant. Nonetheless these methods are widely used, especially in the developing world, and therefore it is important to know how well they are performing in the field. Glucose Measurements Single point measurement of blood sugar can be determined from venous samples and capillary glucose measurements. Depending upon the meter used, this error can lead to a significant discrepancy between the actual and recorded blood glucose. Reinstitute only after renal function has been reevaluated and found to be normal. Do not restart until oral intake has resumed and renal function has been evaluated as normal. Do not Anaphylaxis, use in type 1 diabetes for angioedema, treatment of diabetic ketoacidosis hypersensitivity Use with caution in patients reactions receiving oral medications that Reports of require rapid gastrointestinal altered renal absorption function Very expensive Module G: Glycemic Control: Appendices Page 31 Version 4. Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk. Often combined, when needed, Detemir (Levemir) 1-2 6-8 Up to 24 Not to be mixed with rapid- or short-acting with other insulins insulin. Patients with an acute change in vision or a change in ocular function should be urgently referred to an eye care provider. Patients with early diabetes onset (age <30 years) or type 1 diabetes at a later age should have an initial examination when the time from diabetes diagnosis is >3 years. Patients who are newly diagnosed with type 2 diabetes and have not had an eye exam within the past 12 months should have a retinal examination performed within 6 months. Patients who have had no retinopathy on all previous examinations may be screened for retinopathy every other year (biennial screening). More frequent retinal examinations in such patients should be considered when risk factors associated with an increased rate of progression of retinopathy are present. Patients with existing retinopathy should be managed in conjunction with an eye care professional and examined at intervals deemed appropriate for the level of retinopathy. Visual inspection should be performed in high-risk patients at each routine primary care visit. High-risk patients are defined as having at least one of the following characteristics: Lack of sensation to Semmes-Weinstein 5. Patients with limb-threatening conditions should be referred to the appropriate level of care for evaluation and treatment. Patients with circulatory symptoms that limit their lifestyle should be referred to a vascular specialist to determine the appropriateness of surgical intervention on a patient-specific basis. Vascular procedures should be justified based on outcomes of vascular interventions. Patients with minor foot wounds or lesions should be referred to a foot care specialist (i. Footwear prescriptions should be determined based upon the individual structural and clinical findings. Y for evaluation and treatment [ E ] [ F ] [ G ] N N 9 Confirm follow-up by foot care specialist if indicated and compliance by patient 12 Is there a minor Y Go to 10 wound or lesion? Y [ L ] N 18 Refer to foot care specialist for wound care treatment [ G ] 22 23 Is this a minor foot Y Treat as appropriate problems? Comprehensive education programs should address the patients fluctuating diabetes clinical state over a lifetime and provide clinically relevant knowledge and skills to facilitate implementation of ever-changing treatment plans. Education in core competencies, also known as survival skills, should be provided to all patients newly diagnosed with diabetes. Comprehensive education on self-management and diet should be provided to all patients newly diagnosed with diabetes. The healthcare team should consider referring the patient to case management or other specialized care, if the patient exhibits poor glycemic control, has high-risk factors, or fails to demonstrate good knowledge of self-care. The healthcare team should coordinate the patients care with caregivers to whom the patient has been referred and obtain updates on the patients condition and needs. The healthcare team should always be ready to respond to the patients ad hoc inquiries about new treatments, problems, or concerns. There is a wide variety of means to provide self-management education and to promote self- management behaviors.

Symptoms often improve once the patient is given a positive diagnosis and no longer fears that underlying heart disease is the cause cheap stromectol 3mg amex ucarcide 42 antimicrobial. Esophageal Neoplasms A large number of different tumors can involve the esophagus (Table 2) buy stromectol 3mg otc antibiotics for uti baby. Classification of esophageal tumors Benign tumours o Epithelial origin Squamous cell papilloma o Non-epithelial origin Leiomyoma Granular cell tumor Hemangioma Lymphangioma Malignant tumors o Epithelial origin Squamous cell carcinoma Adenocarcinoma Adenoid cystic carcinoma Mucoepidermoid carcinoma Adenosquamous carcinoma Undifferentiated carcinoma generic 3mg stromectol otc antibiotics for acne for sale; small-cell carcinoma o Non-epithelial origin Leiomyosarcoma Carcinosarcoma Malignant melanoma o Secondary tumors Malignant melanoma Breast carcinoma Tumor-like lesion o Fibrovascular polyp o Heterotopia o Congenital cyst o Glycogen acanthosis First Principles of Gastroenterology and Hepatology A. Shaffer 76 Carcinoma of the esophagus is a relatively uncommon malignancy in Canada, with only 3 to 4 new cases per 100,000 population per year in males and just over 1 new case per 100,000 population per year in females. Nevertheless, because of its poor prognosis, esophageal cancer ranks among the 10 leading causes of cancer death in Canadian men 45 years of age and older. Although several different types of primary and secondary malignancies can involve the esophagus (Table 2), squamous cell carcinoma and adenocarcinoma are by far the most common esophageal malignancies. Adenocarcinoma Adenocarcinoma used to make up approximately 10% of all esophageal cancers. However, its incidence has been increasing in recent decades such that now it comprises up to 4060% of esophageal cancers in North America. Rarely, primary esophageal adenocarcinomas arise from embryonic remnants of columnar epithelium or from superficial or deep glandular epithelium. Adenocarcinoma of the cardia of the stomach may also involve the distal esophagus and give the appearance that the cancer arises from the esophagus. The true incidence of Barretts-related cancer is uncertain, but most studies suggest that patients with Barretts esophagus will develop adenocarcinoma at a rate of about 0. This is a significant problem given the large number of reflux patients with Barretts metaplasia. Because dysplasia develops prior to frank carcinoma in Barretts epithelium, current guidelines recommend that these patients should undergo surveillance endoscopy with multiple biopsies every 2-3 years to identify those who are likely to progress to cancer (Section 7). The clinical presentation and diagnostic evaluation of patients with adenocarcinoma of the esophagus are similar to those of squamous cell carcinoma (Section 12. Neoadjuvant therapy with concomitant radiation and chemotherapy followed by surgical resection of the esophagus has a 13% absolute benefit in survival at 2 years versus surgery alone. Esophageal squamous cell carcinoma: possible factors o Alcohol o Tobacco o Nutritional exposure Nitrosamines: bush teas containing tannin and/or diterpene phorbol esters o Nutritional deficiencies (riboflavin, niacin, iron) o Chronic esophagitis o Achalasia o Previous lyle-induced injury o Tylosis o Plummer Vinson (Paterson-Kelly) syndrome First Principles of Gastroenterology and Hepatology A. This has led to several theories concerning certain environmental agents that may be important etiologically (Table 3). In North America, squamous cell carcinoma is associated with alcohol ingestion, tobacco use and lower socioeconomic status. Characteristically these cancers, similarly to adenocarcinoma, extend microscopically in the submucosa for substantial distances above and below the area of the gross involvement. They also have a propensity to extend through the esophageal wall and to regional lymphatics quite early. Furthermore, they usually produce symptoms only when they have become locally quite advanced. For these reasons approximately 95% of these cancers are diagnosed at a time when surgical cure is impossible. In most studies, the mid-esophagus is the most common site of origin; however, others have reported distal cancers to be most common. Other symptoms include odynophagia, chest pain (which may radiate to the mid-scapular region), hoarseness (due to recurrent laryngeal nerve involvement) and blood loss. Pulmonary complications due to either direct aspiration or esophagorespiratory fistulas are also quite common during the course of the disease. Hepatomegaly or enlarged cervical or supraclavicular lymph nodes may be detected in cases of disseminated metastases. Barium swallow is usually diagnostic, although small cancers can be missed in up to 30% of cases. Endoscopy with multiple directed biopsies combined with brush cytology is required to confirm the diagnosis. This should be followed by careful attempts to stage the disease prior to deciding on therapeutic intervention. Endoscopic ultrasound appears promising in accurately assessing depth of tumor involvement and presence or absence of enlarged mediastinal lymph nodes. Barium swallow radiograph in a patient with adenocarcinoma of the distal esophagus. When similar lesions are in mid or proximal esophagus, they usually are squamous cell cancers. Shaffer 78 Treatment results of squamous cell carcinoma of the esophagus are discouraging. These tumors are quite radiosensitive; however, most centers give radiotherapy to patients who have advanced unresectable tumors or other health problems that make them poor surgical candidates. In the few reports where radiotherapy is used as the primary mode of therapy in patients who might otherwise be considered surgical candidates, the five-year survival rate is as high as 17%, which compares quite favorably to surgical results. Both forms of treatment have significant morbidity, but the surgical mortality following esophageal resection is 510%. Controlled trials are needed, but in only a small proportion of the total population of esophageal cancer patients is cure a realistic goal. New regimens that combine radiotherapy and chemotherapy, with or without surgery, are currently being evaluated and show promise in improving cure rates and disease-free survival. Both radiotherapy and palliative surgery can be used in this setting; however, other modalities are often necessary. The dysphagia can be relieved with peroral dilation, but in many patients this becomes exceedingly difficult as the disease progresses. If this is the case, a prosthetic device can sometimes be placed across the tumor to maintain luminal patency. These stents can work quite well, although tube blockage, tube migration, erosion through the esophageal wall and sudden massive aspiration are important complications. These prosthetic devices are the best treatment for an esophagorespiratory fistula. Photodynamic therapy and radiofrequency ablation are two relatively new minimally invasive treatment modalities for palliating esophageal cancer. The former involves using a photosensitizing compound that accumulates in cancer cells, which leads to their destruction when they are exposed to light of a certain wavelength. The caring physician must also provide emotional support, nutritional support and adequate pain therapy for these unfortunate patients. Webs and Rings Webs are thin, membrane-like structures that project into the esophageal lumen. They are covered on both sides with squamous epithelium and are most commonly found in the cervical esophagus. Webs are usually detected incidentally during barium x-rays and rarely occlude enough of the esophageal lumen to cause dysphagia. In some instances postcricoid esophageal webs are associated with iron deficiency and dysphagia the so-called Plummer-Vinson or Paterson-Kelly syndrome. This syndrome is associated with increased risk of hypopharyngeal cancer and should be managed with bougienage, iron replacement and careful follow-up.