text:
Geeta Lal MD
Orlo H. Clark MD
Many endocrine diseases are managed by surgical treatment. The details of clinical presentation, diagnosis, and medical management are discussed in other sections of this book. This chapter provides an overview of the principles involved in the surgical therapy for these conditions. The results of endocrine surgical operations are usually most satisfying with removal of the tumor and correction of the metabolic problem it creates.
The thyroid gland arises in the midline as an endoderm-derived pharyngeal diverticulum at about the third week of gestation. It then descends from its origin at the foramen cecum and ultimately forms a bilobed organ anterolateral to the trachea and larynx. The thyroid lobes are connected just below the cricoid cartilage by an isthmus. The connection to the foramen cecum—the thyroglossal duct—ruptures and is partially resorbed by the sixth week of gestation. Its distal remnant forms the pyramidal lobe. The calcitonin-producing C cells, located posteriorly in the superior gland, arise from the fourth pharyngeal pouch and ultimobranchial bodies.
A number of embryologic or developmental abnormalities of the thyroid have been described and are related to the absence or mutations of thyroid differentiation factors, including thyroid transcription factors 1 and 2 (TTF-1, TTF-2) and transcription factor Pax 8. Thyroglossal duct cysts are usually found in the midline, just inferior to the hyoid bone. A lingual thyroid results from maldescent of the median thyroid anlage and is often accompanied by agenesis of other thyroid tissue. Rests of thyroid tissue may be found in the central compartment of the neck and can be mistaken for metastatic thyroid cancer at operation. Aberrant thyroid tissue, unassociated with lymph nodes, can also be found in the lateral neck or mediastinum. In contrast to the above, thyroid tissue in lymph nodes in the lateral neck (lateral aberrant rests) almost always represents metastatic thyroid cancer and is not a developmental abnormality.
The thyroid gland is supplied by paired superior and inferior thyroid arteries. The former arise from the external carotid artery and the latter from the thyrocervical trunk. Occasionally, a thyroid ima artery arises directly from the aorta or innominate artery and enters the isthmus, replacing an absent inferior artery (see Fig. 7-3).
The thyroid is drained by three sets of veins: the superior, middle, and inferior thyroid veins. The first two drain into the internal jugular vein, whereas the last drains into the innominate veins. Both recurrent laryngeal nerves arise from their respective vagus nerves and enter the larynx at the level of the cricothyroid articulation, posterior to the cricothyroid muscle. The left recurrent laryngeal nerve recurs around the ligamentum arteriosum and ascends to the larynx in the tracheoesophageal groove. The right recurrent laryngeal nerve recurs around the subclavian artery and runs 1–2 cm lateral to the tracheoesophageal groove at the level of the clavicle and courses obliquely to the larynx. The superior laryngeal nerves also arise from corresponding vagus nerves and divide into internal and external branches. The former provides sensation to the larynx and the latter innervates the cricothyroid muscles. A description of parathyroid embryology and anatomy is presented in the next section.
There is considerable controversy in the literature regarding the definitions of various thyroid resections. A description of these terms is presented in Table 26-1
Thyroglossal duct remnants may become symptomatic, forming cysts, abscesses and fistulas. There is also a 1% risk of thyroid cancer development in thyroglossal duct
cysts. Most are papillary carcinomas, but very rarely a squamous cell carcinoma may develop. Medullary thyroid cancers do not occur at this site.
Table 26-1. Definitions of various thyroid resections.
Treatment consists of the Sistrunk procedure, which involves removal of the cyst and duct up to the foramen cecum. Since the duct may pass anterior to, posterior to, or through the hyoid bone, the mid section of this bone is also resected. Surgery may also be needed for enlarged lingual thyroid tissue causing symptoms such as choking and dysphagia. Prior to resection, care must be taken to determine whether the patient has any other functioning thyroid tissue, usually via a thyroid scan.
Hyperthyroidism most commonly results from a diffuse toxic goiter (Graves' disease), toxic multinodular goiter, or a single toxic nodule (Plummer's disease). Rarer causes of hyperthyroidism with increased radioactive iodine uptake (RAIU) include a TSH-secreting tumor and a hydatidiform mole. Causes of hyperthyroidism without increased RAIU include subacute thyroiditis, excessive ingestion of medicinal thyroid hormone or cooked thyroid tissue, struma ovarii, and thyroid hormone-secreting metastatic thyroid cancer. These conditions present with the usual symptoms and signs of hyperthyroidism but lack the extrathyroidal manifestations of Graves' disease such as ophthalmopathy, pretibial myxedema, and thyroid acropachy.
Diagnostic Tests
TSH is suppressed and T3, T4, free T4 index, and T3 uptake are increased. As mentioned, RAIU can be used to distinguish the various causes of hyperthyroidism. Graves' disease is also associated with thyroid-stimulating antibodies.
Management of Hyperthyroidism
Hyperthyroidism may be treated medically with antithyroid medications, but medical treatment is associated with a high failure rate, particularly in patients with large goiters. Destruction of the thyroid gland with radioactive iodine (RAI) is the mainstay of treatment in North America for patients over 30 years of age. However, it is associated with a prolonged latency period before effective action, a slightly increased risk of future benign and malignant thyroid tumors, worsening ophthalmopathy, and unavoidable hypothyroidism (3% per year after the first year, independently of dosage). Furthermore, it is contraindicated in pregnant women, of concern in children, and should be avoided in women wishing to become pregnant for up to 1 year after treatment. Surgery overcomes many of the problems associated with RAI.
Absolute indications for thyroidectomy in patients with Graves' disease include biopsy-proved suspicious or cancerous nodules, local compressive symptoms, reluctance to have RAI, or fear of recurrence after RAI. Women who want to become pregnant after treatment and those who are not controlled or who develop side effects from antithyroid drugs during pregnancy are also candidates for surgery, as are children. Relative indications for thyroidectomy include patients in whom rapid control of the disease is desired, poorly compliant patients, and patients with severe ophthalmopathy, very large goiters, or low RAI uptake.
Preoperative Preparation
Patients are usually treated with antithyroid medications to render them euthyroid and to reduce the risk of thyroid storm. Propylthiouracil (100–200 mg three times daily) or methimazole (10–20 mg three times daily and then once daily) is most often used. In patients who develop agranulocytosis, surgery should be deferred until granulocyte counts reach 1000 cells/ľL. In addition, patients are also often treated with propranolol (10–40 mg four times daily) to control the catecholamine response. Relatively large doses may be necessary because of increased catabolism of the drug. Lugol's solution (iodine and potassium iodide) or saturated solution of potassium iodide (3 drops twice daily) is also started about 10 days preoperatively to reduce the vascularity of the gland.
Extent of Surgery
The extent of surgery depends on multiple factors. Patients who have had severe complications with antithyroid drugs, those who want to eliminate the risk of recurrence, and those with carcinoma or severe ophthalmopathy should undergo total or near-total thyroidectomy. The rate of hypothyroidism after surgery ranges from 3% to 48% and is lower than that after RAI therapy. It is primarily determined by the remnant size, the thyroid antibody titer, and whether hypothyroidism was reported to be subclinical or overt. Remnants less than 4 g are associated with an over 50% risk of hypothyroidism, and those greater than 8 g are associated with recurrence rates of 15%. Most surgeons prefer to leave a 4–7 g remnant in adults and a smaller remnant in children. The goal of treatment is usually to make the patient euthyroid while minimizing the risk of recurrence and hypothyroidism. Some surgeons prefer total or near-total thyroidectomy to avoid any chance of recurrence and because it may help patients with Graves' ophthalmopathy. Thyroidectomy can be accomplished safely by bilateral subtotal excision or by the Hartley-Dunhill operation (unilateral lobectomy and isthmusectomy with subtotal contralateral resection). Patients who experience recurrence after surgery are usually treated with RAI.
Patients with hyperthyroidism secondary to toxic multinodular goiter are managed similarly. Those with a solitary toxic nodule are treated by ipsilateral lobectomy and isthmusectomy. Most patients with functioning thyroid nodules and hyperthyroidism have nodules greater than 3 cm.
Acute suppurative thyroiditis is diagnosed by fineneedle aspiration for cytology, smear, Gram stain, and culture and treated by incision and drainage. Thyroidectomy is occasionally needed for clinically coexistent suspicious or cytologically positive thyroid nodules, local compressive symptoms, or persistent infection. Recurrent acute thyroiditis is often due to a fistula from the piriform sinus.
Thyroidectomy is indicated for multinodular goiters enlarging despite thyroxine suppression, those causing compressive symptoms (choking, dysphagia, hoarseness, positive Pemberton's sign—dilation of neck veins upon elevation of arms), and those containing biopsy-proved suspicious or cancerous nodules. Lobectomy is performed on the side with the concerning nodule, and subtotal thyroidectomy is performed if the contralateral side is abnormal.
Approximately 4% of the North American population develop thyroid nodules. However, the incidence of clinical thyroid cancer is much lower (about 40 patients per million). A thyroid nodule is more likely to be malignant if the patient has a history of therapeutic radiation to the head and neck (6.5–3000 cGy to the thyroid), a family history of thyroid cancer, Cowden's syndrome, or MEN 2, and a history of thyroid cancer. Other features suggesting cancer include male sex, young (under 20) or old (over 70) age; a solitary, "cold" solid (or mixed solid-cystic), hard nodule; the presence of ipsilateral palpable nodes or vocal cord palsy; and a fine-needle aspiration biopsy suspicious of or diagnostic for cancer. About 40% of individuals with a history of therapeutic radiation exposure or a family history of thyroid cancer and a "cold" thyroid nodule will have a thyroid cancer. The cancer is in the index nodule in 60% but may be anywhere in the remaining thyroid in 40% of patients.
Patients with thyroid nodules should be evaluated with TSH measurement and a fine-needle aspiration biopsy. If the biopsy suggests a follicular neoplasm, an RAI scan should be performed to rule out a hot nodule. Most of these patients will have a suppressed serum TSH level.
Nodules with any of the worrisome features mentioned above should be removed with—at minimum—an ipsilateral lobectomy and isthmusectomy.
Malignant thyroid tumors include differentiated lesions (which arise from follicular cells), medullary thyroid cancer (MTC), undifferentiated or anaplastic cancers, and other rare tumors such as lymphomas, squamous cell carcinomas, sarcomas, teratomas, plasmacytomas, paragangliomas, and metastatic thyroid cancers (from melanoma or from breast, kidney, lung, and other head-neck tumors).
This group includes papillary, follicular variant of papillary, follicular, and Hürthle cell tumors. Hürthle cell carcinoma has been considered a subtype of follicular carcinoma by some investigators and a unique differentiated thyroid cancer of follicular cell origin by others. The characteristics of these tumors are depicted in Table 26-2. The biologic behavior of the follicular variant is similar to that of papillary carcinoma. In follicular and Hürthle cell tumors, the diagnosis of malignancy
can only be made by the presence of capsular, blood vessel, or lymphatic invasion or when lymph node or distant metastases are present. Familial nonmedullary thyroid cancers—especially if there is a family history of more than two affected relatives—are thought to be more aggressive than the sporadic variant.
Table 26-2. Characteristics of differentiated thyroid cancers.
Surgical Treatment
Occult or minimal papillary carcinomas (< 1 cm) have an excellent prognosis and are adequately treated by lobectomy and isthmusectomy. Patients with high-risk cancers (determined by AGES, AMES, or TNM classification; see Tables 26-3, 26-4, and 26-5) or bilateral cancers are best treated by total or near-total thyroidectomy. Considerable debate exists regarding optimal treatment for low-risk differentiated thyroid cancer.
Proponents of total thyroidectomy argue that this procedure is advantageous for several reasons: RAI can be used to diagnose and treat recurrent or metastatic disease; serum thyroglobulin becomes a sensitive indicator of recurrent disease; the procedure eliminates the risk of occult cancer in the contralateral lobe and reduces the risk of recurrence; it decreases the 1% risk of progression to undifferentiated cancer; it improves survival in patients with tumors over 1.5 cm in diameter; and it decreases the risk of reoperation in case of central neck recurrence. On the other hand, those favoring thyroid lobectomy note that total thyroidectomy is associated with a higher complication rate and that 50% of local recurrences can be cured with surgery. Furthermore, it is argued that under 5% of recurrences occur in the thyroid bed; that multicentricity is not clinically significant; and that the prognosis is excellent in low-risk patients undergoing lobectomy.
Table 26-3. AGES system of classifying high-risk patients.1
Table 26-4. AMES system for classifying high-risk patients.
Retrospective data indicate that the recurrence rate for patients with low-risk differentiated thyroid cancer
is 10% and that the overall mortality rate is about 4% at 10–20 years. However, among patients who have recurrences, 33–50% die from thyroid cancer. These studies also indicate that near-total or total thyroidectomy resulted in a lower incidence of recurrences and improved survival. Since the most important information regarding risk for recurrence is only available postoperatively, the authors recommend near-total or total thyroidectomy for virtually all patients with differentiated thyroid cancer providing that the hospital complication rates are low (< 2%) and comparable to those compiled from experience with lesser procedures.
Table 26-5. TNM1 staging system for papillary or follicular thyroid cancer.2,3
It is not usually possible to distinguish follicular and Hürthle cell carcinomas from corresponding adenomas preoperatively. If there are no obvious signs of cancer at surgery (lymphadenopathy, extra-thyroidal invasion), a lobectomy is performed since more than 80% of these tumors will be benign. If final pathology confirms cancer, a completion thyroidectomy is usually recommended.
This tumor comprises 7% of thyroid malignancies but accounts for about 17% of thyroid cancer-related deaths. It arises from the parafollicular (C cells) of the thyroid, which are derived from the neural crest and secrete calcitonin. Medullary thyroid cancers may be sporadic (75%) or may occur in the setting of MEN 2a, MEN 2b, and familial non-MEN medullary thyroid cancer. In the hereditary setting, the tumors are often bilateral and multicentric (90%). About 50% of patients with sporadic or familial disease have nodal metastases in the central or lateral neck at presentation. All patents presenting with medullary thyroid cancer should be screened for pheochromocytomas, hyperparathyroidism, and mutations of the RET proto-oncogene.
Pheochromocytomas should be treated prior to thyroidectomy. Total thyroidectomy and bilateral central compartment lymphadenectomy is the treatment of choice.
This tumor type constitutes about 1% of thyroid cancers and is the most aggressive variant. The peak incidence is in the seventh decade of life. Lymph node involvement is early and common (84%), as is local invasion into the larynx, vocal cords, recurrent laryngeal nerve, esophagus, and major vessels. About 75% of patients have distant metastases. The role of surgery is usually limited to palliation of obstruction by tumor debulking and tracheostomy. In patients without advanced disease, total or near-total thyroidectomy can be performed for cure in a minority of cases. External beam radiation and chemotherapy are usually recommended.
Several retrospective studies have suggested that lymph node metastases do not have a significant effect on survival in papillary thyroid cancers. However, some studies report that when patients are matched for age and have matted nodes—or extranodal invasion—the recurrence rate is higher and the prognosis is worse. Routine prophylactic lymph node dissections are not recommended for papillary and follicular thyroid cancers.
The lymph node regions of the neck are depicted in Figure 26-1. Central compartment nodes (medial to the carotid sheath) are removed at the time of thyroidectomy if involved with tumor. Gross nodal disease in the lateral compartments (II, III, IV, and V) is removed via ipsilateral modified radical neck dissection, which removes all the fibrofatty and lymph node tissue while preserving the internal jugular vein, the accessory nerve, the sensory nerves, and the sternocleidomastoid muscle. Since both Hürthle cell and medullary thyroid cancers have a worse prognosis and do not routinely take up RAI, prophylactic central neck lymph node clearance is recommended. An ipsilateral (or bilateral) prophylactic modified radical neck dissection is also recommended for medullary cancers over 1.5 cm in diameter and when the central neck nodes are involved. Contralateral neck nodes are often involved in medullary thyroid cancers. Since thyroid cancers rarely metastasize to compartment I, these nodes are not routinely removed.
Thyroid cancers metastasize to the lungs, bone, liver, and brain. In general, patients with macronodular disease (> 1 cm in diameter) should be treated surgically followed by RAI therapy and TSH suppression (see Chapter 7).
A 4- to 5-cm incision is placed in or parallel to a natural skin crease 1 cm below the cricoid cartilage. The subcutaneous tissue and platysma are divided, and the strap muscles are separated in the midline from the thyroid cartilage to the suprasternal notch. Initial dissection is begun in the midline by identification of delphian
nodes and the pyramidal lobe, followed by division of the fascia just cephalad to the isthmus. The trachea is then cleared just caudal to the isthmus. The thyrothymic ligaments and the inferior thyroid veins are ligated and divided. The side with the dominant or suspicious mass is approached first. In case of a proposed lobectomy or the absence of cancer, the isthmus is divided. The superior pole vessels are then individually ligated and divided low on the thyroid gland to decrease the risk of injury to the external branch of the superior laryngeal nerve. Tissues are swept lateral to the thyroid by blunt dissection, and the middle thyroid veins are ligated and divided. The recurrent laryngeal nerve and the superior parathyroid gland are identified at the level of the in ferior thyroid artery just caudal to the cricoid cartilage. Once this is accomplished, the ligament of Berry is divided and the thyroid is sharply dissected off the trachea. The same procedure is repeated on the other side for a total thyroidectomy.
Figure 26-1. Lymph node regions of the neck. Level I = submandibular; level II, III, and IV = upper, middle, and lower jugular nodes; level V = posterior triangle nodes; and level VI = central compartment nodes. (Reproduced, with permission, from Roseman BJ, Clark OH: Neck masses. In: ACS Surgery—Principles and Practice. Wilmore DW et al [editors]. WebMD Corporation, 2002.)
Postoperatively, patients are positioned with the back and head elevated 20 degrees. Oral intake is resumed in a few hours, and they are discharged on the first postoperative day.
Several approaches to minimally invasive thyroidectomy such as video-assisted thyroidectomy and endoscopic thyroidectomy via axillary incisions have been
proposed. These methods are feasible, but clear benefits over the traditional open approach have not been established.
Complications of Thyroidectomy
General complications after thyroid surgery include bleeding, and wound complications including infection and keloid formation. Specific complications include injury to the recurrent laryngeal nerve (< 1%), or external branch of the superior laryngeal nerve, temporary hypocalcemia (1.6–50%), permanent hypocalcemia (< 2% for total thyroidectomy), and injury to surrounding structures such as the esophagus, major vessels (carotid artery, internal jugular vein), and the cervical sympathetic trunk. Complications increase with tumor stage and decrease with surgeon experience.
Around the fourth week of gestation, the embryo forms five pairs of endoderm-lined pharyngeal pouches. The inferior parathyroid glands are derived from the third branchial pouch (with the thymus), whereas the superior glands arise from the fourth branchial pouch. Since the inferior glands migrate farther, they are more liable to be found in ectopic locations.
Most individuals have four parathyroid glands that are found as paired structures on the posterior aspect of the thyroid gland. Supernumerary glands occur in up to 22% of people. Fewer than four glands have also been reported in 3–5% of individuals. About 85% of parathyroid glands are found within 1 cm of the point of intersection of the recurrent laryngeal nerve and the inferior thyroid artery. The superior parathyroid glands are usually dorsal to the nerve, whereas the inferior glands are usually ventral to it. The glands may also be found in several ectopic locations (Table 26-6 Figure 26-2). The blood supply to the parathyroid glands is primarily via the inferior thyroid arteries, but the superior thyroid arteries may also supply both the upper and the lower glands.
Table 26-6. Ectopic positions of parathyroid glands.
Figure 26-2. Ectopic locations of parathyroid tumors found at reoperation after an initial failed neck exploration. The numbers indicate the actual number of glands found at each location (n = 54). (Reproduced, with permission, from Shen W et al. Reoperation for persistent or recurrent primary hyperparathyroidism. Arch Surg 1996;131:861. Copyright Š 1996 by the American Medical Association.)
This disorder occurs in 1:500 women and 1:2000 men. It is the most common cause of hypercalcemia in the outpatient population, and along with malignancy-associated hypercalcemia accounts for about 90% of cases of hypercalcemia. It is most often sporadic but may also be inherited as a component of MEN 1 (90–100%), MEN 2a (30%), familial hyperparathyroidism, and familial hyperparathyroidism with jaw tumor syndrome. In sporadic cases, hyperparathyroidism is due to a single enlarged gland (adenoma) in 85% of cases, multiple enlarged glands (hyperplasia) in 11%, double adenomas
in 3%, and parathyroid carcinoma in 1%. Parathyroid carcinoma is suspected if patients present with a short history, profound hypercalcemia, and a palpable parathyroid gland. In heritable disorders, hyperparathyroidism is more frequently associated with multiple abnormal parathyroid glands and a higher risk of persistent or recurrent disease. Familial hyperparathyroidism with jaw tumor syndrome is associated with an increased risk of parathyroid cancer.
The classic symptoms of primary hyperparathyroidism include "painful bones, renal stones, abdominal groans, psychic moans, and fatigue overtones." Other symptoms such as polyuria, nocturia, polydipsia, constipation, and musculoskeletal aches and pains may be present. The disorder may also be associated with hypertension, gout, pseudogout, osteopenia, osteoporosis, peptic ulcer disease, and pancreatitis.
Diagnostic Tests
Other causes of hypercalcemia should be excluded. The laboratory tests useful in making the diagnosis are shown in Table 26-7. Primary hyperparathyroidism is characterized by hypercalcemia (95%), hypophosphatemia (50%), hyperchloremia (30%), chloride to phosphate ratio ≥ 33 (95%), elevated 24-hour urinary calcium, and an increased or inappropriately elevated intact parathyroid hormone (PTH). An elevated alkaline phosphatase level suggests bone disease (osteitis fibrosa cystica). Parathyroid tumors are localized using noninvasive means such as Tc-99m sestamibi and ultrasound scanning. MRI scans and invasive localizing studies, including arteriograms, highly selective venous catheterization for PTH, and fine-needle aspiration biopsy of suspected parathyroid masses are only used in cases of recurrent or persistent hyperparathyroidism. Most studies are less sensitive for detecting multiple abnormal glands. Noninvasive localizing studies (Tc-99m sestamibi, ultrasound) are generally used at initial exploration if a focal approach is planned (see Chapter 8).
Table 26-7. Diagnostic tests for primary hyperparathyroidism.
Surgical Management
The definition and management of this group of patients are controversial. Most of these patients are diagnosed by screening blood tests performed for other reasons. The 1990 National Institutes of Health consensus conference considered patients to be asymptomatic if they had none of the common symptoms or signs of hyperparathyroidism, including bone, renal, gastrointestinal, or neuromuscular disorders. The consensus guidelines for surgical treatment in this population are outlined in Table 26-8. It was also stated that "medical surveillance may be justified in patients over 50 years old whose renal and bone status are close to normal." This view stemmed from observational studies that suggested stability with respect to serum calcium, stones, and renal function with time. However, more recent investigations suggest that true asymptomatic hyperparathyroidism is rare. Renal function and bone density do improve in this group of patients after surgery, as do neuropsychiatric symptoms and nonspecific symptoms such as fatigue and malaise. Furthermore, parathyroidectomy has also been associated with improved survival (in both asymptomatic and symptomatic patients), is more cost-effective than life-long follow-up, and is successful in 95% of patients with a < 1% complication rate. Therefore, most experienced clinicians recommend parathyroidectomy for "asymptomatic" patients.
Table 26-8. 1990 NIH consensus conference indications for surgery in patients with asymptomatic primary hyperparathyroidism.1
A second meeting was held at the NIH in 2002 to re-evaluate the criteria for parathyroidectomy in asymptomatic patients. The new guidelines are essentially similar to previous recommendations except for the following changes: Surgery is currently recommended if (1) serum calcium is 1 mg/dL above reported normal range, and (2) bone mineral density at any site (forearm, spine, or hip) is 72.5 standard deviations below that of gender and not age-matched controls (T-score rather than Z-score).
Patients with classic symptoms and metabolic complications are candidates for surgery.
Conduct of Parathyroidectomy
Issues to consider before deciding on the optimal treatment approach are whether one is dealing with sporadic or familial disease and with the initial operation or reexploration. The presence of concurrent thyroid pathology needing surgical treatment must also be taken into account. The positioning, incision, and dissection are as described previously for thyroidectomy.
Bilateral Versus Unilateral Approach
Traditionally, all four parathyroid glands have been explored without preoperative localizing studies, with a 95% success rate in the hands of an experienced surgeon. Investigators in favor of unilateral exploration have suggested decreased recurrent laryngeal nerve injury, less postoperative hypocalcemia, shorter operative time, and early discharge as advantages of this approach. Potential disadvantages of unilateral exploration include the risk of missing multiple abnormal or ectopic parathyroid glands. Neck exploration has been performed in a unilateral or focal approach with localizing studies and intraoperative gamma probe or PTH measurements.
We have found that when two localizing studies—Tc 99m sestamibi and ultrasound—identify the same solitary parathyroid gland in patients with sporadic hyperparathyroidism, this was the only abnormal parathyroid gland in 95% of patients. In these patients, our current approach is to recommend focused parathyroidectomy via a 2.5 cm incision with intraoperative PTH measurement. If the PTH level falls more than 50% within 10 minutes after removal of an abnormal parathyroid gland, the procedure is terminated. If the level does not fall, a PTH measurement is repeated in another 10 minutes as it may fall slowly in some patients. The bilateral approach is used in patients with known familial disease, secondary or tertiary hyperparathyroidism, or a history of lithium treatment—or if the localizing studies are negative or inconsistent. If parathyroid cancer is suspected intraoperatively, it is resected with the ipsilateral thyroid lobe and regional lymph nodes.
Subtotal Parathyroidectomy Versus Total Parathyroidectomy with Autotransplantation
In the latter technique, 12–20 small fragments (1 × 1 mm) of parathyroid tissue are placed into multiple pockets in the forearm muscle of the nondominant arm. The site is marked with silk sutures and is easily accessible under local anesthesia should the patient develop recurrent hypercalcemia. The recurrence rates for hyperparathyroidism appear to be similar after subtotal or total parathyroidectomy. However, a 5% failure rate has been reported after autotransplantation of parathyroid tissue. Therefore, subtotal parathyroidectomy is preferred. The most normal gland is biopsied first, leaving a 50 mg remnant (the size of a normal parathyroid gland); if it appears viable, the remaining glands are excised. Patients undergoing either of these procedures should have tissue cryopreserved. Parathyroid glands should not be routinely biopsied at exploration but rather to confirm parathyroid tissue or help determine if the gland is normal or abnormal. As with thyroid surgery, video-assisted and endoscopic axillary approaches are feasible, but clear benefits compared with the open approach are not apparent.
Kidney stones, bone disease, neuromuscular symptoms, and psychiatric symptoms respond well to surgery, whereas hypertension does not.
Persistent hypercalcemia occurs after about 5–10% of explorations. Recurrent hypercalcemia is rare except in patients with familial disease and occurs after an intervening period (over 6 months) of normocalcemia. The most common reasons for persistent hyperparathyroidism are a missed gland in normal or ectopic location, regrowth of hyperplastic tissue, recurrent carcinoma, or parathyromatosis (implantation of tumor broken at the initial procedure). The management of these patients involves confirmation of the diagnosis—in particular, exclusion of familial hypocalciuric hypercalcemia; review of original operative notes and pathology reports; and localization studies, which are a must in this group of patients. The issue of reexploration in mildly symptomatic patients is controversial. The neck is usually reexplored first, and median sternotomy may be needed in 1–2% of patients. Cryopreservation should be performed routinely and autotransplantation selectively. Reexploration by an experienced surgeon is successful in over 90% of patients but is associated with more complications than initial operation.
This disorder occurs most often in individuals with end-stage renal failure but may also occur in other conditions resulting in hypocalcemia such as vitamin D deficiency, idiopathic hypercalciuria, hypermagnesemia, and long-term lithium therapy.
Indications for surgery include situations where the product of serum calcium and phosphate is > 70, renal osteodystrophy with bone pain, severe pruritus, ectopic soft tissue calcifications and tumoral calcinosis, serum calcium > 11 mg/dL with markedly elevated PTH, and calciphylaxis.
These patients should undergo dialysis the day prior to surgery to correct electrolyte (specifically potassium) abnormalities. Patients with this disorder require bilateral exploration and either subtotal parathyroidectomy, leaving a 50–60 mg histologically confirmed well-vascularized remnant of hyperplastic parathyroid distant from the recurrent laryngeal nerve; or total parathyroidectomy with autotransplantation of a similar amount of tissue. The former is usually preferred, as not all autografts function. Upper thymectomy is usually performed in these patients, since up to 15% of patients will have a fifth hyperplastic gland.
MEN 1 patients should have hyperparathyroidism treated before coexisting gastrinoma. All glands should be identified; ectopic glands should be sought in the neck and upper mediastinum; and bilateral cervical thymectomy should be routinely performed due to the occurrence of thymic carcinoids. All but about 50 mg of the most normal parathyroid gland should be removed. MEN 2a patients should undergo screening for the presence of a pheochromocytoma and RET mutation prior to thyroid or parathyroid surgery. Since the parathyroids are at risk during thyroidectomy and central neck node dissection, and hyperparathyroidism is less virulent in these patients, only obviously enlarged glands should be removed. Normal-appearing glands should be marked and parathyroid tissue cryopreserved.
General complications are similar to those associated with thyroidectomy. Specific complications include recurrent laryngeal nerve injury, hypomagnesemia, and hypocalcemia. The latter may arise due to suppressed function of the remaining glands after removal of an adenoma; injury to the parathyroid remnant; or bone hunger, which is the influx of calcium and phosphorus into metabolically active bones. Bone hunger can be predicted based on the severity of bone disease and the preoperative alkaline phosphatase level and is generally more severe in individuals with secondary hyperparathyroidism. Hypocalcemia can be treated with oral calcium and vitamin D supplementation (calcitriol, 0.25–0.5 ľg twice daily). Intravenous calcium is seldom required except in patients with osteitis fibrosa cystica.
The adrenals are paired structures located superior to the kidneys. The adrenal is divided into an outer cortex and an inner medulla. The cortex originates from mesodermal tissue near the gonads on the adrenogenital ridge at about the fifth week of gestation. Adrenocortical tissue can thus be found in the ovaries, spermatic cord, and testes. The adrenal medulla originates from the neural crest, which is ectodermal in origin.
Each adrenal is supplied by three sets of arteries: the superior adrenal (from the inferior phrenic artery), the middle adrenal (from the aorta), and the inferior adrenal (from the renal artery). These vessels branch into as many as 50 arteries. The left adrenal vein empties into the ipsilateral renal vein, whereas the right adrenal vein drains into the inferior vena cava (see Fig. 9-1).
This disorder accounts for 1% of hypertensive patients and results from an adrenal adenoma (Conn's syndrome, 75%), adrenal hyperplasia (24%), or adrenocortical cancer (1%). Patients present with hypertension, muscular weakness, polydipsia, polyuria, headaches, and fatigue. It is important to distinguish between adenoma and hyperplasia because surgery is virtually always curative for the former (see Chapter 10).
Diagnostic Tests
Plasma electrolyte determinations reveal hypokalemia, hypernatremia, alkalosis, and hypochloremia. Elevated plasma and urine aldosterone levels with suppressed serum renin levels confirm the diagnosis. Tumors are localized with the aid of CT scans, MRI, iodocholesterol
scans, or selective venous catheterization for aldosterone and cortisol.
Surgical Management
Patients are prepared for surgery with potassium supplementation, sodium restriction, and treatment with spironolactone (an aldosterone antagonist) or amiloride (a potassium-sparing diuretic). Postoperatively, patients may require saline infusions, fludrocortisone (50–100 ľg/d), or, rarely, glucocorticoids if they become addisonian. Patients who respond well to spironolactone also do well after surgery. About 80% experience an improvement in blood pressure, and almost all become normokalemic. Patients with hyperplasia require bilateral adrenalectomy, so that medical therapy is often preferred (see Chapter 10).
Cushing's syndrome arises from elevated corticosteroid levels resulting from pituitary ACTH secretion leading to bilateral adrenal hyperplasia (Cushing's disease), adrenal adenoma, adrenal carcinoma, ectopic ACTH-secreting tumors (small cell lung cancer; pancreatic, thyroid, thymic, and other cancers), or the exogenous administration of steroids. Patients present with weight gain, muscular weakness, polyuria, emotional lability, moon facies, acne, hirsutism, central obesity, hypertension, diabetes mellitus, and virilization.
Diagnostic Tests
In order to confirm the diagnosis and determine the cause, a low-dose (1 mg) dexamethasone suppression test, urine free-cortisol, plasma ACTH, and high-dose (8 mg) dexamethasone suppression test are performed. Tumors are localized using CT, MRI, or iodocholesterol scans and selective venous catheterization of petrosal veins after corticotropin-releasing factor stimulation (see Chapter 9).
Surgical Management
Cushing's syndrome can be treated with medications that inhibit steroid production (ketoconazole, metyrapone, aminoglutethimide). Cushing's disease is treated with transsphenoidal hypophysectomy and microsurgical excision of the pituitary adenoma. Irradiation may also be used, but the response is delayed and the treatment results in panhypopituitarism. Unilateral adrenalectomy is the treatment of choice in patients with adrenal adenomas or carcinomas, whereas bilateral adrenalectomy is used to treat patients with Cushing's disease who fail to respond to radiation or hypophysectomy and selected patients with Cushing's syndrome secondary to ectopic ACTH production.
Preoperatively, electrolyte abnormalities are corrected and all patients are given exogenous steroids (hydrocortisone, 100 mg intravenously every 8 hours). After unilateral adrenalectomy, steroids are tapered off over months. After bilateral surgery, lifelong treatment with hydrocortisone (20 mg each morning and 10 mg in the evening) is necessary. Fludrocortisone (0.1 mg orally daily) is sometimes needed, and cortisone supplementation must be increased in situations of stress. The prognosis after adrenalectomy for adenoma is excellent. After bilateral adrenalectomy, about 20% of patients develop Nelson's syndrome (hyperpigmentation, head aches, exophthalmos, and blindness) from continuing growth of the pituitary tumor.
Virilization and feminization can be caused by many disorders including congenital adrenal hyperplasia, adrenal adenomas or carcinomas, ovarian or testicular tumors, hypothalamic or pituitary disease, placental disorders, and exogenous sex steroid administration. Six different variants of congenital adrenal hyperplasia occur, each caused by a specific enzyme defect. Adrenal virilization occurring postnatally usually results from an adenoma or carcinoma. Virilization presents in females with hirsutism, clitoromegaly, alopecia, breast atrophy, and hypomenorrhea. In males, feminizing tumors lead to gynecomastia, testicular atrophy, acne, and hypertension.
Diagnostic Tests
Karyotype analysis; plasma 17-hydroxyprogesterone, 11-deoxycortisol, and testosterone analysis; and urine tests for 17-ketosteroids, pregnanetriol, testosterone, aldosterone, and corticosteroid levels are needed to establish the particular enzyme deficiency. The dexamethasone suppression test (2–4 mg/d in divided doses four times daily for 7 days) can be used to distinguish adrenal hyperplasia from neoplasia. CT, MRI, and iodocholesterol scans are used to localize the tumors.
Surgical Management
Congenital adrenal hyperplasia is generally not amenable to surgical therapy. Adrenalectomy is reserved for treatment of adrenogenital syndrome caused by an adenoma or carcinoma. The perioperative management is similar to that for patients with Cushing's syndrome. Progression of virilization or feminization ceases after adrenalectomy. Adrenal carcinomas have a poor prognosis.
This catecholamine-secreting tumor of the adrenal medulla and extra-adrenal chromaffin tissue accounts for 0.1–0.2% of all patients with hypertension. It is often called "the 10% tumor" because 10% are bilateral, 10% are malignant, 10% occur in children, 10% are extra-adrenal, and 10% are familial (occurring in association with MEN 2a, MEN 2b, von Hippel-Lindau syndrome, neurofibromatosis, and other neurocutaneous syndromes). Headache, palpitations and diaphoresis constitute the classic triad of pheochromocytoma. Nonspecific symptoms include anxiety, tremulousness, severe headaches, paresthesias, flushing, chest pain, shortness of breath, abdominal pain, nausea, and vomiting as well as others. The most common clinical sign is hypertension, which may be sustained or episodic.
Diagnostic Tests
These should be performed in a nonstressed patient. Twenty-four-hour urine collections should be tested for vanillylmandelic acid, metanephrines, and catecholamines. Plasma catecholamines and chromogranin A levels can also be measured. Provocative tests such as glucagon infusion and clonidine suppression are rarely necessary. Radiologic investigations such as CT scan, MRI scan, and metaiodobenzylguanidine scans are used to localize the tumors and assess for possible extra-adrenal tumors (see Chapter 11).
Surgical Treatment
Adrenalectomy is the treatment of choice. Preoperative preparation involves treatment with an alpha-adrenergic blocker such as phenoxybenzamine (10–40 mg four times daily; maximum: 300 mg/d). Beta-blockers such as propranolol (5–40 mg four times daily) are added in patients who have persistent tachycardia and arrhythmias but only after adequate alpha blockade has been established in order to avoid the effects of unopposed alpha stimulation, ie, hypertensive crisis and congestive heart failure. Patients should also be volume-repleted to avoid postoperative hypotension, which ensues with the loss of vasoconstriction after tumor removal. Nitroprusside is the drug of choice for intraoperative blood pressure control. After surgery, 95% of patients with paroxysmal hypertension and 65% with sustained hypertension become normotensive. Malignant pheochromocytoma has a poor prognosis.
This rare neoplasm is slightly more common in women than in men and has a bimodal age distribution, occurring more frequently in children under 5 years of age and in adults in their forties and fifties. About 50% of these tumors are nonfunctioning. The remainder secrete cortisol (30%), androgens (20%), estrogens (10%), aldosterone (2%), or multiple hormones (35%). Adrenocortical cancers are often characterized by the rapid onset of Cushing's syndrome with virilizing features. Nonfunctioning tumors usually present with an enlarging abdominal mass and abdominal pain or, less commonly, with weight loss, hematuria, varicocele, and dyspnea. Most tumors are sporadic, but they can occur within the tumor spectrum of the Li-Fraumeni and MEN 1 syndromes.
The biochemical workup of a unilateral adrenal mass is outlined in the section on adrenal incidentaloma. CT scan and MRI are the most commonly employed radiologic diagnostic tests. The size of the mass remains the single most reliable indicator of malignancy. Carcinomas are more likely to be present in lesions over 6 cm in diameter. Other features suggesting malignancy on CT include irregular shape and margins, heterogeneity, and hemorrhage. On MRI, carcinomas have a moderate signal intensity on T2-weighted image (adrenal tumor to liver ratio 1.2–2.8). Fine-needle aspiration biopsy is usually performed in patients with an isolated adrenal mass and a history of carcinoma of the lung, breast, stomach, kidney, colon, melanoma, or lymphoma and in those with symptoms and signs of underlying malignancy. Care must be taken to exclude pheochromocytoma prior to biopsy to avoid precipitating a hypertensive crisis (see Chapter 9).
Surgical Treatment
Complete surgical excision offers the only chance of prolonged survival. Transabdominal adrenalectomy with en bloc excision of contiguously involved structures (liver, kidney, spleen, pancreas, or inferior vena cava) is usually recommended. A thoracoabdominal approach may also be used for large (> 10 cm) right-sided tumors. Laparoscopic adrenalectomy is not usually recommended for adrenal cancers. The adrenolytic agent mitotane and other antitumor drugs such as etoposide, cisplatin, and doxorubicin have also been used with partial success for metastatic tumors. Five-year actuarial survival rates of 32–48% have been reported in patients who underwent complete resection. Features predicting poor survival include tumor size over 12 cm, six or more mitoses per high power field, and intratumoral hemorrhage.
This entity is defined as an adrenal mass discovered during imaging done for other reasons. Adrenal masses
have been identified in up to 8% of individuals in autopsy series and 4.4% in those undergoing abdominal CT scans. The widespread use of ultrasound, CT, and MRI scans over the last 2 decades has led to the great increase in the number of these lesions identified.
Table 26-9. Differential diagnosis of the adrenal incidentaloma.
Most of these lesions are benign nonfunctioning adenomas. The differential diagnosis of these lesions is summarized in Table 26-9.
The workup is used to discern whether the lesion is functional or malignant. Asymptomatic patients with obvious cysts, hemorrhage, myelolipomas, or diffuse metastatic disease do not mandate further testing. All other patients should undergo biochemical testing for hormonally active tumors. At a minimum, this should include serum electrolytes, low-dose (1 mg) dexamethasone suppression testing, and a 24-hour urine collection for catecholamines, metanephrines, vanillylmandelic acid, and 17-ketosteroids. Confirmatory tests can be performed based on the results of these screening tests. Functional tumors and nonfunctional masses over 4 cm (in good-risk patients) are treated by adrenalectomy, as are heterogeneous, irregular or enlarging tumors. Fine-needle aspiratory biopsy should be performed only in patients with a history of carcinoma and a suspected isolated adrenal metastasis (see Chapter 9).
Laparoscopic adrenalectomy has become the procedure of choice for most of the lesions described above except those suspected of being or known to be malignant. Patients with nonfunctioning homogeneous lesions less than 4 cm in diameter should be followed with serial examinations and CT or MRI at 3 and 12 months. Adrenalectomy is indicated for any lesion that grows during the observation period. Patients with stable lesions may be discharged from follow-up.
There are no randomized controlled trials comparing laparoscopic and open adrenalectomies. However, several retrospective studies have shown that the laparoscopic technique is safe and associated with less post operative pain, shorter mean hospital stay, lower morbidity, and more rapid complete recovery. Laparoscopic adrenalectomy has become the procedure of choice for most adrenal lesions, and the indications are similar to those for open procedure.
Laparoscopic adrenalectomy is contraindicated in patients with adrenocortical cancer or coagulopathy—and relatively contraindicated after previous adrenal surgery. Two approaches have been defined: transperitoneal (lateral and anterior) and posterior retroperitoneal. The former provides a conventional view of anatomy and the anterior approach allows for bilateral procedures without repositioning the patient. The latter approach may be preferable in reoperative cases and obese patients but provides a limited working space.
In general, the adrenal gland is dissected from surrounding tissue using electrocautery or the Harmonic Ultrasonic Scalpel. These methods are also useful for control of the small adrenal arteries, but the adrenal veins need to be clipped. The adrenal is placed in an endocatch bag and morselled prior to extraction.
Specific procedure-related complications include trocar site-associated hematoma and subcutaneous emphysema, injury to surrounding organs such as the spleen, and bleeding from vena caval injury.
The pancreas is a retroperitoneal organ located at the level of L2. It weighs 75–100 g, is about 15–20 cm in length, and is divided into the head and uncinate process, the neck, the body, and the tail. The uncinate process forms part of the head and surrounds the superior mesenteric vessels. The main pancreatic duct (duct of Wirsung) is 2–3.5 mm wide, runs in the center of the pancreas, and drains the body, tail, and uncinate
process. The lesser duct (duct of Santorini) usually drains the head, communicates with the duct of Wirsung, and drains separately via a minor papilla located 2 cm proximal to the ampulla of Vater. The common bile duct is found posteriorly in the pancreatic head and joins the main pancreatic duct before draining into the ampulla.
Table 26-10. Rare functioning tumors of the endocrine pancreas.1
The pancreas originates as dorsal and ventral pancreatic buds from the primitive endoderm around the fifth week of gestation. The former gives rise to the superior head, neck, body, and tail, whereas the later forms the inferior head and the uncinate process. The ventral duct fuses with the dorsal bud to form the duct of Wirsung, and the proximal portion of the dorsal duct forms the duct of Santorini. In 10% of individuals, the ducts fail to communicate, resulting in pancreas divisum, where the entire pancreas is drained by the lesser duct.
Endocrine pancreatic tumors arise from the islet cells, which are derived from the neural crest.
Common functioning tumors are described below and rare functioning tumors of the endocrine pancreas are described in Table 26-10.
This β cell-derived neoplasm is the most common pancreatic endocrine tumor. Insulinomas are evenly distributed throughout the pancreas (one-third each in the head, body, and tail). Most patients (90%) have a benign, solitary lesion. Approximately 10% of patients have malignant insulinomas with metastatic disease to the liver and peripancreatic lymph nodes. The insulinoma syndrome is characterized by the Whipple triad, which includes symptoms of hypoglycemia during fasting, serum glucose < 50 mg/dL, and relief of hypoglycemic symptoms by exogenous glucose. Symptoms arise from neuroglycopenia (confusion, seizures, personality change, coma) or due to a catecholamine surge (tachycardia, diaphoresis, trembling). Other causes of hypoglycemia should be excluded, eg, reactive hypoglycemia, adrenal insufficiency, end-stage liver disease, nonpancreatic tumors (mesothelioma, sarcoma, adrenal carcinoma, carcinoid), and surreptitious administration of oral hypoglycemics or insulin.
Diagnostic Tests
The diagnosis is made if glucose levels fall to < 50 mg/dL while insulin levels are > 20 ľU/mL and the insulin to glucose ratio is > 0.4 (normal: < 0.3) during a 72-hour monitored fast. Increased levels of C peptide and proinsulin are also diagnostic, whereas low levels suggest factitious hyperinsulinemia.
Once the diagnosis is confirmed biochemically, noninvasive tests such as double-contrast, fine-cut (5 mm) CT or MRI scan can identify large tumors or liver metastases. Transgastric endoscopic ultrasound is the most successful preoperative localization test (sensitivity 83–93%). Selective arteriography with calcium stimulation of insulin secretion and catheterization of the right hepatic vein (sensitivity 88%) may also be used. Some pancreatic neuroendocrine tumors also express somatostatin receptors and can be imaged using radiolabeled octreotide. Unfortunately, this is only effective in about 30% of patients with insulinomas (see Chapter 18).
Operation is the only curative treatment. Prior to surgery, patients are instructed to take several small frequent meals, and diazoxide administration is helpful to avoid hypoglycemic attacks. Glucose levels are monitored perioperatively. The combination of inspection, palpation, and intraoperative ultrasound allows detection of nearly all tumors and their relationship to the pancreatic duct. Small, (< 2 cm) benign tumors in any part of the pancreas not intimately associated with the main pancreatic duct are enucleated. Larger tumors (up to 5 cm) are usually enucleated if in the pancreatic head but are removed by spleen-preserving distal pancreatectomy if located in the tail. Large tumors in the head
that appear malignant are usually resected by a Whipple procedure. When a tumor cannot be identified, "blind" distal resections should generally not be performed. However, a small distal pancreatic resection may be sufficient to rule out nesidioblastosis (β-cell hyperplasia). Resection of peripancreatic and duodenal nodes should be performed in patients with probable malignant tumors. Hepatic resection should be attempted for cure or palliation in patients with metastatic tumors. Patients with insulinomas and MEN 1 require distal pancreatectomy and enucleation of tumors from the head of the pancreas. Surgical resection is curative in about 95% of cases. Malignant insulinomas recur in about 33% of cases.
Diazoxide and verapamil are often used to decrease insulin secretion from insulinoma. Combination chemotherapy (streptozocin, fluorouracil, and doxorubicin) has also been used for unresectable insulinomas.
GASTRINOMA (Zollinger-Ellison Syndrome)
This neoplasm leads to abdominal pain and peptic ulceration of the proximal gastrointestinal tract (90%) and diarrhea (50%). The diagnosis should be suspected in patients with recurrent postoperative and postbulbar ulcers, ulcer associated with diarrhea, a family history of ulcer diathesis or MEN 1, and failure to respond to adequate medical therapy. Up to 75% of gastrinomas occur sporadically. In contrast to insulinomas, 60% of gastrinomas are malignant and present with local invasion and metastases.
Diagnostic Tests
Fasting serum gastrin levels are usually over 200 pg/mL, and values over 1000 pg/mL are diagnostic of gastrinomas unless the patient is hypochlorhydric. Elevated gastrin levels may also be found in several other disease states (Table 26-11), and other tests are therefore necessary. Basal gastric acid output > 15 mEq/h (> 5 mEq/h in patients with previous vagotomy) or a ratio of basal to maximal acid output greater than 0.6 suggests a gastrinoma. An increase of gastrin > 200 pg/mL above the basal level upon stimulation with 2 units/kg secretin confirms the diagnosis.
Radiologic tests used to localize gastrinomas are similar to those used for investigation of insulinomas. However, endoscopic ultrasound and visceral angiograms are less sensitive for gastrinomas. Radiolabeled octreotide scanning is usually positive for tumors larger than 1 cm in diameter. Selective pancreatic angiograms utilizing secretin stimulation for gastrin levels may be helpful. However, about 70% of gastrinomas are in the duodenum in patients with MEN 1, and 90% are found to the right of the superior mesenteric vessels.
Table 26-11. Causes of hypergastrinemia.1
Patients are given proton pump inhibitors preoperatively. Most gastrinomas are located in the "gastrinoma triangle," which is bounded by the cystic duct superiorly, the second and third portions of the duodenum inferiorly, and the junction of the neck and body of the pancreas medially. The Whipple procedure is recommended for large (> 6 cm) or clinically malignant tumors in the head of the pancreas. Intraoperative ultrasound, endoscopy with duodenal transillumination, and a longitudinal duodenotomy may be necessary to identify the tumor. All enlarged peripancreatic and periduodenal lymph nodes should be removed. Single hepatic metastases may be resected. Total gastrectomy is rarely indicated today except in noncompliant patients or those refractory to medical therapy when the gastrinoma cannot be identified or completely removed. Most gastrinomas in sporadic disease are solitary, whereas in MEN 1 they are multiple. About 34% of patients with sporadic gastrinomas and 50% with familial gastrinomas remain disease-free at 10 years. Overall survival rates are 94% at 10 years. Patients with radiologically identified recurrent disease may be candidates for repeat resection to avoid obstruction.
Octreotide can be used to decrease gastrin secretion. Hepatic artery embolization of liver metastases may provide palliation.
This disorder is also known as the WDHA (watery diarrhea, hypokalemia, achlorhydria) or pancreatic cholera syndrome. Patients typically present with high-volume diarrhea (> 5 L/d), muscular weakness and lethargy (due to hypokalemia), hyperglycemia, hypercalcemia, and, rarely, cutaneous flushing. Other common causes of diarrhea should be excluded.
Diagnostic Tests
Since secretion can be episodic, multiple fasting levels of VIP should be measured. Localizing studies should be performed as previously described.
Fluid and electrolytes should be aggressively repleted prior to surgery. Diarrhea may be treated with octreotide. Most of these tumors are located in the body and tail and are hence treated by a distal pancreatectomy. Small tumors may be enucleated. If the tumor is not localized, the autonomic chain and adrenals should be examined for extrapancreatic tumors. If no tumor is identified, distal pancreatectomy may be considered. Palliative debulking may be performed for metastatic disease.
Octreotide and hepatic artery embolization may provide palliation of symptoms.
Patients with this tumor have mild diabetes, stomatitis, anemia, malnutrition, hypoproteinemia, and a characteristic severe dermatitis (necrolytic migratory erythema). The latter is thought to be secondary to the hypoaminoacidemia.
Diagnostic Tests
The clinical presentation and biopsy of the rash are sufficient for the diagnosis. Hyperglycemia, hypoproteinemia, and an elevated fasting glucagon level (> 150 pg/mL) confirm the diagnosis. Localizing and staging tests described earlier should also be performed.
Patients need preoperative octreotide, hyperalimentation, and routine deep venous thrombosis prophylaxis. Up to 70% of these tumors present with metastases, and surgery is the only potentially curable treatment. Most tumors are solitary and located in the tail, where they are amenable to distal pancreatectomy. Palliative debulking in the setting of metastatic disease may help refractory symptoms.
Octreotide and embolization of hepatic metastases may help control symptoms.
The somatostatinoma syndrome is characterized by steatorrhea, diabetes, hypochlorhydria, and gallstone disease. Most somatostatinomas are malignant (75% have metastases at presentation) and are located in the pancreatic head. The diagnosis is established by fasting somatostatin levels over 100 pg/mL.
Somatostatinoma is usually treated by pancreaticoduodenectomy. Fluid and electrolytes should be repleted preoperatively.
About 33% of patients with pancreatic endocrine neoplasms have no evidence of a defined clinical syndrome and are deemed to have nonfunctioning tumors. However, some of these tumors produce pancreatic polypeptide. These tumors usually present with abdominal pain, weight loss, and jaundice—similar to ductal adenocarcinoma of the pancreas. They are most commonly present in the head, neck, and uncinate process. The tumors are localized and staged similar to functional tumors. Endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography are used for the evaluation of jaundice.
Surgical Treatment
About 50–90% of these tumors are malignant. Surgical resection (pancreaticoduodenectomy—Whipple procedure—or distal pancreatectomy) is the treatment of choice, as these tumors are not amenable to enucleation. Biliary and gastric bypasses may be necessary for palliation. These tumors grow in an indolent fashion. Five-year survival rates after resection are 50%. In patients with unresectable disease, combination chemotherapy (streptozocin and doxorubicin) may provide palliation.
Technique of Pancreatic Resection
Patients are explored through a midline or bilateral subcostal incision. The gastrocolic ligament and the inferior
retroperitoneal attachments are divided to permit examination of the body and tail. Kocher's maneuver is performed to facilitate bimanual examination of the head and uncinate process. The duodenum, splenic hilum, small bowel mesentery, gonads (in women), and lymph nodes are assessed for extrapancreatic disease. The liver is examined for metastatic disease. Intraoperative ultrasound may facilitate identification of tumors. Early experience suggests that a laparoscopic approach is also feasible in these tumors when the lesion is identified with localization studies.
Complications of Pancreatic Surgery
The most important complications of pancreatic surgery (tumor enucleation, distal pancreatectomy, or Whipple resection) are pancreatic fistula, pseudocyst, or abscess formation; which may lead to necrotizing retroperitoneal infection; and hemorrhage. Other complications include upper gastrointestinal tract bleeding, marginal ulceration, and biliary fistula formation. The mortality of a Whipple procedure is less than 5% and that of other pancreatic surgical procedures is less than 1%.
The Thyroid Gland
Alsanea O, Clark OH: Familial thyroid cancer. Curr Opin Oncol 2001;13:44.
Alsanea O, Clark OH: Treatment of Graves' disease: The advantages of surgery. Endocrinol Metab Clin 2000;29:321.
Alsanea O et al: Is familial non-medullary thyroid carcinoma more aggressive than sporadic thyroid cancer? A multicenter series. Surgery 2000;128:1043.
Bergman P, Auldist AW, Cameron F: Review of the outcome of management of Graves' disease in children and adolescents. J Pediatr Child Health 2001;37:176.
Chi DD, Moley JF: Medullary thyroid carcinoma: genetic advances, treatment recommendations, and the approach to the patient with persistent hypercalcitoninemia. Surg Oncol Clin N Am 1998;7:681.
Giuffrida D, Gharib H: Anaplastic thyroid carcinoma: current diagnosis and treatment. Ann Oncol 2000;11:1083.
Kebebew E, Clark OH: Differentiated thyroid cancer: "Complete" rational approach. World J Surg 2000;24:942.
Kebebew E et al: Medullary thyroid carcinoma: clinical characteristics, treatment prognostic factors, and a comparison of staging symptoms. Cancer 2001;88:1139.
Kebebew E et al: Total thyroidectomy or thyroid lobectomy in patients with low-risk differentiated thyroid cancer: Surgical decision analysis of a controversy using a mathematical model. World J Surg 2000;24:1295.
Miccoli P et al: Minimally invasive Video-assisted thyroidectomy: multi-institutional experience. World J Surg 2002;26:972.
Moley JF, DeBenedetti MK: Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 1999;229:880. (Over 75% of patients with palpable medullary thyroid cancer had associated nodal metastases.)
Reeve T, Thomson NW: Complications of thyroid surgery: how to avoid them, how to manage them and observations on their possible effect on the whole patient. World J Surg 2000;24:971. (Common and uncommon complications associated with thyroidectomy.)
Shaha AR: Management of the neck in thyroid cancer. Otolaryngol Clin North Am 1998;31:823. (Treatment of lymph node metastases.)
Witte J et al: Surgery for Graves' disease: Total versus subtotal thyroidectomy—results of a prospective randomized trial. World J Surg 2000;24:1303.
The Parathyroid Gland
Arici C et al: Can localization studies be used to direct focused parathyroid operations? Surgery 2001;129:720.
Bilezikian JP et al: Summary statement from a workshop on asymptomatic primary hyperparathyroidism: A perspective for the 21st century. J Clin Endocrinol Metab 2002;87:5353.
Brandi ML et al: Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001;86:5658.
Consensus Development Conference Panel: Diagnosis and management of asymptomatic primary hyperparathyroidism: Consensus Development Conference statement. Ann Intern Med 1991;114:593.
Eigelberger M, Clark OH: Surgical approaches to primary hyperparathyroidism. Endocrinol Metab Clin North Am 2000; 29:479.
Howe JR: Minimally invasive parathyroid surgery. Surg Clin North Am 2000;80:1399.
Lee PC et al: Parathyromatosis: a cause for recurrent hyperparathyroidism. Endocr Pract 2001;7:189.
Lundgren E et al: Increased cardiovascular mortality and normalized serum calcium in patients with mild hypercalcemia followed for 25 years. Surgery 2001;130:978.
Miccoli P: Minimally invasive surgery for thyroid and parathyroid disease. Surg Endosc 2002;16:3.
Miura D et al: Does intra-operative quick parathyroid hormone assay improve the results of parathyroidectomy? World J Surg 2002;26:926.
Pasieka JL, Parsons LL: Prospective surgical outcome study of relief of symptoms following surgery in patients with primary hyperparathyroidism. World J Surg 1998;22:513.
Perrier ND et al. Parathyroid surgery: Separating promise from reality. J Clin Endocrinol Metab 2002;87:1024.
Shaha AR, Shah JP: Parathyroid carcinoma: a diagnostic and therapeutic challenge. Cancer 1999;86:378.
Silverberg SJ: Natural history of primary hyperparathyroidism. Endocrinol Metabolism Clin North Am 2000;29:451.
Tominaga Y: Surgical management of secondary hyperparathyroidism in uremia. Am J Med Sci 1999;317:390.
The Adrenal Gland
Brunt LM et al: Adrenalectomy for familial pheochromocytoma in the laparoscopic era. Ann Surg 2002;235:713.
Brunt LM, Moley JF: Adrenal incidentaloma. World J Surg 2001; 25:905.
Dackiw APB et al: Adrenal cortical carcinoma. World J Surg 2001; 25:914.
Gordon RD, Stowasser M, Rutherford JC: Primary aldosteronism: are we diagnosing and operating on too few patients? World J Surg 2001;25:941.
Kebebew E, Duh Q-Y: Benign and malignant pheochromocytoma: diagnosis, treatment and follow-up. Surg Oncol Clin N Am 1998;7:765.
Lam KY, Lo CY: Metastatic tumors of the adrenal glands: a 30-year experience in a teaching hospital. Clin Endocrinol 2002;56: 95.
Norton JA et al: Cushing's syndrome. Curr Probl Surg 2001;38: 488. [11427876]
Raeburn CD, McIntyre RC: Laparoscopic approach to adrenal and endocrine pancreatic tumors. Surg Clin N Am 2000;80: 1427.
Reincke M: Subclinical Cushing's syndrome. Endocrinol Metab Clin North Am 2000;29:43.
The Endocrine Pancreas
Akerstrom G, Hessman O, Skogseid B: Timing and extent of surgery in symptomatic and asymptomatic neuroendocrine tumors of the pancreas in MEN 1. Langenbecks Arch Surg 2002;386:558.
Anderson MA et al: Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas. Am J Gastroenterol 2000;95:2271.
Azimuddin K, Chamberlain R: The surgical management of pancreatic neuroendocrine tumors. Surg Clin North Am 2001; 81:511.
De Herder WW, Lamberts SW: Somatostatin and somatostatin analogues: diagnostic and therapeutic uses. Curr Opin Oncol 2002;14:53.
Green BT, Rockey DC: Duodenal somatostatinoma presenting with complete somatostatinoma syndrome. J Clin Gastroenterol 2001;33:415.
Norton JA et al: Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med 1999;341:635.
Editors: Greenspan, Francis S.; Gardner, David G.
Title: Basic & Clinical Endocrinology, 7th Edition
Copyright Š2004 McGraw-Hill
> Back of Book > Resources > Appendices


text: My artwork can be viewed at the Mountain Arts Network Gallery in Lake Arrowhead and in Big Bear at the Wild Coyote Gallery both in California. I love painting abstracts as well as landscapes, and still life. I started with oils, although watercolor is my favorite medium, lately I have been experimenting with acrylic and collage. Some paintings just connect with your soul, maybe it's the colors or shapes that touches you. What I see is not always what others see. One thing about a paintings, You can enjoy them every time you look at it. . . . It's eye candy . . .. . . Thanks for you interest, Marly

subset: commoncrawl


text:
Gateway – Signs of the Times
Somewhere, on a continuum of approval, lies the prospect of new Gateway Signs for Southampton and Port Elgin.
Those are the installations that greet visitors and locals alike as they drive into either town. It's all part of a Bruce County signage strategy. Which is all well and good. But, there seems to be a problem. No one can agree on anything. The curse of committee consensus is upon the project. Which is not a surprise.
Consensus is not a creative force. Good design is seldom the end result of approval committees. Public Meetings, Focus Groups and research can provide direction, but, more often then not, they are misinterpreted and their dictums carved in stone. Everyone has a different take on objectives, creative strategy and tactics. A quick reading of all the articles on this subject proves me accurate.
What is even more surprising is that a American Firm is charged with designing for small town Ontario. More surprising is that the cost of these Gateway Signs is approximated at $40,000 to $50,000. Really! Just looking at some of their proposals shows you how off-base they are.
I have only one question – Are there not creative, competent design houses in Canada? Having worked in the business, I would have to say "Yes!" Why we went across the border for an American interpretation of our County is beyond me. That's a question for Bruce County Tourism.
Nonetheless, I can't recall the Port Elgin sign. But, the one for Southampton features a visual of the Imperial Light on Chantry Island and the line – "The Oldest Port on the Bruce Coast." You can't turn around in 'South' without seeing some replica/picture of that beacon. And so it should be.
The lighthouse identifies the town. That place, where the Saugeen flows into Lake Huron, the reference to the harbour, radiates years of historical importance.
It's a great sign. Relevant, intriguing and instant in its communication. Sure it could stand a little freshening up – or some new reincarnation – but it needs no more than that. Southampton's Gateway Sign needs no change as far as content is concerned.
Port Elgin faces a bigger challenge. Committees, consensus and politics are bad designers. Yet, there doesn't seem to be any other way. I wish them luck.
2 Responses
Hi Ed,
I can't believe this is actually happening. It's embarrassing, like you said there's no shortage of world-class design houses in this province and country. And you can't throw a rock up in the county without hitting an artist of some sort that lives and breathes and celebrates where they call home. I think there should be a petition to shame the ministry of tourism to rethink at least the use of an american firm. Yikes.
I'm a little late getting to your blog. But did you realize that county council is spending more than $200,000 on this consulting work. That doesn't include specific signs construction for each community. We could have 10-15 road signs worth $50,000 each. Hmmm…for a total closing in on $1 million. And it's not that difficult to get to Southampton and Port Elgin from the south. Maybe the money would be better spent on attractions rather than signage.


text:
CHARLOTTE — Authorities arrested a man they accuse of purposely flying a drone near a Charlotte-Mecklenburg police helicopter as it tracked a wanted suspect early Thursday.
The helicopter pilot had to "immediately and abruptly" alter the helicopter's flight path to avoid a mid-air collision with the drone, the Charlotte-Mecklenburg Police Department said in a news release.
At approximately 12:40 a.m., officers were using the helicopter to help search for a suspect who was running from police. The pilot was notified by officers on the ground that a man had launched a drone in the area at about the same altitude and flight path as the helicopter.
Christopher Baucom, 26, initially refused officers' orders to land the drone, the release states. After speaking further with officers, he eventually landed it.
The drone was of such a size that it is required to be registered with the FAA, and flying drones at night is prohibited.
Police said Baucom refused to provide officers with a drone registration or personal identification, and told officers that he did not need to comply with their requests to do so.
Officers charged him with interference with manned aircraft by unmanned aircraft system (felony) and resist (misdemeanor), the release states.
Baucom had been listening to a scanner and told officers that he drove to the scene to take video footage of the helicopter as it worked the call, the release states.
Original article can be found here: http://www.journalnow.com
Friday, March 25, 2016
Man accused of purposely flying drone near Charlotte police helicopter
Posted by Kathryn on 3/25/2016
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text:
January is almost over and it's time to push forward and re-examine the goals you've set for your organization this year. According to Business Insider, 80% of enthusiasm for resolutions can dwindle out by February. At Van Petten Group, we want to help you stick with your big plans and create actionable goals for your team! Here are some ideas in how to strategize for a successful 2019.
When formulating resolutions or goals for your organization, remember that not all of the responsibility falls on your shoulders. In our previous Insight, "Celebrate and Motivate: Creating Intuitive Catalysts for Winter Productivity in Your Organization", we speak to the importance of reflecting on your successes in 2018 in order to encourage gratitude and to maximize your chances for growth within your organization. Sit down with your team and pull data from your accomplishments in the last year. How did they improve your organization holistically? Who worked on what project and how can they learn and grow from their work? Each team member or department can share this information and create goals within your organization to keep the momentum going.
You will then look at your "why". This is where we find the gold standard of knowledge. Writing out goals is just step one; continuing to answer "why" is one of the most important parts of the process. How can your organization stay focused and on-task to reach set goals if this isn't clear and routinely examined? Taking the time to write clearly why you're undertaking a certain plans may surprise you, and with it comes a tangible taste of what you have to gain.
When clarifying our goals together, keep them realistic. This will assist in solidifying strong willpower. According to the American Psychological Association, "Some experts liken willpower to a muscle that can get fatigued from overuse." Work to empower resilience as an organization by focusing on strategizing with S.M.A.R.T. goals: Specific, Measurable, Attainable, Relevant, Timebound.
Specific – Create a clear definition of the action you want to take; write it down.
Measurable – How can you measure this goal?
Attainable – Ground your goals in your reality. These aren't wishes, they are attainable goals!
Relevant – How are your goals relevant to your organization?
Time-Bound – Set specific (realistic) deadlines for your team. This is a key factor when creating goals
These S.M.A.R.T. goals will help create structure and success!
With this structure, it will be feasible to create one broad goal for the entire year, with additional smaller goals that complement and support your main goal. Create an outline of how you'll reach those goals, when you want to accomplish them, and ways that ensure your organization stays on track. This enlightens your action plan for the year. Your team will be inspired and focused by a clear path through the entire year.
May your organization's 2019 be supported by continued refinement of processes and emboldened planning! Van Petten Group is rooting for you.
Megan Van Petten
Van Petten Group
CEO & President
Van Petten Group, Inc.


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Travel To
Tortola is one of the most beautiful and the biggest Island in the Caribbean. A part of the British Virgin Islands, the place is filled with white sandy beaches which offer great visual aesthetics as well as enjoyable experience. Being an island, it obviously offers a lot of beautiful shores, and also is known for the famous Smugglers' Cove. Tortola is a place that should be visited at least once, since it, is going to be a once in a lifetime experience so that you can come back all tanned and enjoy to your fullest. So, now we are going to show you some of the best things in Tortola which are not going to let you leave the place to your flight from Tortola back to your home!
With the white Sandy beaches covering most of the landscape and the beautiful mountains on both sides, it is going to be a whole lot of fun if you are able to sweat through the day and get all and venue bask in the sun at those beaches. I think you might have got a good idea of what time I am suggesting you go to this place, so make sure you are able to make the most out of your visit to this Paradise during the summer season while keeping in mind that the crowd will also be at its Prime during this period. Get your next summer vacations booked for this city and book your tickets to Tortola in advance.
As is the case in the whole Tortola, this place is where you need to spend at least a day. A full day of sightseeing and beautiful areas where you can go diving or snorkeling as well. The most special thing about this place is that there are beautiful white beaches here which are not a lot crowded, unlike all the other places that the island offers. So, if you want to enjoy the beach in the calmest manner.
One thing the Caribbean is the most famous for is its seafood delicacies as well as the fresh snacks. This is what you are going to be provided with if you are able to be a part of the Tango Caribbean Dinner Cruise. The chipsets sales from the coast of St. Martin, and capture some of the most ethnic scenic beauties including the good old sunset. The buffet-style dinner is then provided to you while you dance the evening off!
If adventure trips are the things that excite you, the only thing that you need to do is visit Saba. It is truly a Paradise and one place that you need to get away too if you are a diver or a hiker. You can go snorkeling in the sea or can go on a hike over the mountains. With steep clips on both the sides, there is an aged path from where goods are transported to the villages.
Nanny Cay is an island of the British Virgin Islands in the Caribbean. It is made up of three cays originally known as Big Cay, Little Cay and Miss Peggy Cay. In the 1970s these were consolidated into a single land mass for a marina and resort development. It is connected to Tortola by a short bridge
Mount Sage National Park is a protected area of the British Virgin Islands. It is named after the highest peak of the island of Tortola, Mount Sage. The Mount Sage volcanic peak rises to a height of 1,716 feet, and is thus the highest point in all of the Virgin Islands.
Fort Recovery is a fort on the West End of Tortola in the British Virgin Islands. In historical records, the fort is often referred to as Tower Fort, and the area around the fort is still referred to as "Towers" today. A hotel is now built around the Tower.


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Sam Leigh, the former Hemsworth Miners Welfare and Athersley Recreation goalkeeper – now plying his trade at Wombwell Town, after spells with Penistone Churchand Goole Town is perfectly qualified to assess the 'Access All Areas' fixture between the teams this Saturday – and he admits that he's seen more of his former colleagues from Fitzwilliam, writes Colin Muncie.
From a league position perspective, the bottom line is the table never lies and we're approaching Christmas now," Sam told us.
"Looking at the games Hemsworth have lost, they never ever get out-footballed and unfortunately it's usually down to individual errors which have cost them points – that individual used to be me! Athersley are where they are; looking at the squad early on I thought it was a case of square pegs in round holes in most games. In the last few weeks, though, they've started picking up vital points and they do seem to have settled down now, I think they'll be fine."
Sam rates Hemsworth's Manager highly and believes that he can lead Wells out of the NCEL. "Benno knows his stuff – FACT – and if anyone could guide them there, he will be the one to do it. I don't think he would leave the club for any other job, other than probably Bradford Park Avenue, who he mentioned in his Football League Paper article not long ago – but not until he's achieved promotion."
The Penguins are an unknown quantity to Sam since he left Sheerien Park at the start of the season. "I've not seen much of Athersley since leaving in all honesty – mainly highlights and social media updates. I have seen the odd Hemsworth game and I've been impressed on those occasions."
So what's Sam up to now? "I've put myself in retirement from the semi-pro scene as I'm enjoying my football with new side, Wombwell Town F.C., under Karl Rose and Doug O'Connor," he told us. "It's a great little project for me to be part of, and in all fairness through work and family I just couldn't commit the time and effort to semi-pro football."
"Wombwell Town filled that gap for me; and the running of the club and the set-up, arebetter than most clubs in the NCEL."
"I do miss the fans, without a word of a lie," Sam added. "Both sides are blessed with top, top fans; but Hemsworth's were unreal. The numbers were guaranteed – home and away – and with the exception of Worksop, you'd be hard pushed to beat that at NCEL level."


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When it comes to traffic monetization, the most successful sites are those that employ a variety of traditional methods as well as some techniques that aren't "mainstream" at all. While large "high quality" sites tend to stick to the standard, plain vanilla monetization methods, there are more and more examples of top tier websites getting a bit more creative in their efforts to turn pageviews into revenue.
Below are seven examples of creative monetization in action at some of the largest websites in the world.
Travel comparison site Orbitz has embraced co-registration as a way to make some incremental revenue. This process involves allowing users to opt-in to a third party product, which is typically a newsletter or email list. (In the example below, visitors have the option to sign up for a Texas travel guide.) Whenever someone opts in, Orbitz will pass that contact information to their partner and receive payment in return.
While the vast majority of tweets sent out don't generate any direct revenue, a few publishers and accounts have embraced sponsored tweets as a way to make a bit of money. The Onion does this somewhat regularly, usually as part of a larger sponsorship that includes a dedicated section of its website. (Yes, this is a real ad campaign.)
The Onion isn't the only big time Twitter account willing to put out sponsored tweets. For a mere $4,600 you can get Paris Hilton to tweet to her 12 million followers. (Also see our feature on 101 Ways to Make Money on Twitter.)
Sponsored content links, the practice of dedicating sections of a site to highlight content from other properties, has become an increasingly popular way for publishers to gain some incremental revenue. In fact, most major publishers now have sponsored content sections of some kind, leading to headlines like "Miley Cyrus' Shocking Shower Selfie" and "30 Hottest Jewish Women Under 40" on sports super-site ESPN.com:
CAPTCHA technology is nothing new as a tool to prevent bots from creating memberships and clogging up your site. But the concept of sponsored CAPTCHA, which incorporates ads into the process, is a novel idea. A growing number of properties are implementing this feature, which we think both improves the signup process and generates a bit of revenue in the process:
This example is perhaps not the sexiest example of creative advertising, but interesting nevertheless. Below is the footer of Weather.com (owned by The Weather Channel). In addition to the normal navigation links are several links to partners, including sponsors within the site as well as to third party properties such as WebMD, Go Daddy, and Georgia Tourism:
Movie review site Rotten Tomatoes uses a very high impact, disruptive ad unit on some of its visitors. This interstitial ad pops up in front of the content to play what is essentially a 30-second TV ad (in the screenshot below, a PlayStation 4 commercial). This ad unit seems to appear after a visitor has viewed a few pages as opposed to displaying on the first contact with the site, a common tactic to avoid scaring off first-time visitors too quickly.
Below is a screenshot from an article written by Martha Burk and published on HuffingtonPost.com. At the conclusion of the article is a fairly large section dedicated to highlighting a couple books that Ms. Burk has written. If you're interested in picking either of them up, there's a handy link that will direct you to Amazon to place your order.
Through these Amazon Associates affiliate links, HuffPo earns a commission for each sale of these books (and likely any other products) that it refers to Amazon:
If you're interested in monetizing your existing base of Web traffic more efficiently, your monetization hat should always be on. There's no need to reinvent the wheel; instead, pay attention to what other sites, both large and small, are doing in order to generate revenue from their pageviews.
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Grace is very smart and more than a little stubborn. This is not always a terrifically fun combination for her dad and me.
Case in point – we thought Grace did not know her own name. We were convinced of it, in fact. I was worried that there was some reason that Grace did not understand that her name was Grace. I mentioned it to my friends, and then I mentioned it to my sister.
My sister, Amanda, laughed at my incredulously. "Yes, she does."
"No, she doesn't. She never says it."
"Yes, she does. Grace, what's your name?"
Grace looked at her, shrugged her shoulders, put her palms in the air, and said, "I don't know!"
Later in the same day, Grace and my sister were riding in the back of the car when I heard Amanda say, "Who's that?"
I assumed (correctly) that they were looking at a picture on my iPhone.
Grace replied, "That's you."
Amanda said. "Good! Who's that with me?"
"That's 'racie!" Grace said. This conversation happened over and over, each time they looked at a new picture.
Until Grace thought I was paying attention, and then her answer changed back to "I don't know!"
The same thing played out a few times when we were talking about Grandma or about some other person.
Plus, we can't tell the difference between "nana" when it means Nana and when it means Amanda.
So Joe used Grace's bath crayons and drew some portraits on the wall of the shower. For the most part, they look like the members of our family.
Each night, at bath time, we talk about all of the people, their names, and what they were doing when we last saw them. My other sister, Ginny Rose, is missing, and so is my niece, Devin. My sister, Amanda, has been so loved that she has sort of rubbed off. And I don't understand why my head is the biggest one on the wall.
Nonetheless, Grace likes to talk to all of her people each time she takes a bath. She says hello to them, she says good bye to them, and she blows them kisses.
And best of all? She says all of their names.
Happily submitted to Tackle It Tuesday, Talk to me Tuesday, and Talk About Tuesday
Don't forget to stop back on Thursday for Grace's Kitchen!
© 2009 – 2018, Tara Ziegmont. All rights reserved.


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Othard is one of the three great continents on Hydaelyn in Final Fantasy XIV. Although currently inaccessible in gameplay, it is referenced throughout Eorzea. When revealing the design concept behind the Au Ra race, it was also stated they hail from Othard. Othard will be accessible in the expansion Final Fantasy XIV: Stormblood.
Othard is under control of the Garlean Empire , being the first continent the empire walked into when they began expanding out of Ilsabard. It was home to the city-state of Doma before its people rebelled against the imperial control and were forced to flee before their home was razed to the ground. The Garlean occupation has resulted in increasing numbers of displaced Au Ra seeking refuge in Eorzea.
Little is known about Othard's climate beyond it being described as having deep valleys and high mountain peaks in its eastern reaches. One known geographical area is the Azim Steppe, a vast grasslands that is home to numerous small tribes of nomadic Xaela ruled by khans.[1]
This region is home to the city-state of Doma.
Azim Steppe
A vast plain inhabited by the nomadic Xaela tribes.
The Ruby Sea
A sea area infested with pirate activity.
An archipelago off the east coast of Othard, with a strict isolationist policy.
The Burn
A blasted wasteland filled with impact craters.
Known city-states
Often referred to as the "Far East" of the eastern continent, Doma was home to the Raen clan of the Au Ra race and Yugiri Mistwalker. The Ninja job also originates in Doma.
Nothing is known about this city-state other than the fact it is under Garlean rule.
A port town located on southern Hingashi, and the only one open to foreign trade. Violence is prohibited within the city limits.
Nothing is known about this city-state. It is located in eastern Hingashi.


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Doing Politics Differently
We're the Peoples Party of Canada team representing the Federal riding of the Beaches East-York. Our candidate for the upcoming October 2019 Federal election is Deborah McKenzie.
The People's Party of Canada (PPC) was launched by Maxime Bernier on September 14, 2018 and recognized by Elections Canada on January 18, 2019.
We're one of the fastest growing parties in Canadian history and we're on a mission. Our party platform for the upcoming October 2019 general election is available on-line at https://www.peoplespartyofcanada.ca/platform and summarized in the chart below.
Compare and contrast the PPC platform to the other Canadian political parties and then make an informed choice this October.
Canada's future demands it.


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I don't set New Year's resolutions, knitting or otherwise. Occasionally, I'll send an intention, often vague, into the universe — "try not to worry so much" or "live more mindfully" or "don't buy new yarn until you've used at least as much from your stash."
Just kidding about that last one.
But even though I've not set a "sock of the month" goal, I'm quite pleased and a bit surprised that my first socks of 2019 are knit and blocked.
Yarn is Patons Kroy Sock in Blue Striped Ragg with contrasting toe and heel in an anonymous yarn from aforementioned stash. They're now wrapped in tissue paper and tucked away for someone special.
Those of you who've been with me for a while have seen a few of friend Judy's socks, starting with her very first sock about five years ago when she took my knitting class. She's made many pairs since, including this lovely pair of knee socks (her preferred length for her own socks), which she modeled at the gym this week.
She's puzzled — and a bit bothered — by the relative droopiness of the left one, but since they're knee socks, no one will know. Except you, of course, and I know you won't say a thing.


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United States District Court, D. Montana, Great Falls Division
May 2, 2018
DAVID BREWER Plaintiff,v.BNSF RAILWAY COMPANY, a Delaware Corporation, Defendant.
Morris United States District Court Judge
David Brewer filed a Motion for Discovery Sanctions pursuant
to Federal Rule of Civil Procedure 37 on January 12, 2018.
(Doc. 261.) United States Magistrate Judge John T. Johnston
issued Findings and Recommendations in this matter on
February 27, 2018. (Doc. 285.) Judge Johnston recommended
that the Court deny Brewer's request. Id. at 15.
When a
party makes no objections, the Court need not review de
novo the proposed Findings and Recommendations.
Thomas v. Arn, 474 U.S. 140, 149-52 (1986). This
Court will review Judge Lynch's Findings and
Recommendations, however, for clear error. McDonnell
Douglas Corp. v. Commodore Bus. Mach., Inc., 656 F.2d
1309, 1313 (9th Cir. 1981).
Rule of Civil Procedure 37(e) governs when a court may
sanction a party who fails to preserve electronically stored
information ("ESI"). A party may destroy evidence
in the ordinary course of business based on its document
retention policies, but a party may not destroy documents if
the party has "notice" of potential litigation.
United States v. Kitsap Physicians Serv., 314 P.3d
995, 1001 (9th Cir. 2002). Three types of sanctions exist for
the spoliation of evidence: (1) judgment against the party
who remains responsible for the spoliation; (2) the exclusion
of evidence or witness testimony corresponding to the
evidence destroyed; or (3) an adverse jury instruction.
Kopitar v. Nationwide Mut. Ins. Co., 266 F.R.D. 493,
499-500 (E.D. Cal. 2010).
sanction of default judgment requires a court to find
"willfulness, fault, or bad faith" by the party
that destroyed the evidence. Leon v. IDX Systems
Corp., 464 F.3d 951, 958 (9th Cir. 2006). The Ninth
Circuit has determined that a court must consider the
following factors before issuing a dispositive sanction: (1)
the public's interest in expeditious resolution of
litigation; (2) the court's need to manage its dockets;
(3) the risk of prejudice to the party seeking sanctions; (4)
the public policy favoring disposition of cases on their
merits; and (5) the availability of less drastic sanctions.
contends that BNSF had a duty to preserve relevant ESI and
failed to do so. BNSF failed to "migrate" its
emails from one server to another, and did not retain
specific devices from current and former employees, which may
have had non-duplicative ESI saved on the device itself.
Brewer argues that BNSF had its own process of designating
computers subject to re-formatting and preserving them, but
failed to follow that process in this matter. Brewer further
argues that this failure prevents him from proving his claims
or disputing BNSF's asserted defenses.
37(e) requires a court to inquire whether the ESI should have
been preserved in anticipation of litigation and whether the
ESI can be restored or replaced through additional discovery.
Brewer argues that BNSF received notice of litigation when he
filed his complaint with OSHA on February 19, 2013. Brewer
officially filed his Complaint against BNSF on September 10,
2014. BNSF does not dispute Brewer's contentions. Judge
Johnston determined, and this Court agrees, that Brewer
fulfilled the notice element of a Rule 37(e) motion. (Doc.
285 at 6.) BNSF needed to preserve relevant ESI in
anticipation of litigation as of February 2013.
A court
must next inquire into whether the party seeking sanctions
can show that it suffered prejudice from the loss of
information. Fed.R.Civ.P. 37(e)(1). Upon a finding of
prejudice, a court "may order measures no greater than
necessary to cure the prejudice." Id. Judge
Johnston determined that the alleged spoliation in this case
does not warrant a default sanction. (Doc. 285 at 8.) The
Court agrees. Brewer fails to specify what information he
believes has been wrongfully withheld or not preserved.
Id. Judge Johnston determined that without
specificity of relevant documents that are missing or being
withheld, the Court cannot determine actual prejudice.
Id. at 9.
points to the deposition of BNSF's trainmaster, Connan
Moler, as a specific example of BNSF's failure to
preserve ESI. Judge Johnston determined, and the Court
agrees, that Brewer has not shown how the ESI he presumes to
be missing will prevent him from going to trial or threaten
to interfere with the rightful outcome of the case.
Id. Judge Johnston further determined that any
claims of prejudice related to Moler are ineffective because
the Court previously ruled that Moler's devices are
beyond the scope of discovery. Id. at 10. Brewer has
not shown that he suffered prejudice so great as to amount to
a default sanction.
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