Classification of Gastric Carcinoid tumors

Gastric carcinoids are rare tumours. Clinical setting: -  Type I  - Associated with chronic atrophic gastritis with or without pernicious anemia. In autoimmune gastritis progressive destruction of the specialised parietal and chief cell zone leads to atrophy , intestinal metaplasia , hypochlorhydria and hypergastrinemia. - Type II - In Zollinger Ellison syndrome, particularly in patients associated with multiple endocrine neoplasia type 1.           - Type III - Sporadic tumours    - Not related to hypergastrinemia    - In the antrum or corpus    - Larger lesion, may be ulcerated.    - May have an aggressive course.

http://www.ncbi.nlm.nih.gov/pubmed/15362575

Anti fungal therapies

Amphotericin B
Azoles: block Ergosterol synthesis which is an component of fungal cell wall
Echinocandins: Inhibit glucan synthase which is specific for fungal wall (eg: caspofungin)

Link

Colitis Cystica Profunda

http://www.ajronline.org/cgi/reprint/131/3/529.pdf

Laparoscopic Abdominal Wall Reconstruction

Movie link

Definition of hypersplenism

- Splenomegaly
- cytopenia(s) - usually thrombocytopenia, anemia or neutropenia
- normal or hyperplastic bone marrow
- response to splenectomy

Meckler's Triad

http://www.ncbi.nlm.nih.gov/pubmed/20935623

GAIL model for breast cancer risk assessment

http://www.cancer.gov/bcrisktool/

- age
- age of menses
- age of first child
- first degree relative with breast cancer
- previous breast biopsies
- History of ADH
- race

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Drugs that cause acute pancreatitis

"DEFEATS"

D: didanosine (anti-HIV drug)
E: erthyromycin
F: furosemide
E: estrogens
A: azithromycin (Imuran)
T: tetracycline
S: sulfa

Drugs Associated with Pancreatitis:

Definite Cause
·       5-Aminosalicylate ·       6-Mercaptopurine ·       Azathioprine ·       Cytosine arabinoside ·       Dideoxyinosine ·       Diuretics ·       Estrogens ·       Furosemide	·       Metronidazole ·       Pentamidine ·       Tetracycline ·       Thiazide ·       Trimethoprim-sulfamethoxide ·       Valproic acid
Probable Cause
·       Acetaminophen ·       α-Methyl-DOPA ·       Isoniazid ·       L-Asparaginase	·       Phenformin ·       Procainamide ·       Sulindac

Etiology - Acute Pancreatitis

"IT HURTS BADLY"

80-90% due to EtOH and gallstones

I: infection
T: trauma
H: hypercalcemia
U: ulcer (penetrating)
R: renal disease
T: tumor (pancreatic, biliary, duodenal)
S: structural (annular pancreas, pancreas divisum)
B: biliary gallstones
A: alcohol
D: drugs ("DEFEATS")
L: lipids
Y: "y"atrogenic

Parenteral Fluid composition

Solution	Na	K	Ca	Mg	Cl	HCO3
ECF	142	4	5	3	103	27
NS	154				154
RL	130	4	2.7		109	28
D5/0.45%NS	77				77
2/3 & 1/3	56				56

Osmolarity:
Ringer's: 275 mmol/L
Normal saline: 310 mmol/L
Plasma normal range: 300-310 mmol/L

pH:
Ringer's: 6.75
Normal saline: 5.5

Remicade vs. Humira

Adalimumab (Humira)
- human mAb to human TNF receptor
- 5-7 days until maximal serum concentration
- dosed every week 40mg I'M
- terminal half-life is 2 weeks

Infliximab (Remicade)
- Humanized mouse mAb to human TNF
- terminal half-life is 7-10 days
- dosed every 2-6 weeks 3-10 mg/kg depending on indication
- for Crohns typically 5 mg/kg

Timing after surgery.
- DMARDS can impair healing. For Remicade suggested to wait 6 weeks before elective surgery. For humira ? 2 weeks

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Hinchey 3/4 diverticulitis

ACS surgery:
- 1-2 resection and immediate anastamosis are suitable.
In setting of perforated, peritonitic diverticulitis, resection with diversion is gold standard.
- other potential options (without great evidence) include on-table lavage and primary anastamosis (more for obstructing colon lesions with minimal contamination), laparoscopic lavage and creation of loop ileostomy (and delayed laparoscopic sigmoid resection)
- one stage resection: argument is that colostomy takedown and reanastamosis associated with 4% mortality and 30-40% never go back for reversal.
In a healthy patient mortality of 4% seems too high. In an elderly and sick patient primary anastamosis would carry too high risk of leak with attendant risks of getting sicker
- diversion: loop ileostomy vs. Transverse colostomy. Higher risk of obstruction with ileostomy but transverse colostomy associated with paying problems, scar issues and harder to reverse.

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Diverticulitis: special circumstances

Cecal diverticulitis.
- 15% of north American patients. Majority are pseudodiverticula
- medical management is mainstay for uncomplicated disease
- localized diverticulotomy can be performed for very localized and mild disease

Young patients:
- patients younger than 40 yo
- current textbooks suggest treating in same fashion as in older patients.
- elective resection is individualized to the patient but generally does not follow a single attack.

Immunosuppressed patient:
- included in his group are chronic alcoholics, transplant patients, chemotherapy patients.
- incidence is not higher but consequence of a complicated attack is more significant
- corticosteroids cause thinning of colonic wall, suppressed physical exam, attenuated inflammatory response
- are RA patients on methotrexate and IBD patients on biologics considered Immunosuppressed?
- prophylactic colectomy not needed if diverticulosis found but aggressive investigation and treatment of diverticulitis warranted.

Trivia:
- diverticulitis has replaced appendicitis as most common source of liver abscess of portal origin.
- recurrence of diverticulitis after colectomy in the range of 1-10%
- level of anastamosis is only identifiable risk factor.

Classification of Wounds

Clean: 

• nontraumatic, no break in technique, no tract entered.
• Infection rate: 1.5 – 2.9%

Clean contaminated: 

• GI or resp tract entered without significant spillage, oropharynx, vagina, or noninfected GU or biliary tract entered, minor break in technique.
• Infection rate: 2.8 – 7.7%

Contaminated: 

• major break in technique, fresh traumatic wound, gross spillage from GI tract, entrance into GU or biliary tree in presence of infection.
• Infection rate: 6.4 – 15.2%

Dirty: 

• pus encountered, traumatic wound with retained devitalized tissue, foreign bodies, fecal contamination, or delayed treatment, or from a dirty source.  This definition suggests that organisms were present in the operative field before the operation.

Barrett's Esophagus - Surveillance

4 quadrant biopsies every 2 cm intervals - beginning 1 cm below GE jxn and extending 1 cm above squamocolumnar junction

In absence of dysplasia: 
- every 3 years

Low grade dysplasia: 
- every 6 months for 1st year, if no progression then every 1 yr

High grade dysplasia: 
- confirm by an independent, experienced pathologist.  Confirmation of diagnosis warrants agressive treatment
- endoscopic vs. surgical options

Mallampati Airway classification

Look for soft palate, uvula, tonsillar pillars
Class I: tonsillar pillars and all of uvula (only 0.4% were difficult)
Class II: more than base of uvula but not pillars
Class III: only base of uvula
Class IV: no uvula or soft palate

False positives and negatives do occur

Informed Consent

http://www.cmpa-acpm.ca/cmpapd04/docs/resource_files/ml_guides/consent_guide/com_cg_practicalconsiderations-e.cfm

Adequacy of informed consent is judged by what a "reasonable patient" would want to know about a procedure.

Inguinal hernia tissue repairs

McVay repair:
- for direct and femoral hernias
- transversalis aponeurosis and fascia sutured laterally to Cooper's ligament.
- sutures are placed beginning medially at the pubic tubercle and extending as far laterally as the femoral vein
- next suture (transition stitch) placed deeply into the pectineus fascia and more laterally through the anterior layer of the femoral sheath
- if conjoined to coopers stitches carried out too far lateral before transition stitch then patient can get femoral vein thrombisis
- treatment of femoral vein thrombosis involves anti-coagulants, recanalization and collateral venous formation usually occurs

Condon Repair:
- anterior approach similar to McVay repair but you are suturing the conjoined tendon to coopers and to iliopubic tract/poupart's ligament
- ?higher risk of femoral vein compression
- double closure of femoral canal
- but does this neccessarily add anything beyond a McVay repair?

Nyhus repair:
- Preperitoneal approach to hernia repair
- from posteriorly similar to a condon repair you close femoral canal by suturing iliopubic tract to cooper's ligament

Poupart's ligament is the reflection of the external oblique aponeurosis
iliopubic tract extends from ASIS to the pubic tubercle

Stages of wound healing

Physiological Stages

Physiological Stages of Wound Repair

1.) Inflammatory Phase

• Initial response to injury
• Day 1-4 post injury
• Characterized by rubor, tumor, dolor, calor
• Platelet aggregation and activation
• Leukocyte (PMNs, macrophages) migration, phagocytosis and mediator release
• Venule dilation
• Lymphatic blockade
• Exudative
• In wounds closed by primary intention, lasts 4 days
• In wounds closed by secondary or tertiary intention, continues until epithelialization is complete

2.) Proliferative Phase

• Day 4-42
• Fibroblast proliferation stimulated by macrophage-released growth factors
• Increased rate of collagen synthesis by fibroblasts
• Granulation tissue and neovascularization
• Gain in tensile strength

3.) Remodeling Phase

• 6wks-1 year
• Intermolecular cross-linking of collagen via vitamin C-dependent hydroxylation
• Characterized by increase in tensile strength
• Type III collagen replaced with type I
• Scar flattens

Imperforate Anus

Low vs high.
Low perineal procedure.
High colostomy and pull through

Best to wait 24 hrs to define high or low.
- invertogram
>1 cm high
<1cm low High create colostomy then come back in 3 mos. Low cutback anoplasty High posterior sagital anorectal pullthrough Cloaca. Combined uretral and anal opening. Need to separate all and create new openings

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Rectal surgery sexual and bladder function

Since advent of TME, impotence reported ~10-30% of patients.
- hypogastric plexus. Sympathetic innervation, ejaculation
- Nervi erigentes. Parasympathetic function. Erection and urinary dysfunction.


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Rectal cancer margins

Distal margins.
- traditionally 5 cm. However no difference in local recurrence rateswhethwr 5, 2 or <2 cm distal margins.

Current recommendations. NCI
- proximal margin 5cm
- distal margin of >= 2 cm
- however, if 1cm margin needed to preserve sphincters then acceptable.
- distal spread beyond 1cm associated with aggressive disease or advanced stage tumors and a longer distal margin will not improve prognosis.

CRM: circumferential radial margin.
- most important determinant of local recurrence.
- TME has largely ensured that adequate circumferential margins routinely obtained.
- preTME era local recurrence was in the realm of 15-30%
- now recurrence rates should strive for 4-7%
- if mesorectal margin involved then local recurrence rates 11 vs 5%

Nodal clearance:
- 12 LNs required for adequate pathological staging. NCCN.
- can be challenging in pts who have had neoadjuvant therapy.

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Other antithyroid medications

Lugol's iodine (KI)
- short term antithyroid medication
- inhibits thyroglobulin proteolysis (which prevents release of T4/3)
- also prevents organification of thyroid hormone
- effects last 10-14 days

T3 production inhibitors
- major role of beta-blockers is to block the peripheral conversion of T4 to T3
- they do this in addition to treat symptomatic effects of hyperthyroidism.

Radioactive iodine.
- 131I
- trapped by follicular cells incorporated into tyrosine complex and deposited into colloid where beta dray destroys surrounding parenchyma

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Thionamide drugs

Two common antithyroid drugs used in north America
- propothiouracul (PTU)
- methimazole (tapazole)

PTU is preferred in the treatment of thyroid storm because it acts both on the thyroid and also peripherally

- in the thyroid both drugs inhibit TPO which converts iodide to iodine to be incorporated into thyroid hormone.
- PTU also prevents the peripheral conversion of t4 into the more active T3

Both drugs can cause skin rash. Agranulocytosis is rare but occurs with both
- 0.44% PTU
- 0.12% methimazole

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Amyloidosis Diagnosis

Diagnosis is via abdominal fat pad biopsy.
- easier and less morbid than biopsy of affected organ
- fat droplet place on glass slide and smeared to single layer
- sent air dried to lab for congo red staining which will allow pathologist to see amyloid deposits within fat

easiest to do an excisional biopsy of fat
core biopsy of fat also described.

http://www.amyloid.nl/investigations.htm

Pathological Subtypes of Breast Cancer

There are over 12 subtypes of breast cancer - though most of them are rare
- Invasive carcinoma (No Special Type) is by far the most common followed by Invasive lobular
- the remaining subtypes are quite rare

1) Invasive carcinoma: No Special Type
- majority 70-80%
Subtypes:
- Luminal A (ER +ve, HER2/neu -ve)
- Luminal B (Triple +ve)
- Normal Breast-Like (ER +ve, HER2/neu -ve)
- Basal-Like (ER -ve, PR -ve, HER2/neu -ve)
- HER2 positive (ER -ve, HER2/neu +ve; associated with brain mets)

2) Invasive Lobular Carcinoma
- increased bilateral

3) Medullary Carcinoma
- 6th decade of life
- slightly better prognosis than NST carcinomas despite negative histological features
- high nuclear grade, aneuploidy, absence of hormone receptors, high proliferative rate
- rapidly growing with smooth borders and thereforeon imaging can resemble a benign lesion

4) Mucinous (Colloid) Carcinoma
- older women
- grow slowly
- ER +ve, LN mets uncommon
- slightly better prognosis vs. NST

5) Invasive Papillary Carcinoma
- <1% of invasive ca
- ER +ve
- favorable prognosis
- much different outcome compared to micropapillary carcinoma

6) Micropapillary Carcinoma
- ER -ve, HER2/neu _ve
- LN mets
- poor prognosis

7) Metaplastic carcinoma
- rare type of breast cancer (<1% of cases)
- Matrix-producing carcinomas
- Triple negative
- LN mets infrequent but poor prognosis

Source:
Robbins

Neoadjuvant Therapy for Breast Cancer

Standard of care foe bulky breast or axillary disease:
- primary tumor 2-5cm
- <2cm but metastatic axillary LNs

Early skeptisism for this approach is unfounded: concern initially that pts would have poorer operative outcomes due to wound complications

McCready and Colleagues:
- ALN retains prognostic value after neoadjuvant Rx
- Not clear if neoadjuvant Rx impacts survival (but it's at least equivalent overall survival)
- 80% of pts have ~50% shriknage of tumor
- only 2-3% have signs of progression during neoadjuvant Rx

If there is complete pathologic regression there is a survival benefit

NSABP B-18:
- 4 cycles of doxorubicin and cyclophosphamide
- 5 year survival of complete response pts ~50%
- however, only 12% of pts achieve this kind of response

Advantages:
- Down size tumor in 80% of pts
- Determine which are chemo-responsive

Lower Limb 4 Compartment Fasciotomy

Compartments:
- Anterior
- Lateral
- Superficial Posterior
- Deep Posterior

Lateral incision: (Over fibula)
- releases anterior and lateral compartments
- watch out for superficial peroneal nerve which can be in lateral but also anterior compartment near intermuscular septum

Medial incision: (2-3 cm medial to edge of tibia)
- releases superficial and deep posterior compartments
- incise superficial compartment then release soleus muscle from posterior edge of tibia to arrive at deep compartment
- watch for saphenous vein which is superficial and runs at the posterior edge of tibia
- watch out for posterior tibial neurovascular bundle and achilles tendon which runs in superficial posterior compartment

http://www.youtube.com/watch?v=-1NDJkFH1vM&feature=related
http://www.youtube.com/watch?v=6c5r5brMOso

MELD score

MELD = 3.78[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.57[Ln serum creatinine (mg/dL)] + 6.43

In interpreting the MELD Score in hospitalized patients, the 3 month mortality is:

• 40 or more — 71.3% mortality
• 30–39 — 52.6% mortality
• 20–29 — 19.6% mortality
• 10–19 — 6.0% mortality
• <9 — 1.9% mortality

Branches of the Internal Iliac Artery

I Love Going Places In My Very Own Underwear:

Ileolumbar
Lateral sacral
Gluteal (superior and inferior)
Pudendal (internal)
Inferior vesicle (uterine in females)
Middle rectal
Vaginal
Obturator
Umbilical

Branches of the Long Saphenous Vein

6 tributaries off the long saphenous at the sapheno-femoral junction.
- important clinically when ligating and stripping the long saphenous for varicose veins
- also need to know and likely ligate when doing a superficial groin LND

2 circumflex femoral veins (medial and lateral)
2 circumflex iliac veins (superficial and deep)
superficial inferior epigastric
external pudendal

Endoscopic management of upper GI bleed

Forrest classification helps to predict who is at high-risk of re-bleed
1a: active, pulsatile bleeding. 50-90% rebleed
1b: active, non-pulsatile bleeding, 10-50% rebleed

2a: no active bleed, visible vessel. high risk rebleed (50-80%)
2b: adherent clot. low risk rebleed

3: no visible stigmata of bleeding. low risk rebleed

If you inject high risk lesions with 1:10,000 epinephrine risk of rebleed ~10-30%
other option is endoscopic coagulation or clips

Reasonable to repeat endoscopy in the case of rebleed

Consider OR if:
- large ulcer
- large bleeding vessel
- eldery >60
- active hemorrhage
- hypotension

angiography plays little role in controlling gastric ulcer bleeding as the vascular network is too rich

Perioperative Cardiac Risk Assessment

Assessment:
- History, physical
- Resting 12 lead ECG
- should be enough to stratify patients into low, intermediate and high cardiac risk

Risk of cardiac death and nonfatal MI also depends on procedure:
High risk >5%:
- Emergency operations (particularly in elderly)
- aortic, major vascular, peripheral vascular surgery
- Extensive operations with large volume shifts or blood loss

Intermediate risk <5%
- intraperitoneal or intrathoracic
- CEA
- H&N surgery
- Orthopedic
- Prostate

Low (<1%:
- endoscopic procedures
- superficial biopsy
- Cataract
- Breast surgery

Some merit has been shown in perioperative B-blockade to reduce perioperative cardiac risk.
The POISE study was reviewed in EBRS
- at adose of Metoprolol 100mg BID there is cardioprotective effect at this dose (lower doses do not afford same protective effects)
- however, patients need to be aware of the increased risk of hypotension, stroke and death

MAnagement of perioperative MI:
- STEMI: should be revascularized ASAP (within 12 hours). In post-op pt this likely means angiography as early post-op pts may not be eligible for throbolytics
- NSTEMI: stabilize medically and undergo risk stratification when stable
- Therapy with ASA, B-blocker and often ACEi (particularly in pts with low EF or anterior MI)
- Most post-MI pts should also be placed on a statin at discharge.

CHOP

Chemotherapeutic regimen for treatment of non-hodgkin's lymphoma

CHOP consists of:

• Cyclophosphamide, an alkylating agent which damages DNA by binding to it and causing cross-links
• Hydroxydaunorubicin (also called doxorubicin or Adriamycin), an intercalating agent which damages DNA by inserting itself between DNA bases
• Oncovin (which is the trade name for vincristine), which prevents cells from duplicating by binding to the protein tubulin
• Prednisone or prednisolone is a corticosteroid.

Normal cells are more able than cancer cells to repair damage from chemotherapy drugs.

This regimen can also be combined with the monoclonal antibody rituximab if the lymphoma is of B cell origin; this combination is called R-CHOP or CHOP-R. Typically, courses are administered at an interval of two or three weeks (CHOP-14 and CHOP-21 respectively). A staging CT scan is generally performed after three cycles to assess whether the disease is responding to treatment.

In patients with a history of cardiovascular disease, doxorubicin (which is cardiotoxic) is often deemed to be too great a risk and is omitted from the regimen. The combination is then referred to as COP (cyclophosphamide, Oncovin, and prednisone or prednisolone) or CVP (cyclophosphamide, vincristine, and prednisone or prednisolone).

Radiation Proctitis

Can result from external beam radiation or brachytherapy for cervical or prostate cancer.
Radiation oncologists can try and reduce incidence by using differential dosing during radiation or by using spacer techniques to increase distance between treated organ and rectum.

Complications of radiation proctitis include:
- bleeding
- tenesmus
- stricturing
- incontinence
- fistulas
- diarrhea

Mild radiation proctitis is usually self-limiting and decreases over time
proctitis can be acute or chronic and can present late even in the absence of immediate proctitis

Treatment options include:
- nothing
- enemas (cortisone, 5-ASA); evidence for these treatments is sparse and potentially can even cause more harm
- medium chain fatty acids
- Formalin/methanol topical application
- YAG laser
- thermal cautery
- if severe stricturing or fistulization then procetectomy or diverting colostomy maybe required

Hepatic Abscess

Potential routes for hepatic seeding are:
1) Biliary tree (currently most common)
2) Portal vein (usually GI source)
3) Hepatic artery (can be from any distant infection site/sepsis)
4) Direct extension (usually from abscess in vicinity of liver)
5) Trauma
Cryptogenic abscesses are very common and often a source is not identified

Microbiology:
most common organisms: E coli, Klebsiella pneumoniae

Antibiotic therapy and percutaneous drainage are currently the mainstays of treatment.
However, when this fails or the pt has a concomitant disease process that requires operative management, surgical drainage is indicated:
- use imaging to help guide site of drainage
- needle aspirate to confirm location and to get C&S sample (aerobic, anaerobic and gram stain - for ameobae too)
- abscess drained and finger dissection to break loculations
- biopsy wall of abscess cavity to rule out amebic trophozoites and presence of necrotic tumor
- biopsy normal liver --> presence of micro-abscesses will warrant a longer course of IV antibiotics
- closed suction drains in abscess cavity

Hypergastrinemia

Non-Ulcerogenic causes:
- Renal failure
- Atrophic gastritis
- Pernicious anemia
- Previous vagotomy
- Short-gut syndrome
- PPI

Ulcerogenic causes:
- ZES
- Retained or excluded antrum
- G-cell hyperplasia
- Gastric Outlet Obstruction

Gastrinoma

Most common site of gastrinoma:
- D2: 70%
- D1: 57%
- Pancreatic head: 27%, body: 23%, tail 50%

Gastric Ulcer Classification

Type I: Lesser curve at or proximal to incisura
Type II: 2 ulcers, Type I and an active or chronic duodenal ulcer
Type III: Located 2cm from pylorus
Type IV: Proximal stomach or gastric cardia
Type V: NSAID induced (diffuse)

Types II and III are associated with high-acid states.

Forrest Classification

1a: arterial, spurting hemorrhage

1b: Ozzing hemorrhage

2a: Visible vessel

2b: adherent clot

2c: Hematin-covered lesion

3: no signs of recent hemorrhage

Upper GI Bleed presentation:

http://fhs.mcmaster.ca/surgery/documents/gi_bleeding.pdf
Forrest class 2 lesions (Visible vessel or adherent clot will have) ~10% risk of rebleeding in first 24 hours
- risk of bleeding drops significantly in following 48-72 hours

Upper GI premalignant screening recommendations

American society of gastroenterologists recommendations:

http://www.guideline.gov/summary/summary.aspx?doc_id=9306


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Gastric polyps

Gastric Polyps are encountered in ~3-4% of upper endoscopies

Hyperplastic polyps
- 80% of all types of polyps
- overgrowth of normal gastric epithelium
- atypic is rare and has no neoplasticism potential

Adenomatous polyps
- premalignant lesions
- risk of malignancy is 10-20% in polyps >2cm
- operative management for sessile polyps >2cm suggested.
- some centers are also using submucosal resection.

References:
- greenfield

Hashimoto's Thyroiditis

AKA: struma lymphomatosa

- transformation of thyroid tissue to lymphoid tissue

- most common inflammatory disorder of the thyroid

- most common cause of hypothyroidism

Etiology:

- autoimmune process caused by activation of CD4 T cells specific for thyroid antigens.  Innate and adaptive immune response against thyroid

Clinical Presentation

Hashimoto's thyroiditis is also more common in women (male:female ratio 1:10 to 20 ) between the ages of 30 and 50 years old. The most common presentation is that of a minimally or moderately enlarged firm granular gland discovered on routine physical examination or the awareness of a painless anterior neck mass, although 20% of patients present with hypothyroidism, and 5% present with hyperthyroidism (Hashitoxicosis). In classic goitrous Hashimoto's thyroiditis, physical examination reveals a diffusely enlarged, firm gland, which also is lobulated. An enlarged pyramidal lobe often is palpable.

Diagnostic Studies

- When suspected clinically, an elevated TSH and the presence of thyroid autoantibodies usually confirm the diagnosis.
- FNAB  indicated in patients who present with a solitary suspicious nodule or a rapidly enlarging goiter.
- Thyroid lymphoma is a rare but well-recognized, ominous complication of chronic autoimmune thyroiditis and has a prevalence 80 times higher than expected frequency in this population than in a control population without thyroiditis. Recent studies of clonal similarity indicate that lymphoma may, in fact, evolve from Hashimoto's thyroiditis.14
- Path: FNA sample will show Hurthle cells in conjunction with heterogeneous populations of lymphocytes

Treatment

Thyroid hormone replacement therapy is indicated in overtly hypothyroid patients, with a goal of maintaining normal TSH levels. The management of patients with subclinical hypothyroidism (normal T4 and elevated TSH) is controversial. Treatment is advised especially for middle-aged patients with cardiovascular risk factors such as hyperlipidemia or hypertension and in pregnant patients.15 Treatment also is indicated in euthyroid patients to shrink large goiters. Surgery may occasionally be indicated for suspicion of malignancy or for goiters causing compressive symptoms or cosmetic deformity.

Hypercalcemic Crisis

Presentation:
- severe dehydration
- hypotension,
- altered mental status
- dysrhythmias

Management:
- hydrate: normal saline at a rate of 300 ml/hr; rehydration promotes calcium excretion in proximal tubule which is associated with Na flux
- Loop diuretics: reduce fluid overload and inhibit calcium resorption in the loop of Henle, thus promoting increased renal calcium excretion. 
- Dialysis: Patients with renal failure should be dialyzed with low-calcium dialysate

Pharmacologic agents to be used after rehydration:
- Steroids: Glucocorticoids lower calcium by inhibiting effects of vitamin D, increasing renal calcium excretion, and inhibiting osteoclast-activating factor. 
- hydrocortisone is 200 to 400 mg IV per day for 3 to 5 days
- Bisphosphonates inhibit osteoclast activity, thus preventing bone resorption induced by PTH. 
- Pamidronate (90 mg IV) or zoledronic acid (4 mg IV initial treatment, 8 mg on retreatment) normalizes calcium levels in most patients
- Calcitonin acts quickly (within 24 to 48 hours) to lower serum calcium levels and is more effective when used in combination with glucocorticoids. It should not be used in patients with salmon allergies. 

After patients with PHPT and hypercalcemic crisis are stabilized and serum calcium levels have been reduced to acceptable levels, preoperative localization studies should be obtained expeditiously in anticipation of an urgent parathyroidectomy.

Cameron 9th ed

Parathyroid Hormone

Single most important regulator of calcium and phosphate homeostasis in the body.

Effects:
Direct effects on bone and kidneys
Indirect effects on intestines (mediated viaVitD)

Effects on Bone:
- complex interaction activating osteoblasts and osteoclasts
- act indrectly on osteoclasts but have direct ligands on osteoblasts
- acts first to mobilize minerals from areas of rapid equilibrium
- prolonged PTH exposure results in further bone mineralization as lysozomal and hydrolytic enzymes are synthesized

Effects on Kidney:
- PTH has 3 effects on kidneys
- increases production of alpha-hydroxolase, resulting in increased hydroxylation of cholecalciferol to calciferol.
- increases reabsorption of calcium in distal nephron (loop of henle and proximal tubule Ca reabsorption is linked to Na and not influenced by PTH)
- prevents reabsorption of both phosphate and bicarbonate

Effects on Intestine:
- indirect and results in increased calcium absorption by increased VitD hydroxylation in kidney

Feedback inhibition is regulated by calcium levels.
- increased calcium normally results in inhibition of PTH secretion
- decreased calcium levels result in increased PTH secretion