Ebook The mont reid surgical handbook (6th edition): Part 2

(BQ) Part 2 book The mont reid surgical handbook presents the following contents: Benign and malignant liver lesions, renal transplantation, liver transplantation, pancreas transplantation, malignant skin lesions, diseases of the breast, breast reconstruction, gastric tumors, malignant pancreas disease, colorectal cancer,... and other content.

531

The presence of solid asymptomatic liver lesions is increasingly recognized because of the availability of sophisticated imaging Management depends

on knowledge of the pathology, radiologic appearance, and clinical behavior

of each lesion Generally, liver lesions can be morphologically differentiated into solid and cystic The most common diagnosis of each category is de-scribed in this chapter, and a common clinical problem for each is discussed briefl y

I SOLID LIVER LESIONS

Most importantly, one must differentiate between malignant and benign disease, and if benign (which is far more common), whether the patient needs any further follow-up or treatment

A BENIGN

1 Hemangioma

a This is the most common benign tumor; prevalence rate is 7% to 20%

in ultrasound and autopsy series Female/male ratio is 3:1

b Vascular malformation that enlarges by ectasia

c Generally remains stable over time but occasionally may demonstrate growth Rapid expansion may cause symptoms by stretching of Glisson’s capsule or pressure on neighboring organs

d In contrast-enhancing computed tomography (CT), during the arterial phase, the tumor appears as a sharply defi ned mass with sequential globular opacifi cation from “outside in.” In magnetic resonance imaging (MRI), the tumor appears higher in signal density on T2-weighted images

e Technetium-99m pertechnate-labeled red blood cell scan can usually

provide defi nitive diagnosis

f The majority of patients can be managed by observation alone.

g Resection or enucleation is indicated in symptomatic patients or ity to exclude malignancy Usually hemangiomas smaller than 10 cm

inabil-do not produce symptoms

h Kasabach-Merritt syndrome is a rare entity of giant hemangioma ated with diffuse intravascular coagulopathy Patients need urgent ther-apy including embolization or resection with concomitant treatment of coagulopathy

2 Focal nodular hyperplasia (FNH)

a FNH is the second most common benign liver tumor Autopsy series show a prevalence rate of 0.31% Occurs in male and female individu-als but more common in female sex

Benign and Malignant Liver

Lesions

Andreas Karachristos, MD, PhD

b Developmental vascular malformation that induces a vascular plastic process Unclear relation with oral contraceptives.

c Majority of patients are and remain asymptomatic; however, symptoms occur in up to 10% of patients

d In contrast-enhanced CT, it appears as homogenous hyperattenuating in

arterial phase with central scar and radiating bands In MRI,

T1-weighted images appear isointense or slightly hypointense, and T2-weighted images appear isointense or slightly hyperintense

e Technetium-99m–labeled sulfur colloid scan may be useful in confi

rm-ing diagnosis

f The lesion that resembles FNH is fi brolamellar carcinoma

g The majority of patients can be managed by observation alone In

asymptomatic patients, if defi nite diagnosis is provided by imaging, no further follow-up is necessary.

3 Hepatocellular adenoma (HA)

a Rare, benign proliferation of hepatocytes

b The annual incidence is approximately 1 in 1,000,000 people in contraceptive users, and the risk is increased 500-fold in women who are long-term users

c Female/male ratio is up to 11:1

d Documented link with long-term oral contraceptive use

e More patients with HA are symptomatic than with FNH Up to one third can present with acute rupture

f HAs can undergo malignant transformation, although the exact risk is

not well defi ned

g Usually are solitary but can be multiple in up to 30% of cases

h In contrast-enhanced CT, adenomas often demonstrate moderate hancement during the arterial phase that tends to be less than that seen in FNH In MRI, the majority of adenomas are hyperintense in T1-weighted images and isointense or hyperintense on T2-weighted images There is overlap with FNH, and it sometimes is diffi cult to dif-ferentiate the tumor

i Most HAs should be resected Discontinuation of oral contraceptives

should be advised

j Behavior of HAs during pregnancy is unpredictable; therefore, it may be advisable to resect them before pregnancy

k Ruptured adenomas are often surgical emergencies Embolization may

be helpful to stabilize the patient

B MALIGNANT

1 Metastatic lesions to the liver

a Metastatic lesions are the most common malignant lesions to the liver,

mainly from colorectal, lung, pancreas, breast, carcinoid, crine, and urogenital cancer Metastasis from colorectal cancer is the most common form, and resection in selected patients provides a sur-vival advantage

b The liver is the second most common site of colorectal metastases after the lymph nodes: 25% of all patients with colorectal cancer will have hepatic metastases at presentation, and 50% will experience develop-ment of them in the future

c Nearly 10% of these patients will be amenable to aggressive surgical treatment

d Keep in mind that in a patient with known malignancy, the likelihood

of a solitary liver mass ⱕ1 cm being a metastasis is less than 20%.

e Most metastases, including colorectal, are hypovascular and appear to

be hypoattenuating on portal venous CT images During the arterial phase, they most commonly appear with a ringlike peripheral enhancement

f Hypervascular metastases are renal cell carcinoma, carcinoid tumors, adrenal tumors, thyroid carcinoma, pancreatic islet cell tumors, and neuroendocrine tumors

g Colorectal liver metastases are associated with elevated onic antigen

h Previously, colorectal liver metastases were considered resectable under the following circumstances: four or fewer lesions occupying one lobe, with a margin of at least 1 cm

i Recently, improved combination chemotherapy has signifi cantly improved survival

j Criteria for resection include:

(1) Patient is fi t for surgery

(2) All detectable liver tumors can be removed, leaving adequate liver parenchyma, as long as a clear margin can be achieved

(3) At the University of Cincinnati, the following algorithm is applied:

(a) For patients with resectable metachronous metastases, ate surgical resection is an attractive option

(b) For patients with questionably resectable lesions or in whom negative margins may be diffi cult to achieve, as well as in those patients with synchronous metastases or recurrent disease, neoadjuvant chemotherapy followed by restaging and resection,

if possible, is a better option

(c) For patients who are surgically resectable but do not have quate hepatic reserve, portal vein embolization (which is thought to increase the size of the remaining liver) is an attrac-tive adjunct before resection

(d) Finally, in those patients who remain unresectable despite all these measures, radiofrequency ablation should be strongly considered

2 Primary hepatocellular carcinoma (HCC)

a This is one of the most common cancers worldwide Its incidence in the United States is relatively low: approximately 6 cases (of liver and intra-hepatic biliary cancers) per 100,000 people Male/female ratio is 3:1 Consensus exists among experts that the incidence is increasing

b The most common causative factor is the presence of cirrhosis

Hepatocellular injuries related to alcohol, hepatitis C infection, hepatitis

B infection, and fatty liver disease (nonalcoholic steatohepatitis) are the leading causes in the United States Other causes are hemochromato-sis, Wilson’s disease, tyrosinemia, -1-antitrypsin defi ciency, and Budd-Chiari syndrome

c Symptoms of malignancy are common at the time of presentation and may include anorexia, weight loss, lethargy, nausea, right upper quad-rant pain, and symptoms related to cirrhosis, such as ascites, jaundice, and encephalopathy

d The radiologic appearance of HCC is quite variable In enhanced CT, it most commonly appears as a transiently heteroge-neously hyperattenuating mass in the arterial phase Vascular invasion

contrast-or vein thrombosis may be present

e -Fetoprotein level is increased in approximately 75% of HCCs, but it

is nonspecifi c and related to size Percutaneous biopsy of a suspicious lesion should be performed with caution because of the risk for needle seeding (approximately 2%) -Fetoprotein level 200 ng/ml together with an imaging study showing a hypervascular mass is considered diagnostic of HCC

f Options that improve survival include liver resection or liver tion Management depends on the extent of the disease Important preoperative determinants are presence of vascular invasion, multiple tumors, and presence of hepatic fi brosis, as well as the general condi-tion of the patient In general, Child A and early B (Child–Pugh–Turcotte score

best treated by transplantation The best outcomes in liver tion are achieved when there is one tumor less than 5 cm or no more than three tumors, none of them more than 3 cm, without vascular invasion (Milan criteria)

g Recently, radiofrequency ablation has been shown to have comparable results with resection for small HCCs Other treatment options for inop-erable patients used at the University of Cincinnati are transarterial che-moembolization and transarterial yttrium-90 theraspheres

h Fibrolamellar carcinoma is a variant of HCC that is more common in young women -Fetoprotein is usually normal, is not associated with liver disease, and has better prognosis than HCC Therapy is complete

surgical resection Must be differentiated from FNH.

3 Intrahepatic cholangiocarcinoma

a This is the second most common liver cancer after HCC Originates from intrahepatic bile ducts

b In most patients, the tumor is discovered incidentally

c Most patients do not have underlying liver disease.

d On CT, usually appears as a large hypovascular tumor with central necrosis It is important to identify before surgery the extent of the portal or hepatic artery involvement

e Resection with negative margins remains the only viable therapy

Che-motherapy or radiotherapy has not been shown to improve survival.

Clinical scenario: A 39-year-old woman after injury during exercise had persistent

right upper quadrant pain Her primary care physician ordered an ultrasound that showed a 4-cm solid mass in the right lobe of the liver The patient was referred for further management.

In differentiating between the above entities, one must consider the age of the patient, history or clinical signs of liver disease, or any history of malignancy A breast examination, liver palpation for presence of hepatomegaly, and rectal exami- nation are of paramount importance Laboratory tests are in order: a complete blood cell count, liver function tests, and serology for hepatitis B and C viruses, as well as tumor markers -fetoprotein, carcinoembryonic antigen, and CA 19-9 In one study,

all patients with asymptomatic liver lesion and age older than 55, with increased alkaline phosphatase level and hepatomegaly, had cancer An imaging study should

be ordered next At the University of Cincinnati, a triple-phase liver CT is the ity of choice and provides helpful insight If malignancy cannot be excluded by imag- ing, then one should proceed with laparoscopic or open biopsy and/or resection Per- cutaneous biopsy of benign lesions often gives indeterminate results In addition, when HCC is suspected, percutaneous biopsy should be avoided because of the risk for seeding This particular patient had no history of liver disease, normal laboratory tests, and a CT suggestive of FNH An MRI scan confi rmed the result The patient will be managed with another MRI in 6 months, and if the lesion is unchanged, no further follow-up is necessary She was advised to avoid oral contraceptives, and the pain resolved with symptomatic therapy.

modal-II CYSTIC LESIONS

Cystic lesions of the liver are also quite common Most are benign Cystic neoplasms are complex lesions and rare Following is an outline of the most common cystic lesions

A BENIGN

1 Pyogenic hepatic abscess

a Results from bacterial infection of the liver parenchyma

b Most common cause is ascending cholangitis (caused by lithiasis, cer, or manipulation), followed by pyelophlebitis (complicated appendi-

can-citis, diverticulitis, pancreatitis, infl ammatory bowel disease) or any other cause of intraabdominal sepsis, septicemia, direct extension, or trauma

c No clear causative factor can be identifi ed in 20% to 45% of cases.

d Most common organisms are aerobic gram-negative (Escherichia coli, Klebsiella spp, Enterococcus spp), Streptococcus spp, Staphylococcus aureus, and anaerobes (Bacteroides sp, Clostridia) Fungal abscesses

are common in immunocompromised patients

e Blood cultures are positive in only 50% of patients at presentation

f Clinical presentation is often subacute, and mild symptoms may cede admission Fever, right upper quadrant pain, and hepatomegaly are common symptoms and signs.

g Characteristic contrast CT appearance is that of a round or irregularly shaped hypoattenuating mass with a peripheral capsule that shows enhancement

h Once the diagnosis has been made, broad-spectrum antibiotics acillin/tazobactam) should be started and modifi ed according to avail-able cultures

i Antibiotic therapy is not enough Percutaneous catheter drainage is the

usual treatment modality If lithiasis or biliary strictures are present, they should be treated with ERCP or surgery The underlying source, if present, should be treated

j Surgical drainage is indicated when percutaneous drainage has failed (48 hours after percutaneous drainage without improvement), location inaccessible to percutaneous drainage, multiloculated abscesses, or concomitant pathology that requires surgery

k Mortality rate has signifi cantly declined since the late 1980s, reaching 2% to 6% in many recent series Ruptured hepatic abscess carries a high mortality rate of 30% to 43%

2 Amebic hepatic abscess

a Caused by entamoeba histolytica Travels to the liver from the intestines via the portal blood

b A concomitant hepatic abscess is found in only one third of patients with amebic colitis Male/female ratio is 10:1 Usually patients have a

history of traveling to a tropical area.

c Typically, the onset of the illness is abrupt with right upper quadrant pain, fever, anorexia, and acute colitis

d Diagnosis is made by serum indirect hemagglutination assay

e Findings in CT are nonspecifi c and usually appear as solitary, round, hypoattenuating mass with an enhancing ring; 70% to 80% of the abscesses occur exclusively in the right lobe

f Usually therapy with metronidazole (750 mg three times daily for 5–10 days) is effective, with a 95% success rate

c E granulosus has an active cyst wall consisting of a germinal layer and

a laminar layer A reactive fi brous layer surrounds the active cyst, called

the pericyst, which becomes calcifi ed in 50% of liver cases The nal layer produces the daughter cysts.

d Liver cells undergo liquefaction necrosis and produce a cavity fi lled with

pus appearing as “anchovy paste.”

e Diagnosis is made by enzyme-linked immunosorbent assay or indirect hemagglutination tests Eosinophilia is present in 40% of cases

f Classic ultrasonographic or CT fi ndings are a thick wall, often with cifi cations and with daughter cysts

g Most cysts are asymptomatic at presentation Patients with complicated conditions present with cholangitis from rupture into a bile duct or with acute abdomen and anaphylaxis from rupture into the peritoneal cavity

h Medical therapy with albendazole (the best regimen) has a less than 30% success rate

i Defi nitive therapy includes complete excision of living parasites.

j Extreme caution should be used to avoid spillage, and all surrounding sues should be packed with 20% normal saline–soaked gauze Open cyst evacuation with aspiration of the contents and removal of the active cyst lining, complete pericystectomy, or liver resection are acceptable options

k If the patient presents with jaundice or cholangitis, then ERCP with sphincterotomy should precede surgery

4 Simple hepatic cyst

a Prevalence rate of asymptomatic liver cysts in ultrasound or CT series is approximately 3% in adults Equal distribution among sexes, although symptomatic cysts are more common in female individuals

b Adult polycystic kidney disease is associated with liver cysts in mately 60% of patients

c In general, these cysts grow slowly, lack septa, and do not have nant potential In most cases, they are asymptomatic and only large cysts produce symptoms Therefore, any patient with abdominal pain and sim-

malig-ple liver cysts should be evaluated for other pertinent pathology.

d Most patients do not require any treatment In symptomatic patients,

laparoscopic or open fenestration and rarely partial liver resection are acceptable treatments

5 Hepatic cystadenoma

a Uncommon single, usually large tumor

b Abdominal pain or discomfort is common presenting symptom because

of size

c Ultrasonography is probably the best modality and shows a single large

fl uid-fi lled cyst with irregular margins, septations, and mural nodules

d Must be differentiated from hydatid cyst and simple cyst

e Treatment is complete surgical resection

B MALIGNANT

1 Cystic subtypes of primary liver neoplasmsThese lesions are rare and usually are the result of central necrosis or sys-temic or local treatment The two most common neoplasms that can pres-

ent as cystic lesions are HCC and giant hemangioma Characteristic CT

features of the mass and liver parenchyma will help identify the nature of these lesions

2 Cystic metastasesCystic metastases may be seen in mucinous adenocarcinomas from colorec-tal or ovarian origin Also, hypervascular metastases, such as carcinoid, neuroendocrine, sarcoma, and melanoma, may have cystic appearance be-cause of central necrosis.

Clinical scenario: A 42-year-old man presents to the emergency department with a

1-week history of malaise and currently fever up to 102°F, upper abdominal fort, diaphoresis, and tachycardia An upper abdominal ultrasound showed at least two separate large (7 and 3 cm) cystic lesions in the right lobe of the liver.

discom-Again, history and physical examination are of paramount importance History of

recent travel to tropical areas, pathology related to the liver, and recent therapeutic interventions to the liver and bile ducts, as well as recent history of intraabdominal infections, should be defi ned in detail A triple-phase CT should be ordered to better delineate the lesion At the same time, serology for hydatic and amebic disease should be ordered Our patient was resuscitated, and intravenous broad-spectrum antibiotics were started immediately CT showed lesions compatible with pyogenic abscesses that were subsequently percutaneously drained His condition did not im- prove and a new CT scan 30 hours later showed that the abscesses were enlarged

He underwent a formal right lobectomy Gallbladder was signifi cantly infl amed He had an uneventful postoperative course.

RECOMMENDED READING

Blumgart LH (ed): Surgery of the Liver and Biliary Tract, 4th ed Saunders, 2007,

Philadelphia.

Cameron JL (ed): Current Surgical Therapy, 9th ed Mosby, 2004, St Louis.

Lee JKT, Sagel SS, Stanley RJ, Heiken JP (eds): Computed Body Tomography with MRI

Correlation, 4th ed Lippincott Williams & Wilkins, 2006.

a End-stage renal disease from a variety of causes

b Patient life expectancy longer than graft half-life

1 Detailed history and physical examination with special emphasis on:

a Underlying renal disease

b Estimated urine output

c Cardiovascular history

d History of infectious disease

2 Routine pretransplant studies

a Routine screening laboratory studies; renal panel, liver function tests, complete blood cell count, coagulation screen, urinalysis, calcium, phosphorus, magnesium

b Hepatitis screen, human immunodefi ciency syndrome, Venereal Disease Research Laboratory, viral titers (cytomegalovirus, Epstein–Barr virus, varicella), throat and urine cultures, tuberculin skin test

c Chest radiograph, electrocardiogram

d Blood typing, human leukocyte antigen (HLA), panel-reactive antibodies

3 Indication for pretransplantation native nephrectomy

a Chronic renal parenchymal infection

II IMMUNOLOGY OF RENAL TRANSPLANTATION

1 The ABO blood group antigens behave as strong transplantation

antigens, and transplantation across ABO barriers usually leads to irreversible hyperacute rejection

2 Disproportionate percentage of waiting patients who are type O or B

generally mandates that ABO identity (same blood type) rather than ABO compatibility (B → B or O) determines the distribution of deceased donor kidneys

3 For living-related donor transplantation, ABO compatibility is

adequate

4 A2 kidneys can be safely transplanted into O or B recipients with low

preoperative titers of isoagglutinin

5 ABO-incompatible transplants may be performed if isoagglutinins are

removed by splenectomy and plasmapheresis

B HLA MATCHING IN TRANSPLANTATION

1 Class I antigens consist of A, B, or C loci antigens located on the

surface membranes of all nucleated cells

2 Class II antigens consist of DP, DQ, and DR loci found primarily on

immune, dendritic, and endothelial cells

3 In clinical transplantation, the most important major histocompatibility

genes are HLA-A, -B, and -DR

4 HLA-DR matching provides a greater benefi t than class I antigen

matching

1 The patient’s serum is incubated separately with B and T cells from a

panel of donors selected to represent the HLA antigens commonly found in the local population

2 The results are usually expressed as the percentage of panel cells that

are killed by the serum

3 The anti-HLA antibodies that are detected are called panel-reactive

antibodies.

4 The fi nding of 60% of panel-reactive antibodies suggests that 60% of

donors will be unacceptable for the patient because there are ing antibodies that react with one or more of the donor’s HLA antigens

3 Preliminary cross-match is performed by testing donor lymphocytes

with stored sera of patients at the time of donor HLA typing

of candidates.

4 When the preliminary cross-match is negative, a fi nal cross-match is

performed with recent or fresh sera

III IMMUNOSUPPRESSION

A IMMUNOSUPPRESSIVE AGENTS IN CURRENT CLINICAL USE

1 Calcineurin inhibitors: cyclosporine (Sandimmune or Neoral) and

5 Monoclonal and polyclonal antibodies: muromonab-CD3 (OKT3),

antithymocyte globulin (Thymoglobulin), basiliximab (Simulect), daclizumab (Zenapax)

1 Conventional immunosuppressive protocols consist of a calcineurin

inhibitor, an adjunctive agent, corticosteroids, and the possible addition of antibody induction

2 Conventional immunosuppressive protocols that can provide 90% to

95% 1-year graft survival rate and 10% to 20% incidence rate of acute rejection include:

a Cyclosporin/mycophenolate mofetil/steroids

b Tacrolimus/mycophenolate mofetil/steroids

c Cyclosporin/sirolimus/steroids

d Tacrolimus/sirolimus/steroids

IV KIDNEY DONATION

A LIVING DONOR KIDNEY TRANSPLANTATION

1 Risks of donation

a The risk rate for mortality as a result of donor nephrectomy is estimated

to be 0.03%

b The reoperation rate and the readmission rate are both less than 1%

c The incidence rate of other postoperative complications approximates 3%

d A follow-up of more than 356 donors for at least 20 years reported one case of chronic renal failure in an aged patient

2 Exclusion criteria for living kidney donation include:

a Inadequately treated psychiatric disease

b Active drug or alcohol abuse

c Evidence of renal disease

d Abnormal renal anatomy

e Recurrent nephrolithiasis or bilateral kidney stones

f Collagen vascular disease

g Diabetes

h Hypertension

i Prior myocardial infarction or treated coronary artery disease

j Moderate-to-severe pulmonary disease

k History of cancer

l Active infection

m Chronic active viral infection (hepatitis B or C, human immunodefi ciency syndrome, human T-cell lymphocytic virus)

n Signifi cant chronic liver disease

o Signifi cant neurologic disease

p Disorders requiring anticoagulation

q Current pregnancy

r History of thrombotic disease with risk factors for future events (such as anticardiolipin antibody, factor V Leiden mutation)

B DECEASED DONOR KIDNEY TRANSPLANTATION

1 Donor age is an important determinant of long-term graft function.

2 Expanded criteria for donor kidney

a Kidneys from donors older than age 60 years

b Age 50 to 59 years with two additional risk factors, including a history

of hypertension, death as a result of cerebrovascular accident, or an increased terminal serum creatinine concentration 1.5 mg/dl

c Approximately 15% of transplantations are deceased donor kidneys

d At least a 70% increased risk for failure within 2 years when compared with standard criteria kidneys (On the positive side, this means that if a standard kidney has a 2-year graft survival rate of 88%, an expanded criteria donor [ECD] kidney has an estimated survival at 2 years of ap-proximately 80%.)

V SPECIFIC OPERATIVE CONSIDERATIONS

A LIVING DONOR NEPHRECTOMY

1 Left kidney is preferred because of longer renal vein and better access

b Colon is refl ected medially, away from the kidney

c The spleen or the liver is mobilized and retracted away from the upper pole of the kidney

d The perinephric tissues are freed, and the ureter and periureteral tissues are then mobilized

e The renal artery and vein are carefully identifi ed and isolated.

f The renal artery and vein are divided with a vascular stapler

g The ureter is ligated distally and kidney is brought out through hand port

h The kidney is fl ushed with preservation solution, placed on ice, and transported to the recipient room

1 Kidney graft is placed in pelvic cavity (heterotopic) because of less

surgical burden and easier access for evaluation after transplant

2 Generally, the right iliac fossa is favored for transplant site because

the vessels are more superfi cial

3 Oblique incision cranial to inguinal ligament—muscles are divided;

then the peritoneum is exposed and retracted medially to expose the iliac vessels

4 Vascular anastomoses are performed as follows:

a Renal artery to external iliac artery (end to side)

b Renal artery to hypogastric artery (end to end)

c Renal vein to external iliac vein (end to side)

d Accessory renal arteries can be anastomosed end to side to the largest renal artery and then anastomosed to the recipient vessels This is usually done ex vivo on ice

5 Ureteroneocystostomy

a Tension-free suture

b Water-tight suture

c One-centimeter submucosal tunnel to prevent refl ux

VI POSTOPERATIVE CONSIDERATIONS

1 Observation and documentation of hourly urine output is critical to

determine the early degree of initial function of the graft

2 Beware of volume depletion caused by posttransplant diuresis This

can be avoided by replacing urine output milliliter per milliliter every hour with intravenous fl uid of similar electrolyte composition

3 Central venous pressure monitoring is a useful guide to intravascular

volume status

4 It is not uncommon for electrolyte abnormalities to develop, including

hyperkalemia or hypokalemia, hypocalcemia, and hypomagnesemia

5 Sutures or wound clips are generally left in place for 21 days because

of delayed wound healing in patients with renal failure and suppressed patients

6 Foley catheters are left in place for 2 to 5 days after surgery.

B ASSESSMENT OF GRAFT FUNCTION

1 Urine output—nonspecifi c; decreased urine output may indicate

hypovo-lemia, urinary obstruction, ureteral compromise, vascular compromise, acute tubular necrosis, rejection

2 Creatinine and blood urea nitrogen—nonspecifi c.

3 Ultrasound—demonstrates patency of artery and vein, detects fl uid

col-lection and hydronephrosis; fi rst-step study after laboratory abnormality

4 Radionucleotide imaging—can image fl ow and function.

5 Renal biopsy—may yield defi nitive pathologic diagnosis in cases of

dysfunction; it is diffi cult to assess cyclosporine nephrotoxicity

VII COMPLICATIONS

1 Wound infection rate 1%

2 Lymphocele—many are asymptomatic, some present with mass effects,

lymph fi stula; diagnosed by sonography; percutaneous drainage or intraperitoneal window

3 Bleeding

4 Graft thrombosis—most often within the fi rst 2 to 3 days after

trans-plantation; sudden cessation of urine output and rapid increase of creatinine; diagnosed by Doppler ultrasound or isotope fl ow scan;

most of the time, kidney will be lost

5 Renal artery stenosis—usually occurs 3 months to 2 years after

trans-plantation; presents with refractory hypertension, unexplained increase

in creatinine concentration; diagnosed by Doppler sonography or ography; percutaneous transluminal angioplasty offers the safest mode

angi-of treatment

6 Urine leaks

a Incidence rate of 3% to 10%

b Related to ureteral ischemia, anastomotic tension

c Usually in fi rst month after transplant

d Symptoms—pain with graft swelling, fever, sepsis, and urine fi stula

e Diagnosis—CT scan, ultrasonogram may demonstrate fl uid collection

f Management (1) Percutaneous nephrostomy and stenting (2) Ureteroneocystostomy revision (3) Boari fl ap, donor-recipient pyeloureterostomy

7 Ureteral stenosis

a This is the most common urinary complication

b Causative agents include hematoma, kinking, or edema

c Late-onset obstruction is related to fi brosis from ischemia

d Presentation depends on degree of obstruction

e Oliguria, increased creatinine concentration, sepsis, anuria

f Diagnosis by sonography, antegrade pyelography (most sensitive), renal venography (less sensitive)

1 Infections

a First month (1) Cause related to surgical procedure

(2) Wound infections, urinary tract infection, infections related to indwelling catheters

(3) Pneumonia (4) Also infections transmitted with graft (human immunodefi ciency syndrome, cytomegalovirus, hepatitis)

b Months 1 to 6—high mortality because of degree of immunosuppression

Viral infections are common

c After 6 months—risk is reduced because of reduced immunosuppression

2 Malignancy

a Immunosuppression predisposes to the development of malignancy

b The incidence of nonskin malignancies in renal transplant recipients is

up to 3.5-fold greater than that of age-matched control subjects

c Posttransplant lymphoproliferative disorders and Kaposi’s sarcoma tend

to occur early after transplant; other tumors tend to occur later

d The cumulative incidence of skin cancer is much greater, but few patients die of skin cancer after renal transplantation

e Decision regarding cancer screening should be made on an individual basis

VIII STATISTICS OF RENAL TRANSPLANTATION

A SURVIVAL BENEFIT OF RENAL TRANSPLANTATION

1 Survival benefi t of transplantation versus remaining on the waiting list

(Fig 49-1) Note that in the early period after a transplant, the risk for death is greater for transplant recipients than for wait-listed patients

Within a short period, somewhat longer for recipients of marginal kidneys, the risk of death and chances of survival equalize Thereafter, transplantation has a persistent survival benefi t

2 The longer patient receives dialysis, the greater the risk for

posttrans-plant morbidity, mortality, and graft loss

B SURVIVAL

1 Graft versus patient survival is shown in Figure 49-2

Survival after kidney transplant.

Deceased donor non-ECD KT graft survival

Ideal donor kidney(IDK) recipient

Marginal donor kidney(MDK) recipient

Time to equal risk (ER)Time to equal survival (ES) 122d256d

MDK185d531d

4.003.753.503.253.002.752.502.252.001.751.501.251.000.750.500.25

Danovitch GM: Handbook of Kidney Transplantation, 4th ed Philadelphia, Lippincott

Williams & Wilkins, 2005.

Stuart FP, Abecassis MM, Kaufman DB: Organ Transplantation, 2nd ed Georgetown,

TX, Landes Bioscience, 2003.

Organ Procurement and Transplantation Network: 2005 OPTN/SRTR Annual Report

Available at http://www.optn.org/AR2006/default.htm Ojo AO, Hanson JA, Meier-Kriesche HU, et al: Survival in recipients of marginal cadaveric

donor kidneys compared wih other recipients and wait-listed transplant candidates J Am

Soc Nephrol 12:589, 2001.

551

I GENERAL CONSIDERATIONS

A HISTORY

1 1967—Starzl performed the fi rst successful liver transplant

2 1983—venovenous bypass was introduced for use during anhepatic phase; cyclosporin approved for transplant immunosuppression

3 1984—Broelsch and associates introduced the reduced-size liver transplantation

4 1989—fi rst successful living-related transplant

5 Today, almost 6500 liver transplants are performed yearly in the United States

B INDICATIONS AND LISTING PROCESS FOR TRANSPLANTATION

For a patient to be placed on the waiting list, he/she must have a Child–

Turcotte–Pugh score of 7 or greater Generally, patients are transplanted for complications of portal hypertension, encephalopathy, hepatic synthetic dysfunction, or growth failure (children) Organs in each geographic area are distributed by United Network for Organ Sharing based on the patient’s MELD (Model for End-stage Liver Disease) score MELD score is based

on the following factors: creatinine, bilirubin, and international normalized ratio

C SPECIFIC INDICATIONS AND CONTRAINDICATIONS

1 Alcoholic cirrhosis—most common causative factor of liver failure in the United States

2 Hepatitis—virtually all patients with chronic hepatitis B or C ultimately become reinfected, with variable outcomes

3 Acute fulminant hepatic failure—secondary to drug toxicity, hepatitis, Wilson’s disease, pregnancy, Budd-Chiari syndrome, mushroom intoxi-cation, and others Acetaminophen toxicity is the most common cause

4 Inborn errors of metabolism—glycogen storage disease, Wilson’s disease, 1-antitrypsin defi ciency, protein S defi ciency, among others

5 Biliary disease—primary biliary cirrhosis, primary sclerosing tis, extrahepatic biliary atresia (most common causative factor in children)

6 Primary hepatic malignancy—controversial indication, associated with high likelihood of recurrent disease Milan criteria for transplant for hepatocellular carcinoma: 1 nodule

or less

7 Contraindications—extrahepatic malignancy, active infection, severe organ impairment (excluding renal), acute substance abuse, poor social support, inability to comply with medical regimen, fi xed pulmo-nary hypertension (does not respond to prostaglandin E1)

Liver Transplantation

Mubeen A Jafri, MD

D ORGAN SELECTION

In general, standard criteria apply, including a hemodynamically stable donor with no evidence of sepsis or non–central nervous system primary malignancy, and ABO compatibility

1 Cadaveric whole organ

2 Cadaveric reduced-sized grafts—full right, full left, or left lateral lobe graft With a left lateral lobe, a size discrepancy of 10:1 can be overcome

3 Living related liver donation—increases the limited pool of sized livers; graft and patient survival rates as high as 95%

pediatric-II SPECIFIC OPERATIVE CONSIDERATIONS

A TRADITIONAL OPERATIVE TECHNIQUE

1 Bilateral subcostal incision with midline extension to xiphoid process

2 Mobilization of the native liver Isolation of the suprahepatic and hepatic venae cavae Skeletonization of the hilar structures—portal vein, bile duct, and hepatic artery

3 Establishment of venous-venous bypass to decompress the splanchnic venous system; selectively used with intestinal edema, hypotension after test clamping of the vena cava, extensive portal hypertension bleeding, and diffi cult hepatectomy Cannulas (percutaneous or cut-down) from the portal and femoral veins drain blood into the axillary vein

2 Hilar dissection performed as in traditional technique

3 Recipient liver remains attached to vena cava only by hepatic veins

4 Recipient hepatectomy

5 Vascular anastomosis—donor suprahepatic vena cava to recipient inferior vena cava in end-to-side fashion, donor infrahepatic vena cava ligated, hepatic artery and portal vein

6 Remainder of procedure done as in traditional technique

III POSTOPERATIVE CONSIDERATIONS

3 Ventilatory support often for 24 to 48 hours after transplantation

4 Electrolyte management—correction of glucose, calcium, potassium, magnesium, and phosphate are particularly important

5 Infection surveillance and prophylaxis—trimethoprim/sulfamethoxazole,

fl uconazole, and ganciclovir

6 Immunosuppression—protocols vary among institutions

a Antilymphocyte induction therapy available but has not been widely used

b Calcineurin inhibitors remain the baseline postoperative pression Tacrolimus (Prograf; FK506) is the most widely used agent

immunosup-Renal toxicity is an important adverse effect

c Steroids are generally given as intravenous methylprednisolone sodium succinate (Solu-Medrol) after surgery, and patients are transitioned to oral prednisone as advancement of diet permits

d Mycophenolate mofetil (CellCept) is a commonly used third baseline immunosuppressive agent

B ASSESSMENT OF GRAFT FUNCTION

1 Routine laboratory tests: Transaminase levels, alkaline phosphatase, factor V function (best predictor of early graft function), serum bilirubin, and coagulation parameters are nonspecifi c but are usually used to follow trends in graft function

2 Radionuclide imaging can be used to assess hepatocellular function and continuity of biliary drainage

3 Liver biopsy: This is most specifi c for differentiating rejection from recurrent hepatitis, steatosis, ischemia, or other causes of graft dysfunction

C COMPLICATIONS

1 Primary nonfunction—has become a relatively rare cause of graft dysfunction since the introduction of UW (University of Wisconsin) solution Manifested by failure to regain hepatic function in the early postoperative period Urgent retransplantation is usually indicated

2 Rejection—occurs at some time in 60% of liver transplant patients

Diagnosis is made by biopsy of graft

3 Hepatic artery thrombosis—diagnosis is made by angiogram, after screening with ultrasound/Doppler examination; increased risk with pediatric transplant

4 Portal vein thrombosis—usually requires retransplantation but may respond to thrombolytic therapy It is less common than arterial complications

5 Biliary complications—manifested by fever and increasing bilirubin and alkaline phosphatase levels; diagnosed by cholangiogram; bili-ary stricture (resulting from technical error with anastomosis or hepatic artery thrombosis/stenosis) managed by conversion to choledochojejunostomy or stent placement.

6 Vena caval obstruction

7 Renal dysfunction

8 Infection and immunosuppressive drug complications

9 Recurrence of native disease

10 Hyperlipidemia and obesity in up to 60% of patients after transplant

D RESULTS (UNITED NETWORK FOR ORGAN SHARING DATA 1997–2004, PRIMARY LIVER TRANSPLANT)

1 Patient survival rates at 1 and 5 years are 88% and 74%, respectively

2 Graft survival rates at 1 and 5 years are 83% and 68%, respectively

RECOMMENDED READING

Abecassis M, Blei A, Koffron A, et al: Liver transplantation In Stuart FP, Abecassis MM,

Kaufman DB (eds): Organ Transplantation, 12th ed Georgetown, TX, Landes

Biosci-ence, 2003, pp 205–243.

USTransplants.org Scientifi c Registry of Transplant Recipients Available at: http://www.

ustransplant.org Accessed September 30, 2006.

555

I GENERAL CONSIDERATIONS

A HISTORY

1 1921—Banting and Best report the discovery of insulin

2 1966—Kelly and Lillehei perform the fi rst pancreas transplant

3 1986—Corry and associates develop technique of urinary bladder diversion of exocrine secretions

4 1999—Edmonton protocol increases success of pancreatic islet transplant

5 Currently, approximately 1500 pancreas transplants are performed yearly in the United States The majority (85%) occur simultaneously with kidney transplant (simultaneous pancreas-kidney transplant [SPK]), followed by those (10%) that occur after kidney transplant (pancreas alone after kidney transplant), and a minority (5%) occur alone (pancreas transplant alone [PTA])

B INDICATIONS FOR PANCREAS TRANSPLANTATION

Insulin-dependent diabetes mellitus is associated with increased risk for blindness (25 times), kidney disease (17 times), gangrene (20 times), and heart disease or stroke (2 times each) compared with patients without diabetes Pancreas transplant is performed in three categories of patients:

1 SPK—patient with insulin-dependent diabetes with end-stage renal disease who is also in need of kidney transplant

2 Pancreas alone after kidney transplant—patient with functioning renal transplant, to prevent the development of nephropathy in the transplanted kidney; may improve kidney graft survival

3 PTA—nonuremic, labile diabetic with hypoglycemic unawareness The risks of surgery and immunosuppression must be balanced against the likelihood of development of secondary complications of diabetes

C SPECIFIC INDICATIONS AND CONTRAINDICATIONS

1 Insulin-dependent diabetes mellitus documented by absence of lating C peptide

2 Microalbuminuria with a creatinine clearance of 60 ml/min

3 Proteinuria with a projected dialysis requirement

4 Autonomic neuropathy

5 Retinopathy

6 Labile diabetes and failure of medical management (brittle diabetes)

7 Absence of coronary artery disease

8 Absence of gangrene or ongoing sepsis

9 Age 18 to 50 years

Pancreas Transplantation

Mubeen A Jafri, MD

D ORGAN SELECTION

Most are performed from cadaveric donors In addition to standard criteria for donor selection, specifi c contraindications to pancreas transplantation include the following:

1 Presence of diabetes mellitus

2 Chronic pancreatitis

3 Pancreatic damage secondary to trauma

4 History of alcohol abuse or relapsing pancreatitis (center specifi c)

II SPECIFIC OPERATIVE CONSIDERATIONS

1 The recipient bed is prepared in the right iliac fossa

2 Venous drainage is fi rst established by portal vein-external iliac vein anastomosis

3 Arterial infl ow is determined by manner of donor harvest With the whole graft, the celiac axis and superior mesenteric artery are prefer-entially removed together on an aortic patch that is anastomosed end

to side to the recipient external iliac artery

A MANAGEMENT OF EXOCRINE SECRETIONS

1 Diversion into the bowel with anastomosis to the second portion of the donor duodenum, which is harvested en bloc with the pancreas,

is the preferred technique at the University of Cincinnati

2 Diversion to the urinary bladder has the advantage of using urinary amylase to monitor graft function but is associated with cystitis and acid-base abnormalities

3 Pancreatic duct occlusion with injectable synthetic polymer pletely blocks exocrine secretion but can lead to severe infl ammation and fi brosis, and is rarely practiced

com-III POSTOPERATIVE CONSIDERATIONS

1 Vascular thrombosis is the most common cause of early graft loss, necessitating some form of perioperative anticoagulation Suggested protocols include aspirin, systemic heparinization, and low-molecular-weight dextran

2 Graft function can be monitored by amylase levels and glucose homeostasis Because 90% of the pancreas may be lost before glucose homeostasis is impaired, this is not sensitive Use of insulin

is generally avoided

3 No reliable technique exists for the diagnosis of rejection In the patient undergoing SPK, rejection is usually monitored by following serum creatinine levels Increases in serum creatinine levels precede

a decrease in pancreatic exocrine function 90% of the time Rejection demonstrated on biopsy of the renal allograft is also an indication of pancreatic rejection

or mycophenolate mofetil Rejection accounts for up to 32% of graft loss in the fi rst year.

5 Radionuclide perfusion scans can be used to evaluate blood fl ow to the allograft

B ASSESSMENT OF GRAFT FUNCTION

1 Urinary or systemic amylase

2 Concomitant renal function (creatinine) to assess rejection

3 Transplant biopsy

C COMPLICATIONS

1 Graft pancreatitis

a Occurs in 3% to 5% of transplants

b Secondary to preservation injury and ischemia

c Suggested by hyperamylasemia and local graft pain

d May require drainage of peripancreatic collections or operative ment of necrotic pancreas

2 Graft thrombosis

a Most common cause of sudden early graft loss—10% to 20% of cases

b Attributed to the fact that the pancreas is a low-fl ow organ

c If confi rmed by radionuclide scan, the graft must be removed urgently

to prevent septic or vascular complications

3 Anastomotic failure (3.5–6%)

a Presents with fever, leukocytosis, and drainage of clear fl uid from the operative wound

b Rare with bladder drainage of the exocrine pancreas, but it can be fatal

if not addressed early

4 Sepsis—almost always related to the development of graft tis or anastomotic failure

5 Bleeding (5%)

a Site is usually gastrointestinal tract

b Usually related to the use of anticoagulation in perioperative period

6 Peripheral hyperinsulinemia—result of systemic venous delivery of insulin Limited trials are under way to assess the viability of portal venous drainage

3 Pancreas alone patient survival rate at 1 and 5 years is 94% and 83%, respectively.

4 Pancreas alone graft survival at 1 and 5 years is 79% and 53%, respectively

5 Insulin independence at 1 year—SPK, 81%; pancreas alone after kidney transplant, 71%; PTA, 62%

6 Insulin independence improves quality of life Data support potential reversal of diabetic neuropathy, decreased recurrence of nephropathy

in SPK for end-stage renal disease Advanced, secondary diabetic complications such as retinopathy and vascular disease are unlikely to

be improved Increased rate of thrombosis and rejection after solitary pancreas transplant

IV ISLET CELL TRANSPLANTATION

A BACKGROUND

1 Currently, PTA is performed rarely for patients with diabetes with labile disease who do not experience symptoms of life-threatening hypoglycemia

2 PTA occurs less commonly than SPK and pancreas alone after kidney transplant because of the need for immunosuppression and the high perioperative morbidity

3 By isolating insulin-producing beta cells within the islets of Langerhans, organ transplantation may be obviated

1 Pancreatic tissue obtained from pancreatectomy or cadaveric source

is enzymatically digested Usually requires two cadaveric pancreas grafts to harvest about 1 million islets or 300,000 islet cell equivalents in autotransplant

2 Islet cells are extracted and purifi ed via gradient separation

3 Microencapsulation to decrease immunogenicity in allotransplant

4 Islet tissue infused into hepatic parenchyma via injection into portal vein or directly into liver

D RESULTS

Multiple challenges must be overcome before islet cell transplantation can become routinely successful Paramount is the creation of an ideal microen-capsulation vehicle that may ultimately facilitate further xenotransplantation efforts

563

The skin is the largest organ of the human body and one of the most tant structures of the immune system It is the barrier for all chemical and physical trauma, and it provides the body with the most effi cient form of thermoregulation More recently, it has become the subject of dedicated research involving wound healing and synthetic skin substitutes As the most common malignancies of the human body, skin carcinomas are discovered

impor-on a regular basis in everyday surgical practice The three most commimpor-on skin carcinomas are basal cell carcinoma, squamous cell carcinoma, and malignant melanoma

I BASAL CELL CARCINOMA

A GENERAL

1 Most common skin malignancy

2 Associated with ultraviolet exposure

3 Clinical presentation

a Waxy or cream-colored

b Classically described with pearly, rolled borders

c Central ulceration common

d Slow growing

e Local destruction; rarely metastatic disease

4 Types

a Nodular—classic type

b Superfi cial—slow growing, scaly, pink plaque

c Sclerosing/Morpheaform—rarest form, resembles scar

B DIAGNOSIS

1 Punch biopsy

2 Excisional biopsy for smaller lesions

C TREATMENT

1 Surgical excision with 2- to 4-mm margins ideal

2 Curettage/laser ablation for smaller lesions/premalignant lesions

3 Mohs micrographic surgery

a For cosmetically sensitive areas

b Serial excision of tumor with immediate evaluation of frozen sections until normal tissue margins obtained

II SQUAMOUS CELL CARCINOMA

A GENERAL

1 Second-most common skin malignancy

2 Squamous cell carcinoma 2 cm has increased likelihood of sis compared with basal cell carcinoma of similar size

3 Associated with ultraviolet exposure, chronic scars, and irradiated skin

4 Clinical presentation

a Arise in sun-exposed areas (i.e., face, extremities)

b Erythematous, scaly plaque, ulcerated mass or nodule

5 Bowen’s disease

a Squamous cell carcinoma in situ

b Five percent develop into invasive squamous cell carcinoma

6 Marjolin’s ulcer—squamous cell carcinoma arising in burn scar

7 Erythroplasia of Queyrat—in situ squamous cell carcinoma of penis

B DIAGNOSIS—PUNCH BIOPSY VERSUS EXCISIONAL BIOPSY

C TREATMENT

1 Surgical excision with 2- to 4-mm margins

2 Regional lymph node dissection if palpable lymphadenopathy

3 Sentinel lymph node biopsy if large tumor or carcinoma arising in chronic wounds

III MALIGNANT MELANOMA

A GENERAL

1 Increasingly more common diagnosis

2 No increase in mortality—refl ects increases in detection and treatment

3 Risk factors

a Previous melanoma

b Large number of dysplastic nevi

c Ultraviolet exposure

d Fair complexion, light-colored eyes

e Family history (6–14% of melanomas with some family history)

1 Superfi cial spreading (70%)

a Long radial growth phase before vertical growth

2 Nodular (15–30%)

a Predominately vertical growth phase

b More aggressive lesion

c Equal mortality with superfi cial spreading type of equivalent depth

3 Lentigo maligna (4–15%)

a Increased incidence in elderly adults

b Targets face/neck/dorsum of hands

c Best prognosis given thin depth

4 Acral lentiginous (2–8%)

a Palms/soles/subungual region

b Predominant subtype in dark-skinned individuals

c “Hutchinson’s sign”—pigmented proximal/lateral nail folds

d Most aggressive but least common type

1 Depth of invasion is most important prognostic factor

2 Presence of ulceration increases aggressiveness

a Ulceration shown to correlate with increased angiogenesis

3 Vertical growth phase and mitotic rate are inversely related to prognosis

4 Findings of regression on pathology signifi es worse prognosis

5 Anatomic location—extremities more favorable than trunk/face

6 Sex—female patients have increased survival with respect to male counterparts

E STAGING

1 Clark level of staging—based on anatomic depth

a Level I—superfi cial to basement membrane (in situ)

b Level II—papillary dermis

c Level III—papillary and reticular junction

d Level IV—reticular junction

e Level V—subcutaneous fat

2 Breslow level of staging—based on vertical thickness

a More important than Clark level for prognosis

T1: 1.0 mmT2: 1.01 to 2.0 mmT3: 2.01 to 4.0 mmT4: 4.01 mm

b Nodal status (N)

N1: 1 node positive N1a—micrometastasis N1b—macrometastasisN2: two to three nodes positive N2a—micrometastasis N2b—macrometastasis N2c—negative nodes with in-transit metastasesN3: 4 nodes positive or in-transit metastases with positive nodes

c Metastases (M)M0: no evidence of metastatic diseaseM1: distant skin, subcutaneous, or nodal disease with normal LDHM2: lung metastases with normal LDH

M3: all other visceral metastases

d StagesStage 1a: T1a, N0, M0Stage 1b: T1b, N0, M0 T2a, N0, M0Stage IIa: T2b, N0, M0 T3a, N0, M0Stage IIb: T3b, N0, M0 T4a, N0, M0Stage IIc: T4b, N0, M0Stage III: any T, N1-3, M0Stage IV: any T, any N, M1-3

1 Wide local excision of remaining lesion and biopsy scar

a Lesions with 1-mm depth or less require 1-cm margins

b Lesions 1 to 2 mm in thickness require 1- to 2-cm margins

c Lesions with 2-mm depth require 2-cm margins

d Must excise to the level of underlying fascia

2 Lymph-node evaluation

a Regional lymph nodes most common site of metastatic disease

b All palpable lymphadenopathy requires therapeutic nodal dissection

c Sentinel lymph node dissection

(1) Appropriate for clinically node-negative disease in most lesions

1 mm, and in select patients with thin lesions (2) Techniques: Radiolabeled isotope is injected before surgery around the lesion, using a gamma probe intraoperatively to detect sentinel lymph nodes; 1% isosulfan blue dye is also injected around the

targeted lesion, highlighting the appropriate sentinel lymph node for excision

3 Any positive node mandates therapeutic nodal dissection

4 Additional treatment options

a Interferon- 2b (1) Only Federal Drug Administration–approved adjuvant for stage IIB/III disease

(2) Proven increase in disease-free survival

b Radiation therapy is adjunct treatment of choice for nodal basins with multiple involved lymph nodes

c Hyperthermic regional chemoperfusion/infusion (1) Melphalan

(2) Used only if the extremity lesion is not amenable to surgical excision or if many in-transit metastases are present

(3) Risks for vascular damage, compartment syndrome, and thromboembolic events

(4) Isolated brain, lung, or gastrointestinal metastases may be surgically excised for cure

(5) High dose interleukin-2 may lead to cure in less than 10% of patients with stage IV disease

(6) Many immunotherapy trials are currently under way with potentially promising results

2 Each mammary gland consists of 15 to 20 lobules drained by ous ducts that may coalesce The nipple has 5 to 20 orifi ces.

3 Fibrous septa (Cooper’s ligaments) interdigitate the mammary chyma and extend from the deep pectoral fascia to the superfi cial layer of fascia within the dermis These provide structural support to the breast

4 The base of the breast extends from the second to the sixth rib

Medial border  lateral margin of sternum; lateral border 

midaxillary line Axillary tail of Spence pierces deep fascia and enters axilla

1 Lymph node involvement is the most important prognostic factor for survival

2 Any part of the breast can drain to any set of nodes

3 Axillary nodes—75% of drainage from ipsilateral breast; contains up

to 40 to 50 nodes Axillary nodes secondarily drain to supraclavicular and jugular nodes

4 Levels of axillary nodes—all nodes are below the axillary vein

Level I—lateral to pectoralis minor; includes external mammary,

subscapular, axillary vein, and central nodal groups

Level II—deep to pectoralis minor muscle; includes central nodal

groups

Level III—medial to pectoralis minor and extending up to apex of

axilla; includes central nodal groups

5 Internal mammary nodes—account for up to 20% of drainage;

contain about four nodes per side, with one node in each of the fi rst three interspaces and another in the fi fth or sixth interspace

6 Interpectoral (Rotter’s) nodes—lie between pectoralis major and pectoralis minor muscles

7 Abdominal and paravertebral nodes—account for 5% of drainage

C NERVES

1 Intercostobrachial nerve—traverses the axilla from chest wall to supply cutaneous sensation to upper medial arm Sacrifi cing this nerve results in anesthesia of upper medial arm Runs below the axillary vein

Diseases of the Breast

Kelly M McLean, MD

2 Long thoracic nerve (of Bell)—arises from roots of C5, C6, and C7 Courses close to chest wall along medial border of axilla to innervate serratus anterior muscle Injury results in a “winged”

scapular deformity Runs with lateral thoracic artery, also to serratus anterior

3 Thoracodorsal nerve—arises from posterior cord of brachial plexus (C5, C6, C7) Courses along lateral border of axilla to innervate latis-simus dorsi muscle Loss weakens arm adduction and pull-ups

Thoracodorsal artery supplies the latissimus dorsi

4 Lateral pectoral nerve—arises from lateral cord of brachial plexus

Innervates pectoralis major muscle only Exits medial to the medial pectoral nerve

5 Medial pectoral nerve—arises from the medial cord of the brachial plexus Innervates both the pectoralis minor and major muscles

Emerges lateral to the lateral pectoral nerve

c Prolactin (from the anterior pituitary)—involved in milk production

d Oxytocin (from the posterior pituitary)—involved in milk ejection

2 Menopause: Menstrual cycle allows for cyclic growth Declines in both estrogen and progesterone levels lead to cellular apoptosis, resulting in involution of breast tissue with atrophy of lobules, loss of stroma, and replacement with fatty tissue

C NIPPLE DISCHARGE (TABLE 53-1)

1 Bloody—benign intraductal papilloma most common Rule out invasive papillary cancer Discharge cytology notoriously poor for determining cancer because dying cells usually look atypical Need to excise papilloma

2 Milky (galactorrhea)—pregnancy, lactation, pituitary adenoma, acromegaly, hypothyroidism, stress, drugs (oral contraceptives, antihypertensives, certain psychotropic drugs) Evaluation should include urine or serum pregnancy tests and prolactin levels

3 Serous—normal menses, oral contraceptives, fi brocystic change, early pregnancy

4 Yellow/green—fi brocystic change, galactocele

5 Purulent—superfi cial or central breast abscess

D BREAST PAIN (MASTODYNIA)

1 Rarely a symptom of breast cancer Pain can be cyclic or continuous Associated with menstrual irregularity, premenstruation, exogenous ovarian hormones during or after menopause, or

fi brocystic change

2 Query regarding its type, relation to menses, duration, and location

3 Discontinue caffeine and nicotine

4 Treat with evening primrose oil or nonsteroidal antiinfl ammatory drugs If symptoms are debilitating, danazol (Danocrine) may be used for a maximum of 4 to 6 months

E GYNECOLOGIC HISTORY (SEE SECTION VII)

1 Woman’s age at the birth of her fi rst child, age of menarche, age

at menopause, use of oral contraceptives, and use of estrogen replacement

CHARACTERISTICS OF NIPPLE DISCHARGE

TABLE 53-1

Physiologic Pathologic Bilateral Unilateral Clear/milky Bloody Multiple ducts/quadrants Single duct/quadrant Not spontaneous Spontaneous Negative for occult blood Positive for occult blood

No mass Palpable mass

2 Note breast size, shape, contour, and symmetry; skin coloration, skin dimpling, edema, erythema, peau d’orange, and excoriation, as well

as nipple inversion, retraction, symmetry, or discharge

B PALPATION

1 With the patient in the sitting position, support the patient’s arm and palpate each axilla to detect axillary adenopathy Also palpate the supraclavicular fossae and cervical region Note node size, character, and mobility

2 Palpation of the breast is performed with the patient in the supine position with the arms stretched above the head and with the arms

at her sides Identify any masses, noting location, size, shape,

consistency, tenderness, skin dimpling, and mobility Use the 4 D’s

to distinguish a true lump from a lumpy area: dominant, discrete, dense, and different Carcinoma is typically fi rm, nontender, poorly

circumscribed, and relatively immobile Use the fl at portion of your

fi ngers for the examination

3 Nipples, including pressing on the areola, should be palpated to identify any discharge

RECOMMENDATIONS)

1 Mammography and clinical breast examination: Emphasize breast examination Most breast masses are found by patients themselves

2 Breast self-examination on monthly basis beginning at 20 to 25 years

of age Breast self-examination should be performed about 5 days after completion of menses in the premenopausal woman and at the same time each month in the postmenopausal woman

3 Physician examination every 1 to 3 years depending on risk factors

In general, every 3 years beginning at age 18 and annually beginning

at age 40

4 Baseline mammogram for women by age 40 years or 10 years before the youngest age of diagnosis in fi rst-degree relative The density of breast tissue in young women limits the interpretation of early mammograms

5 Perform mammogram yearly thereafter

IV RADIOGRAPHIC STUDIES

A MAMMOGRAPHY

1 Sensitivity and specifi city varies with breast density, around 90%

for both

1 Irregularly marginated stellate or spiculated mass

2 Architectural distortion with retraction and speculation

3 Asymmetrical localized fi brosis

4 Fine pleomorphic microcalcifi cations with a linear, branched,

or rodlike pattern, especially when focal or clustered

Increased likelihood of cancer with increased number of microcalcifi cations

5 Increased vascularity

6 Altered subareolar duct pattern

7 Unclear border with the rest of breast tissue

8 BIRADS (breast imaging reporting and data system) classifi cation—

recommendations are changing rapidly (Table 53-2)

C ULTRASONOGRAPHY

1 Useful for distinguishing between cystic and solid masses

2 Effective for lesions larger than 0.5 cm in diameter

3 Helpful in evaluating young women whose breast tissue is too dense for mammogram

V EVALUATION OF BREAST MASS

2 Treatment—excise intraductal lesion on ultrasound or galactogram or persistent discharge.

1 Cystic—well-demarcated, mobile, fi rm, and fl uctuates with menstrual cycle Most common in women in their 40s Perform fi ne-needle aspiration (FNA)

a Premenopausal (1) Nonbloody fl uid and mass disappears—requires no further workup (2) Bloody fl uid, mass remains, or cyst recurs more than twice—

excisional biopsy Send fl uid for cytology

b Postmenopausal (1) Reexamine in 4 to 6 weeks for recurrence

(2) A simple cyst on ultrasound does not require further workup

C FNA BIOPSY

1 Accuracy rates approach 90% to 94%

2 Nondiagnostic cytology (no epithelial cells present in aspirate)—

excisional biopsy

3 Diagnostic cytology—discuss cancer treatment options

4 Inconsistent with mammogram—perform excisional biopsy

D CORE NEEDLE BIOPSY (PERCUTANEOUS)

1 Used for palpable masses, nonpalpable masses, or calcifi cations

2 Can be used in conjunction with image guidance such as mammogram

or ultrasound for nonpalpable masses

BIRAD (BREAST IMAGING REPORTING AND DATA SYSTEM) CLASSIFICATION

TABLE 53-2

Class Interpretation Recommendations

0 Unable to determine Additional studies needed

1 Negative—no abnormalities seen Routine follow-up

2 Benign Routine follow-up

3 Probably benign Repeat mammogram in 3–6 months

May biopsy

4 Suspicious Strongly consider biopsy

5 Probably malignant Biopsy

3 Papilloma has 10% sampling error rate

4 Atypia has 25% chance of missing adjacent cancer

E EXCISIONAL BIOPSY

1 Defi nitive method for tissue diagnosis

2 Nonpalpable lesion—image-guided core biopsy or excision with wire localization If core shows papilloma or atypical cells, then must excise

Obtain postbiopsy radiograph of the specimen to confi rm the adequacy

of the biopsy Postbiopsy mammogram in 3 to 6 months to confi rm removal of the lesion

3 Biopsy incisions—plan incision with regard to natural skin tension lines: curvilinear incisions in the upper hemisphere of the breast, radial incisions in the lower hemisphere of the breast, and circumareolar incisions for masses just beneath the areola Incision should be made

so that subsequent mastectomy can incorporate biopsy site All breast biopsies should be performed with the assumption that the lesion is malignant

4 The entire mass with a surrounding 1-cm rim of normal tissue should

be excised The specimen should be processed for hormone receptor analysis, human epidermal growth factor receptor 2 (HER-2)/neu, and

2 Can be induced by frequent nipple stimulation

3 Often associated with amenorrhea

1 Encompass a wide spectrum of clinical and histologic fi ndings, including cyst formation, breast nodularity, stromal proliferation, and epithelial hyperplasia May represent an exaggerated response

of normal breast stroma and epithelium to circulating and locally produced hormones and growth factors

2 Three categories—nonproliferative lesions, proliferative lesions, and atypia

3 Incidence greatest around age 30 to 40 years but may persist into 8th decade of life

4 Usually presents as breast pain, swelling, and tenderness associated with focal areas of nodularity, induration, or gross cysts Frequently bilateral Varies with menstrual cycle

5 Not associated with an increased risk for breast cancer unless gross cysts are combined with family history of breast cancer

6 Treatment

a Rule out carcinoma by aspiration or excisional biopsy of any discrete mass Any sampling biopsy should be interpreted in light of examination and imaging Any discordance requires excisional biopsy.

b Frequent breast examinations (physician and self-examination)

c Baseline mammogram for ages 35 to 39 years and annual mammogram for age older than 40 years to identify any new or changing lesions

d Patient should avoid xanthine-containing products (coffee, tea, chocolate, cola drinks) and nicotine

e Danazol, a weak androgen, may be prescribed for severe mastalgia

Must be continued for 2 to 3 months to see a potential effect

Administer for maximum of 4 to 6 months Recurrence rate of 50%

within 1 year of discontinuing drug

f Tamoxifen, which binds to estrogen receptors, has been used for severe symptoms, although it is not FDA approved for this indication Adverse effects include hot fl ashes, thrombosis, cataracts, and increased risk for uterine cancer

C FIBROADENOMA

1 Most common breast lesion in women younger than 30 years Present

in 9% to 10% of women Comprises 50% of breast biopsies and 75%

of those in women younger than 20 years

2 Round, well-circumscribed, fi rm, rubbery, mobile, nontender mass

1 to 5 cm in diameter that is usually solitary Lesions larger than

5 cm, referred to as giant fi broadenomas, must be differentiated from cystosarcoma phyllodes Usually solitary but may be multiple and bilateral Hormonally dependent; may increase in size with normal menses, pregnancy, lactation, and use of oral contraceptives

3 It increases risk for breast cancer, especially if a family history of breast cancer is present or if postmenopausal

4 Treatment—excisional biopsy to remove the tumor and establish the diagnosis, or combination of physical examinations, ultrasonography, and FNA

D PHYLLODES TUMOR/CYSTOSARCOMA PHYLLODES

1 Differentiated from fi broadenoma by the number of mitoses per high-power fi eld

2 May occur at any age, but mean patient age is 30 to 40 years

3 Presents as a smooth, rounded, multinodular, painless mass

Overlying skin is red, warm, and shiny, with venous engorgement The tumor itself is smooth, well circumscribed, and freely mobile, with a median size of 4 to 5 cm Characterized by rapid growth

4 Spreads hematogenously

5 Contains both mesenchymal and stromal components

Approximately 90% are benign Malignancy is based on occurrence

of metastases

6 High rate (30%) of local recurrence after simple excision or enucleation

7 Treatment—wide local excision (WLE) with at least 1-cm margins for smaller tumors; simple mastectomy for larger tumors

1 It is a benign, solitary polypoid lesion involving epithelium-lined major subareolar ducts

2 May present as bloody nipple discharge in premenopausal women

Although most do not cause discharge, it is the most common lesion

to cause serous or serosanguineous discharge

3 Major differential diagnosis is between intraductal papilloma and invasive papillary carcinoma

4 Treatment—excision of involved duct after localization by physical examination

5 Diffuse papillomatosis—involves multiple ducts of both breasts

Increased risk for breast cancer

F FAT NECROSIS

1 Presents as an occasionally ecchymotic, tender, fi rm, ill-defi ned mass, often accompanied by skin or nipple retraction Almost impossible to differentiate from carcinoma by physical examination or mammography

Usually located in superfi cial breast tissue, averaging only 2 cm in diameter More common in overweight women or those with pendulous breasts

2 History of antecedent trauma may be elicited in about 65% of patients Can also be caused by surgery, infection, duct ectasia, and aseptic saponifi cation

3 Treatment: If a clear history of trauma, observe; otherwise, excise to rule out malignancy

G PLASMA CELL MASTITIS/PERIDUCTAL MASTITIS

1 It is a subacute infl ammation of ductal system characterized by dilated mammary ducts (mammary duct ectasia) with inspissated secretions, marked periductal infl ammation, and infi ltration of plasma cells causing yellowish white viscous nipple discharge

2 Occurs at or after menopause History of diffi cult nursing may be elicited

3 Presenting symptoms include noncyclical, focal breast pain (mastodynia) associated with nipple retraction or discharge, and subareolar masses

4 A benign lesion that is diffi cult to differentiate from carcinoma cally or radiographically Excisional biopsy is indicated to rule out car-cinoma Multiple biopsies may be required because of the diffuse na-ture of the lesion Curative treatment usually requires subareolar duct excision

MDK185d531d

4.003.753.503 .25 3.0 02. 7 52. 5 02. 2 52. 001.751.501 .25 1.000.750.500 .25

Danovitch GM: Handbook of Kidney Transplantation,... interdigitate the mammary chyma and extend from the deep pectoral fascia to the superfi cial layer of fascia within the dermis These provide structural support to the breast

The base of the breast... mass in the right lobe of the liver The patient was referred for further management.

In differentiating between the above entities, one must consider the age of the patient,