Cholecystectomy of double gallbladder

Pilo Nidal Sinus Excision

Rhomboid flap for Pilo Nidal Sinus Disease

Stapled Hemorrhoidectomy

GI POLYPOSIS - Classification

A GI polyp is defined as a mass of the mucosal surface protruding into the lumen of the bowel.
Polyps can be

• neoplastic,
• non-neoplastic, or submucosal.

GI polyposis is characterized by multiple polyps within the GI tract.
A variety of polyposis syndromes can affect the GI tract. These polyposis syndromes may be classified as

• familial inherited (autosomal dominant) or
• nonfamilial.

The inherited polyposis syndromes can be further subdivided into 2 groups depending on whether the polyps are

• adenomas or
• hamartomas.

The adenomatous polyposis syndromes include the classic

• familial adenomatous polyposis (FAP),
• Gardner syndrome,
• Turcot syndrome.

Hamartomatous familial polyposis syndromes include

• Peutz-Jeghers syndrome,
• juvenile polyposis syndrome,
• Cowden disease,
• Ruval-Caba-Myhre-Smith syndrome.

The non-inherited polyposis syndromes include

• Cronkhite-Canada syndrome,
• and a variety of miscellaneous non-familial polyposis.

• From a prognostic viewpoint, these syndromes must be recognized, because the adenomatous polyps are premalignant.
• These syndromes should be considered when
• an intestinal polyp is recognized in the young,
• when 2 or more polyps are seen in any patient,
• when colonic carcinoma is discovered in patients younger than 40 years, and
• when extraintestinal manifestations associated with these syndromes are discovered.
  
  
• GI polyps may be asymptomatic, but may also occur with rectal bleeding and diarrhea.

The urgency of case tracing and genetic counseling is related not so much to the symptoms of the disease but to the potential for the development of a colonic carcinoma. It is probable that patients with familial polyposis, if untreated, will develop a colonic carcinoma.

HYPERPLASIA

The enlargement of normal terminal duct lobular units (TDLUs)(FIG. 1A) by hyperplastic epithelial cells is one of the most common abnormalities of growth in the adult female human breast. 

FIG 1A FIG 1B

These hyperplastic enlarged lobular units (HELUs) are often multifocal, bilateral, and up to 100-fold larger (volume and numbers of cells) than the TDLUs they evolve from, representing a major alteration of growth (Fig.1B). 

• The majority of HELUs are lined by one or two layers of crowded columnar epithelial cells, but many exhibit more diverse histological features, contributing to the complex terminology that has evolved to describe them. 
• Currently, they are most commonly referred to as columnar cell lesions (CCLs), which encompass several putative subtypes including 
• columnar cell change (CCC; 
• characterized by a generally single layer of hyperplastic columnar epithelium), 
• columnar cell hyperplasia (CCH; 
• characterized by stratified hyperplastic columnar epithelium), and 
• CCLs with cytological atypia, sometimes referred to as flat epithelial atypia (FEA), among others. 

The CCH/HELUs are 

• much more common in cancerous than noncancerous breasts, and 
• it is supported by pathological studies, 
• epidemiological studies showing that they are weak (about 1.5-fold) risk factors for developing breast cancer, and 
• they may share identical genetic abnormalities (e.g., allelic imbalances) with cancer in the same breast, 
• although the overall frequency of these abnormalities appears to be quite low. 

Wellings and Jensen proposed that CCH/HELUs (which they referred to as atypical lobules type A) are precursors of ADH primarily because of the striking gradual histological continuity between them. 

• Similar continuity is also observed between CCH/HELUs and other alterations of growth in the breast, including microcysts (often with apocrine change) and usual ductal hyperplasia (UDH). 
• However, most CCH/HELUs probably remain stable or become cystic based on the higher incidence of these lesions compared to UDH and (especially) ADH. 
• UDH has also been identified as a weak (approximately 1.5-fold) risk factor for developing breast cancer, but the absence of convincing histological continuity with cancer and recent immunohistochemical (IHC) studies suggesting that the progenitor cells in UDH may be different from CCH/HELUs and ADH suggest that UDH may be a side branch of the family tree of ductal cancers, and their risk may be due to shared ancestry with CCH/HELUs.

The underlying causes of the hyperplasia leading to CCH/HELUs are unknown. Some evidence suggests that estrogen may be involved, including the observations that CCH/HELUs are more common in premenopausal compared to postmenopausal breasts and in cancerous compared to noncancerous breasts where increased estrogen exposure is such a strong risk factor for developing cancer. 

• Several recent studies have shown highly elevated expression of ERα in the epithelial cells lining CCH/HELUs. 
• Essentially all CCH/HELUs express ERα in some cells, and 80% to 90% show very high levels in nearly all cells, which is about threefold above normal. 
• They also show a corresponding threefold increase and decrease in average proliferation (about 5%) and apoptosis (about 0.2%), respectively, although the ranges of these phenomena are quite large. 
• Since estrogen, mediated by ERα, stimulates proliferation and suppresses apoptosis in normal cells, elevated ERα in CCH/HELUs may be a fundamental alteration leading to increased growth, although the cause of the elevation is unknown. 
• A recent study in mice overexpressing ERα in normal murine breast epithelium noted the rapid development of hyperplasias, which occasionally progressed to cancer, supporting the idea that elevated ERα may be partially responsible for the development and progression of CCH/HELUs. 
• Similar to ERα, recent studies have shown that PR is also highly elevated in CCH/HELUs, which may also contribute to their growth.

Recent microarray studies have identified some of the other pathways and genes that may be involved in the development of CCH/HELUs including, especially, the erb-b tyrosine kinases (TKs). 

• For example, compared to normal epithelium, the cells lining CCH/HELUs show a prominent uniform decrease in the expression of epidermal growth factor (EGF) and increase in amphiregulin (AREG), which are important in differentiation of adult breast and embryonic breast development, respectively. 
• Interestingly, EGF and AREG are both ligands for the erb-b1 TK receptor (also referred to as the epidermal growth factor receptor). 
• However, the levels of erb-b1 do not appear to change significantly, nor do the levels of the other erb-b TK receptors, including erb-b2 (also referred to as HER2 or ERBB2), which is amplified and overexpressed in about 20% of DCIS and IBCs. 
• Certain other alterations common in DCIS and IBCs, such as mutation of the p53 tumor suppressor gene, are also rarely if ever observed in CCH/HELUs.

Because CCH/HELUs are so common in the population and share important biological characteristics such as highly elevated ERα, their beginnings seem more likely to reflect alterations of development or differentiation than genetic defects per se. 

• This idea is supported by the microarray evidence of suppressed differentiation and reactivated embryonic developmental pathways and by the generally low frequency of genetic alterations identified so far.
• Regardless, the end result is increased growth, creating fertile soil for accumulating random genetic defects, leading to diversity and progression to other types of lesions, including more committed breast cancer precursors such as ADH.

Reference :     

1. Diseases of the Breast, 4th Edition

2. Atlas_of_breast_surgery

3. Bailey Love’s short practice of surgery     25^th ed.

4. Greenfield's Surgery, 5th Edition

5. Pathophysiology of Disease

Premalignant Breast Disease

Premalignant Breast Disease

Pathology and Biological Features

The human breast is capable of producing a very large number histologically defined abnormalities of growth. However, only a handful appear to have any significance as risk factors or precursors of breast cancer.

• One of the first attempts to incorporate these premalignant lesions into a comprehensive model of breast cancer evolution was published by Wellings and Jensen over 30 years ago.
• The model was based primarily on the evidence of gradual histological continuity and proposed that the cellular origin of breast cancers occurs in the normal terminal duct lobular unit (TDLU) and that the putative precursors represent a nonobligatory series of increasingly abnormal stages that progress to cancer over long periods of time, probably decades in most cases.

The key stages in the model are generically referred to as

• hyperplasias,
• atypical hyperplasias,
• in situ carcinomas, and
• invasive carcinomas,

but there are multiple lineages and subtypes.

In the largest so-called ductal lineage (representing about 80% of all breast cancers), the terminology of hyperplasias is diverse and still evolving, while the other stages are referred to as

• atypical ductal hyperplasia (ADH),
•  ductal carcinoma in situ (DCIS), and
• invasive ductal carcinoma (IDC).

IDCs are also referred to as no-special-type or not-otherwise-specified invasive breast cancers (IBCs) to distinguish them from the major so-called special histological subtypes, which include invasive tubular, mucinous, medullary, and lobular carcinomas.

All of the special subtypes except lobular carcinomas can be considered as subtypes of IDC in the sense that they appear to evolve from the same precursors.

The progression of the lobular lineage (representing the remaining 20% of carcinomas) is histologically relatively distinct, and the key precursors in this setting are referred to as

• atypical lobular hyperplasia (ALH) and
• lobular carcinoma in situ (LCIS).

However, the practice of referring to breast cancers as ductal or lobular implies that they originate and reside in ducts and lobules, respectively, which is a historical misconception in the sense that both lineages are thought to arise from progenitor cells in normal TDLUs and both can occupy ducts and lobules (4).

Furthermore, many IBCs show complex combinations of ductal (including special subtypes) and lobular features, emphasizing that these histology-based classifications, while very useful, oversimplify enormous diversity.

Epidemiological studies have shown that women with a history of these lesions in a previous biopsy are at increased relative risk for developing breast cancer, ranging from about

• 1.5-fold for hyperplasias, to
• 5-fold for ADH and ALH, to
• 10-fold or higher for DCIS and LCIS, and precursors must also be risk factors, although the opposite is not always true.

Some studies suggest that the elevated risks associated with ADH, ALH, and LCIS are equal in both breasts, implying that they are only risk factors.

However, these lesions (especially ALH and LCIS) are often multifocal and bilateral (2,3,6), so it is possible for them to be both risk factors and precursors, and their wide distribution suggests that they may be initiated during early breast development.

Recent comprehensive studies of ALH and LCIS place the majority of the risk in the ipsilateral breast, supporting a precursor role, although the apparently equal bilateral risk associated with ADH remains an enigma.

DCIS is usually a localized disease with a predominately ipsilateral risk for developing IBC, consistent with the notion that DCIS is a relatively advanced and committed precursor.

Some of the most compelling evidence comes from recent laboratory studies showing that the putative precursors share identical genetic abnormalities with breast cancers, especially when they occur in the same breasts as well as histological and biological similarities with genetically engineered mouse models.

There are important general characteristics that distinguish one stage from the next in the Wellings-Jensen model that accumulate and increase with progression.

• The transition from TDLUs to hyperplasias is characterized by increased growth due to epithelial hyperplasia.
• Alterations of cell adhesion and polarity distinguish ADH from hyperplasias as the epithelium begins to pile up and distend acini.
• DCIS is characterized by further growth and the appearance of enormously increased histological and biological diversity compared to earlier precursors.
• Invasion into surrounding stroma defines the transition of DCIS to IBC.

Reference : 
  
1. Pathophysiology of Disease of Disease

2. Diseases of the Breast, 4th Edition

3. Bailey Love’s short practice of surgery 25^th ed.

4. Greenfield's Surgery, 5th Edition

5. Atlas of breast surgery

Small bowel perforation after blunt injury abdomen and causes of delay in diagnosis

INTRODUCTION

The diseases of the small bowel are very rare in occurrence. In contrast, there are various kinds of contributory causes to perforation of the small bowel. These are classified as follows, traumatic, foreign body, ulcerative, tumorous, ileus, vessel originated-disease and idiopathic. Needless to say, the death of perforation is closely associated with the time interval from onset to operation.
The small intestine occupies a relatively large surface area within the peritoneal cavity and thus is frequently injured in patients with penetrating abdominal trauma. Because the small bowel is relatively mobile, has a lower bacterial flora, and has fewer anaerobes than the colon, peritoneal contamination secondary to small bowel injuries is better tolerated than that associated with colon injuries.
The Penetrating Abdominal Trauma Index (PATI), which quantitates the severity of abdominal injury based on risk factors associated with specific organs, employs a multiplier of 3 for small bowel injuries (compared with 4 for colon and liver, and 5 for pancreas and duodenum).

• The management of penetrating small bowel injuries for these reasons is generally straightforward, with simple repair being the rule.

INCIDENCE

• Estimates of the incidence of small bowel rupture associated with blunt abdominal injury range from 3 to 18%.
• The death related to perforation of the small bowel 17.1% which is between those of the colon (27.3%) and the stomach and duodenum (1 1.1%), respectively.

DELAY IN DIAGNOSIS

• It is generally accepted that delay in diagnosis in common because definite clinical signs is prone to being concealed. It is due to a low incidence of the appearance of free gas in the peritoneal cavity on abdominal X-ray film. To salvage the patients in early stage, surgeons should be alert to a latent interval in this stage.
• The diagnosis of SBI is now more frequently made on the basis of clinical signs or an abnormal CT scan, than as an associated injury during a trauma laparotomy. As a result, delays in the diagnosis of SBI may occur and contribute significantly to morbidity and mortality.
• Small-bowel perforations are often minute and may seal temporarily before free air is noted." Associated spasm of the circular muscle above and below the level of the perforation, results in a localised ileus which further prevents leakage. After 5 or 6 hours the spasm passes off and contamination of the peritoneal cavity occurs as the isolated segment takes part in the peristaltic activity again.
• ' Klinger" described 50 patients of all ages, in only 10 of whom he noted free air; in one of them the perforation only became evident on delayed films. Delay in diagnosis may occur as a result of late rupture of an intramural haematoma'" or after serosal and tunica muscularis tears, or after interference with the blood supply, as occurs in avulsion injuries." Delayed diagnosis may also be the result of lack of careful examination in patients with multiple injuries."
  
• In the digestive organ with the lumen, it is necessary that traumatic perforation should be quickly detected and treated. It is without saying that a presence of free gas is a confirmable finding.
• In contrast, abdominal free gas is unlikely to appear and often fails to detect in the early stage.

Pathogenesis of perforation of the gut is much different from each other. It is well known that perforation of lower part of the gut more frequently provokes endotoxic shock.

Summary of Amount and Location of Free Air according to Perforation Sites
Perforation ------------Site --------------Amount Location
Stomach/duodenum -----Abundant --------Around liver and stomach
Post-bulbar duodenum ---------------------Right anterior pararenal space
Small bowel -------------Small -------------Mesenteric folds, around liver
Appendix ---------------Small/absent -----Around appendix
Large bowel ------------Variable ----------Pelvis, mesenteric folds, retroperitoneal space

• Motor vehicle accidents are the main cause of blunt SBI. The increase in seat belt use has resulted in lower fatality rates and injury severity, but has been accompanied by a concomitant increase in rates of intestinal injuries.
• Blunt trauma commonly occurs as a result of motor vehicle crashes, falls from heights, and interpersonal assaults with blunt objects.
  

Intestinal injuries can occur secondary to blunt trauma by two major mechanisms:

1. Horizontal deceleration or shearing can occur in patients involved in collisions. The regions that are affected most commonly are near junctions between fixed and nonfixed points of bowel (i.e., proximal jejunum, terminal ileum).

2. Direct blow with a linear object (seat belt) across loop of bowel, with a subsequent "blowout" injury, can occur at any point of the intestine or the mesentery.

• Serial clinical evaluations of the abdomen are extremely useful in the diagnosis of SBI, particularly in patients with additional associated intra-abdominal injuries.
• A bruise across the abdomen inflicted by a seat belt ("seat belt sign") and ongoing abdominal pain are known associated risk factors of SBI.
• Fakhry et al. observed that 67.7% of 198 patients with blunt SBI initially presented with signs or symptoms highly suggestive of this lesion, and 84.3% were taken to the operating room without delay. In this study, of the patients involved in motor vehicle crashes, only 30% had the abdominal seat belt sign, which is less than that commonly reported in the literature (nearly 50%). Consistent with prior reports, the most frequent clinical signs were abdominal pain upon admission (75.6%) and abdominal tenderness upon physical examination (46.7%).
  
• Diagnosis of these injuries remains problematic. Early recognition of SBI is important in the prevention of morbidity. DPL is more sensitive than CT imaging for diagnosis of SBI; however, in many cases, it results in nontherapeutic laparotomy. CT imaging is newer than DPL, and it has become popular in recent years. The major advantages of CT include noninvasiveness, capacity to quantify free fluid, the ability to select patients with solid organ injury for non-operative management, and the ability to view retroperitoneal organs.
• Saku et al. analyzed the CT findings of 12 patients with SBI perforation due to blunt trauma, all patients underwent radiography and CT, and five underwent presurgical follow-up CT. Radiography demonstrated free air in only 8% (1/12) and 25% (3/12) at the initial and follow-up examinations, respectively. In contrast, the initial and followup CT scans detected extraluminal air in 58% (7/12) and 92% (11/12), respectively, suggesting that the incidence of extraluminal air increases as time elapses, prompting the authors to recommend a repeat CT, particularly after 8 h, in suspect cases to increase sensibility. Mesenteric fat obliteration was seen in 58% (7/12) and 75% (9/12) at initial and follow-up CT, respectively.

Liver haemangioma

INTRODUCTION
Haemangioma is the most common benign tumour of the liver (prevalence has ranged from 0.4 to 20 percent).

• At necropsy, the prevalence of liver haemangioma is 2–5%.
• Hepatic hemangiomas are also referred as cavernous hemangiomas because of the cavernous vascular space seen histologically.
• Hemangiomas are vary in size from a few millimeters to more than 20 cm.
• most of them are of less than 5 cm.
• Larger ones ( >5 cm) are referred to as giant hemangiomas.
• The size of liver haemangioma is greater in women than in men as well as the occurrence.
  
• In most of the cases they are solitary and many on the surface of roght lobe, but in 40 % of patients, hemangiomas may occur in multiples in bilateral lobes.
• Diagnosis is mostly made in the age range between 30 to 50 years.
• A symptomatic patient is mostly a young woman.

ETIOLOGY

1. In incompletely understood etiology, they are considered to be vascular malformation or hamartomas of congenital origin that enlarge by ectasia rather than by hyperplasia or hypertrophy.
2. Hormonal influence over tumor growth is suggested by enlargement during pregnancy and estrogen and progesterone therapy and regression after withdrawal of therapy.

PATHOLOGY

• On macroscopic examination, haemangioma may be located at the surface of the liver or inside the liver, can be found in both lobes of the liver but more oftenly in the right lobe.
• Lesions are well circumscribed and often surrounded by a thin capsule.
• The larger lesion may be pedunculated and on gross examination appear as cystic lesions with a dark color.
• On section it appears round or wedge shaped, dark red in colour and has a honeycomb pattern with spongy consistency and a fibrous capsule which may be calcified.
• Large hemangiomas may develop a collagenous scar or fibrous nodule as thrombosis occurs.
• On microscopic examination, liver haemangioma are composed of large vascular channels lined by mature, flattened endothelial cells, enclosed in a loose fibroblastic stroma with various amounts of connective tissue.
• Occasionally, there is a marked fibrous component.

In a few cases, they are associated with

• focal nodular hyperplasia of the liver,
• extrahepatic haemangioma or
• Rendu–Osler– Weber disease and
• bile duct hamartomas.

PRESENTATION

In most cases, liver haemangioma is asymptomatic and is recognized fortuitously by ultrasonography performed for symptoms that are either non specific or unrelated to haemangioma. Hemangiomas are typically discovered incidentally at laparotomy, autopsy, or during an imaging test performed for unrelated conditions.

• In a few patients, liver haemangioma is recognized because of abdominal pain which is often due to associated irritable colon.
• In one report, for example, abdominal pain was due to other causes in 54 percent of patients .
• The most common symptoms are abdominal pain and right upper quadrant discomfort or fullness.
• Lesions >4 cm are more likely to cause symptoms .
• Acute abdominal pain can result from thrombosis or bleeding within the tumor and associated stretching and inflammation of Glisson's capsule.
• Discomfort from an acute thrombosis can last up to three weeks and be associated with fever and abnormal liver function tests.
• Giant hemangiomas in children have been associated with high output cardiac failure and hypothyroidism. Hypothyroidism is due to the presence of high levels of 3 iodothyronine deiodinase activity in the hemangioma tissue, which catalyzes the conversion of thyroxine and triiodothyronine to biologically inactive hormones, reverse triiodothyronine, and 3,3'-diiodothyronine.
• High output cardiac failure is reported in numerous case reports.
• Cutaneous hemangiomas in children may be a marker for hepatic hemangiomas.
• The presence of a single large cutaneous hemagioma was generally associated with a single hepatic hemangioma while multiple or milliary cutaneous hemangiomas were associated with the presence of multiple hepatic hemangiomas.
  
• Large haemangiomas can be complicated by thrombocytopenia, consumptive coagulopathy, and microangiopathic anaemia (Kasabach–Merritt syndrome).

Clinical examination is normal in most cases, except in the few patients in whom a large haemangioma results in a palpable tumour. A bruit is seldom heard over the hemangioma.

Liver tests are normal, except in patients in whom haemangioma is associated with an unrelated diffuse liver disease.

DIAGNOSIS

Radiology. A plain X-ray may show a calcified capsule.

Ultrasonography

• liver haemangioma appears as a well-defined hyperechoic area.
• If the liver is fatty, haemangioma may be as echoic as, or even less echoic, than the rest of the liver parenchyma.
• The hemangioma may be hypoechoic in patients with fatty infiltration of the liver due to the bright signal from the surrounding parenchyma.
• Blood flow within the hemangioma can be demonstrated by color Doppler in only 10 to 50 percent of hemangiomas, and thus color Doppler does not improve the accuracy of ultrasound.
• Sonographic findings also depend upon the size of the hemangioma.

One study characterized 158 hemangiomas as follows:

• Lesions <2>
• Lesions between 2 and 5 cm were mainly echogenic.
• Lesions >5 cm had mixed echogenicity probably because of intratumoral thrombosis and fibrosis.

CT

• On a computed tomography (CT) scan without contrast, liver haemangioma appears as a hypodense area.
• Calcifications are seen in approximately 10 percent of cases.
• On a CT scan after intravenous injection of a contrast bolus, there is an irregular, globular enhancement in the periphery of the lesion; this anomaly is very characteristic; after several minutes, the area of enhancement increases towards the center of the lesion.
• Peripheral nodular or globular enhancement representing venous lakes is seen in up to 94 percent of hemangiomas >4 cm in size.
• A pattern of globular enhancement isodense to the aorta is seen in 67 percent of hemangiomas, a feature that helps distinguish them from hepatic metastases.
• The lesions classically opacify after a delay of three or more minutes and remain isodense or hyperdense on delayed scans.
• Possible exceptions are hemangiomas >4 cm, in which the center of the lesion may not opacify completely.
• Variations in vascular enhancement among hemangiomas may be due to differences in the size of the vascular spaces, the presence of cystic spaces, and the amount of scar tissue within hemangiomas.
• Absence of enhancement is seen in hemangiomas with large cystic areas or scar tissue.

MRI

The most sensitive and specific procedure for diagnosing hepatic haemangioma is magnetic resonance imaging (MRI):

• The typical MRI appearance is a smooth, well-demarcated homogeneous mass that has low signal intensity on T1-weighted images and is hyperintense on T2-weighted.
• The presence of intratumoral fibrosis results in areas of low intensity on T2-weighted images.
• In a few patients, haemangioma appears as an hypervascular area and/or is associated with an arterioportal shunt.
• Administration of gadolinium results in early peripheral discontinuous nodular or globular enhancement on arterial phase imaging with progressive centripetal enhancement or "filling-in" on delayed scans similar to that seen on CT scanning.
• This enhancement pattern is typical of most hemangiomas >2 cm;
• tumors <2>
• Small hemangiomas that demonstrate rapid uniform enhancement are sometimes indistinguishable from hypervascular metastases of hepatocellular carcinoma.

Arteriography is no longer used for the diagnosis of haemangioma.

• Large arterial branches are displaced.
• The hepatic arteries divide to form small vessels before filling the vascular space. Prolonged, up to 18 s, opacification of the lesion may be shown.

SPECT
Scanning with 99Tcm-labelled human red cells is no longer used for the diagnosis of haemangioma (labelled red cells accumulate within the haemangioma).

• The diagnosis of haemangioma is reinforced by the absence of changes of the lesion on a second series of imaging procedures (ultrasound or CT scan) six months later.
• Single-photon emission CT (SPECT) using 99mTc-RBC increases the spatial resolution of planar scintigraphy, providing sensitivity and accuracy close to that of MRI for lesions >1 cm.
• SPECT with 99mTc-labelled red blood cells shows persistent blood pool activity within the lesion.
• The best use of 99mTc-RBC SPECT is for lesions >2 cm to confirm a suspected hemangioma seen as a hyperechoic lesion in ultrasound and to clarify the diagnosis when CT findings are unclear.

Imaging in patients with cirrhosis — The diagnosis of a hepatic hemangioma can frequently be made confidently with ultrasound in patients without a prior history of malignancy or chronic liver disease.

In contrast, the hyperechoic metastases and hepatocellular carcinoma (HCC) may have similar sonographic characteristics and are more likely in such patients. As a result, multiple imaging modalities and serum AFP determination may be required to differentiate a benign hemangioma from a malignant lesion in these settings.

• This was illustrated in a study that included 1982 patients with cirrhosis of whom 166 (8 percent) had a focal lesion. Of these 166 patients:
• Ultrasound showed the presence of a hemangioma-like lesion in 44 patients with a normal AFP.
• Contrast-enhanced CT confirmed hemangioma in 12 of the 44 patients.
• 99mTc-RBC confirmed hemangioma in 10 of the remaining 32 patients.
• Fine needle aspiration biopsy (FNAB) confirmed the presence of HCC in the remaining 22 patients.
• During follow-up a further 26 hemangioma-like lesions were identified on US, 22 of which were confirmed as HCC and four as dysplastic nodules.

BIOPSY -

• It is generally admitted that liver biopsy may be dangerous because of the risk of haemoperitoneum.
• However, liver biopsy has been performed in some patients without being complicated by intraperitoneal bleeding.
• Because liver haemangioma is soft, the tumour is pushed by the liver biopsy needle and therefore, often no fragment of the tumour is collected.

NATURAL HISTORY

1. Unchanged - Usually, liver haemangioma does not increase in size with time.
2. Growth- However, it has been reported that, during pregnancy or during estrogen therapy, the tumour may grow. In a small number of patients, in the absence of pregnancy and oestrogen therapy, the tumour may increase in size.
3. Spontaneous rupture of liver haemangioma is very rare. It usually occurs in large hemangiomas that are peripherally located, however, follow-up of giant hemangiomas (tumors >5 cm in size) has shown that even these rarely enlarge or rupture.
4. Traumatic rupture of cavernous hemangioma following blunt trauma to the abdomen is also rare but highlights that traumatic rupture of the liver may be associated with underlying liver pathology.
5. Iatrogenic rupture or intratumoral bleeding has been described following liver biopsy or fine needle aspiration, which has resulted in a reluctance of most physicians to perform such tests in patients with known or suspected hemangiomas.
6. Other complication –

• Thrombosis, which results in a triad of symptoms consisting of fever, right upper quadrant abdominal pain, and normal white cell count.
• thrombocytopenia,
• consumptive coagulopathy, and
• microangiopathic anaemia (Kasabach–Merritt syndrome).
• In the few cases with arterioportal shunt, heart failure can develop. Large haemangiomas can result in abdominal discomfort.

TREATMENT

• In most patients, liver haemangioma needs no treatment.
• Asymptomatic patients, particularly those with lesions <1.5>
• A close radiologic follow-up is required in patients with lesions >5 cm, particularly those in a sub capsular location.
• Complicated liver haemangioma must be treated surgically by liver resection, enucleation, hepatic artery ligation, and liver transplantation.
• Patients who have pain or symptoms suggestive of extrinsic compression of adjacent structures should be considered for surgical resection.
• Orthotopic liver transplantation has also been used successfully to treat symptomatic patients with unresectable giant hemangiomas and hemangiomas associated with Kasabach-Merritt syndrome.
• Spontaneous rupture of liver haemangioma can be treated by transcatheter hepatic arterial embolization, which can be followed by surgical resection.

Non-surgical techniques include

• hepatic artery embolization,
• radiotherapy, and
• interferon alpha-2a.

Interferon alpha-2a has been used in infants with life-threatening hemangiomas in extrahepatic sites, although success has not been uniform. Its efficacy for hepatic hemangiomas has not been well studied. Interferon probably works as an antiproliferative/antiangiogenic agent.

• Neither oral contraceptives nor pregnancy are contraindicated in women with uncomplicated liver haemangioma.

Hepatic haemangiomatosis
Hepatic haemangiomatosis, i.e. haemangioma involving the liver entirely and diffusely, is very rare. It can be isolated or associated with extrahepatic haemangioma or with Rendu– Osler–Weber disease. A case has been reported in a patient receiving metoclopramide. Heart failure , intraperitoneal bleeding and Kasabach–Merritt syndrome are common.

SUBACUTE THYROIDITIS

SUBACUTE THYROIDITIS
Synonyms: granulomatous thyroiditis, pseudotuberculous thyroiditis, giant cell thyroiditis
Subacute de Quervain’s thyroiditis is a self-limiting disease accounting for 0.5–3% of all thyroid pathologies and lasts a few weeks to 2 months. Women are 3–6 times more affected than men. The peak incidence is between the second and fifth decade of life.
ETIOLOGY

• The etiology of subacute de Quervain’s thyroiditis remains uncertain, but evidence implicates viral infection.
• Subacute thyroiditis is an inflammatory disorder of the thyroid gland.
• Previously, this condition was termed granulomatous thyroiditis, De Quervain thyroiditis, struma granulomatosa, and pseudotuberculous thyroiditis.
• The pathologic hallmarks are granulomas and pseudo giant cells.

Evidence that suggests a viral infection includes the following:

1. A postviral cytokine-mediated inflammation of
   the thyroid is suspected because a seasonal frequency
   and an association with upper respiratory tract infection
   is noted.
2. There is no associated polymorphonuclear leukocytosis.
3. In half of the patients antibodies against mumps, measles, influenza, adenovirus, coxsackievirus, or echovirus are found.
4. The mumps virus has been cultured from thyroid tissue of patients with subacute thyroiditis.
5. The process is self-limited.
6. Furthermore, a genetic predisposition exists with the haplotype HLA-Bw35. Hashimoto disease, have a higher frequency of a certain human leukocyte antigen (HLA) haplotype (HLA-B35)7; it is possible that this HLA association may reflect a genetic susceptibility to subacute thyroiditis after various viral infections

All current evidence suggests that subacute thyroiditis is not an autoimmune disease.

• Although low levels of antithyroid antibodies may appear transiently during the course of the disorder, the levels are not of the same magnitude seen in patients with other autoimmune thyroid disorders. Subjects with subacute thyroiditis, but not those with.

CLINICAL FEATURES

• These patients characteristically present with a painful, tender goiter that is firm, with pain radiating to the ears, mandible, or occiput.
• In some patients, however, these features may be minimal or even absent.
• Cervical lymphadenopathy usually is not present, but many patients have prodromal symptoms of an upper respiratory tract infection, fever, myalgia, or arthralgia.
• Additionally, patients with subacute thyroiditis often experience a series of changes in thyroid function related to the inflammatory effects in the gland.

Early in the course, symptomatic thyrotoxicosis may arise from the leakage of thyroid hormones from damaged follicular cells.

Subsequently, patients may develop transient hypothyroidism after passing through a euthyroid phase.

The hypothyroidism results from a depletion of thyroxine (T4) and triiodothyronine (T3) from the thyroid gland after the destructive, inflammatory process.

• However, patients usually experience a spontaneous recovery of normal thyroid function.

Not all patients with subacute thyroiditis experience all phases of these alterations in thyroid function.

• The duration of the illness often is 6 weeks but may be 3 to 6 months.
• The inflammatory process may migrate from one area of the thyroid to another and often crosses between the two lobes (“creeping thyroiditis”).

The differential diagnosis encompasses acute suppurative thyroiditis. In contrast to acute suppurative thyroiditis, the gland sonographically reveals irregular hypoperfused areas instead of hyperperfused tissue. On fine-needle biopsy, the differential diagnosis further includes palpation thyroiditis, as well as other granulomatous diseases such as sarcoidosis, tuberculosis,
and rheumatoid diseases.

LABORATORY EVALUATION
Laboratory evaluation usually reveals the following:

• elevated erythrocyte sedimentation rate (often >55 mm per hour);
• normal or near-normal leukocyte count;
• transient elevations of antithyroid antibodies in low titers;
• and serum T4 and T3 values that may be high, normal, or low, depending on the phase of the disease.
• In the thyrotoxic phase, the serum thyroid-stimulating hormone (TSH) value is suppressed but may be detectable in third-generation assays in nearly 80% of those evaluated.

TSH is normal during the euthyroid phase and elevated during the hypothyroid phase. A thyroid scan during an episode of subacute thyroiditis shows a cold region in the involved section of the thyroid.

Additionally, during the thyrotoxic and euthyroid phases, the radioactive iodine (RAI) uptake is often <1%.>

• This finding is of diagnostic importance in the evaluation of patients with suspected thyrotoxicosis, as a low uptake reflects the underlying etiology of destructive thyroiditis—not increased thyroid hormone production and secretion, as in Graves disease or toxic nodular goiter (in which the uptake is normal or high).
• Further, the serum thyroglobulin is frequently markedly elevated, a finding that is of value in the differential diagnosis of thyrotoxicosis that is due to surreptitious ingestion of thyroid hormone (thyrotoxicosis factitia).
• In the latter disorder, the RAI uptake and the serum thyroglobulin are low.

Although the diagnosis of subacute thyroiditis usually is apparent in patients with typical clinical features, occasionally there is difficulty in establishing the diagnosis—such as with sudden enlargement of the thyroid gland—raising the possibility of anaplastic carcinoma.

• In this situation, a thyroid biopsy may be helpful.

The usual microscopic features include degeneration of the follicular epithelium; infiltration of the tissue with leukocytes, lymphocytes, and histiocytes; and formation of granulomas composed of giant cells surrounding colloid. In approximately one-half of patients, microabscesses may be found. In most patients with subacute thyroiditis, the diagnosis can be made clinically.

TREATMENT
The management of patients with subacute thyroiditis is based on relief of symptoms, because no specific therapy is available.

Two aspects of this therapy must be addressed in each patient:

1. the local symptoms
2. and the effects of thyroid dysfunction.

Frequently, pain and tenderness in the neck respond to treatment with salicylates, 0.65 g every 4 hours. If no benefit ensues within 48 hours, nonsteroidal antiinflammatory agents may be administered, although it is unclear whether these agents are superior to the salicylates.

• Approximately 5% of patients require cortico-steroids for the relief of symptoms.
• Prednisone in doses of 30 to 40 mg per day usually results in prompt improvement; however, it may be difficult to reduce the dose without return of pain, so that treatment for 4 to 8 weeks may be necessary before a successful tapering is accomplished.
• If the patient does not respond to prednisone within 24 to 48 hours, the diagnosis of subacute thyroiditis should be reevaluated.
• Thyroidectomy occasionally is used in patients with severe or recurrent pain that is unresponsive to other therapy, but this approach is required infrequently.
• If thyrotoxic symptoms are foremost, the patient should be managed with b-blockade (e.g., propranolol).
• The thyrotoxic phase in these patients is transient, and definitive therapy with RAI is neither indicated nor of value because the thyroid uptake is low.
• Likewise, the antithyroid drugs propyl-thiouracil or methimazole (Tapazole) should not be given because these medications are also ineffective.
• These drugs impair thyroid hormone synthesis, but the excess serum thyroid hormone levels in subacute thyroiditis result from leakage of T3 and T4 from the damaged follicles and not from enhanced synthesis and secretion.
• The hypothyroid phase of subacute thyroiditis is usually transient and is often asymptomatic; therefore, thyroid hormone replacement frequently is not necessary.
• Additionally, the increased TSH secretion at this time may be important in the recovery of thyroid gland function; consequently, there may be a relative contraindication to thyroid hormone treatment unless the patient is clearly symptomatic.
  
• The long-term prognosis for patients with subacute thyroiditis is excellent.
• Recurrent episodes, although uncommon, do occur, in as many as 2% of affected patients yearly, but eventual normal thyroid function is the rule.
• Discomfort in the thyroid area can, however, continue for many months.
• Rarely, patients with subacute thyroiditis may develop permanent hypothyroidism.
• Patients who have had prior thyroid surgery or who have coexistent autoimmune thyroiditis may be especially prone to such an outcome.