25. 1 Acute pancreatitis
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Cancer
Pain dose not commonly accompany the onset of breast cancer moreover a neoplastic lump is usually painless. However, mastalgia may, at times, announce malignancy at its early stage. There are no specific features of this pain to identify it from a benign condition. The pain Is usually localised to the lesion.
Mtecellaneous
Cyst or cysts in the breast associated with flbrocystic disease may be associated with pain. Its management is dealt with later.
Fibroadenoma is generally painless but may rarely be associated with pain.
Mondor's disease is characterised by superficial thrombophlebitis of the veins over the breast. There is breast pain; on examination, the breast is tender and with time the veins become a string-like band and may be associated with skin dimpling. There is no specific treatment.
Treatment
Of the many empirical treatments, diuretics have been the most popular. Bromocriptine has been found effective with cyclical symptoms but not with noncycllcal ones. This drug, however, is associated with nausea, dizziness-and headache. Danazol has been shown to be effective in the treatment of painful lumpy breasts. Whether the benefit is confined to cyclical mastalgia alone is not clear. The dose ranges from 100 mg twice a day to 200 mg four times a day. It induces amenorrhoea and adequate contraceptive precautions are necessary.
Trigger point pain associated with signs of mammary duct ectasia can be relieved by subareolar mammary duct excision. At times, excision of areas of focal sclerosing adenosis and old scars may provide pain relief.
Tietze's syndrome may be benefitted by peri-chondral Injection of a local anaesthetic mixed with hydrocortlsone.
DISORDERS OF CYCLICAL CHANGE (FIBROADENOSIS)
Premenstrual nodularity and breast discomfort, is rather common but if pain is severe it is known as cyclical pronounced mastalgia. Painful nodularity has also been given the label "flbroadenosis" but it really refers to the histological diagnosis.
The cause is unknown but there is evidence of excessive prolactin release from the pituitary.
Young women between twenties and thirties are mostly affected and symptoms last up to menopause. The chief feature is lumpiness or multiple lumps. Palpable lumpiness is diffuse as opposite to being discrete or localised. Commonly both breasts are affected and the upper-outer quadrants and axillary tails tend to be most involved. The lumps have ill-defined margins, perhaps better felt with a finger and thumb rather than the flat of the hand. Lumps may be more evident in the week before menstruation is due and least evident just after menses. The associated pain is similarly cyclical. Cysts frequently coexist with fibroadenosis but should not be regarded ai 1 an essential feature of the syndrome. '
Fibroadenosis, as the name implies, contaiiu j two elements — connective tissue stroma and the | epithelial cells of ducts and acini. Both elementi | undergo proliferation. Usually the stromal reaction 1 is dominant. There may be proliferation of breast epithelium, usually that of the terminal ducts and acini. This proliferation is generally a regular increase in the epithelial cells. Rarely there mayq Irregular cells with nuclear pleomorphtsm and-increased density of staining, i.e. carcinoma In situ.
Management
Because certain benign conditions and breast cancer can present with breast pain, it is important to exclude these by a full clinical examination, and in women over 35 years by mammography.
When pain and nodularity do not interfere with the patient's quality of life, then reassurance Is all that is required. For severe debilitating cyctlcal pain, a number of drugs including danazol, bromocriptine and tamoxifen have been shown to be effective. Occasionally, needle biopsy of a particular mass may be necessary to ensure its benign nature,
y CYSTIC DISEASE OF THE BREAST (DISORDERS OF INVOLUTION)
The involutional changes are usually obvious by the age of thirty-five. The changes Include disappearance of lobular epithelium and specialised lobular connective tissue with replacement by the | more usual fibrous tissue found in the interlobular | region. The cysts form due to obstruction in the ductules due to epithelial proliferation or failure of Involution to occur in a ductule that had dilated during the phase of proliferation.
Thus the aberrations from the normal process include cyst formation, flbrosis and epithelial hyperplasia.
Cysts can be macroscopic or large enough to bt palpated or seen by the naked eye. When microscopic, cysts are frequently multiple and aggregated as a discrete mass. Palpable cysts present with discrete, smooth breast lumps which may be fluctuant. Nonfluctuant, so-called tension cysts, may clinically mimic a carcinoma. If a breast lump is suspected to be cystic, a needle aspiration (with 21 G needle) should be performed to confirm or refute the diagnosis and if a cyst is confirmed, then it should be aspirated completely. The fluid aspirated from cysts varies in colour from psde yellow, through dark green, to brown. Occasionally, the fluid is blood stained and this should be subjected to cytological examination.
Mammography should be performed on all patients with cystic disease, over the age of 35.
All patients who have cysts aspirated should be carefully examined after cyst aspiration to ensure there is no residual mass. If there is a mass or there Is cytological suspicion, an excision biopsy is done.
Goloctocole
Galactocele is a rare cystic lesion of the breast. The cyst appears during lactation and contains breast milk which may be inspissated. It may arise as a result of blockage of one of the main lactiferous ducts. It is also said to occur in women who stop breast feeding suddenly. Galactocele forms a painless, round and fluctuant swelling under the areola.
A galactocele may settle after lactation is over. In case it does not, is may be aspirated, which both confirms the diagnosis and usually cures the condition. If aspiration is not successful, it may need to be excised, preferably with a para-areolar incision.
FIBROADENOMA
Fibroadenoma is a common benign tumour of the breast. It arises in breast lobules and is most common in young women at a time when the breast is undergoing immense physiological change. It may be caused by an increased sensitivity to oestrogen in a localised part of the breast.
Pathology
It has been seen that the fibrous tissue of the breast has two different components separated by the elastic lamina that wraps the ductules. Depending on which of these two components share in the proliferative process, two types of flbroadenoma may be found.
1. Perlcanalicular The fibrous tissue outside the elastic lamina undergoes proliferation.
2. Intracanalicular The fibrous tissue lying within the elastic lamina (i.e. the periductal and perllobular fibrous tissue) undergoes proliferation. Both tumours are encapsulated and well localised.
Clinical Features
Fibroadenoma is a firm, painless, encapsulated lump and extremely mobile within the breast substance (the breast mouse). Pericanalicular (hard) flbroadenoma is seen between 20 to 30 years of age. It is of a small size and seldom attains massive size. The intracanalicular (soft) flbroadenoma is seen between 30 to 50 years and can attain a big size. Pericanalicular (hard), as the name implies is firmer in consistency than the intracanalicular (soft) flbroadenoma.
The patient usually presents with a painless, slowly growing lump in the breast. Usually, there is a solitary lump, but sometimes there may be more than one lump or both the breasts may contain the tumour. There is no adherence to the overlying skin. There is no nipple change, neither any discharge from it. Axillary nodes are not enlarged. In intracanalicular (soft) flbroadenoma the size of the tumour may become so immense that when the growth is benign a probe can be passed between the fungating tumour and the overlying skin. This large fibroadenoma is also known by the name cystosarcoma phylloides.
On mammography, a flbroadenoma is seen as a well-rounded opacity.
Treatment
Treatment is by excision of the tumour followed by biopsy. Enucleation is not advisable as the left behind capsule is susceptible to form a recurrent tumour.
One of the following incisions may be used for the purpose of excision.
1. Para-areolar incision This is a cosmetic incision as the scar merges with the coloured areolar skin.
2. Ga(((ard Thomas' submammary incision This is indicated for lower outer quadrant tumours.
3. Radial Incision This is not usually preferred because of the ugly scar. The incision should follow Langer's lines.
INTRADUCT PAPILLOMA
An intraduct papllloma is a benign lesion which usually occurs in a major duct of the breast and presents with a nipple discharge which is often blood stained. The position of the papilloma may be suspected if pressure expresses blood from one duct opening on the nipple. Opening the affected The main problem is to distinguish malignant from benign conditions. In fibrocystic disease, individual cysts are round or oval with discrete smooth edge. When the fibrous tissue is predominant, the breast can have a diffuse, almost homogeneously dense stroma with or without cysts. Thin curvilinear lines of calcification may be seen, whereas fine sand-like calcifications are uncommon. Mammogram may show the presence of a lesion with an irregular outline, increased vascularity and patchy calcification even before a lump is clinically palpable. A doubtful lump on mammogram reveals its true characteristics. A malignant lump with characteristic infiltration of the surrounding tissues, an increased density and fine stippling of calcium can be recognised from the smooth outline of an encapsulated lesion like fibroadenoma.
Ultrasound
Ultrasound examination can be useful in patients who are under 35 and have dense breasts where mammography is less accurate; it is also of great value in revealing whether a clinical or mammo-graphic lesion is cystic or solid.
Fine Needle Aspiration Cytology (FNAC)
A 20 to 22 gauge needle is introduced several times through the tumour while suction is exerted on the attached syringe. The material obtained is spread on a slide and fixed. This is cytological rather than a histological technique. Cancer cells are much less adherent to adjacent tissue than normal cells, and the thin needle seems to dislodge them preferentially and satisfactory smear is obtained.
Cells are more difficult to obtain from benign lesions than from breast cancers. An acellular aspirate needs to be interpreted in the clinical context and benign clinical and mammographic examination may help in assessing the need for biopsy.
CARCINOMA OF THE BREAST
Epidemiology and Aetiology
The breast is one of the most common sites of malignancy in women. There is a distinct difference in the distribution of disease in various geographical areas. By and large, areas of high incidence include northern and western Europe and North America while a low rate is found in most countries of Africa, Latin America and Asia.
The low Asian incidence has been related to high parity and prolonged lactation. Japan has the lowest rate and this Includes also the single Japanese women. The geographical difference thus, cannot be explained satisfactorily by the factors of lactation and parity.
Breast Cancer Risk
The risk of breast cancer is increased 1.8 fold when there is a family history of the disease. Late onset of menarche, early pregnancy and breastfeeding have been considered to be factors that protect against breast cancer. Table 33.1 outlines some of the factors which influence the risk of developing breast cancer.
Obesity (high socioeconomic status)
Oestrogen window hypothesis Korenman has suggested that carcinogens may induce cancer in a breast, made susceptible by the unopposed action of oestrogens and this is supported by the following observations.
1. In nulliparous women, there is overexposurc to oestrogens unopposed by progesterone.
2. There is high incidence of breast cancer in women who have an early menarche and late menopause.
3. An artificial early menopause by oophorectomy or ovarian irradiation has been shown to be protective against cancer. •
4. Hyperoestrogenism has been thought to explain a higher Incidence of cancer in obese women as it is known that aromatlsation of androgens to oestrogens occurs in peripheral fat.
However, direct measurements of oestrogens in the blood have failed to show any differences between women with cancer and control subjects.
Genetic and environmental factors The Bittner factor is an oncogenic virus found in mice. It is transmitted through the mother's milk and causes breast cancer in the suckling young. There is, however, no evidence to support this in humans.
A family history of cancer in the mother or sister certainly carries an increased risk of breast cancer but the risk increase is only some two to four-fold, demonstrating that mendelian type inheritance is not usual.
The environmental factors perhaps are more powerful than genetic factors as shown by the observation that second generation Japanese women In Hawaii who eat western-style diet tend to Increase their chances of breast cancer. The role of dietary saturated fat intake with increased breast cancer incidence has also received attention.
Previous benign breast disease The modem oral contraceptive pill contains oestrogens and progestogens. The overall consensus is that there is no great effect on breast cancer incidence in users of the modern combined oral contraceptive.
Pathology
The majority of breast cancers originate from the epithelium lining the terminal ductules, and proliferate entirely within the lumen of the ductules, limited by the basement membrane of the ductular wall. As long as they remain in this state they are called the noninflltrating cancer or ductal carcinoma (n situ (DCIS). Sooner or later, they infiltrate outside the basement membrane into the neighbouring breast tissue and become infiltrating (invasive ductal) cancers. The cells in the neighbouring breast tissue may show a glandular arrangement (adeno-carcinoma), however, in the vast majority, the cells assume a spheroidal shape, do not show any regular glandular pattern, and grow in the form of solid processes into the surrounding tissue (spheroidal cell carcinoma).
An atrophic breast predominantly contains fibrous tissue (sctrrhous carcinoma). In a well-developed breast with abundant blood supply, the malignant cells grow in large solid masses whereas the fibrous tissue proliferation is much less (medullary carcinoma). In some cases, the growth may show large areas ofmucoid degeneration (colloid carcinoma). The invasive ductal (infiltrating) carcinomas constitute around 80-90% of all carcinomas of the breast.
A minority (2-10%) of breast carcinomas appear to originate from the epithelium lining the acini and small intralobular ductules, the so-called lobular carcinomas. These also after a while grow from a noninvaslve type ((n s(tu) to an Invasive type.
The noninvasive cancers are becoming increasingly important as modem screening methods are detecting more of these types. Screen detected cancers show much higher levels of DCIS. This is due to the fact that they often present as fine microcalciflcation on mammography. Lobular carcinoma (n situ is very uncommon. The risk of metastasis in DCIS is very low. As already stated, invasive ductal cancers form the majority of breast cancers.
Paget's disease of the nipple is a special category of invasive epithelial cancer where histologically the nipple skin is infiltrated by large pale cells and eventually nipple erosion occurs. This is invariably associated with an underlying invasive or intra-ductal carcinoma.
It has been customary to describe certain broad types of carcinoma breast. Though their clinical significance may not be much but it Is relevant to recognise the various types.
Sclrrhous Carcinoma
It is the commonest form and is met with principally in the middle-aged or elderly women. Due to abundance of fibrous tissue the lump feels very hard and when it is cut through, there is a typical gritty sensation and the cut surface Is concave. It has a typical greying appearance with white specks in it. The tumour is usually of a small size, but having no capsule, and it invades the breast in all directions.
As the tumour grows it may cause indrawing of the nipple, and tethering to the overlying skin and to the pectoral fascia. In advanced cases'-the overlying skin may ulcerate and there may be fixity to the chest wall.
Duct Carcinoma
This occurs in a main lactiferous duct. This may arise de novo or by malignant change in a duct papilloma. Usually, the only complaint is painless bleeding from the nipple and patient often reports early.
Medullary Carcinoma It affects the somewhat younger age group. The primary tumour is soft and circumscribed and may attain a large size.
It has a good prognosis and is less Invasive than the sctrrhous carcinoma.
Certain Variants of Breast Carcinoma
Medullary Carcinoma with Lymphold Stroma
It has a better prognosis than some other forms of invasive breast cancer. It has a circumscribed outline.
Mucoid Carcinoma
This also has a circumscribed outline and relatively good prognosis. The gross appearance is characteristically gelatinous.
Inflammatory Carcinoma
This should actually be seen as a clinical entity. It is rare and has no special age incidence. The first symptom is often pain. The histologlcal features associated with this condition are extensive infiltration of dilated lymphatics and blood vessels with malignant cells. The dermal permeation of lymphatics causes gross oedema and redness of the overlying skin simulating an inflammatory condition. The affected breast is usually diffusely enlarged, oedematous, inflamed and indurated. and warm to touch. The characteristic mammographic feature is oedema.
The prognosis is poor and local surgery is not advised. Control of disease, even by radiotherapy, is difficult. Endocrine and chemotherapy are recommended.
Breast Cancer Occurring during Pregnancy
Only 1-2% of breast cancers occur during pregnancy or lactation. The diagnosis of breast cancer during pregnancy is frequently delayed because physiologic changes in the breast may obscure the true nature of the lesion.
A mass in a pregnant patient should not be disregarded by the clinician. Any sign of skin thickening, retraction or fixation, a particularly large tumour, and suspicious axillary nodes are Indications for surgical consultation.
A needle aspiration cytology is helpful in getting an expedient histological diagnosis. Mammograms taken during pregnancy are of questionable value. The Increased density of the breast that occurs with pregnancy tends to obscure the signs.
Pregnancy is not a contraindication to operation. Modified radical mastectomy is the most accepted procedure for localised carcinoma of the breast in the pregnant patient. Radiation should be avoided as long as the patient is pregnant.
For patients with metastatic disease, a limited resection for palliation and cytoreduction is advised.
These patients will need systemic therapy. There is a fear of Inducing congenital malformations in the foetus and abortion may be advised in the first trimester. It may not, however be recommended for those in the second or third trimester. It is better to advise a regime that does not contain methotrexate.
Paget's Disease
Paget's disease is very rare. It manifests as a slowly progressive eczematous lesion of the breast lasting from 6 months to 2 years. Itching may be the earliest symptom. Later follows crusting and then ulceration. The nipple may be completely destroyed, eventually leaving behind a flat red ulceration. Its unilateral nature differentiates it from simple eczema. An underlying intraduct or infiltrating ductal carcinoma is invariably present and may be palpable in some cases.
Nipple biopsy will give the diagnosis. The epidermis of the nipple is infiltrated by Paget's cells which are either single or in clusters. They are large cells with prominent nuclei and abundant cytoplasm.
Even though Paget's disease is often an expression of only (n situ ductal carcinoma, an adequate and most satisfactory treatment Is mastectomy and axillary clearance.
Intracystic Neoplasia
If a cyst aspirate is blood stained or its cytology is typical, carcinoma is suspected. On mammo-graphy, the outline of a malignant cyst is often Indistinct for part of its circumference. Pneumo-cystography will show a ragged cavity. Carcinoma in a cyst tends to occur in the older age group, is slow growing and not very invasive.
Bilateral Breast Cancer
Clinically evident simultaneous bilateral breast cancer occurs in less than 1 per cent of cases, but there is 5-8 per cent incidence of later recurrence of cancer in the second breast. Bilateralism is more common in lobular carcinoma. The incidence of second breast cancers increases directly with the length of survival after the first cancer — about 0.5 per cent per year.
Mammography should be performed for the opposite breast before primary treatment and at regular intervals thereafter to search for cancer in the opposite breast.
SPREAD OF CARCINOMA OF THE BREAST
Local Spread
The tumour tends to involve the overlying skin and to penetrate the pectoral muscles and even the chest wall.
Lymphatic Spread
This occurs in two ways; by emboli when detached tumour cells are swept along the lymph channels, and by permeation when solid columns of cancer cells grow along the lumen of the lymph vessels. The axillary lymph nodes and the internal mammary lymph nodes are Involved comparatively early. Later the supraclavicular lymph nodes, the opposite breast and the mediastinum are possible lymph node stations and followed finally by more distant nodes.
In advanced disease, secondary to the blockage of lymph nodes by the malignant cells and the lymphatic statis thereupon, oedema of the skin overlying the breast ensues. This oedematous skin (Figs 33.9 and 33.10) has the characteristic appearance of the peal of an orange (Peau d'orange).
Blood Spread
This may occur to lungs, liver, bones, (with red marrow) and brain. The bony lesions are almost always of osteolytic nature. Secondary deposits may also be carried to the liver via the lymphatics within the rectus sheath and the falciform ligament. The adrenal glands are also common sites for blood-home metastasis.
Diagnosis
To achieve optimum results of any treatment, one should aim to diagnose carcinoma breast at its early stage. The following clinical picture actually profiles an advanced case.
The presenting symptoms are: (1) lump, (II) nipple complaint, (Ill) pain. and (iv) symptoms from metastases.By far the commonest of these is a lump, it I painless and usually found by chance by the patient herself. Ignorance, shyness and fear of operation often lead to remarkable delay in reporting. The symptoms related to the nipple are skin changes, blood-stained or serous discharge, and retraction. Pain in the breast, however, is a fairly uncommon presentation of a small breast cancer.
The presentations associated with metastatic disease are weight loss, debility, ascites or jaundice with liver secondaries and central nervous symptoms with brain metastases. A patient with bony secondaries may present with pathological fractures, especially of the long bones and ribs.
Clinical examination consists of careful inspection and then palpation with the flat of the hand, examining all four quadrants, nipple, areolar area, and axillary tail in turn. Lymph nodes in the axilla should then be palpated. Lungs and liver should also be examined.
In women over 35 years, mammography should be performed. It is less accurate in the younger denser breast and in deep-seated tumours. The mammographic signs of malignancy are a dense mass with irregular margins, a characteristic infiltration of the surrounding tissues (Fig. 33.7), and fine scattered microcalcifications. Ultrasound may be useful to show an underlying cystic disease but this is not yet a routine investigation.
All dominant lumps should be aspirated and if they are not cysts, the material should be sent off fur cytology. Fine needle aspiration cytology can establish diagnosis in most cases.
Differential Diagnosis
An important dictum is that every lump in the breast is carcinoma till proved otherwise. However, there are certain benign conditions which may resemble carcinoma.
1. Chronic breast abscess
2. Cystosarcoma phylloides
3. Duct ectasia
4. Tuberculosis of the breast
There are certain conditions which may cause retra6tion of the nipple.
1. Congenital
2. Following flbrosis due to breast abscess or tuberculosis of the breast
3. Duct ectasia (plasma cell mastitis)
Early Detection of Cancer Breast
Prognosis of carcinoma breast is related to the stage of disease at diagnosis and treatment. Detecting breast cancer before it has spread to the axillary nodes greatly increases the chances of survival. Both physical examination and mammography are necessary for maximum yield in screening programmes. Because of early diagnosis, it may be possible to perform more conservative surgery of the breast.
All women over the age 20 should be advised to examine their breasts monthly. The woman should inspect her breasts initially while she is standing before a mirror with her hands at the sides, overhead with the pectoral muscles contracted. Lump, asymmetry and dimpling of the skin may thus become apparent. Next, in a supine position, she should carefully palpate each breast with the fingers of the opposite hand.
Mammography is a sensitive method for early detection but mass screening involves considerable cost and organisation. Two-views technique (cranio-caudal and mediolateral) of mammography is more sensitive. In Great Britain, Forrest Committee has recommended mass mammographic screening programme every 3 years for women between 50 to 64 years of age. This may be effective in reducing the mortality. However, high motivation of the population is essential for compliance. The disadvantages of population screening are expensive but selective screening is specially indicated in high risk groups, e.g. those with a strong family history of breast cancer, and in the other breast following mastectomy.
Clinical Staging of Carcinoma Breast
Though TNM system is now receiving increasing acceptance but the Manchester staging system still remains in wide use.
Manchester System of Staging
Stage I Growth confined to breast; not adherent to pectoral muscles or chest wall. If skin adherence present, this must be smaller than the size of the tumour.
Stage II Stage I plus palpable mobile lymph nodes In the axilla of the same side.
Stage III Skin involvement larger than the tumour but still limited to the breast, tumour fixed to pectoral muscle but not to the chest wall, or homolateral supraclavicular nodes mobile or fixed, or oedema of the arm.
Stage IV Skin involvement wide of the breast. Complete fixation of the tumour to the chest wall, distant metastases either blood borne or lymph borne; this includes Involvement of the opposite breast or axilla and deposits in bones and viscera such as the lungs and liver.
TNM System
The International Union against Cancer has recommended the staging system. T stands for the description of tumour, N for the regional lymph nodes and M for distant metastasis.
Primary Tumour (T)
t0 No evidence of primary tumour.
tis Paget's disease of the nipple with no demonstrable tumour. (Paget's disease with demonstrable tumour is classified according to size of the tumour.)
T1 Tumour 2 cm or less in greatest dimension.
Tia No fixation to underlying pectoral fascia or muscle.
Tib Fixation to underlying pectoral fascia and/or muscle.
T2 Tumour more than 2 cm but not more than 5 cm in its greatest dimension.
T2a No fixation to underlying pectoral fascia and/or muscle.
T2b Fixation to underlying pectoral fascia and/ or muscle.
T3 Tumour greater the n 5 cm in diameter.
T4 Tumour of any size with direct extension to the chest wall or skin. (Chest wall includesribs, intercostal muscles and serratus anterior muscle, but not pectoral muscle.)
T4a Fixation to chest wall.
T4b Oedema (including peau d'orange),ulceration of the skin of the breast, or
satellite skin nodules confined to the same breast.
T4c Both of above.
T4d Inflammatory carcinoma.
Nodal involvement (N)
n0 No nodes palpable.
n1 Mobile axillary nodes
- not considered involved by tumour.
- b. considered involved by tumour.
N2 Fixed axillary nodes.
N3 Palpable supraclavicular nodes.
Distant metastasis (M)
m0 No known distant metastasis.
M1 Distant metastasis present, specify site.
Treatment of Carcinoma Breast
For treatment, the patients may be grouped as below.
1. Clinical stage I and II (T1 T2 and N0, N1)
2. Clinical stage III (T3, T4 and N2, N3)
3. Clinical stage IV (distant metastasis)
Treatment may be curative or palliative. Curative treatment is advised for clinical stage I and II of the disease. Treatment can only be palliative for stage III and IV.
CLINICAL STAGE I AND II (T1 T2 AND No, N1)
The aim of treatment is loco regional control, which can be achieved by either surgery alone or in combination with radiotherapy. There is a great deal of controversy regarding the therapeutic options.
Surgery The basis of surgery for many years has been the Halsted radical mastectomy but a modified radical mastectomy, by not removing pectoralis major, has now replaced it. The axillary clearance in modified radical mastectomy should be essentially the same as in the Halsted radical mastectomy. Postoperative radiotherapy is often advised when the axillary nodes contain the tumour.
Radical mastectomy, however, ignores the internal mammary chain of lymph nodes. Extended radical mastectomy to include the internal mammary nodes has been tried but there is no further improvement in survival and, therefore, this operation has now been given up.
Total mastectomy (local mastectomy) without disturbing the axilla has also been suggested. This operation provides adequate local control provided the axillary nodes contain no deposits. In view of the inaccuracy of clinical assessment alone of the axilla, total mastectomy should be combined with a careful follow-up and the axillary clearance performed if nodes subsequently appear. Alternatively, total mastectomy should be followed by irradiation to the axilla. This routine postoperative irradiation to the axilla after total mastectomy may unnecessarily treat some, whose nodes are not harbouring any malignancy. To overcome this situation, it has been suggested that the lower axillary nodes (sampled) in a case of total mastectomy if found to be positive for malignancy, additional radiotherapy is given.
More recently, there has been a marked move towards breast conservation on the grounds of better cosmesis. To avoid the mutilation of mastectomy, early lesions (tumour size up to 3 cm) may be treated by segmental mastectomy, i.e. excision of the tumour with adequate margin of healthy breast tissue, and this is followed by radiotherapy to the entire remaining breast. Axillary sampling at the time of excision of the primary will indicate the possible need for axillary irradiation.
Postoperative radiotherapy Surgery and radiotherapy are often complimentary in the locoregional control of operable breast cancer. Radiotherapy (4500-5000 rad) is prescribed under the following, situations.
1. For the internal mammary and supraclavicular nodes, not included in the standard surgical field of radical mastectomy.
2. For axilla, internal mammary and supraclavicular nodes in the operation of local mastectomy.
3. For the remaining breast and axilla when conservative surgery (segmental mastectomy) has been performed for a small primary. Postoperative Irradiation may not improve
survival but it does reduce the incidence of local
recurrence.
Adjuvant therapy for stage I and II Hormones and chemotherapy are now being used as adjunctive treatment of patients with operable breast cancer (stage I and II) and positive axillary nodes since there is a great likelihood that these patients harbour occult metastases. The objective of adjuvant chemotherapy is to eliminate the occult metastases responsible for recurrences while they are microscopic and theoretically more vulnerable to anticancer agents. Important studies by Bonadonna In Milan, Itlay, and Bernard Fisher in the USA, have used the combination of cyclophosphamlde, methotrexate and fluorouracil (CMF) in both premenopausal and postmenopausal patients. The drugs were given for 12 months after operation in patients with positive nodes. (CMF regime used for 6 months has been found as good as 1 year of treatment and this should now be the treatment of choice.) Both trials showed benefit for the treated patients as compared to controls in both disease-free survival and mortality. The advantage was maximum in premenopausal patients with 1 -3 metastatic nodes in the axilla. However, the toxictty of the therapy has been a problem.
Patients with negative nodes have not been treated with adjuvant therapy until recently. Several reports have shown beneficial effects of adjuvant chemotherapy or tamoxifen in delaying recurrence, but as of yet, no effect has been seen on survival.
For postmenopausal patients with positive nodes and oestrogen positive receptor tumours, tamoxifen (antioestrogen substance) 20 mg daily for 2 to 3 years as an adjuvant treatment has also been found useful.
Stage /// and IV (Advanced Disease)
Patients with locally advanced disease are deemed incurable. Most Tg lesions can be treated by local mastectomy plus radiotherapy to the chest wall and all surrounding nodal drainage areas. Toilet mastectomy may need to be performed for foul-smelling, fungating mass. At times, chemotherapy for a large bulky tumour may be prescribed (anterior chemotherapy). This may produce regression in the size of the mass and the resident nimour may later be irradiated or excised.
Signs of inoperability are skin oedema and peau d'orange, skin ulceratlon, chest fixity and satellite nodules. Where the primary tumour is inoperable or where the patients has metastasis, then radiotherapy is often the treatment of choice for the local problem.
Where the tumour Is found to be oestrogen receptor positive or the biopsy is of a slow growing tumour, endocrine therapy (tamoxifen 20-40 mg/ day) has a better response rate compared with chemotherapy, moreover endocrine therapy is less toxic.
For metastatic disease, treatment is directed at relief of symptoms as cure is not possible. It Involves a multidiscipllnary approach which Includes hormonal manipulation, systemic chemotherapy, local radiotherapy, etc.
Hormone therapy Hormone therapy may comprise (1) administration of hormone; (11) ablation of ovaries, adrenals or pituitary; or (ill) administration of drugs that block hormone receptor sites (e.g. antioestrogen tamoxifen) or drugs that block the synthesis of hormones (e.g. aminoglutethimide blocks adrenal steroid synthesis).
The hormonal treatment is more effective In postmenopausal patients and in those whose tumours contain oestrogen receptors. The choice of treatment depends on the menopausal status of the patient.
The premenopausal patient In the premenopausal and postmenopausal patient within one year of menopause, oophorectomy has been the first choice and the same can be achieved by radiotherapy with 1500-2000 rad over 2 weeks if surgery is contraindicated.
The potent antioestrogen tamoxifen 10 mg twice daily has been tried as an alternative to oophorectomy in the premenopausal patient. It has few side effects. Good response has been reported in about 70 per cent of patients, if their tumours were oestrogen receptor positive.
Those patients who do not respond to tamoxifen should be treated with cytotoxic drugs. However, those who respond and then relapse may later respond to another form of hormonal treatment. The choice should be aminoglutethimide. (This is an inhibitor of adrenal hormone synthesis and when combined with a corticosteroid provides a therapeutically effective medical adrenalectomy.) Ablative endocrine procedures as adrenalectomy and hypophysectomy have now been supplanted by the wide range of medical hormonal therapies that are available.
Megestrol acetate (Megace) is a progesterone derivative that offers effective palliation In metastatic breast cancer.
7"he postmenopausal patient Tamoxifen 10 mg twice daily is the therapy of choice for postmenopausal women with metastatic breast cancer, amenable to endocrine manipulation.
Those who do not respond to tamoxifen should be given cytotoxic drugs. However, those who respond and then relapse respond to progesterone derivatives like megestrol acetate (Megace). Chemotherapy Chemotherapy should be considered for the treatment of metastatic breast cancer in the following conditions.
1. If visceral metastases are present (especially brain or lungs)
2. If hormonal treatment Is unsuccessful
3. If the tumour is oestrogen receptor negative.
A combination of drugs is more effective than single agents. The drugs used most often are cyclophosphamlde, methotrexate, 5 fluorouracil, adriamycin and vincrlstlne.
To summarise, the treatment of metastatic disease is directed at relief of symptoms as cure is not possible and less toxic endocrine therapy is used if the tumour is slow growing and is oestrogen receptor positive. If the receptor status is unknown, then, response is most likely in a patient who is postmenopausal with slow growing disease confined to the bones and soft tissues. Tamoxifen is the first line of treatment. In premenopausal women, ovarian ablation or radiation can be performed. If the metastatic disease involves the viscera, cytotoxic chemotherapy is preferred as the first line of treatment.
Localised painful bony metastases are best treated by palliative radiotherapy and analgesics. Brain metastases are treated by radiotherapy and high dose steroids.
Malignant pleural effusion may develop in some patients with advanced breast cancer. Intercostal tube drainage is instituted and the plural space is emptied as much as possible. 500 mg of tetracycline is dissolved in 30 ml of saline and injected into the pleural cavity through the tube which is clamped for six hours. The patient's position is changed frequently to distribute the tetracycline within the pleural space. The tube is kept for a week and visceral and parietal pleura adhere. As fluid drainage becomes very minimal, the tube is removed.
Operative Surgery for Breast Cancer
Mastectomy Procedures
Halsted radical mastectomy was the standard curative procedure from the turn of the century to about two decades ago. This comprises excision of the breast, both pectoral muscles and axillary clearance.
There is a trend now-a-days to modify the Halsted radical mastectomy by not removing the pectoralis major. Patey advocated excision of pectoralis minor to get a better access to the axillary glands. Others just retract the muscle to facilitate removal of the axillary nodes. This modified radical mastectomy gives superior cosmetic and functional 'results compared to Halsted radical mastectomy.
Radical mastectomy, however, ignores the internal mammary chain of lymph nodes. The extended radical mastectomy to Include the internal mammary nodes has been tried but there was no further improvement in survival and. therefore, this procedure has fallen into disrepute and no longer practised.
Total mastectomy means complete removal of the breast but the axilla is left undisturbed except for the region of the axillary tail which usually has attached to it, a few nodes low in the anterior group. This operation is adequate for local control provided the low axillary glands removed have no deposits, otherwise radiotherapy to the axilla is indicated.
Excision of Tumour
When performed as a diagnostic open biopsy, this should be done through a circumareolar incision or a circumferential incision placed in such a way that the scar can be excised if mastectomy becomes necessary at a later date. Transverse incision can be used in the medial half of the breast. Radial and vertical incisions are avoided as these heal poorly.
When performed as a part of conservative treatment (segmental mastectomy, lumpectomy, quadrantectomy, partial mastectomy), the tumour is excised with a margin of surrounding 'normal' breast tissue which should be at least 2 cm wide of the palpable tumour. Excision of the entire quadrant in which the tumour is situated along with adequate margin of healthy breast tissue, as advocated by the Milan group, gives wide clearance but the cosmetic result is not so good. Ideally, the clearance should be obtained and verified by biopsies of the residual margins. Good haemostasis is essential as haematoma is a common problem. Axillary dissection may be in continuity if the tumour is in the upper and outer quadrant and with a separate Incision if the tumour is situated elsewhere. The patient, thereafter, receives full radiotherapy over the residual breast tissue.
In patients with a small lump (2-3 cm), this may be an ideal procedure. In patients with small breasts and with tumours close to the nipple and areola, the cosmetic results after excision are often unsatisfactory. Clinically detectable multifocality is a relative contraindication to breast conserving surgery as is fixation to the chest wall or skin or involvement of the nipple or overlying skin.
Breast Reconstruction
Breast reconstruction with the implantation of a prosthesis is usually feasible after standard (Halsted) or modified (Patey) mastectomy. Reconstruction should probably be discussed with the patients prior to mastectomy because it may provide an important psychologic prop towards recovery.
Reconstruction may be performed at the same time as the mastectomy or more frequently, delayed for 3-9 months, when adjunctive treatment is over. Some surgeons, for patients with stage I breast cancer, may start reconstruction at the same time. Immediate reconstruction provides the patient the benefit of emerging from her operation with a reconstructed breast mound.
The type of reconstruction depends on local factors e.g. amount of skin, previous radiotherapy, size of the other breast, etc. The techniques vary from simple placement of an implant under the skin flaps to insertion of myocutaneous flap into the mastectomy defect.
A simple implant can only be used when plenty of skin is available after completion of the mastectomy. The reconstructive surgeon positions the silicone breast implant beneath the musculofasclal layer of the chest wall. The implants are possible
CARCINOMA OF THE STOMACH
The stomach is an important site of cancer in the gastrotntestinal tract. It is widely prevalent in countries like Chile, Japan and Iceland. The incidence of gastric cancer is declining in western countries but the reason is unknown.
Its incidence in India is variable in different geographic areas. It is found to be more common in the south than the northern parts of India.
Diet has been incriminated in various high risk areas. Smoked meat produces 3-4 benzpyrine which is carcinogenic. In Japan, high risk has been associated with the consumption of raw fish. N-nitroso compounds are potent carcinogens. These may be formed at low pH by purely chemical means and at high pH by bacteria. Bacteria enzymatlcally reduce dietary nitrate to nitrate and then further reduce nitrite to N-nitroso compounds by combining it with dietary amines or amides. This bacterial formation of N-nitroso compounds accounts for the excess incidence of gastric cancer found in conditions of high intragastric pH such as chronic atrophic gastritis (CAG), pernicious anaemia and after gastric surgery.
H. pylori is known to be a cause of chronic atrophic gastritis which in turn is a recognised precursor of gastric cancer. The greatest incidence of gastric cancer is found in blood group A. Several precancerous lesions of the stomach have been identified. Chronic gastric ulcer leading to cancer occurs, however, only in 1 to 2 per cent. Carcinoma may develop In a case of pernicious anaemia. Gastric polyposis Is another premalignant condition.
Chronic Gastritis and Stomach Cancer
Chronic gastritis is frequently found In association with gastric cancer. Chronic gastritis may be classified as autoimmune, hypersecretory and chronic atrophic gastritis. Autoimmune gastritis is the gastritis of pernicious anaemia. The inflammatory process Involves the body and fundus diffusely. This type of gastritis increases in prevalence and severity with age, and is found more frequently In men than In women. Intestinal metaplasia commonly accompanies autoimmune gastritis and there is a higher risk of malignancy.
Hypersecretory gastritis is found in association with an ulcer. There is no significant metaplasia or association with malignant change.
Chronic atorphic gastritis is prevalent in some parts of the world and its geographical distribution matches areas where there Is a high risk of Intestinal type gastric cancer. This gastritis involves the antrum and body.
Early Gastric Cancer (EGC)
Early gastric cancer is defined as cancer limited to the mucosa and submucosa, and accounts for up to 30 per cent of newly diagnosed cases in Japan as a result of screening for the disease. Results of surgery (5 year survival rates exceeding 80 per cent), are excellent. The different endoscopic appearances have been classified as below.
1. Protruding
2. Superficial
This may be elevated, flat or depressed
3. Excavated.
Some 10 to 15 per cent of gastric carcinomas confined to the mucosal and submucosal layers have metastasised to the regional lymph nodes and have poorer prognosis.
EGC is occasionally encountered In other parts of the world including the West, and detection of such cases has become possible only after the availability of GI endoscopy.
Advanced Gastric Cancer
A tumour which has Involved the muscularis propria of the stomach wall is an advanced cancer and accounts for the majority of the cases diagnosed in our country. In most, the lymph node spread in association with peritoneal and liver deposits is present.
Borrmann classified gastric cancer on the basis of gross morphology.
Type I Polypoid
Type II Ulceratlve, circumscribed with everted margins
Type III Ulcerative, noncircumscribed with ill-defined margins
Type IV Diffuse infiltrating type
The commonest type of lesion that is encountered belongs to type II and III. The diffuse infiltrating type is the next common tumour, and presents as a localised or a generalised variety. The commonest site of tumour Is the antrum. Fundal growths are next in frequency, and usually spread to involve the lower oesophagus. However, the duodenal involvement is comparatively rare. The lesion confined to the body alone is less commonly encountered.
Adjacent organ involvement is frequently encountered as most lesions by the time detected have transgressed the serosa.
Pathology
The majority of lesions are either well differentiated or moderately differentiated adenocarcinomas. Anaplastic tumours are less frequent.
Stomach cancer can be classified Into intestinal type and the diffuse type. It has been found that the intestinal type is more common in the elderly and the diffuse type in young males.
Intestinal Type
There is an attempt at intestinal type gland formation in autoimmune gastritis and chronic atrophic gastritis. This is seen in the elderly and involves body of the stomach. Growth tends to be expansive rather than Inflltrative. This type has a somewhat better prognosis. The Intestinal type accounts for a much larger proportion of cases in countries such as Japan and Finland where gastric cancer is especially common.
Diffuse Type
Intestinal gland formation is poor. Cells are scattered through the large amount of stroma. There is usually mucin secretion, and the mucin is dispersed throughout the stroma and within cells (Signet ring cells). It is often an undlfierentiated cancer with propensity for early diffuse infiltration.
Diffuse type of adenocarcinoma is not accompanied by chronic gastritis. It is commoner in blood group A and does not have as good a prognosis as the intestinal type.
It has been seen that by the. time, the patient presents with symptoms, the disease is no longer an early cancer. Detailed Investigations of patients over 50 years of age who have dyspepsia of recent onset help to detect an early lesion. The other high risk factors are: (i) family history of gastric cancer, (11) pernicious anaemia, [W gastric surgery 10 years ago or earlier, and (iv) chronic atrophic gastritis (CAG).
Spread
Direct
Direct spread In the stomach wall occurs early. The neighbouring mesocolon is often involved making resection difficult, and transverse colon may at times be Invaded giving rise to a malignant gastrocollc fistula.
Lymphatic Spread
Spread by lymphatics also occurs early. The lymphatic vessels in the gastric wall form sub-mucosal and subserosal plexus. Further lymphatic drainage to the nodes follows the arterial supply of the gastric and gastro-epiploic arteries (Fig. 44.3). From here the spread is directly or via the sub and suprapyloric nodes, to the coellac axis and porta hepatis.
The lymphatics of the proximal half of the stomach drain primarily into the left gastric and the splenic lymph nodes and thence into the left, middle, and right superior pancreatic lymph nodes.
The lymphatics of the antrum drain into the right gastric lymph nodes superiorly and the right gastroepiploic and subpyloric lymph nodes inferiorly.
The lymphatics of the pylorus drain into the right gastric nodes (suprapyloric) superiorly and the subpyloric lymph nodes situated around the gastroduodenal artery, inferiorly. The efferent lymphatics from the suprapyloric lymph nodes converge on the para-aortic lymph nodes around the coeliac axis, while the efferent lymphatics from the subpyloric nodes pass to the main superior mesenteric lymph nodes situated around the origin of the superior mesenteric artery.
Blood Spread
For blood spread, the most important sites are the Liver and the Lungs. Bone metastases are rare.
Transperltoneal Spread
Transperltoneal spread is important in gastric carcinoma since tumour cells may spread to the ovaries causing Krukenberg tumours which may be the presenting feature of gastric carcinoma. Peritoneal seedlings found at laparotomy Indicate incurability.
Staging
An international staging system has now been agreed upon by Union International Centre Cancer (UICC), American Joint Committee (AJC), and Japanese Joint Committee (JJC) is depicted below.
Primary Tumour ( T)
t0 No evidence of primary tumour
t1 Tumour limited to mucosa and submucosa regardless of its extent or location
T2 . Tumour Involves the mucosa, the submucosa and muscles on to the serosa, but does not penetrate through the serosa
T3 Tumour penetrates through the serosa without involving contiguous structures
T4 Tumour penetrates through the serosa and invades the contiguous structures.
Nodal Involvement (N)