Breast cancer surgery: an historical narrative. Part II. 18th and 19th centuries.

During the 18th and 19th centuries, management of breast cancer was greatly improved. The humoral theory of Galen, which dominated for centuries, was fallen into disfavour. Axillary nodal involvement was recognised as an adverse prognostic factor, while LeDran, in the middle of the 18th century, proposed the theory of lymphatic spread of breast cancer; he also favoured the idea that breast cancer at its earliest stage was a local disease, which could be effectively treated by surgery. The need to excise enlarged axillary lymph nodes was recognised by other surgeons of the 18th century, including Petit, who proposed a procedure very similar to radical mastectomy. During the 19th century, significant advances were noted, including the development of anaesthesia and antisepsis, a better understanding of the biology of cancer and the introduction of microscopic examination. Radical mastectomy was widely used in clinical practice by Halsted. However, this radical procedure was used by other surgeons of that time, including Meyer. Halsted was able to report a very low local recurrence rates (approximately 6%), a very important achievement given the advanced stages of the breast cancer when diagnosed in women at that time.

Breast cancer surgery: an historical narrative. Part III. From the sunset of the 19th to the dawn of the 21st century.

The 20th century is marked by significant advances regarding the management of breast cancer. A clear trend towards less aggressive surgical operation was constantly noted. Modified radical mastectomy gradually replaced radical mastectomy during the second half of the 20th century, while during the last two decades breast-conservation therapy became the treatment of choice for the treatment of breast cancer. This type of therapy includes segmental mastectomy (either quadrantectomy or lumpectomy) with axillary lymph node dissection, followed by postoperative irradiation. Other significant advances during the 20th century include the introduction of systemic therapy (chemotherapy, hormonal therapy) and radiation therapy. Better patient follow-up, statistical analysis, development of staging systems and the introduction of frozen section, the development and wide use of mammography (including screening mammography), breast reconstruction following mastectomy and the development of newer diagnostic methods [including breast magnetic resonance imaging and the advanced breast biopsy instrumentation (ABBI)] are other advances that contributed to a better management of breast cancer patients. Sentinel lymph node biopsy has been introduced during the 1990 s in an attempt to reduce morbidity due to axillary lymph node dissection. Despite these advances, breast cancer remains a significant problem and represents a field of active and intense research.

Duodeno-pancreatic neuroendocrine tumours.

Duodeno-pancreatic neuroendocrine tumours (DP-ETs) are increasingly diagnosed today due to the widespread use of modern imaging methods. Duodeno-pancreatic endocrine tumours should be treated by radical surgical resection, which offers a high chance for cure when the disease is localized. A high index of suspicion is required in these patients for the presence of a multiple endocrine neoplasia type syndrome. We present four patients with DP-ET surgically treated at our department between 2000 and 2004. Histological/immunohistochemical diagnosis was somatostatin-producing tumour in the first patient, oncocytic endocrine tumour positive for neurone-specific enolase and focally for chromogranin in the second patient, glucagonoma and pancreatic polypeptide-producing endocrine pancreatic tumour in the third patient, and gastrin, somatostatin, calcitonin, insulin and adrenocorticotropic hormone (ACTH)-producing tumour in the fourth. The second patient died 6.5 years following surgery due to disseminated disease.

Early (mucosal) gastric cancer with synchronous osteosclerotic bone metastases: a case report.

Early gastric cancer (EGC) is defined as an adenocarcinoma confined to the gastric mucosa or submucosa, regardless of the presence of lymph node metastases. Early gastric cancer carries an excellent prognosis, with a 5-year survival rate at least 85% in most series. However, there are rare cases where distant metastases exist. Bone metastases are rare in gastric cancer; osteoblastic bone metastases are even rarer. We report a patient with EGC (mucosal) and synchronous osteosclerotic bone metastasis. To our knowledge, this is the first reported case of submucosal EGC with synchronous bone metastases. The patient was operated and he received adjuvant chemotherapy and radiotherapy. He died 18 months after gastric surgery from generalized disease.

Nipple discharge: current diagnostic and therapeutic approaches.

Nipple discharge is a complex diagnostic challenge for the clinician. A variety of diseases (such as intraductal papillomas, mammary duct ectasia, breast cancer, pituitary adenomas, breast abscesses/infections, etc.) can manifest as nipple discharge. The importance of nipple discharge for both the patient and the physician is the possible association of this condition with an underlying carcinoma. With heightened public awareness of breast cancer, an increasing number of women are asking their health care providers about nipple discharge. A detailed clinical evaluation is invaluable to determine the pathophysiology, assess the risk of malignancy, and plan treatment of the patient with nipple discharge. A combination of diagnostic tests, including mammography, breast ultrasonography, and possibly galactography can help the clinician to establish the diagnosis and plan proper management. Depending on the underlying breast pathology, a central or single lactiferous duct excision is the procedure of choice. Breast carcinoma associated with nipple discharge should be treated by either a modified radical mastectomy of breast-conservation therapy (i.e. duct-lobular segmentectomy with adequate, free margins [ideally>1cm], levels I and II axillary lymph node dissection, followed by breast irradiation).

Ductal carcinoma in situ (DCIS) of the breast: evolving perspectives.

Ductal carcinoma in situ (DCIS) of the breast is an early, localized stage of carcinoma in the process of multistep breast carcinogenesis. The incidence of DCIS is increasing, mainly due to screening mammography, which results in diagnosing the disease in an increasing proportion of asymptomatic patients. Consequently, clinicians are being confronted with growing numbers of women who present with DCIS of the breast; thus, the concepts of managing such patients are assuming greater importance. The most common presentation is calcifications on mammography. DCIS is a biologically and morphologically heterogeneous disease. If left untreated, a significant proportion of these tumours will evolve into invasive cancer. However, when appropriately treated, the prognosis of DCIS is excellent. Optimal management of DCIS remains controversial. The goal in the treatment of patients with DCIS is to control local disease and prevent subsequent development of invasive cancer. For several decades, total mastectomy was the treatment of choice for DCIS and it should still be considered the standard of care, to which more conservative forms of treatment must be compared. Mastectomy is associated with a risk for chest wall recurrence of approximately 1%. Axillary lymph node dissection is not routinely recommended in the management of DCIS. However, mastectomy probably represents overtreatment in a substantial number of patients, especially those with small, mammographically detected lesions. Local excision alone has been suggested in carefully selected patients, whilst the rest of the patients undergoing breast-conservation surgery should be treated with breast irradiation. There is evidence that breast-conservation therapy is an effective option in the management of selected patients with DCIS. The use of radiotherapy after lumpectomy significantly decreases the rate of recurrence. Nuclear grade, presence of comedo necrosis, and margin involvement are the most commonly used predictors of the likelihood of recurrence. There is no role for adjuvant chemotherapy in the management of this disease. The role of tamoxifen in the treatment of DCIS is not clearly defined; tamoxifen should be given only in patients enrolled in clinical trials. Following breast-conservation therapy, about 50% of the tumours recur as invasive cancer. Most patients with recurrent disease can be treated effectively, usually by salvage mastectomy, but also in selected cases by breast-conservation therapy.

Pancreatic cancer in patients with chronic pancreatitis: a challenge from a surgical perspective.

Chronic pancreatitis (CP) is generally considered as a risk factor for pancreatic adenocarcinoma (PAC). However, the cumulative risk differs among the epidemiological studies. In the individual patient, the differential diagnosis between PAC and CP cannot be always resolved preoperatively and even intraoperatively. In those cases, the uncertainty can only be answered with histological studies of the resected specimen after a radical resection, provided that this type of surgery can be performed with a reasonable risk in a surgically fit patient. The type of resection depends on the location of the suspicious mass. For masses in the tail of the pancreas, a distal pancreatectomy is the procedure of choice. For suspicious lesions in the head of the pancreas, a pancreatoduodenectomy (PD) should be performed. The surgeon and the patient should also acknowledge that a radical resection will occasionally be performed for a suspected malignancy only to find that another etiology (i.e. CP) accounts for the suspicious pancreatic mass. In the presence of a strong suspicion for an underlying malignancy in a patient with head dominant CP, PD should probably be preferred over the newer organ-preserving Beger and Frey procedures, since it is an adequate procedure for both CP and PAC.

Molecular biology of pancreatic cancer; oncogenes, tumour suppressor genes, growth factors, and their receptors from a clinical perspective.

Pancreatic cancer represents the fourth leading cause of cancer death in men and the fifth in women. Prognosis remains dismal, mainly because the diagnosis is made late in the clinical course of the disease. The need to improve the diagnosis, detection, and treatment of pancreatic cancer is great. It is in this type of cancer, in which the mortality is so great and the clinical detection so difficult that the recent advances of molecular biology may have a significant impact. Genetic alterations can be detected at different levels. These alterations include oncogene mutations (most commonly, K-ras mutations, which occur in 75% to more than 95% of pancreatic cancer tissues), tumour suppressor genes alterations (mainly, p53, p16, DCC, etc.), overexpression of growth factors (such as EGF, TGF alpha, TGF beta 1-3, aFGF, bTGF, etc.) and their receptors (i.e., EGF receptor, TGF beta receptor I-III, etc.). Insights into the molecular genetics of pancreatic carcinogenesis are beginning to form a genetic model for pancreatic cancer and its precursors. These improvements in our understanding of the molecular biology of pancreatic cancer are not simply of research interest, but may have clinical implications, such as risk assessment, early diagnosis, treatment, and prognosis evaluation.

Paget's disease of the breast.

Paget's disease of the breast is a rare disorder of the nipple-areola complex that is often associated with an underlying in situ or invasive carcinoma. A change in sensation of the nipple-areola, such as itching and burning, is a common presenting symptom. Objectively, eczematoid changes of the nipple-areola complex are common. The later stages of Paget's disease of the breast are characterized by ulceration and destruction of the nipple-areola complex. Eczematoid changes of the nipple-areola complex and persisting soreness or itching, without obvious reason, is a suspicious symptom for Paget's disease of the breast and calls for thorough evaluation, including mammography. Exfoliative cytology with demonstration of Paget's cells may be useful, but a negative finding does not exclude Paget's disease of the breast. Surgical biopsy is the diagnostic standard and therefore the diagnosis should always be confirmed by open (surgical) biopsy. The histogenesis of Paget's disease of the breast continues to be debated. The epidermotropic theory holds that Paget's cells are ductal carcinoma cells that have migrated from the underlying breast parenchyma to the nipple epidermis. According to the in situ transformation theory, the Paget's cells arise as malignant cells in the nipple epidermis independent from any other pathologic process within the breast parenchyma. This theory has been proposed to explain those cases in which there is no underlying mammary carcinoma or when there is a carcinoma remote from the nipple-areola complex. Each of these theories is plausible; however, treatment approaches differ markedly depending on the theory of histogenesis. Mastectomy has been considered the standard of care in the management of patients with Paget's disease of the breast. Nowadays, however, some patients with Paget's disease of the breast are candidates for breast-conserving therapy. Patients must be selected carefully on an individual basis. Until there is a better understanding of the relationship of Paget's disease of the breast to the underlying cancer the surgeon should understand the natural history and behaviour of this lesion and be aware of both the risks of under- and over-treating patients with Paget's disease of the breast.

Prophylactic mastectomy; evolving perspectives.

It is not at all uncommon for surgeons dealing with breast disease to be confronted with the issue of prophylactic mastectomy. Recent advances in understanding the genetic basis of susceptibility to breast cancer and a better identification of the histological factors affecting a woman's lifetime risk of developing breast cancer have contributed to placing prophylactic mastectomy in a proper clinical perspective. Existing data suggest that prophylactic total mastectomy significantly reduces, but does not totally eliminate, the risk of subsequent development of cancer. However, the benefit of prophylactic mastectomy over alternative strategies (surveillance and chemoprevention) remains to be proven. Currently, prophylactic mastectomy may be considered in a few, carefully selected patients. The decision to perform a prophylactic mastectomy should be a multidisciplinary one. Detailed patient' counselling is very important; the patient should understand the limitations of prophylactic mastectomy and the need for postoperative follow-up. Furthermore, she should be well informed about the alternative strategies.

Management of biliary tract disease in heart and lung transplant patients.

BACKGROUND: Preexisting gallstones and pharmacologic alterations in both bile lithogenicity and immune function may predispose organ transplant recipients to the complications of biliary calculi. METHODS: Records of all 178 patients undergoing heart, lung, or heart-lung transplantation at our institution between 1980 and 1998 were reviewed. Patients with biliary tract disease were grouped as follows: group I, pretransplantation diagnosis and treatment; group II, pretransplantation diagnosis and posttransplantation treatment; group III, normal pretransplantation biliary tree with posttransplantation diagnosis and treatment; group IV, unknown pretransplantation biliary status with posttransplantation diagnosis and treatment. Comparison among groups was made with regard to ultrasound findings, presentation, indication for operation, procedure, and outcome. RESULTS: Of the 141 patients undergoing pretransplantation and/or posttransplantation ultrasound surveillance, the prevalence of abnormal ultrasonography was 36%. All patients in group I (n = 11) underwent elective intervention without complication. Of the 14 patients (groups II through IV) undergoing posttransplantation operation, intervention was mandated by acute complications of biliary tract disease in 7. The mortality rate in these 7 patients was 29%. CONCLUSIONS: Cholecystectomy in the posttransplantation period is often required emergently and has a high mortality. Posttransplantation surveillance of the biliary tree is crucial because of the high rate of de novo stone formation. All biliary calculi should be eradicated electively in stable patients before transplantation and on diagnosis after transplantation.

Pancreatoduodenectomy for chronic pancreatitis: long-term results in 105 patients.

HYPOTHESIS: For patients with head-dominant, small-duct chronic pancreatitis who require operative intervention, pancreatoduodenectomy can be performed safely and affords satisfactory pain relief in most. DESIGN: Retrospective case series. Follow-up was complete in 86% of study subjects (average, 6.6 years). SETTING: Tertiary care center. PATIENTS: Among 484 consecutive cases of chronic pancreatitis treated surgically from January 1976 through April 1997, 105 (22%) in which pancreatoduodenectomy was performed were reviewed with regard to criteria for selection, operative procedure, postoperative course. and long-term outcome. MAIN OUTCOME MEASURES: The main outcome measure was degree of pain relief. Additionally, late mortality, cause of death, the presence of endocrine and exocrine insufficiency, and quality of life were recorded. RESULTS: There were 72 men (69%) and 33 women (31%) with a mean age of 51 years (range, 24-77 years). The cause of chronic pancreatitis was alcohol related in 58 patients (55%) and idiopathic in 41 (39%). Clinical manifestations included abdominal pain in 86 patients (82%), obstructive jaundice in 27 (26%), and vomiting in 11 (11%). Suspicion of malignant neoplasm was a concern in 67 patients (64%). Operative morbidity was 32%, and mortality, 3%. Mean hospital stay was 16 days (range, 12-82 days). Survival was significantly lower than that of age-matched controls. Among 66 patients with preoperative pain, pain relief was achieved in 59 (89%); it was complete in 44 patients (67%) and partial in 15 (23%). Operation resulted in a significant increase in patients with normal functional status (73 patients [81%] vs 51 [49%]; P<.001). Forty patients (48%) had diabetes. Steatorrhea was observed in 39 patients (43%), while weight maintenance or gain occurred in 59 (66%). CONCLUSIONS: Pancreatoduodenectomy achieves pain relief and good quality of life in a large percentage of selected patients with small-duct, head-dominant disease and is especially useful when a malignant neoplasm must be excluded. Morbidity and mortality are acceptable in experienced hands. Onset of diabetes and steatorrhea, while reflecting the natural course of the disease, is likely accelerated by pancreatoduodenectomy.

Postobstructive chronic pancreatitis: results with distal resection.

HYPOTHESIS: For most patients with chronic obstructive pancreatitis, distal pancreatectomy confers pain relief. DESIGN: Retrospective case series. Follow-up was complete in 80% of study subjects (mean follow-up, 6.7 years). SETTING: Tertiary care center. PATIENTS: Among 484 patients with chronic pancreatitis undergoing operation from 1976 to 1997, 40 with postobstructive chronic pancreatitis were identified. Criteria for selection included an isolated, dominant major pancreatic duct stricture or cutoff, changes of chronic pancreatitis in the distal pancreas, and ostensibly normal parenchyma without calcification in the proximal gland. The patients were reviewed with regard to operative procedure, postoperative course, and outcome. MAIN OUTCOME MEASURES: Outcome measures included degree of pain relief, morbidity and mortality of operation, survival, rates of endocrine and exocrine insufficiency, and ability to return to work and/or normal activities. RESULTS: All but 1 of the 40 patients had abdominal pain, and 20 (50%) had recurrent episodes of acute pancreatitis. Suspicion of malignancy was a concern in 16 patients (40%). Thirty-eight patients underwent distal pancreatectomy; 1 had a central resection and another a Roux-en-Y cystojejunostomy. There was no operative mortality, but significant morbidity occurred in 15%. Among 31 patients with preoperative pain in whom long-term follow-up was available, complete or significant pain relief was achieved in 25 (81%); 74% returned to normal social function, but about half had some element of pancreatic insufficiency. CONCLUSIONS: Distal pancreatectomy is a safe procedure and achieves pain relief and good quality of life in a large percentage of patients (80%) with presumed postobstructive chronic pancreatitis. However, some of these patients with chronic pancreatitis involving the entire gland have disease masquerading as postobstructive chronic pancreatitis secondary to an ostensibly isolated dominant pancreatic ductal stricture.

Molecular biology of pancreatic cancer: potential clinical implications.

The development of cancer involves the accumulation of genetic changes. Over the past decade there has a been spectacular advance in the knowledge of the genetic basis of cancer, mainly as a result of the rapid progression of molecular technology. Pancreatic cancer is one of the most lethal cancers. Conventional therapeutic approaches have not had much impact on the course of this aggressive neoplasm. Knowledge of the molecular biology of pancreatic cancer has grown rapidly. Genetic alterations in pancreatic cancer include oncogene mutations (most commonly K-ras mutations), and tumour suppressor gene alterations (mainly p53, p16, DCC, etc.). These advances have potential implications for the management of this deadly disease. Identification of a hereditary genetic predisposition to pancreatic cancer has led to the formation of pancreatic cancer registries around the world, with voluntary screening of patients and siblings for the hereditary genetic defect. Asymptomatic population screening remains unrealistic, but the recognition of subpopulations at increased risk from pancreatic cancer, along with novel and sensitive detection techniques, means that targeted population screening is a step closer. Intensive research is performed in specialist laboratories to improve the diagnostic approach in patients with pancreatic cancer. The use of such molecular diagnostic methods is likely to expand. Molecular biology may also have a great impact on the treatment of pancreatic cancer, and many therapeutic approaches are being evaluated in clinical trials, including gene replacement therapy, genetic prodrug activation therapy, antisense immunology and peptide technology. The 'molecular age' has the promise of delivering still better results. This review summarises recent data relating to the molecular biology of pancreatic cancer, with emphasis on features that may be of clinical significance for diagnosis and/or therapy.

Extrapancreatic necrotizing pancreatitis with viable pancreas: a previously under-appreciated entity.

BACKGROUND: Necrotizing pancreatitis is generally considered to involve the pancreatic parenchyma in all patients, and, as an extension of the necrotic process, the peripancreatic tissues as well. We identified a subgroup of patients in whom the necrotic process involves apparently extrapancreatic tissues alone (EXPN), as opposed to the usual combined parenchymal and peripancreatic necrosis (PN). STUDY DESIGN: The objective of this study was to compare clinical courses of EXPN and PN. Data were reviewed on 82 consecutive patients with necrotizing pancreatitis treated operatively between 1983 and 1997. The extent of pancreatic parenchymal necrosis (expressed as percent of pancreas based on contrast-enhanced CT and operative findings) was estimated in 62 patients. Diagnosis of EXPN required normal enhancement of entire pancreas on dynamic CT and operative documentation of viability of the gland. RESULTS: Twelve patients (19%) had EXPN and 50 (81%) had PN. Gender, age, body mass index, etiology of pancreatitis, prevalence, and type of infection were similar between groups, but APACHE-II scores on admission were less in EXPN (6+/-2 versus 10+/-1, p = 0.02). Patients with EXPN required fewer reoperative necrosectomies (0.7 versus 3.2, p = 0.009) and did not develop pancreatic or gastrointestinal fistulas (0 versus 19 patients) or hemorrhage (0 versus 8 patients). ICU stays were similar, but hospital stays in EXPN were shorter (29+/-6 versus 54+/-5 days, p = 0.01) and mortality was less (8% and 20%, p<0.001). CONCLUSIONS: Necrotizing pancreatitis manifesting as EXPN is not rare. EXPN is a less aggressive form of necrotizing pancreatitis, locally and systemically, and signifies a better prognosis.

Occult breast cancer: a challenge from a surgical perspective.

Patients with occult breast cancer pose a challenging diagnostic and therapeutic problem. High-quality mammography is required to decrease the false-negative rates. A number of other imaging methods have been proposed in the diagnostic evaluation of these women, including breast ultrasonography, color Doppler ultrasonography, breast magnetic resonance imaging (MRI), positron emission tomography (PET), and scintimammography. Among them, MRI may be particularly helpful, since it has a high sensitivity and may enable preoperative localization of the primary, thus allowing the surgeon to perform a breast conserving procedure. Treatment options include surgery, radiotherapy and watchful waiting (followed by mastectomy when a breast tumor is detected). Systemic therapy is usually required in the management of these patients.

Villous tumors of the duodenum: reappraisal of local vs. extended resection.

Benign villous tumors of the duodenum are often managed by transduodenal local excision. Risk of local recurrence, coupled with improving safety of radical pancreaticoduodenectomy, has prompted reexamination of the roles of conservative and radical operations. The aim of this study was to determine long-term outcome after local and extended resection in order to identify factors to consider in planning operative strategy. Eighty-six patients (mean age 64 years) with villous tumors of the duodenum managed surgically from 1980 to 1997 were reviewed. Histologic findings, size, presence of polyposis syndromes, and extent of resection were correlated with outcome. Villous tumors were benign adenomas in 64 patients (74%), contained carcinoma in situ in three (4%), and invasive carcinoma in 19 (22%). The presence of cancer was not known preoperatively in 9 (47%) of the 19 with invasive carcinoma. Operative treatment included transduodenal local excision in 53 patients, pancreaticoduodenectomy in 20, pancreas-sparing duodenectomy in five, full-thickness excision in four, and other in six. Among the 50 patients with benign tumors managed by local excision, 17 had a recurrence with actuarial rates of 32% at 5 years and 43% at 10 years; four of the recurrences (24%) were adenocarcinomas. The recurrence rate was influenced by the presence of a polyposis syndrome but not by tumor size. Recurrence of benign villous tumors after local excision is common and may be malignant. Pancreaticoduodenectomy is appropriate for villous tumors containing cancer and may be considered an alternative for select patients with benign villous tumors of the duodenum. If local excision is performed, regular postoperative endoscopic surveillance is mandatory.

Multi-step pancreatic carcinogenesis and its clinical implications.

The poor prognosis of pancreatic cancer relates mainly to its delayed diagnosis. It has been repeatedly shown that earlier diagnosis of pancreatic cancer is associated with a better outcome. Molecular diagnostic methods (mainly detection of K-ras mutations in pure pancreatic or duodenal juice, on specimens obtained by percutaneous fine-needle aspirations or in stool specimens) can achieve earlier diagnosis in selected subgroups of patients, such as patients with chronic pancreatitis (especially hereditary), adults with recent onset of non-insulin-dependent diabetes mellitus and patients with some inherited disorders that predispose to the development of pancreatic cancer. There is increasing evidence that pancreatic carcinogenesis is a multi-step phenomenon. Screening procedures for precursor lesions in these selected subgroups of patients may reduce the incidence and mortality from pancreatic cancer.

Local excision of periampullary villous tumours of the duodenum.

AIMS: Our goal was to describe our technical approach to transduodenal submucosal resection of periampullary villous tumours of the duodenum. METHODS: We address technical tips to aid in exposure and reconstruction of pancreaticobiliary continuity with special reference to the indications for adding biliary sphincteroplasty, pancreatic septectomy, and local resection of neoplasms extending past the immediate ampullary mucosa into the bile and/or pancreatic ducts. CONCLUSIONS: This approach has proven safe, easy and without significant morbidity.

The clinical significance of axillary lymph node micrometastases in breast cancer.

OBJECTIVE: To evaluate the clinical significancer of axillary lymph-node micrometastases, in the era of sentinel lymph node (SLN) biopsy. DATA SOURCES: Searches of MEDLINE (1966-2003) and an extensive manual review of journals were performed using the key search terms breast cancer, axillary lymph-node micrometastases, micrometastatic disease, and SLN biopsy. STUDY SELECTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for this review. CONCLUSIONS: Axillary lymph-node micrometastases can be detected by serial sectioning, immunohistochemistry, or reverse transcriptase-polymerase chain reaction (RT-PCR). The presence of axillary SLN micrometastases is generally associated with a worse prognosis and is an indication for axillary lymph node dissection (ALND) and adjuvant therapy. The clinical significance of micrometastases identified by RT-PCR remains unknown and further research with longer follow-up is needed to ascertain the clinical implications of a positive result.