***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Pathologists are under increasing pressure to su bmi t fresh tissue for ancillary studies and research protocol s. In several tumor types ( breast , lung , melanoma , colorectal , prostate ) , increased interest in detecting su bmi croscopic nodal metastases through reverse transcriptase polymerase chain reaction analysis of mRNA from portions of lymph nodes has precluded histologic analysis of the entire node for metastases . A retrospective review was undertaken of 227 breast cancer patients prospect ively entered on a research protocol examining the usefulness of sentinel lymph node surgery .  All of the patients ultimately underwent complete lymph node dissection .  The research protocol required that all nodes greater than 8 mm in size be bisected and su bmi tted separately . Positive lymph nodes were evaluated for unilateral or bilateral involvement in the node sections . Sixty node-positive patients were identified , yielding 230 positive nodes . One hundred seven of these nodes were confirmed to have been bisected . Carcinoma was identified in both lymph node sections in 64 ( 59.8 % ) nodes and in only one-half of the bisected lymph node in 43 ( 40.2 % ) nodes . Involvement of both sections was more likely when patients had multiple nodes positive . In 12 patients , involvement of one-half of the bisected nodes was the only evidence of metastatic disease ( 20.0 % of node-positive patients ) . This evidence suggests that su bmi ssion of less than the complete lymph node for histologic evaluation of metastatic disease decreases the accuracy of lymph node staging . Furthermore , a significant proportion of patients may be erroneously classified as histologically node negative Background Internationally , there is no consensus on the pathology protocol to be used to examine the sentinel lymph node ( SN ) . At present , therefore , various hospitals use different SN pathology protocol s of which the effect has not been fully eluci date d. We hypothesized that differences between hospitals in SN pathology protocol s affect subsequent surgical treatment strategies . Methods Patients from four hospitals ( A – D ) were prospect ively registered when they underwent an SN biopsy .  In hospitals A , B , and C , three levels of the SN were examined pathologically , whereas in hospital D , at least seven additional levels were examined . In the absence of apparent metastases with hematoxylin and eosin examination , immunohistochemical examination was performed in all four hospitals . Results In total , 541 eligible patients were included . In hospital D , more patients were diagnosed with a positive SN ( P < .001 ) as compared with hospitals A , B , and C , mainly because of increased detection of isolated tumor cells . This led to more completion axillary lymph node dissections in hospital D ( 66.3 % of patients ( P < .0001 ) , compared with 29.0 % in hospitals A , B , and C combined ) . Positive non-SNs were detected in 13.9 % of patients in hospital D , compared with 9.7 % in hospitals A , B , and C ( P = .70 ) . That is , in 52.4 % of patients in hospital D , a negative completion axillary lymph node dissection was performed , compared with 19.3 % of patients in hospitals A , B , and C combined . Conclusions Differences in SN pathology protocol s between hospitals do have a substantial effect on SN findings and subsequent surgical treatment strategies . Whether ultrastaging and , thus , additional surgery can offer better survival remains to be determined PURPOSE To develop a guideline for the use of sentinel node biopsy ( SNB ) in early stage breast cancer . METHODS An American Society of Clinical Oncology ( ASCO ) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer . The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB . The guideline was review ed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors . RESULTS The literature review identified one published prospect i ve r and omized controlled trial in which SNB was compared with axillary lymph node dissection ( ALND ) , four limited meta-analyses , and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND ( completion axillary dissection ) . There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer . However , a review of the available evidence demonstrates that , when performed by experienced clinicians , SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes . CONCLUSION SNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinical ly negative axillary nodes . Completion ALND remains st and ard treatment for patients with axillary metastases identified on SNB . Appropriately identified patients with negative results of SNB , when done under the direction of an experienced surgeon , need not have completion ALND . Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance . Although such specialized techniques are often used , they are not a required part of SLN evaluation for breast cancer at this time . Data suggest that SNB is associated with less morbidity than ALND , but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown Background Routine axillary lymph node dissection ( ALND ) after selective sentinel lymphadenectomy ( SSL ) in the treatment of breast cancer remains controversial . We sought to determine the need for routine ALND by exploring the relationship between sentinel lymph node ( SLN ) and non-SLN ( NSLN ) status . We also report our experience with disease relapse in the era of SSL and attempt to correlate this with SLN tumor burden . Methods This was a retrospective study of 390 patients with invasive breast cancer treated at a single institution who underwent successful SSL from November 1997 to November 2002 . Results Of the 390 patients , 115 received both SSL and ALND . The percentage of additional positive NSLNs in the SLN-positive group ( 34.2 % ) was significantly higher than in the SLN-negative group ( 5.1 % ; P = .0004 ) . The SLN macrometastasis group had a significantly higher rate of positive NSLNs ( 39.7 % ) compared with the SLN-negative group ( 5.1 % ; P = .0001 ) . Sixteen patients developed recurrences during follow-up , including 6.1 % of SLN-positive and 3.3 % of SLN-negative patients . Among the SLN macrometastasis group , 8.7 % had recurrence , compared with 2.2 % of SLN micrometastases over a median follow-up period of 31.1 months . One regional failure developed out of 38 SLN-positive patients who did not undergo ALND . Conclusions ALND is recommended for patients with SLN macrometastasis because of a significantly higher incidence of positive NSLNs . Higher recurrence rates are also seen in these patients . However , the role of routine ALND in patients with a low SLN tumor burden remains to be further determined by prospect i ve r and omized trials BACKGROUND Examination was performed on pathologic material from patients enrolled in the National Surgical Adjuvant Breast Project ( NSABP ) protocol B-18 , in which the clinical effects of preoperative ( preop ) and postoperative ( postop ) doxorubicin and cyclophosphamide ( AC ) were compared . METHODS Of the total number of 1523 patients , 1234 patients ( 81 % ) were in the pathologically evaluable cohort . Six hundred twenty-six patients had been r and omized prospect ively to receive AC postop and 608 had been r and omized to receive AC preop .  Preentry diagnosis was made by fine-needle aspiration ( FNA ) and /or Tru-cut biopsy ( TC ) . AC-induced and other pathologic changes were identified , and their relation to pathologic response and overall survival ( OS ) and disease-free survival ( DFS ) was determined . Frequencies of the number of lymph node metastases , their size , stromal reaction , and extracapsular extension ( ECE ) were compared in the two treatment groups , as was their correlation with OS and DFS . Survival estimates were based on 9 years of follow-up . RESULTS Approximately 13 % of primary breast carcinoma cases exhibited both a clinical complete response ( cCR ) and a pathologic complete response ( absence of invasive tumor [ pCR ] ) to preop AC . An additional 7 % of patients exhibited a pCR in the absence of a cCR . A pCR occurred in 38 % of those patients determined to have achieved a cCR . Poor nuclear grade of the tumor cells in the pre-entry FNA and /or TC specimens significantly predicted a pCR . Patients with the latter exhibited a better OS and DFS compared with those with a pathologic partial response ( presence of sparse invasive tumor [ pPR ] ) or no pathologic response ( pNR ) . Epithelial alterations considered to be induced in tumors by preop AC were comprised of types 1 and 2 giant cells with meganuclei , apocrine metaplasia , and cytoplasmic vacuolation . They had a high degree of specificity ( range , 86 - 99 % ) but a low sensitivity ( range , 7 - 38 % ) . All were predictive of a pPR and were found to be related adversely to OS and DFS . A fibrous stromal reaction noted in tumors or their putative sites in the preop group was found to have only modest degrees of specificity ( 63 % ) and sensitivity ( 74 % ) . Moderate/marked sclerosis of basement membranes of the ductal and ductular elements of the terminal ductolobular unit ( TDLU ) was significantly more frequent in nontumor-bearing areas of breasts from patients in the preop treatment group compared with those in the postop treatment group ( 67 % vs. 48 % ; P < 0.0001 ) . The degrees of change in the TDLU in patients in the postop treatment group were found to be unrelated to age . Lymphatic tumor extension in the primary tumor , as well as a positive lymph node status , were less frequent in the preop treatment group compared with the postop treatment group . The OS and DFS were nearly identical in both treatment groups , being 69 % and 55 % and 70 % and 53 % in the preop and postop treatment groups , respectively , at 9 years . A fibrous stromal response to lymph node metastases was found to be significant for DFS but not OS . ECE was similar in both groups ( 55 % vs. 48 % ; P = 0.12 ) . Only 1 % of ECE was found to be related to axillary failure in both treatment arms combined . There was no significant difference with regard to the parameters of survival for patients in the postop treatment group whose lymph nodes contained micrometastases ( < 2.0 mm ) or mini micrometastases ( < 1.0 mm ) ( the latter detected immunohistochemically with anticytokeratin ) , and a true-negative lymph node status ( not immunohistochemically converted to positive ) . Conversely , there was no apparent difference with regard to OS in preop treated patients with lymph node micrometastases , mini micrometastases , and macrometastases ( P = 0.19 ) . Those with mini micrometastases had a significantly worse OS compared with those with a true-negative lymph node status ( P = 0.0007 ) . DFS remained worse for patients in that treatment group with micrometastases and mini micrometastases compared with those with negative lymph nodes , although it was better than that for patients with macrometastases ( P = 0.02 ) . CONCLUSIONS Poor nuclear grade of tumor cells in the preentry FNA or TC specimens in the preop group was predictive of a pCR . AC-induced meganuclear giant cells and apocrine changes and nuclear and histologic grade s of the primary tumors also were found to be prognostically significant in patients in the preop treatment group , and the latter two variables were found to be significant for those patients in the postop treatment group . No evidence was found to support the need for axillary lymph node radiation for ECE of lymph node metastases . Extended pathologic or immunohistochemical procedures also appear to be unnecessary for the detection of lymph node mini micrometastases , at least when traditional postop chemotherapy is used . The adverse relation between such small metastases and OS and DFS after preop AC appears to be related to the timing of the chemotherapy administration rather than any pathobiologic reasons The current findings completely affirm the validity of our original observations indicating the appropriateness of grouping primary breast cancer patients into those with negative , 1 to 3 , or ≫4 positive nodes . Results , however , reveal that there is a risk in combining all patients with ≫4 positive nodes into a single group . Since there was a 25 % greater disease‐free survival and an 18 % greater survival in those with 4 to 6 than in those with ≫13 positive axillary nodes , such a unification may provide misleading information regarding patient prognosis , as well as the worth of a therapeutic regimen when compared with another from a putatively similar patient population . Of particular interest were findings relating the conditional probability , i.e. , the hazard rate , of a treatment failure or death each year during the 5‐year period following operation to nodal involvement with tumor . Whereas the hazard rate for those with negative , or 1 to 3 positive nodes , was relatively low and constant , in those with ≫4 positive nodes the risk in the early years was much greater , but by the fifth year it was similar to that occurring when 1‐3 nodes were involved , and not much different 
    Output:
    
The presence ( vs the absence ) of metastases of 2 mm or less in diameter in axillary lymph nodes detected on single-section examination was associated with poorer disease-free and overall survival