Proven Lymph Node Research Articles

Proposal of new classification for stage III colon cancer based on the lymph node ratio: analysis of 4,172 patients from multi-institutional database in Japan.

We retrospectively examined the optimal lymph node ratio (LNR) cutoff value and attempted to construct a new classification using the LNR in stage III colon cancer. The clinical and pathological data of 4,172 patients with histologically proven lymph node metastasis who underwent curative surgery for primary colon cancer at multiple institutions between 1995 and 2004 were derived from the multi-institutional database of the Japanese Society for Cancer of the Colon and Rectum (JSCCR). We determined independent prognostic factors and constructed a new classification using these factors. Finally, we compared the discriminatory ability between the new classification and the TNM seventh edition (TNM 7th) classification. The optimal LNR cutoff value was 0.18. Multivariate analysis revealed that year of surgery, age, gender, histological type, TNM 7th T category, lymphatic invasion, venous invasion, TNM 7th N category, and LNR were found to be significant independent prognostic factors. We attempted to construct a new classification based on the combination of TNM 7th T category and LNR. As a result, the cancer-specific survivals were well stratified (P<.0001). According to the Akaike's information criteria value, the new classification was judged to be superior to the TNM 7th classification with respect to both a better fit and lower complexity. The optimal LNR cutoff value that was found using the Japanese multi-institutional database and the new classification using LNR are considered to be extremely significant. Therefore, these findings strongly support the application of LNR in the stage classification in stage III colon cancer.

Outcomes and prognostic factors of non-small-cell lung cancer with lymph node involvement treated with induction treatment and surgical resection.

Induction therapy (IT) has gained popularity in recent years, becoming a standard of treatment in resectable lymph node-positive NSCLC. IT aims to downstage the disease (shrinkage of tumour and clearance of lymph node-metastases), clear distant micrometastases and prolong survival. Potential disadvantages are increased morbidity and/or mortality after surgery and risk of progression of disease that could have been initially resected. The purpose of this study was to evaluate the outcomes and prognostic factors in a series of patients with lymph node-positive NSCLC receiving IT followed by surgery. A total of 86 patients (75.6% males, median age 63 years) affected by NSCLC in clinical stage IIIA (n = 80) or IIIB (n = 6), with pathologically proven lymph node involvement, underwent platinum-based IT followed by surgery between 2000 and 2009. Eighty (93%) patients received a median of 3 cycles of chemotherapy, and 6 (7%) underwent induction chemoradiotherapy. Response to IT was complete in 3.5%, partial in 59.3% and stable disease in 37.2% of patients. Postoperative morbidity and mortality were 25.6 and 2.3%, respectively. At pathological evaluation, 38.4% of patients had a downstaging of disease with a complete lymph node clearance in 31.4%. Median overall survival was 23 months (5-year survival 33%). Univariate analysis found clinical stage (P = 0.02), histology (P = 0.01), response to IT (P = 0.02) and type of intervention (P = 0.047) to have predictive roles in survival. A better but not significant survival was also found for pN0 vs pN+ (P = 0.22), downstaged tumours (P = 0.08) and left side (P = 0.06). On multivariate analysis, clinical response to neoadjuvant therapy (P = 0.01) and age (P = 0.03) were the only independent predictors of survival. The use of IT for lymph node-positive NSCLC seems justified by low morbidity and/or mortality and good survival rates. Patients with response to IT showed greater benefit in the long term.

Quantitative Volumetric CT-Histogram Analysis in N-Staging of 18F-FDG–Equivocal Patients with Lung Cancer

Lung cancer often coexists with acute and chronic lung diseases such as chronic obstructive pulmonary disease. Therefore, mediastinal lymph nodes may be false-positive on (18)F-FDG PET because of the inflammatory disease alone. Nevertheless, (18)F-FDG PET/CT is the primary imaging modality used for staging patients with lung cancer, including nodal status. The purpose of this study was to evaluate whether volumetric CT histogram analysis can improve the characterization of lymph nodes on PET/CT staging of patients with lung cancer. Sixty histologically proven lymph nodes of 45 patients aged 43-76 y diagnosed with lung cancer were investigated. (18)F-FDG PET/CT, contrast-enhanced CT, and nonenhanced CT were performed before surgery or biopsy as part of the clinical staging procedure. Lymph nodes were analyzed on the basis of the (18)F-FDG standardized uptake value and volumetric CT histogram analysis. These findings were correlated to the gold standard of histopathology. Histologic examination revealed 36 positive and 24 negative lymph nodes, which were also successfully analyzed by volumetric CT histogram. Median CT density was significantly higher for histologically positive lymph nodes (33.2 Hounsfield units [HU]; range, -29.8 to 59.1) than for histologically negative lymph nodes (10.1 HU; range, -21.0 to 87.4; P = 0.002). The incidence of malignancy was 88% above a cutoff value of 20 HU in the ten (18)F-FDG-equivocal lymph nodes; the incidence of benign findings was 100% in the interval between -20 and +20 HU. Visual- and density-based analysis on contrast-enhanced CT failed to differentiate affected from nonaffected lymph nodes. Three-dimensional histogram analysis is a promising and potentially valuable imaging surrogate for N-stage stratification in patients with lung cancer with unclear glucose uptake during (18)F-FDG PET imaging. In cases of equivocal (18)F-FDG PET status, this technique might potentially bridge the diagnostic gap between noninvasive techniques and invasive lymph node sampling and could help improve the yield of core biopsies.

Impact of Histologically Confirmed Lymph Node Metastases on Patient Survival After Surgical Resection for Hepatocellular Carcinoma

To clarify the clinical significance of resection of lymph node metastases in patients' hepatocellular carcinoma (HCC). Although the presence of lymph node metastasis form HCC has been considered as a systemic disease, prognosis after resection of them remains unknown. From the database of a Japanese nationwide survey, 14,872 patients of HCC treated by surgical resection between 2000 and 2005 were enrolled. We modified the current Japanese staging system for HCC, by further dividing stage IVA into stage IVAnon-n1 and stage n1, according to the absence or presence of pathologically proven lymph node metastasis. Thus, the patients classified into 6 disease stages, that is, I (n=1494), II (n=8056), III (n=4243), IVAnon-n1 (n=701), n1 (n=112), and IVB (n=266), and their long-term outcomes were compared. The median follow-up period was 20.6 months. The 3-year overall survival rates of the patients with stage IVAnon-n1, stage n1, and stage IVB were 51.6%, 38.9% and 27.2%, respectively. A multivariate analysis showed that stage IVAnon-n1 would have a similar impact on the survival as stage n1 (hazard ratio: 0.88, 95% confidence interval: 0.59-1.33, P=0.555), and that stage n1 still represented one class less advanced than stage IVB (hazard ratio: 0.52, 95% confidence interval: 0.34-0.80, P=0.003). The prognosis of patients with histologically node-positive HCC was similar to that of patients with locally advanced HCC (stage IVA), which supports the validity of the current Japanese staging system and also partially validates the system proposed by the UICC/AJCC.

Sentinel node biopsy after neoadjuvant therapy: Relevance of sentinel node micrometastases, isolated tumor cells, and value of immunohistochemistry.

52 Background: Sentinel node biopsy (SNB) is used in breast cancer patients that present with clinically negative nodes. In this setting, most guidelines do not support the use of immunohistochemistry (IHC) and recommend against completion node dissection (CND) when only isolated tumor cells (pN0(i+)) or micrometasases (pN1mi) are identified. When SNB is used after neoadjuvant therapy (NAT), the relevance of ypN0(i+) and ypN1mi sentinel nodes (SNs) and the value of IHC are not well established. The goals of this study are to determine if CND should be recommended in the presence of ypN0(i+) or ypN1mi SNs and if IHC should be used to evaluate SNs after NAT. Methods: From March 2009 to December 2012, 152 women with biopsy proven node positive breast cancer were accrued to the multicentric prospective SN FNAC trial. After NAT, SNB was followed by a CND in all participants. SNs were cut in serial slices no thicker than 2 mm. Hematoxylin and eosin stains (H and E) were done on all slices, and if negative, IHC was used. The size of the largest SN metastasis and the primary method of identification (H and E or IHC) were recorded. ypN0(i+), ypN1mi and ypN1 SNs were considered as positive. Pathology was centrally reviewed. Results: 145 women were eligible for the trial. Axillary pathologic complete response rate = 34% (49/145). SNB success rate = 88% (127/145). False negative rate = 8.4% (7/83). If ypN0(i+) SNs are classified as node negative, the false negative rate is increased to 13.3% (11/83). For patients with ypN0(i+) (n=7), ypN1mi (n=8) and ypN1 (n=61) SNs, the rates of non-SN involvement are 57%, 38% and 56% respectively (p=NS). 40% (27/68) of positive SNBs are primarily detected by IHC. This is increased to 64% (9/14) for the identification of SN metastases ≤ 2mm. Conclusions: After NAT, particularly when presenting with biopsy proven node positive breast cancer, patients with ypN0(i+) and ypN1mi SNs have a significant rate of non-SN involvement. In the absence of evidence to show that a CND can be safely avoided, efforts should be made to identify even minimal amounts of disease when SNBs are done following NAT. IHC is useful to increase the detection of small SN metastases in this setting. Clinical trial information: NCT00909441.

Options and limitations using 11c-acetate PET/CT imaging for detection of recurrent disease following radical prostatectomy in patients with prostate cancer.

e16003 Background: Patients with rising PSA levels after definitive local therapy of prostate carcinoma often present a diagnostic dilemma . A local recurrence or metastatic lymph node lesions would be amenable to additional local therapy. In this prospective study the effectiveness of 11C-acetate PET (AC-PET) matched with corresponding CT scans in patients with PSA relapse were evaluated. Methods: 103 patients (mean age 70.87 years; range 56 – 90 years) with histologically confirmed adenocarcinoma of the prostate were enrolled in this study because of rising PSA values following RP (n = 97) or radiotherapy (n=6). Whole-body PET images were obtained after iv - administration of 1,000 MBq of 11C-acetate. A CT scan from the neck to the pelvic floor was performed additionally. An image overlay of corresponding CT and PET scans was done. By using attenuation corrected PET data, standardized uptake value (SUV) was calculated, cut-off 2. Results: Out of 103 patients n=42 were AC-PET positive. PSA level in 16 of this subset was between 0.5 and 1.45 ng/mL (mean value 1.14 ng/mL), in 16 patients between 2.7 and 9.01 ng/mL, and 7 patients had a PSA distribution between 13.4 and 30.5 ng/mL, respectively. Analysing the AC-PET positive patients, in 16/42 AC-PET demonstrated hypermetabolic lymphnode lesions, in 10/16 metastatic lesions were histopathologically confirmed, in the remaining 6 unspecific inflammatory tissue alterations were identified. In 9 patients with corresponding AC-PET and CT scans radiotherapy of proven lymphnode metastases was performed followed by decreasing PSA level. 23/42 patients were treated with hormone manipulation (21/23) or chemotherapy (2/23). Combining the patients having undergone surgery and radiotherapy (n=25) there were 19/25 true positive in terms of AC-PET, in 13 / 25 PSA level was &lt; 2.0 ng/mL. Conclusions: Although AC-PET seems to be a promising tool in the detection of recurrent prostate cancer even with PSA levels &lt; 2 ng/ml, false positive patients with a different metabolism marked by 11C-acetate decrease the specificity of the approach. Thus there is still a need for a more specific tracer development.

Sentinel node biopsy following neoadjuvant chemotherapy in biopsy proven node positive breast cancer: The SN FNAC study.

1018 Background: A significant and increasing proportion of patients (&gt;30%) with biopsy proven node positive breast cancer will obtain a pathological complete response (pCR) in the axilla after neoadjuvant chemotherapy (NAC). If sentinel node biopsy (SNB) can accurately identify these patients, they could potentially avoid the morbidity of an axillary node dissection. The primary aim of this study is to evaluate the identification rate (IR), false negative rate (FNR) and accuracy of SNB in this setting. The accuracy of post NAC axillary ultrasound and clinical examination are evaluated as secondary endpoints. Methods: Patients with biopsy proven node positive breast cancer (T0-3, N1-2, M0) treated with NAC were eligible to participate in this multi-centre prospective trial. Following NAC, axillary ultrasound and clinical examination results were obtained. At time of surgery, all participants underwent both a SNB and a completion node dissection. A SNB IR greater than 90% and a FNR of less than 10% were pre-determined as being optimal. Results: From September 2009 to December 2012, 153 patients were accrued to the study. 7 patients were not eligible and 5 patients had not yet undergone surgery at the time of analysis. Axillary pCR rate = 34.0% (48/141). SNB IR = 87.2% (123/141), 95% CI [81.7%-92.7%] and FNR = 9.9% (8/81), 95% CI [3.4%-16.4%]. If only one sentinel node was removed, FNR = 19.0%(4/21); if there were 2 or more sentinel nodes, FNR = 6.6% (4/61) (p &lt; 0.0001). Accuracy of SNB, axillary ultrasound and clinical examination were 93.5%, 63.2%, and 45.5% respectively. Conclusions: SNB following NAC in biopsy proven node positive breast cancer is associated with a suboptimal IR. FNR (less than 10%) and accuracy of SNB in this study are comparable to that of patients that present with clinically negative nodes. The FNR decreases when more than one sentinel node is identified. However, in an era where regional nodal radiation is increasingly used, the relevance of leaving residual disease in the undissected axilla after NAC is unknown and remains to be investigated. Clinical trial information: NCT00909441.

Role of Neck Dissection in the Treatment of Melanoma of the Head and Neck

Despite numerous studies, specific guidelines for cervical lymph node surgery in cutaneous malignant melanoma of the head and neck are still missing.In a retrospective study, the modalities of neck dissection (ND), the histologic results, and the outcome in 59 patients with cutaneous malignant melanoma of the head and neck were evaluated to verify the benefit of this therapy.Patients with proven lymph node metastasis often benefit from complete ND because about 50% of the patients showed more metastases in their ND specimen than before surgery. In addition, suspicious but not surely malignant lymph nodes often proved to be benign.This study reveals that patients with proven lymph node metastasis often benefit from complete ND because the number of infiltrated nodes is often higher than suspected; nevertheless, when planning the surgical therapy, the overall prognosis has to be kept in mind.

Metastatic clear cell papillary renal cell carcinoma: first case report of a previously indolent entity

Aims Clear cell papillary renal cell carcinoma is a recently characterised low grade neoplasm which has not yet been documented to have metastasised. We report a case of clear cell papillary renal cell carcinoma with histologically proven lymph node metastasis. Method H&E sections were reviewed by two experienced uro-pathologists. Immunostaining of both the primary tumour and the lymph node metastases was performed. Results Examination of the radical nephrectomy specimen showed an 85 mm cystic tumour which was grossly organ con-fined. Histologically the tumour was characterised by areas of well developed delicate papillary structures lined by clear cells with reverse polarisation and low-grade nuclear features. Areas of nested and tubular architecture were also present. The tumour invaded into hilar fat although vascular invasion was not identified. The tumour exhibited patchy although strong CK7 immunoreactivity. Metastatic renal cell carcinoma with similar histological features was identified in two paracaval lymph nodes. Discussion We present a case of metastatic clear cell papillary renal cell carcinoma, which is, to our knowledge, the first that has been described.

Comparison of concomitant and subsequent cholangiocarcinomas associated with hepatolithiasis: Clinical implications

To compare the outcomes of concomitant cholangiocarcinoma (C-CCA) and subsequent cholangiocarcinoma (S-CCA) associated with hepatolithiasis. From December 1987 to December 2007, 276 patients underwent hepatic resection for hepatolithiasis in Changhua Christian Hospital. Sixty-five patients were excluded due to incomplete medical records and the remaining 211 patients constituted our study population base. Ten patients were diagnosed with C-CCA based on the preoperative biopsy or postoperative pathology. During the follow-up period, 12 patients developed S-CCA. The diagnosis of S-CCA was made by image-guided biopsy or by pathology if surgical intervention was carried out. Patient charts were reviewed to collect clinical information. Parameters such as CCA incidence, interval from operation to CCA diagnosis, interval from CCA diagnosis to disease-related death, follow-up time, and mortality rate were calculated for both the C-CCA and S-CCA groups. The outcomes of the C-CCA and S-CCA groups were mathematically compared and analysed. Our study demonstrates the clinical implications and the survival outcomes of C-CCA and S-CCA. Among the patients with unilateral hepatolithiasis, the incidence rates of C-CCA and S-CCA were fairly similar (4.8% vs 4.5%, respectively, P = 0.906). However, for the patients with bilateral hepatolithiasis, the incidence rate of S-CCA (12.2%) was higher than that of C-CCA (4.7%), although the sample size was limited and the difference between two groups was not statistically significant (P = 0.211). The average follow-up time was 56 mo for the C-CCA group and 71 mo for the S-CCA group. Regard to the average time intervals from operation to CCA diagnosis, S-CCA was diagnosed after 67 mo from the initial hepatectomy. The average time intervals from the diagnoses of CCA to disease-related death was 41 mo for the C-CCA group and 4 mo for the S-CCA group, this difference approached statistical significance (P = 0.075). Regarding the rates of overall and disease-related mortality, the C-CCA group had significantly lower overall mortality (70% vs 100%, P = 0.041) and disease-related mortality (60% vs 100%, P = 0.015) than the S-CCA group. For the survival outcomes of two groups, the Kaplan-Meier curves corresponding to each group also demonstrated better survival outcomes for the C-CCA group (log rank P = 0.005). In the C-CCA group, three patients were still alive at the time of data analysis, all of them had free surgical margins and did not have pathologically proven lymph node metastasis at the time of the initial hepatectomy. In the S-CCA group, only one patient had chance to undergo a second hepatectomy, and all 12 S-CCA patients had died at the time of data analysis. C-CCA has better outcomes than S-CCA. The first hepatectomy is crucial because most patients with recurrent CCA or S-CCA are not eligible for repeated surgical intervention.

Abstract OT2-1-01: Feasibility of sentinel node detection after neoadjuvant chemotherapy for patient with proved axillary lymph node involvement: the French prospective multiinstitutional GANEA 2 ongoing trial

Abstract Background: Half of the patient treated with neoadjuvant chemotherapy (NAC) for a large operable breast cancer have no axillary lymph node involvement at the time of surgery. Sentinel lymph node detection (SLND), performed after NAC, would select patient who might be spared of an axillary lymphadenectomy (AL). In a previous study, we assessed the feasibility of SLND after NAC in the case of patients without axillary involvement1. Previous published series have shown that, for patients with an axillary lymph node involvement before treatment, SLND after NAC bring a low detection rate and a high false negative rate (FNR), making this technique contra indicated in this situation. The aim of GAEA 2 study is to assess the FNR of SLND after NAC in the particular case of patients with a proven axillary lymph node involvement before NAC. Patients and Method: Prospective study validated by scientific and ethical National boards. Inclusion criteria: FIGO stage T2-T3 infiltrating breast carcinoma, indication of NAC, surgery (radical or conservative) after NAC and signature of the consent form, Exclusion criteria: locally advanced, inflammatory breast cancer, local relapse, previous surgical removal of the tumour, mental disorder, pregnancy or no contraceptive method, contra-indication to NAC, NAC interrupted due to progressive disease. Design of the study: Indication to plan a NAC, control of inclusion and exclusion criteria, consent form signature, axillary sonography before NAC to select the patient in group 1 (patient with a proven lymph node involvement treated with SLND and complementary AL) or 2 (no involvement proven treated with SLND + AL only if detection failure or involvement). Surgery, breast and axilla, performed 4 to 6 weeks after NAC. Pathological procedure: No intraoperative histopathological examination. Pathological analysis, of sentinel and non sentinel nodes, carried out according to standard methods and classified according the last American Joint Committee staging system and Sataloff classification. FNR is defined as the ratio of patients with a false negative case of SLNB to the patients with at least one involved node, SLN or not, among patients with SLN detected. The hypothesis: Taking into account results of lymph node involvement rate found in GANEA 1, to estimate our hypothesis of a FNR between 10 and 15% with a 95% confidence interval will require to include 858 patients in order to obtain 260 patient with a proven axillary lymph node involvement (group 1). A standard follow up is planned for each patient, with a clinical breast and axillary examination two times/ year and an annual mammography, for five years. In case of clinical axillary relapse a fine needle aspiration must be performed guided with sonography. Results: On May 31, 2012, 341 patients were included from 16 French institutions; 130 patients with a proven SLN involvement before NAC and 211 with SLN free of metastasis. 1Classe JM, Bordes V, et al. Sentinel lymph node biopsy after neoadjuvant chemotherapy for advanced breast cancer: results of Ganglion Sentinelle et Chimiotherapie Neoadjuvante, a French prospective multicentric study. J Clin Oncol. 2009 Feb. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-1-01.

Carboplatin Based Induction Chemotherapy for Nonorgan Confined Bladder Cancer—A Reasonable Alternative for Cisplatin Unfit Patients?

We investigated induction carboplatin based chemotherapy in patients with nonorgan confined urothelial carcinoma who were considered unfit for cisplatin. A comparison was made with patients who received induction cisplatin based combination chemotherapy. We identified 167 patients with nonorgan confined urothelial carcinoma who received induction cisplatin based combination chemotherapy (126) or gemcitabine and carboplatin (41) at our hospital between 1990 and 2010. Of the patients 124 completed 4 cycles of cisplatin based combination chemotherapy or gemcitabine and carboplatin. Clinical response (ycTNM) was evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1. Radical cystectomy and bilateral extended pelvic lymph node dissection were performed in 106 patients. A pathological complete response was defined as no evidence of disease (ypT0N0). Disease specific survival was analyzed using the Kaplan-Meier method. Multivariate analysis was performed. Complete clinical response rates did not differ significantly among the treatment groups. A pathological complete response was seen in 33.7% of specimens in the cisplatin based combination chemotherapy group vs 30.3% in the gemcitabine and carboplatin group (p = 0.808). We found no significant difference in disease specific survival between patients who started cisplatin based combination chemotherapy and those who started gemcitabine and carboplatin. For patients who completed 4 cycles and underwent radical cystectomy there was also no significant difference in disease specific survival between the groups. On multivariate analysis a pathological complete response was the only variable significantly associated with disease specific survival (p <0.045). Induction gemcitabine and carboplatin for nonorgan confined urothelial carcinoma achieves clinical and pathological response rates, and survival outcomes comparable to those of the cisplatin based combination chemotherapy schemes. Our data suggest that a carboplatin based regimen can be considered a reasonable alternative for cisplatin unfit patients in the preoperative setting.

Competing Mortality Contributes to Excess Mortality in Patients with Poor-Risk Lymph Node-Positive Prostate Cancer Treated with Radical Prostatectomy

Background: Factors predicting survival in men with lymph node-positive prostate cancer are still poorly defined. Patients and Methods: 193 prostate cancer patients with histopathologically proven lymph node involvement with a median follow-up of 7.3 years were studied. 94% of patients received immediate hormonal therapy. Kaplan-Meier curves were calculated to evaluate overall survival rates and compared with the log-rank test. Cumulative disease-specific and competing mortality rates were calculated by competing risk analysis and compared with the Pepe-Mori test. Cox proportional hazard models were used to determine the independent significance of predictors of all-cause mortality. Results: Age (70 years or older vs. younger), Gleason score (8–10 vs. 7 or lower) and the number of involved nodes (3 or more vs. 1–2) were identified as independent predictors of all-cause mortality. When patients with 0–1 of these risk factors were compared with those with 2–3 risk factors, all-cause (rates after 10 years 21% vs. 71%, p < 0.0001), disease-specific (12 vs. 37%, p = 0.009) and competing mortality (9 vs. 33%, p = 0.02) differed significantly. Conclusions: Some of the excess mortality in patients with poor-risk lymph node-positive prostate cancer may be attributed to increased competing mortality, possibly caused by an interaction between comorbid diseases and hormonally treated persistent or progressive prostate cancer.

Role of axillary ultrasound after neoadjuvant chemotherapy in women with node-positive breast cancer (T1-4, N1-2, M0) at initial diagnosis (ACOSOG Z1071).

1107 Background: The role of axillary ultrasound (AUS) after neoadjuvant chemotherapy (NAC) to assess for residual nodal disease in patients presenting with node positive breast cancer remains unclear. ACOSOG Z1071 is a prospective multi-institutional trial evaluating sentinel node biopsy in patients with biopsy proven node positive breast cancer (T0-4, N1-2, M0) receiving NAC. Herein we report on the secondary objective evaluating the correlation of lymph node (LN) features on AUS with residual nodal disease. Methods: AUS images from diagnosis and after NAC were centrally reviewed for cortex size, LN size and LN morphology. Morphologic features were defined as: type I, no visible cortex, type II, &lt; 3 mm hypoechoic cortex, type III, &gt; 3mm hypoechoic cortex, type IV, generalized lobulated hypoechoic cortex, type V, focal hypoechoic cortical lobulation, and type VI, totally hypoechoic node with no hilum. Type I and II are considered normal. Results: Surgical and imaging data are available on 294 patients. Median age was 50 years (range 23-93 years), mean initial tumor size 3cm (0 to 15cm) and clinical stage II in 64.5% and III in 35.5%. The maximum LN diameter decreased after NAC (mean 22mm pre-NAC to 14mm post-NAC)(p&lt;0.0001); however, there was no significant difference after NAC between the pathologically N+ (13mm, range 5-46mm) and N0 cases (12mm, range 3-32mm)(p=0.13). LN cortical thickness correlated with residual nodal disease after NAC (p-value = 0.04). Using a cutoff point of cortical thickness of 3 mm, the sensitivity was 33% (48/145) and specificity 80% (66/82). AUS morphological features after NAC was associated with false negative rate 62%, false positive rate 28%, sensitivity 38%, and specificity 72%. Conclusions: AUS after NAC is useful to assess nodal response. Cortical thickness was the best predictor of residual nodal metastasis. LN size and morphological features do not reliably exclude residual nodal metastasis in patients after NAC. [Table: see text]

Therapeutic Lymph Node Dissection in Melanoma: Different Prognosis for Different Macrometastasis Sites?

BackgroundThe prognostic significance of primary tumor location, especially the poor prognosis for melanomas in the scalp and neck region, is well established. However, the prognosis for different sites of nodal macrometastasis has never been studied. This study investigated the prognostic value of the location of macrometastasis in terms of recurrence and survival rates after therapeutic lymph node dissection (TLND).MethodsAll consecutive FDG-PET-staged melanoma patients with palpable and cytologically proven lymph node metastases operated at our clinic between 2003 and 2011 were included. Disease-free survival and disease-specific survival (DSS) were compared for nodal metastases in the groin, axilla, and neck regions by multivariable analysis.ResultsA total of 149 patients underwent TLND; there were 70 groin (47 %), 57 axillary (38 %), and 22 neck (15 %) dissections. During a median follow-up of 18 (range 1–98) months, 102 patients (68 %) developed recurrent disease. Distant recurrence was the first sign of progressive disease in 78, 76, and 55 % of the groin, axilla, and neck groups, respectively (p = 0.26). Low involved/total lymph nodes (L/N) ratio (p < 0.001) and absence of extranodal growth pattern (p = 0.05) were independent predictors of a longer disease-free survival. For DSS, neck site of nodal metastasis (p = 0.02) and low L/N ratio (p < 0.001) were independent predictors of long survival. The estimated 5-year DSS for the groin, axilla, and neck sites was 28, 34, and 66 %, respectively.ConclusionsThere seems significantly longer DSS after TLND for nodal macrometastases in the neck compared to axillary and groin sites, although larger series should confirm this finding.

Prospective clinical trial of the feasibility and safety of modified retroperitoneal lymph node dissection at time of nephroureterectomy for upper tract urothelial carcinoma

What's known on the subject? and What does the study add? Very little is known about the safety and potential oncological benefit of performing a retroperitoneal lymph node dissection at time of nephroureterectomy for upper tract tumours. This study is the first clinical trial to prospectively validate the safety and feasibility of a retroperitoneal lymph node dissection at time of nephroureterectomy for upper tract tumours. The onus is now on the scientific community at large to conduct adequately powered multicentre clinical trials to evaluate the potential oncological benefit it may impart to patients with upper tract tumours. • To determine the safety and feasibility of modified retroperitoneal lymph node dissection (RPLND) at the time of radical nephroureterectomy (RNU). • Between 2009 and 2011, 20 patients with suspected upper urinary tract urothelial carcinoma (UUT-UC) underwent open (n= 10), laparoscopic (n= 4), or robot-assisted (n= 6) RNU with modified RPLND. • Demographic, clinical and pathological data, histological nodal status, peri-operative complications and recurrence data were collected. • On histopathological review, one patient had a benign angioma and was excluded from the final data analysis. Of the remaining 19 patients, 10 had pTa, five had pT1, one had pT2, and three pT3 disease. • The mean (range) lymph node count was 7 (2-17), with one patient having pathologically proven lymph node metastasis. The mean (range) operating time was 279 (146-500) min. The mean EBL was 396 (100-1100) mL, with the mean (range) hospital stay 7.1 (4-18) days. The mean (range) duration of follow-up after surgery was 12 (2-24) months. • Overall, nine patients developed postoperative complications, which included eight minor (Clavien Grade I-II) and one major complication (Clavien grade IIIb). The major complication was a postoperative chylous lymphatic leak requiring surgical exploration. • The present results indicate that modified RPLND during RNU for UUT-UC is a feasible procedure with acceptable morbidity. A larger prospective clinical trial is needed to adequately assess its potential therapeutic benefit.

Cost-effectiveness of Adding FDG-PET or CT to the Diagnostic Work-up of Patients With Stage III Melanoma

The aim of this prospective study was to assess predictive value of fludeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) and to analyze their cost-effectiveness in several diagnosis-treatment combinations. The incidence of melanoma continues to rise. A proportion will present or recur with lymph node metastases (American Joint Committee on Cancer/Union for International Cancer Control stage III). To detect distant metastases, CT and/or FDG-PET are available. However, few studies have assessed their value and costs in stage III. All consecutive patients with melanoma with palpable, proven lymph node metastases (2003-2008) referred for examination with FDG-PET and CT were prospectively included. Sensitivity, specificity, and accuracy, and positive predictive value (PPV) and negative predictive value (NPV) were calculated. In economic evaluation, the costs of diagnostic work-up with and without FDG-PET and CT were compared. Overall, 253 patients with melanoma were included. FDG-PET showed a higher sensitivity than CT: 86.1% compared with 78.2%. Specificity was higher for CT (93.7%) compared with FDG-PET (93.1%). Overall, FDG-PET showed a higher PPV and NPV. Cost-consequence analysis showed that adding CT (True-Positive upstaging in 61 patients) to diagnostic work-up decreased cost by 5.5%, adding FDG-PET (True-Positive upstaging in 68 patients) increased cost by 7.2%, and adding both (True-Positive upstaging in 78 patients) increased cost by 15.1%. In this study, FDG-PET had higher sensitivity and predictive value, whereas CT had a higher specificity. Adding one of these diagnostic tools improved the staging of stage III patients with less than 10% cost increase. A proposal for stage-specific use of imaging modalities for clinicians caring for patients with melanoma is presented.

359 Competing mortality contributes to excess mortality in patients with high risk lymph node positive prostate cancer treated with radical prostatectomy

Background: Factors predicting survival in men with lymph node-positive prostate cancer are still poorly defined. Patients and Methods: 193 prostate cancer patients with histopathologically proven lymph node involvement with a median follow-up of 7.3 years were studied. 94% of patients received immediate hormonal therapy. Kaplan-Meier curves were calculated to evaluate overall survival rates and compared with the log-rank test. Cumulative disease-specific and competing mortality rates were calculated by competing risk analysis and compared with the Pepe-Mori test. Cox proportional hazard models were used to determine the independent significance of predictors of all-cause mortality. Results: Age (70 years or older vs. younger), Gleason score (8–10 vs. 7 or lower) and the number of involved nodes (3 or more vs. 1–2) were identified as independent predictors of all-cause mortality. When patients with 0–1 of these risk factors were compared with those with 2–3 risk factors, all

Not the Number but the Location of Lymph Nodes Matters for Recurrence Rate and Disease‐Free Survival in Patients with Differentiated Thyroid Cancer

BackgroundSeveral Japanese studies have focused on identifying prognostic factors in patients with positive lymph nodes to predict recurrence rate and disease-free survival (DFS). However, different treatment protocol is followed in Japan compared with the European and American approach. This study was designed to investigate whether the number and/or location of lymph nodes predicts prognosis in patients with DTC treated with total thyroidectomy, lymph node dissection, and postoperative radioactive iodine ablation.MethodsAll 402 patients who were treated at the Department of Nuclear Medicine between 1998 and 2010 for DTC were reviewed. Patients were treated with (near) total thyroidectomy, lymph node dissection on indication, and postoperative I-131 ablation. Median follow-up was 49 (range, 10–240) months. Outcome measures were recurrence rate, disease-free survival, and mean time to recurrence.ResultsNinety-seven patients had proven lymph node metastases. Recurrence rate was significantly higher in patients with positive lymph nodes in the lateral compartment vs. patients with lymph node metastasis in the central compartment (60 vs. 30%, p = 0.007). Disease-free survival and mean time to recurrence also were significantly shorter (30 vs. 52 months, p = 0.035 and 7 vs. 44 months, p = 0.004, respectively). The number of lymph nodes and extranodal growth were not significantly associated with the outcome measures used.ConclusionsThe location of positive lymph nodes was significantly correlated with the risk of recurrence and a shorter DFS. Hence, the TNM criteria are useful in subdividing patients based on risk of recurrence and DFS.

Phase II trial of preoperative paclitaxel, gemcitabine, and trastuzumab combination therapy in HER2 positive stage II/III breast cancer: The Korean Cancer Study Group BR 07-01

An addition of trastuzumab preoperatively to chemotherapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer improved relapse-free survival (RFS). This study was designed to evaluate the efficacy and safety of preoperative paclitaxel, gemcitabine, and trastuzumab (PGH) combination for HER2-positive breast caner. Pathologically, proven node positive stage II/III breast cancer patients with adequate organ function and no history of anti-cancer therapy were eligible. Patients received weekly trastuzumab with paclitaxel 80 mg/m(2) and gemcitabine 1,200 mg/m(2) on days 1 and 8, every 3 weeks for 6 cycles. Postoperatively, patients completed trastuzumab for 1 year and hormone therapy for 5 years if indicated. All patients received postoperative radiation therapy. Of 53 enrolled patients with a median tumor of 5.3 (range, 2.0 to >12) cm; 43.4%, T3/T4; 75.4%, N2/N3; and 45.3%, positive hormone receptors. The pathologic complete response (pCR) rate was 58.5% in both tumor and lymph nodes. Grade 3/4 adverse events were neutropenia (32%), febrile neutropenia (0.6%), and transient elevation of AST/ALT (1.6%) during a total of 318 cycles. All patients maintained normal cardiac function. With a median follow-up of 40 months, 3-year RFS rate was 84% with 91.7% distant metastasis-free survival rates. Remarkable pCR rate was obtained with non-anthracycline-based PGH therapy for HER2-positive stage II/III breast cancer. Adverse events were mild with few incidences of febrile neutropenia.