Association between sentinel lymph node excision with or without preoperative SPECT/CT and metastatic node detection and disease-free survival in melanoma

Malignant melanoma has become an increasing interdisciplinary public health challenge worldwide. Sentinel lymph node excision (SLNE) is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes.

Quantitative measurements in 3-dimensional datasets of mouse lymph nodes resolve organ-wide functional dependencies

Deep tissue imaging has become state of the art in biology, but now the problem is to quantify spatial information in a global, organ-wide context. Although access to the raw data is no longer a limitation, the computational tools to extract biologically useful information out of these large data sets is still catching up. In many cases, to understand the mechanism behind a biological process, where molecules or cells interact with each other, it is mandatory to know their mutual positions. We illustrate this principle here with the immune system. Although the general functions of lymph nodes as immune sentinels are well described, many cellular and molecular details governing the interactions of lymphocytes and dendritic cells remain unclear to date and prevent an in-depth mechanistic understanding of the immune system. We imaged ex vivo lymph nodes isolated from both wild-type and transgenic mice lacking key factors for dendritic cell positioning and used software written in MATLAB to determine the spatial distances between the dendritic cells and the internal high endothelial vascular network. This allowed us to quantify the spatial localization of the dendritic cells in the lymph node, which is a critical parameter determining the effectiveness of an adaptive immune response.

Sense and nonsense of an extended pelvic lymph node dissection in prostate cancer

Lymph node metastases associated with prostate cancer (PCa) has been shown to be a poor prognostic factor. The role of pelvic lymph node dissection (PLND) itself in relation to survival remains unclear, however. A Medline search was conducted to address this issue. The following conclusions were drawn. Only recently, improved survival due to completion of radical prostatectomy (RP) (compared to abandoning RP) in known or presumed lymph-node-positive patients has been shown. Lymph node sampling can only be considered representative if an adequate number of nodes is removed. While several authors have suggested that a therapeutic benefit in patients undergoing RP is not provided by PLND, the reliability of these studies is uncertain. Contrary to this, several studies have indicated the possibility of long-term survival even in the presence of limited lymph node metastases. The role and timing of initiation of adjuvant androgen deprivation therapy (ADT) in patients who have node-positive disease after RP is controversial. Recent studies suggest that delaying ADT may not adversely impact survival.

Sentinel lymph node biopsy in early-stage breast cancer patients: improved survival through better staging?

The objective of this review is to summarize the evidence demonstrating that the sentinel lymph node (SLN) procedure is not only associated with significantly less morbidity compared to the axillary dissection, but may also result in better staging and improved patient outcomes.

Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging?

A new diagnostic system, called one-step nucleic acid amplification (OSNA), has recently been designed to detect cytokeratin 19 mRNA as a surrogate for lymph node metastases. The objective of this prospective investigation was to compare the performance of OSNA with both standard hematoxylin and eosin (H&E) analysis and intensive histopathology in the detection of colon cancer lymph node metastases.

Sentinel lymph node procedure leads to upstaging of patients with resectable colon cancer: results of the Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer

The value of the sentinel lymph node (SLN) procedure in colon cancer patients remains a matter of debate. The objective of this prospective, multicenter trial was 3-fold: to determine the identification rate and accuracy of the SLN procedure in patients with resectable colon cancer; to evaluate the learning curve of the SLN procedure; and to assess the extent of upstaging due to the SLN procedure.

Prognostic impact of lymph node ratio outperforms positive lymph nodes and lymph nodes harvested: a time-dependent analysis in mismatch repair-proficient and –deficient colrectal cancers

Objective: We compare the prognostic strength of the lymph node ratio (LNR), positive lymph nodes (+LNs) and collected lymph nodes (LNcoll) using a time-dependent analysis in colorectal cancer patients stratified by mismatch repair (MMR) status. Method: 580 stage III-IV patients were included. Multivariable Cox regression analysis and time-dependent receiver operating characteristic (tROC) curve analysis were performed. The Area under the Curve (AUC) over time was compared for the three features. Results were validated on a second cohort of 105 stage III-IV patients. Results: The AUC for the LNR was 0.71 and outperformed + LNs and LNcoll by 10–15 % in both MMR-proficient and deficient cancers. LNR and + LNs were both significant (p<0.0001) in multivariable analysis but the effect was considerably stronger for the LNR [LNR: HR=5.18 (95 % CI: 3.5–7.6); +LNs=1.06 (95 % CI: 1.04–1.08)]. Similar results were obtained for patients with >12 LNcoll. An optimal cut off score for LNR=0.231 was validated on the second cohort (p<0.001). Conclusion: The LNR outperforms the + LNs and LNcoll even in patients with >12 LNcoll. Its clinical value is not confounded by MMR status. A cut-of score of 0.231 may best stratify patients into prognostic subgroups and could be a basis for the future prospective analysis of the LNR.

Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93

PURPOSE: The value of adjuvant tamoxifen after chemotherapy for premenopausal women with breast cancer has not been adequately assessed. PATIENTS AND METHODS: Between 1993 and 1999, International Breast Cancer Study Group Trial 13-93 enrolled 1,246 assessable premenopausal women with axillary node-positive, operable breast cancer. All patients received chemotherapy (cyclophosphamide plus either doxorubicin or epirubicin for four courses followed by immediate or delayed classical cyclophosphamide, methotrexate, and fluorouracil for three courses), which was followed by either tamoxifen (20 mg daily) for 5 years or no further treatment. The primary end point was disease-free survival (DFS). Tumors were classified as estrogen receptor (ER) -positive (n = 735, 59%) if immunohistochemical (IHC) or ligand-binding assays (LBA) were clearly positive. The ER-negative group included all other tumors (n = 511, 41%). A subset of the ER-negative group was defined as ER absent (n = 108, 9%) if IHC staining was none or if the LBA result was 0 fmol/mg cytosol protein. The median follow-up time was 7 years. RESULTS: Tamoxifen improved DFS in the ER-positive cohort (hazard ratio [HR] for tamoxifen v no tamoxifen = 0.59; 95% CI, 0.46 to 0.75; P < .0001) but not in the ER-negative cohort (HR = 1.02; 95% CI, 0.77 to 1.35; P = .89). Tamoxifen had a detrimental effect on patients with ER-absent tumors compared with no tamoxifen in an unplanned exploratory analysis (HR = 2.10; 95% CI, 1.03 to 4.29; P = .04). Patients with ER-positive tumors who achieved chemotherapy-induced amenorrhea had a significantly improved outcome (HR for amenorrhea v no amenorrhea = 0.61; 95% CI, 0.44 to 0.86; P = .004), whether or not they received tamoxifen. CONCLUSION: Tamoxifen after adjuvant chemotherapy significantly improved treatment outcome in premenopausal patients with endocrine-responsive disease, but its use as adjuvant therapy for patients with ER-negative tumors is not recommended.

Early and late urodynamic assessment of ileal orthotopic bladder substitutes combined with an afferent tubular segment

PURPOSE: Limited information is available concerning changes in the urodynamic characteristics of orthotopic bladder substitutes with time. Therefore, we compared early and late urodynamic results in patients with an ileal orthotopic bladder substitute combined with an afferent tubular segment. MATERIALS AND METHODS: Of 139 patients surviving at least 5 years after cystoprostatectomy and ileal orthotopic bladder substitution with an afferent tubular segment 119 underwent urodynamic assessment, including 66 at a median of 9 months (early) and 77 at a median of 62 months (late). Of these patients 24 were assessed at each time point. Simultaneously all patients were asked to complete a bladder diary and questionnaire regarding continence for at least 3 days in the week preceding the urodynamic study. RESULTS: Urodynamic parameters were comparable in patients who were evaluated early and late postoperatively. In addition, median values at early and late urodynamic evaluation in the 24 patients with the 2 examinations showed no statistically significant differences for volume at first desire to void (300 vs 333 ml, p = 0.85), pressure at first desire to void (12 vs 13 cm H2O, p = 0.57), maximum cystometric capacity (450 vs 453 ml, p = 0.84), end filling pressure (19 vs 20 cm H2O, p = 0.17), reservoir compliance (25 vs 28 ml/cm H2O, p = 0.58) or post-void residual urine volume (5 vs 15 ml, p = 0.27). CONCLUSIONS: Urodynamic results after 5 years of living with an ileal orthotopic bladder substitute with an afferent tubular segment show grossly unchanged urodynamic characteristics. Patients maintain a reservoir capacity and micturition pattern consistent with a normal life-style. Reservoir pressure remained low, thereby protecting and preserving upper tract function. To achieve these results patients must be regularly followed, and the causes of bacteriuria, increased post-void residual urine and bladder outlet obstruction must be recognized and dealt with accordingly.

Is Pelvic Lymph Node Dissection Necessary in Patients with a Serum PSA<10ng/ml Undergoing Radical Prostatectomy for Prostate Cancer?

OBJECTIVE: Controversy persists concerning the role of pelvic lymph node dissection (PLND) in patients with preoperative PSA values <10ng/ml undergoing treatment for prostate cancer with a curative intent. The aim of this study was to determine the incidence of lymph node metastasis in this subgroup of patients. METHODS: Patients with clinically localized prostate cancer and a serum PSA<10ng/ml, without neoadjuvant hormonal or radiotherapy, with negative staging examinations who underwent radical retropubic prostatectomy with bilateral extended PLND and with >/=10 lymph nodes detected by the pathologist in the surgical specimen, were included in the study. RESULTS: A total of 231 patients with a median serum PSA of 6.7ng/ml (range 0.4-9.98) and a median age of 62 years (range 44-76) were evaluated. A median of 20 (range 10-72) nodes were removed per patient. Positive nodes were found in 26 of 231 patients (11%), the majority of which (81%) had a Gleason score >/=7 in the surgical specimen. Of the patients with a Gleason score >/=7 in the prostatectomy specimen 25% had positive nodes, whereas only 3% with a Gleason score /=7 in the prostatectomy specimen was 25% after extended PLND. It seems that in this patient group extended PLND, including removal of nodes along the internal iliac vessels, is warranted.

The role of the number of uninvolved lymph nodes in predicting locoregional recurrence in breast cancer

PURPOSE: To identify groups of early breast cancer patients with substantial risk (10-year risk > 20%) for locoregional failure (LRF) who might benefit from postmastectomy radiotherapy (RT). PATIENTS AND METHODS: Prognostic factors for LRF were evaluated among 6,660 patients (2,588 node-negative patients, 4,072 node-positive patients) in International Breast Cancer Study Group Trials I to IX treated with chemotherapy and/or endocrine therapy, and observed for a median of 14 years. In total, 1,251 LRFs were detected. All patients were treated with mastectomy without RT. RESULTS: No group with 10-year LRF risk exceeding 20% was found among patients with node-negative disease. Among patients with node-positive breast cancer, increasing numbers of uninvolved nodes were significantly associated with decreased risk of LRF, even after adjustment for other prognostic factors. The highest quartile of uninvolved nodes was compared with the lowest quartile. Among premenopausal patients, LRF risk was decreased by 35% (P = .0010); among postmenopausal patients, LRF risk was decreased by 46% (P < .0001). The 10-year cumulative incidence of LRF was 20% among patients with one to three involved lymph nodes and fewer than 10 uninvolved nodes. Age younger than 40 years and vessel invasion were also associated significantly with increased risk. Among patients with node-positive disease, overall survival was significantly greater in those with higher numbers of uninvolved nodes examined (P < .0001). CONCLUSION: Patients with one to three involved nodes and a low number of uninvolved nodes, vessel invasion, or young age have an increased risk of LRF and may be candidates for a similar treatment as those with at least four lymph node metastases.