Extent of Lymph Node Retrieval and Pancreatic Cancer Survival: Information from a Large US Population Database

Background Operative therapy of pancreatic cancer is associated with poor survival because of high recurrence rates after pancreatectomy. The effect of lymph node (LN) dissection on survival continues to be debated.Methods A pancreatic cancer data set was created through structured queries to the Surveillance, Epidemiology, and End Results 1973 to 2000 database. Stage information was created according to 6th edition American Joint Committee on Cancer tumor-node-metastasis criteria, and the effect of LN number on survival was analyzed.Results Out of a cohort of 20,631 patients with carcinomas of the exocrine pancreas, surgical details were available for 2,787 patients. Procedures included pancreatoduodenectomies (n = 1848; 66%), radical regional pancreatectomies (n = 516; 19%), other partial resections (n = 316; 11%), and total pancreatectomies (n = 107; 4%). For 1666 of these patients with complete clinicopathologic information, the median age was 66 years (range, 22–96 years), with an equal sex ratio. The median number of total LNs examined was 7 (range, 1–52), of positive LNs was 1 (range, 0–34), and of negative LNs was 6 (range, 0–30). Multivariate survival analysis yielded these prognostic variables: number of LNs examined, number of positive LNs, tumor size, extrapancreatic extension, radiotherapy (all P < .0001), and age (P = .0009). The greatest survival differences were observed for negative LN counts of 10 to 15.Conclusions Stage-based survival prediction of pancreatic cancer is strongly influenced by total LN counts and numbers of negative LNs obtained. Although the mechanism remains unclear and could reflect confounding factors (margin status and institutional volume), an attempt to resect and examine at least 15 LNs to yield preferably between 10 and 15 negative LNs seems sensible for curative-intent pancreatectomy.     

The Lymph Node Ratio is the Strongest Prognostic Factor after Resection of Pancreatic Cancer

Introduction  Survival after surgery of pancreatic cancer is still poor, even after curative resection. Some prognostic factors like the status of the resection margin, lymph node (LN) status, or tumor grading have been identified. However, only few data have been published regarding the prognostic influence of the LN ratio (number of LN involved to number of examined LN). We, therefore, evaluated potential prognostic factors in 182 patients after resection of pancreatic cancer including assessment of LN ratio. Methods  Since 1994, 204 patients underwent pancreatic resection for ductal pancreatic adenocarcinoma. Survival was evaluated in 182 patients with complete follow-up evaluations. Of those 182 patients, 88% had cancer of the pancreatic head, 5% of the body, and 7% of the pancreatic tail. Patients underwent pancreatoduodenectomy (85%), distal resection (12%), or total pancreatectomy (3%). Survival was analyzed by the Kaplan–Meier and Cox methods. Results  In all 204 resected patients, operative mortality was 3.9% (n = 8). In the 182 patients with follow-up, 70% had free resection margins, 62% had G1- or G2-classified tumors, and 70% positive LN. Median tumor size was 30 (7–80) mm. The median number of examined LN was 16 and median number of involved LN 1 (range 0–22). Median LN ratio was 0.1 (0–0.79). Cumulative 5-year survival (5-year SV) in all patients was 15%. In univariate analysis, a LN ratio ≥ 0.2 (5-year SV 6% vs. 19% with LN ratio < 0.2; p = 0.003), LN ratio ≥ 0.3 (5-year SV 0% vs. 18% with LN ratio < 0.3; p < 0.001), a positive resection margin (p < 0.01) and poor differentiation (G3/G4; p < 0.03) were associated with poorer survival. In multivariate analysis, a LN ratio ≥ 0.2 (p < 0.02; relative risk RR 1.6), LN ratio ≥ 0.3 (p < 0.001; RR 2.2), positive margins (p < 0.02; RR 1.7), and poor differentiation (p < 0.03; RR 1.5) were independent factors predicting a poorer outcome. The conventional nodal status or the number of examined nodes (in all patients and in the subgroups of node positive or negative patients) had no significant influence on survival. Patients with one metastatic LN had the same outcome as patients with negative nodes, but prognosis decreased significantly in patients with two or more LN involved. Conclusions  Not the lymph node involvement per se but especially the LN ratio is an independent prognostic factor after resection of pancreatic cancers. In our series, the LN ratio was even the strongest predictor of survival. The routine estimation of the LN ratio may be helpful not only for the individual prediction of prognosis but also for the indication of adjuvant therapy and herein related outcome and therapy studies. Presented in part at the 49th Annual Meeting of the Society for Surgery of the Alimentary Tract, May 2008 in San Diego and at the Annual Meeting of the German Cancer Society, February 2008 in Berlin, Germany     

Nodal Counts and Lymph Node Ratio Impact Survival After Distal Pancreatectomy for Pancreatic Adenocarcinoma

Background

The number of lymph nodes required for accurate staging after distal pancreatectomy for pancreatic adenocarcinoma is unknown.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 1,473 patients who underwent distal pancreatectomy for pancreatic adenocarcinoma from 1998 to 2010. We evaluated the influence of the total number of lymph nodes examined (NNE) and the lymph node ratio (LNR-positive nodes/total nodes examined) on survival.

Results

The median NNE was 8. No nodes were examined in 232 (16 %) of the patients, and 843 (57 %) had <10 NNE. Of the patients who had at least one node examined, 612 (49 %) were node positive. In the node-negative subset, the median and 5-year overall survival for patients with ≤10 NNE was significantly worse than patients with >10 NNE (16 vs. 20 months and 13 vs. 19 %, respectively, p?0.1 (17 vs. 6 %, p?=?0.002).

Discussion

Patients with pancreatic cancer undergoing distal pancreatectomy should ideally have at least 11 lymph nodes examined to avoid understaging. For node-positive patients, LNR may be a better prognostic indicator than the total number of positive nodes.     

Lymph Node Retrieval and Assessment in Stage II Colorectal Cancer: A Population-Based Study

Background: Adjuvant chemotherapy for patients with stage III (node-positive) colorectal cancer (CRC) reduces mortality by one third. Retrieval of an inadequate number of lymph nodes in the surgical specimen may result in incorrectly designating some patients as stage II (node negative), and consequently, such patients may not be offered appropriate chemotherapy. Recent National Cancer Institute guidelines suggest that a minimum of 12 nodes should be examined to ensure accurate staging.Methods: This population-based study identified stage II (T3N0 and T4N0) CRC cases by using CRC pathology reports (1997–2000) from the Ontario Cancer Registry. Patients aged 19 to 75 years were identified, and demographic, surgical, pathologic, and hospital data were extracted. Factors relating to the number of lymph nodes assessed were examined.Results: A total of 8848 CRC cases were reviewed, and 1789 stage II cases were identified. Seventy-three percent of cases were designated as node negative on the basis of assessment of <12 lymph nodes. Multivariate analysis showed that age, tumor size, specimen length, use of a pathology template, and academic status of the hospital were significant predictors of the number of lymph nodes assessed.Conclusions: A subset of patients with CRC in Ontario were assigned stage II disease on the basis of examination of relatively few lymph nodes.     

Impact of Lymph Node Involvement on Long-term Survival after R0 Pancreaticoduodenectomy for Ductal Adenocarcinoma of the Pancreas

Pancreaticoduodenectomy remains the only potentially curative treatment for adenocarcinoma of the pancreas. The aim of this study was to analyze prognostic factors impacting survival after R0 pancreaticoduodenectomy for adenocarcinoma in the head of the pancreas. Between 1995 and 2002, a potentially curative (R0) pancreaticoduodenectomy with pancreatogastrostomy for ductal adenocarcinoma in the head of the pancreas was performed in 81 patients (42 women and 39 men) with a mean age of 64 years (range 35–84). Patients were identified from a prospective database and records were reviewed retrospectively. Postoperative mortality was 1%, and 40% of patients had complications. Median survival was 18 months, and the 5-year survival was 24%. Fifteen patients were alive at 5 years. Factors associated with poor survival in multivariate analysis were (1) two or more positive lymph nodes, (2) tumor diameter greater than 30 mm, and (3) age greater than 70 years. In patients with no or with one positive lymph node, the 5-year survival was 44%. On the other hand, in patients with two or more positive lymph nodes, both the 3- and 5-year survival was 5%. The main risk factor associated with poor survival after an R0 pancreaticoduodenectomy for adenocarcinoma in the head of pancreas was lymph node status: The presence of two or more positive lymph nodes was associated with decreased survival.     

Prognostic Relevance of Lymph Node Ratio and Number of Resected Nodes after Curative Resection of Ampulla of Vater Carcinoma

Background  Nodal metastasis is considered a major prognostic factor in patients with ampulla of Vater carcinoma (AVC). No study has investigated the significance of the ratio between metastatic and resected/examined lymph nodes (LNR) in patients with AVC. Methods  Demographic, operative, and pathology data, including number of resected/evaluated nodes and LNR, were collected from patients who underwent pancreaticoduodenectomy with radical intent for invasive AVC from 1990 to 2005. Survival rates and recurrence patterns were evaluated and predictors were identified. Results  In 90 evaluable patients (51 males, 39 females, median age 62.5 years), 5-year disease-specific survival (DSS) was 61%. The median number of resected/evaluated nodes was 16 (range: 5–47); 50% of the patients had nodal metastases. The 5-year DSS according to LNR was 75%, 49%, 38%, and 0% for LNR = 0, LNR >0 and ≤0.2, LNR >0.2, and ≤0.4, and LNR >0.4 (P = 0.002), respectively. The 5-year DSS was 81% in patients with >16 resected/evaluated nodes compared with 45% in those with ≤16 resected/evaluated nodes (P = 0.001). On multivariate analysis LNR and a number of resected/evaluated nodes >16 were significant predictors of survival; a number of resected/evaluated nodes >16 was also the only independent predictor of recurrence. Conclusions  After curative resection for AVC, LNR and a cutoff of 16 resected/evaluated nodes are powerful prognostic factors. LNR might represent a major parameter for patient stratification in adjuvant treatment trials.     

Lymph Node Dissection Impact on Staging and Survival of Extrahepatic Cholangiocarcinomas,Based on U.S. Population Data

Cholangiocarcinomas (CC) frequently demonstrate lymphatic spread. We investigated lymph node (LN) counts after resection of extrahepatic CC and survival based on the SEER 1973–2004 database. Out of 20,068 CC patients, 1,518 individuals were selected based on M0 stage and at least one LN examined. Primary cancer sites included gallbladder (29%), extrahepatic bile ducts (26%), and intrapancreatic/ampullary bile ducts (45%); 42% of patients were LN-positive. The median number of LNs examined was four (range 1–39). Median survival was 37 months for LN-negative and 16 months for LN-positive cancers. Multivariate prognostic variables were the number of positive LNs, primary site, age (all at p < 0.0001), gender (p = 0.002), size (p = 0.005), T category (p = 0.009), and total LN count (or number of negative LNs obtained, p = 0.01). The impact of total LN counts was seen in LN-negative (median survival, 1 vs 10 or more LNs examined: 27 vs 51 months, p = 0.002) and LN-positive disease (10 vs 22 months, p < 0.0001). Survival prediction of extrahepatic CCs is strongly influenced by total LN counts and numbers of negative LNs obtained. Although the resulting incremental benefit is small, dissection and examination of 10 or more LNs should be considered for curative intent resections.     

Significance of Common Hepatic Artery Lymph Node Metastases During Pancreaticoduodenectomy for Pancreatic Head Adenocarcinoma

Abstact Background Common hepatic artery lymph nodes (CHALN) are frequently sampled during pancreaticoduodenectomy for adenocarcinomas of the head of the pancreas. In some institutions, if metastatic disease is detected intraoperatively in these lymph nodes, the tumor is considered unresectable and a curative operation is not performed. No solid data exist to support this practice. Methods A retrospective review of a prospectively collected database was conducted of the records of all patients who underwent a pancreaticoduodenectomy for pancreatic adenocarcinoma between September 1991 and April 2005. Clinical and pathologic factors were analyzed to determine their influence on survival. Results Fifty-five of 175 patients had CHALN separately identified and evaluated; these patients constituted the study population. Thirty-eight patients (69%) had one or more lymph nodes with metastatic involvement; 10 of these had disease in CHALN. The median overall survival for patients with node-negative, node-positive (but CHALN-negative), and CHALN-positive disease were 22.9, 16.1, and 14.7 months, respectively. The 5-year overall survival rates for the respective groups were 22%, 17%, and 0%. Conclusions CHALN metastases correlate with poor prognosis and no long-term survival. Further studies examining CHALN status are indicated and could lead to modifications of pancreatic cancer staging and management. Poster presentation at the Society of Surgical Oncology Meeting, March 22–25, 2006, San Diego, California. Presented in part at the Pancreas Club Meeting, May 21, 2006, Los Angeles, California.     

Inadequacy of Lymph Node Staging in Gastric Cancer Patients: A Population-Based Study

Background In 1997, examination of at least 15 lymph nodes was recommended for adequate gastric cancer staging. However, the proportion of patients undergoing an adequate lymph node examination (LNE) has not been studied in a population-based manner. Methods We used Surveillance, Epidemiology, and End Results cancer registry data to assess LNE adequacy in adults with nonmetastatic gastric adenocarcinoma. We selected patients aged 18 through 80 years whose disease was diagnosed from 1998 through 2001 and who underwent at least partial gastrectomy. We evaluated the overall number of nodes, estimated the likelihood of adequate LNE (i.e., ≥15 nodes examined), and determined the influence of selected tumor and patient characteristics on LNE. Results In this 4-year period, 3593 patients met our study’s selection criteria. The median number of nodes examined was 10: 32% of patients underwent adequate LNE, and 9% of patients had no nodes examined. Node-positive patients were more likely to have undergone an adequate LNE than node-negative patients (42% vs. 23%; P < .0001). Younger age, female sex, and more radical surgery were associated with adequate LNE in both univariate and multivariate analysis (P < .0001). Geographical site was an important predictor; patients from one registry (Hawaii) were significantly more likely to have undergone adequate LNE than patients from all other registries (56% vs. 30%; P < .0001). Conclusions Our 4-year review of the Surveillance, Epidemiology, and End Results database revealed that only a third of patients with gastric cancer underwent adequate LNE, i.e., had the recommended minimum of 15 nodes examined for gastric cancer staging. Better results at one registry (Hawaii) indicate that substantial improvements could be made.     

Prognostic Value of Lymph Node Yield and Metastatic Lymph Node Ratio in Medullary Thyroid Carcinoma

Introduction  Lymphadenectomy and thyroidectomy is standard treatment for medullary thyroid carcinoma (MTC), but the prognostic importance of the number of lymph nodes removed (lymph node yield, LNY) and the proportion of metastatic lymph nodes resected (metastatic lymph node ratio, MLNR) is unknown. We hypothesized that MTC survival is influenced by LNY and MLNR. Methods  Patients (N = 534) who underwent thyroidectomy with lymphadenectomy for MTC between 1988 and 2004 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan–Meier method was used for univariate comparisons of survival for LNY and MLNR with a maximum follow-up of 12 years. Cox regression models adjusted for age, sex, extent of disease, tumor size, nodal status, LNY, and MLNR. Results  By univariate analysis, increasing LNY was associated with improved survival in all patients (P < 0.002) and node-positive patients (P < 0.001). In a multivariate analysis using LNY and MLNR as categorical variables, significant factors influencing survival included: age (P < 0.001), tumor size (P < 0.001), LNY (P = 0.007), and MLNR (P < 0.02); in node-negative patients: age (P = 0.002); in node-positive patients: age (P < 0.001), tumor size (P < 0.001), and LNY (P = 0.001). Using LNY and MLNR as continuous variables, significant factors influencing survival included: age (P < 0.001), tumor size (P < 0.001), and MLNR (P = 0.01); in node-negative patients: age (P < 0.001); in node-positive patients: age (P < 0.001) and tumor size (P < 0.001). Conclusion  In patients undergoing thyroidectomy and lymphadenectomy for MTC, LNY and MLNR predict poorer survival, but their impact on survival was limited to node-positive patients and was otherwise dominated by the effects of age and extent of disease. Supported by Grant Number KL2RR024144 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Presented in part at the 3rd Annual Academic Surgical Congress, February 12–15, 2008, Huntington Beach, California.     

Increased Expression of Valosin-Containing Protein (p97) is Associated With Lymph Node Metastasis and Prognosis of Pancreatic Ductal Adenocarcinoma

Background: Valosin-containing protein (VCP, also known as p97) exhibits antiapoptotic function and metastasis by activation of nuclear factor kappa-B signaling pathway. Our previous study showed that VCP expression level correlated with prognosis of hepatocellular and gastric carcinoma. In the present study, association of VCP expression with lymph node metastasis and prognosis of pancreatic ductal adenocarcinoma (PDAC) was examined.Methods: VCP expression in 83 patients (46 males and 37 females) of ages ranging from 43 to 80 (median, 66) years who had undergone curative surgery for primary PDAC was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker or equal to (low expression) or stronger (high expression) than that in noncancerous ductal tissue.Results: Thirty-two tumors (38.6%) and 51 tumors (61.4%) were classified as low-VCP-expressing and high-VCP-expressing tumors, respectively. VCP expression correlated significantly with lymph node metastasis (P < .01) but not with various clinicopathologic factors, including age, gender, and histologic differentiation. Multivariate analysis revealed VCP expression as an independent prognosticator for both disease-free and overall survival, along with histologic differentiation, T stage of pathologic tumor-node-metastasis (pTNM) classification, and lymph node metastasis. Furthermore, VCP expression was a prognosticator for disease-free and overall survival in each relatively early stage (I or II) and advanced stage (III) group of pTNM classification.Conclusions: Our results indicate the potential usefulness of VCP expression as a marker of metastasis and overall prognosis of PDAC.     

Accurate Lymph Node Staging is of Greater Prognostic Importance Than Subclassification of the T2 Category for Gastric Adenocarcinoma

Background: Examination of 15 or more lymph nodes is necessary for accurate staging of gastric adenocarcinoma. This study examined whether prognostic discrimination is improved by distinguishing between pT2 tumors limited to the muscularis propria (MP) and those extending to subserosa (SS).Methods: A single-institution, prospectively maintained database for 1985–2000 was reviewed for patients who had had R0 resection of pT2 gastric carcinoma.Results: There were 161 patients with MP and 201 patients with SS. The prevalence of nodal metastasis was significantly lower with MP than with SS (47% vs. 66%, respectively; P < .001). As compared with MP, SS was associated with a similar prevalence of pN1 (44% vs. 43%) but a significantly higher prevalence of pN2 or pN3 (3% vs. 23%; P < .001). Five-year survival was significantly greater for patients with MP than with SS (64% vs. 49%; P = .005). On multivariate analyses, however, only the pN category and tumor site were independently significant prognostic factors. With accurate nodal staging, patients with MP or SS had similar survival in association with pN0 (90% vs. 86%) or pN1 (56% vs. 44%). pN2 or pN3 were mainly limited to SS tumors and these patients had poor survival (26% and 0%).Conclusions: For pT2 gastric adenocarcinoma, the depth of mural invasion was not an independently significant prognostic factor.     

Variations in Surgical Treatment and Outcomes of Patients With Pancreatic Cancer: A Population-Based Study

Background There is ongoing debate on how variations in surgical technique affect outcomes in pancreatic cancer. This population-based study examines current surgical practice and outcomes for cancer of the pancreatic head. Methods All patients 18 to 85 years old diagnosed with nonmetastatic adenocarcinoma of the pancreatic head from 1998 through 2003 were identified from the Surveillance, Epidemiology and End Results (SEER) Program registry. Multivariable regression was used to elucidate factors associated with the type of pancreaticoduodenectomy performed, extent of lymph node (LN) assessment, early mortality, and late survival. Results Overall, 2111 patients were included in the study, with 83.7% treated with a standard Whipple pancreaticoduodenectomy (PD). However, there was marked regional variation in the use of pylorus-preserving pancreaticoduodenectomy (PPPD; range, .03%–32.0%; P < .0001) and total pancreatectomy (TP; range, .04%–19.5%; P < .0001). TP was associated with significantly higher early mortality (odds ratio, 2.6; 95% confidence interval, 1.6 to 4.1; P < .0001), but late survival did not differ significantly between TP, PPPD, and PD (P = .69). Significant variation was also seen in the number of LN assessed (range across SEER regions, 7.3–13.5; P < .0001). Decreased LN assessment reduced the odds of diagnosing a patient as node positive and was associated with worse late survival. Conclusions In this population-based study, we found marked clinically important variability in the surgical treatment of adenocarcinoma of the pancreatic head, with respect to the use of TP, PPPD, or PD, and the extent of LN assessment. Further research is warranted to elucidate the underlying reasons, and to clarify the role of adequate lymphadenectomy.     

Ratio Between Metastatic and Examined Lymph Nodes Is an Independent Prognostic Factor After D2 Resection for Gastric Cancer: Analysis of a Large European Monoinstitutional Experience

Background: In view of the lack of consensus on the level and number of lymph nodes to be examined for accurate staging of patients with gastric cancer, our aim was to evaluate the prognostic significance of lymph node status in a large European monoinstitutional experience.Methods: A review was made of our prospective database from 1980 to 2000, when 314 of 445 patients operated for gastric adenocarcinoma underwent radical resection (R0) with D2 lymphadenectomy. Survival was determined by the Kaplan-Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression.Results: In 277 evaluable patients, 5-year survival was 57% (median follow-up, 48 months; range, 2–251). A total of 7668 lymph nodes were examined (median, 27; range, 11–62). The 5-year survivals according to the metastatic/examined lymph nodes ratio (N ratio) were 14%, 50%, 61%, and 82% in the group of patients with N ratio >25%, 11%–25%, 1%–10%, and 0%, respectively (P < .0001). At multivariate analysis, the N ratio was the best single independent prognostic factor (P = .000).Conclusions: After R0 resection for gastric cancer, the N ratio is a potent prognostic factor. It should therefore be considered in the clinical decision making process.Presented at the 56th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, California, March 5–9, 2003.     

The Prognostic Significance of Micrometastases in Breast Cancer: A SEER Population-Based Analysis

Introduction The prognostic significance of lymph node micrometastases in breast cancer is controversial. We hypothesized that the survival of patients with solely micrometastatic disease (N1mi) would be intermediate to patients with 1–3 tumor-positive lymph nodes (N1) and those with no positive lymph nodes (N0). Methods We queried the surveillance, epidemiology and end results (SEER) database for all patients between 1992 and 2003 with invasive ductal or lobular breast cancer without distant metastases and ≤3 axillary nodes with macroscopic disease. Patients were stratified by nodal involvement and compared using the Kaplan–Meier method. Cox proportional hazards regression was utilized to compare survival after adjusting for patient and tumor characteristics. Results Between 1992 and 2003, N1mi diagnoses increased from 2.3% to 7% among the 209,720 study patients (p < 0.001). In a T-stage stratified univariate analysis, N1mi patients had a worse prognosis in T2 lesions. On multivariate analysis, N1mi remained a significant prognostic indicator across all patients (p < 0.0001) with a hazard ratio of 1.35 compared to N0 disease and 0.82 compared to N1 disease. Other negative prognostic factors included male gender, estrogen-receptor negativity, progesterone-receptor negativity, lobular histology, higher grade, older age, higher T-stage, and diagnosis in an earlier time period. Conclusion Nodal micrometastasis of breast cancer carries a prognosis intermediate to N0 and N1 disease, even after adjusting for tumor- and patient-related factors. Prospective study is warranted and the results of pending trials are highly anticipated. Until then adjuvant therapy trials should consider using N1mi as a stratification factor when determining nodal status.     

Neoplastic Endocrine Differentiation of Pancreatic Ductal Adenocarcinoma in a Metastatic Lymph Node: Report of a Case

The occurrence of non-neoplastic, scattered endocrine cells in pancreatic ductal adenocarcinoma (DAC) is thought to be a general phenomenon. Conversely, neoplastic endocrine differentiation (NED) of pancreatic DAC is extremely unusual. We report a case of NED in a metastatic lymph node from pancreatic DAC. This case is distinct because the main tumor of the pancreas was composed purely of DAC without endocrine differentiation, and the NED was found in only one of four metastatic peripancreatic lymph nodes. To our knowledge, no other such case has ever been reported. The patient was a 61-year-old woman who underwent pylorus-preserving pancreaticoduodenectomy for pancreatic head cancer. Some authors reported that pancreatic DAC with endocrine differentiation was associated with a better prognosis than DAC without endocrine differentiation. However, more cases must be studied to investigate the impact of NED of metastatic lymph nodes in pancreatic DAC.     

Prognostic Factors for Occult Inguinal Lymph Node Involvement in Penile Carcinoma and Assessment of the High-Risk EAU Subgroup: A Two-Institution Analysis of 342 Clinically Node-Negative Patients

Background

The European Association of Urology (EAU) guidelines advise an elective bilateral lymphadenectomy in clinically node-negative (cN0) patients with high-risk penile carcinoma (≥pT2, G3, or lymphovascular invasion [LVI]).

Objective

Our aim was to assess prognostic factors for occult metastasis and to determine whether current EAU guidelines accurately stratify patients at high risk.

Design, setting, and participants

Data of 342 cN0 patients with histologically proven invasive penile squamous cell carcinoma who had undergone the current dynamic sentinel node biopsy (DSNB) protocol were analysed. A complete ipsilateral inguinal lymphadenectomy was only done if the sentinel node was tumour positive.

Measurements

The presence of occult metastasis was established by preoperative ultrasound and tumour-positive fine-needle aspiration cytology, tumour-positive sentinel nodes, and groin metastases during follow-up after a negative DSNB procedure. Median follow-up was 31 mo.

Results and limitations

Sixty-eight of 342 patients (20%) and 87 of 684 groins (13%) had occult nodal involvement including 6 patients (2%) with a groin metastasis after negative DSNB. Corpus spongiosum invasion, corpus cavernosum invasion, histologic grade, and LVI were each significant prognosticators for occult metastasis on univariate analysis. On multivariate analysis, grade (odds ratio [OR]: 3.3 for intermediate and 4.9 for poor, respectively) and LVI (OR: 2.2) remained predictive factors. In total, 245 patients (72%) were classified high risk according to EAU guidelines. Among them, the incidence of occult metastasis was 23% (57 of 245). A potential limitation of this study is the lack of external review.

Conclusions

Histologic grade and LVI are independent prognostic factors for occult metastasis in penile carcinoma. Although both predictors are incorporated into the current EAU guidelines, the stratification of patients needing a lymph node dissection is inaccurate. Approximately 77% of high-risk patients (188 of 245) would have had a negative bilateral inguinal lymphadenectomy. For the time being, DSNB is considered a more suitable staging method than EAU risk stratification for an accurate determination of patients who require lymph node dissection.     

Impact of False-Negative Sentinel Lymph Node Biopsy on Survival in Patients with Cutaneous Melanoma

Background and Objectives Sentinel lymph node biopsy is widely accepted as standard care in melanoma despite lack of pertinent randomized trials results. A possible pitfall of this procedure is the inaccurate identification of the sentinel lymph node leading to biopsy and analysis of a nonsentinel node. Such a technical failure may yield a different prognosis. The purpose of this study is to analyze the incidence of false negativity and its impact on clinical outcome and to try to understand its causes. Methods The Melanoma Data Base at National Cancer Institute of Naples was analyzed comparing results between false-negative and tumor-positive sentinel node patients focusing on overall survival and prognostic factors influencing the clinical outcome. Results One hundred fifty-one cases were diagnosed to be tumor-positive after sentinel lymph node biopsy and were subjected to complete lymph node dissection. Thirty-four (18.4%)patients with tumor-negative sentinel node subsequently developed lymph node metastases in the basin site of the sentinel procedure. With a median follow-up of 42.8 months the 5-year overall survival was 48.4% and 66.3% for false-negative and tumor-positive group respectively with significant statistical differences (P < .03). Conclusions The sensitivity of sentinel lymph node biopsy was 81.6%, and a regional nodal basin recurrence after negative-sentinel node biopsy means a worse prognosis, compared with patients submitted to complete lymph node dissection after a positive sentinel biopsy. The evidence of higher number of tumor-positive nodes after delayed lymphadenectomy in false-negative group compared with tumor-positive sentinel node cases, confirmed the importance of an early staging of lymph nodal involvement. Further data will better clarify the role of prognostic factors to identify cases with a more aggressive biological behavior of the disease.     

内乳淋巴结活检在乳腺癌分期与辅助治疗中的价值

目的分析乳腺癌经肋间隙内乳淋巴结切除活检在乳腺癌分期与辅助治疗中的价值。方法回顾性分析济南军区总医院甲状腺乳腺外科2003年5月至2014年1月期间305例（根据是否行新辅助化疗分为新辅助化疗组和无新辅助化疗组）行乳腺癌各式改良根治术与经肋间隙内乳淋巴结切除活检患者的相关临床与病理资料,包括患者年龄、腋窝淋巴结、内乳淋巴结转移状况等信息,分析内乳淋巴结对乳腺癌分期与治疗的影响。结果新辅助化疗组共收集乳腺癌患者67例,发生腋窝淋巴结转移者45例（67．2％）,内乳淋巴结转移者23例（34．3％）;乳腺癌淋巴结病理（pN）分期改变者23例（34．3％）,乳腺癌肿瘤病理（pTNM）分期改变者8例（11．9％）。无新辅助化疗组共收集乳腺癌患者238例,发生腋窝淋巴结转移者155例（65．1％）,内乳淋巴结转移者30例（12．6％）;乳腺癌pN分期改变者30例（12．6％）,pTNM分期改变者23例（9。66％）。新辅助化疗组的内乳淋巴结转移率明显高于无新辅助化疗组（χ2=15．7,P〈0．05）,pTNM分期改变率也明显高于无新辅助化疗组贸（χ2=5．3,P〈0．05）。结论经肋间隙内乳淋巴结活检对乳腺癌pN分期、pTNM分期有一定的影响。新辅助化疗不能使所有内乳淋巴结转移癌达到病理完全缓解。经肋间隙内乳淋巴结活检不仅可完善乳腺癌pN和pTNM分期,而且能够指导乳腺癌术后辅助治疗,减少内乳区局部过度治疗,有助于乳腺癌患者个体化治疗。