Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection

Purpose

To evaluate the prognostic effect of lymph node ratio (LNR) in patients with locally advanced rectal cancer who were treated with curative resection after preoperative chemoradiotherapy (CRT).

Methods

Between October 2001 and December 2007, 519 patients who had undergone curative resection of primary rectal cancer after preoperative CRT were enrolled. Of these, 154 patients were positive for lymph node (LN) metastasis and were divided into three groups according to the LNR (≤0.15 [n = 80], 0.16–0.3 [n = 44], >0.3 [n = 30]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS).

Results

LNR (≤0.15, 0.16–0.3, and >0.3) was significantly associated with 5-year OS (90.3%, 75.1%, and 45.1%; p < 0.001) and DFS (66.7%, 55.8%, and 21.9%; p < 0.001) rates. In a multivariate analysis, LNR (≤0.15, 0.16–0.3, and >0.3) was a significant independent prognostic factor for OS (hazard ratios [HRs], 1, 3.609, and 8.197; p < 0.001) and DFS (HRs, 1, 1.699, and 3.960; p < 0.001). LNR had a prognostic impact on OS and DFS in patients with <12 harvested LNs, as well as in those with ≥12 harvested LNs (p < 0.05).

Conclusion

LNR was a significant independent prognostic predictor for OS and DFS in patients with locally advanced rectal cancer who were treated with curative resection after preoperative CRT.     

A study of lymph node ratio as a prognostic marker in colon cancer

Aim

The aim of this study was to evaluate and describe the lymph node ratio (LNR) as a prognostic parameter for patients with colon cancer. As lymphatic involvement is the key, focus was set at stage III disease. Interest was directed at the possibility of identifying high-risk groups and the clinical implementation and consequence.

Method

The study was retrospective using a database of clinical data of all cancer patients treated at our unit. It has been continuous in registration, inclusion and update since 1999 including survival and clinical features. All patients (n = 265) diagnosed with stage III colon cancer during 1999–2003 were included for the study. LNR was calculated and quartile groups were created. LNR and associated parameters were analysed towards 3-year disease-free survival (DFS). Basic patient data as well as surgery, pathology and postoperative treatment were taken into consideration.

Results

Significant differences in disease-free survival were found for TNM N-status, tumour differentiation grade and LNR quartile group. There was a difference in 3-year DFS from 80% in LNR group 1 compared with less than 30% in group 4. These results were of prognostic interest both independently and in interaction with each other. High-risk groups could be identified and in the worst prognosis LNR group we also found a tendency towards more side effects with adjuvant chemotherapy.

Conclusion

The lymph node ratio, the quota between the number of lymph node metastasis and assessed lymph nodes, is a highly significant (p < 0.001) prognostic factor in stage III colon cancer. It can be an aid in identifying risk groups that could benefit from a more intense postoperative surveillance and possibly bring changes in adjuvant treatment strategy. More studies of clinical data, genetic and biochemical markers are needed in this patient group to understand the possible difference in tumour behaviour and tailor the treatment.     

Is complete lymph node dissection after a positive sentinel lymph node biopsy for cutaneous melanoma always necessary? A meta-analysis

Background

The current recommendation for patients with cutaneous melanoma and a positive sentinel lymph node (SLN) biopsy is a complete lymph node dissection (CLND). However, metastatic melanoma is not present in approximately 80% of CLND specimens. A meta-analysis was performed to identify the clinicopathological variables most predictive of non-sentinel node (NSN) metastases when the sentinel node is positive in patients with melanoma.

Methods

A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google scholar, Science Direct, and Web of Science. The search identified 54 relevant articles reporting the frequency of NSN metastases in melanoma. Original data was abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI).

Findings

The pooled estimates that were found to be significantly associated with the high likelihood of NSN metastases were: ulceration (OR: 1.88, 95% CI: 1.53–2.31), satellitosis (OR: 3.25, 95% CI: 1.86–5.66), neurotropism (OR: 2.51, 95% CI: 1.39–4.53), >1 positive SLN (OR: 1.77, 95% CI: 1.2–2.62), Starz 3 (old) (OR: 1.83, 95% CI: 0.89–3.76), Angiolymphatic invasion (OR: 2.46, 95% CI: 1.34–4.54), extensive location (OR: 2.22, 95% CI: 1.74–2.81), macrometastases >2 mm (OR: 1.95, 95% CI: 1.61–2.35), extranodal extension (OR: 3.38, 95% CI: 1.79–6.40) and capsular involvement (OR: 3.16, 95% CI: 1.37–7.27). There were 3 characteristics not associated with NSN metastases: subcapsular location (OR: 0.51, 95% CI: 0.38–0.67), Rotterdam Criteria <0.1 mm (OR: 0.29, 95% CI: 0.17–0.50) and Starz I (new) (OR: 0.44, 95% CI: 0.22–0.91). Other variables including gender, Breslow thickness 2–4 mm and extremity as primary site were found to be equivocal.

Interpretation

This meta-analysis provides evidence that patients with low SLN tumor burden could probably be spared the morbidity associated with CLND. We identified 9 factors predictive of non-SLN metastases that should be recorded and evaluated routinely in SLN databases. However, further studies are needed to confirm the standard criteria for not performing CLND.     

Re-appraising the role of lymph node status in predicting survival in resected distal cholangiocarcinoma – A meta-analysis and systematic review

This systematic review and meta-analysis aimed to confirm the prognostic value of lymph node ratio (LNR), and determine an optimal LNR cut-off for overall survival (OS) in patients with distal cholangiocarcinoma (DCC) undergoing curative surgery. We additionally aimed to provide a consolidated review of current evidence regarding prognostic significance of positive lymph node count (PLNC) and total lymph node count (TLNC). A systematic search of PubMed, EMBASE and Cochrane Library was conducted from inception to October 2020. Studies were included into meta-analysis if there was histological diagnosis, curative surgery, restriction to DCC and relevant LNR results. Quality assessment was performed using the Newcastle Ottawa Scale. Findings for 1228 patients were pooled across 6 studies. Meta-analysis delineated a dose-effect gradient in which higher LNR cut-offs correlated with larger pooled hazard ratios: 0<LNR<0.2 (HR 1.54; 95% CI 1.08–2.20; p = 0.02), LNR>0.2 (HR 3.26; 95% CI 2.07–5.13; p < 0.00001) and LNR>0.4 (HR 3.59; 95% CI 2.31–5.58; p < 0.00001) when compared against a control group of LNR = 0. LNR of 0.2 (HR 2.12; 95% CI: 1.57–2.86; p < 0.0001) was found to be a significant and ideal cut-off for prognostication of poorer OS. A review of current literature reveals an ongoing debate regarding the comparative prognostic value of differing PLNC cut-offs (0/1/3 versus 0/1/4). TLNC of 10–13 is widely reported to be the minimum necessary to ensure improved long term outcomes. PLNC and LNR are strong prognostic factors for OS in DCC. An ideal LNR cut-off of 0.2 is most significantly associated with poorer OS.     

Prognostic influence of immunohistochemically detected lymph node micrometastasis and histological subtype in pN0 oesophageal cancer

Introduction

Differences in frequency and clinical impact of lymph node micrometastasis between histological subtypes of oesophageal cancer have not been determined.

Methods

1204 lymph nodes from 32 squamous cell carcinomas and 54 adenocarcinomas with complete resection and pN0 status were re-evaluated using a serial sectioning protocol including immunohistochemistry. Intra-nodal tumour cells were classified as micrometastases (0.2–2 mm) or isolated tumour cells (<0.2 mm).

Results

There was no significant difference in the frequency of micrometastases between adenocarcinoma and squamous cell carcinoma (11.3% vs. 3.1%, p = n.s.). In the squamous cell carcinoma group, Kaplan–Meier curves showed a significantly prolonged 5-year survival (p = 0.02) and disease free interval (p < 0.01) for immunohistochemically node negative versus node positive patients. In patients with adenocarcinoma, no such difference (p = n.s. and p = n.s., respectively) was seen. In patients who did not undergo pre-treatment, those with adenocarcinoma had a significant 5-year survival (65% vs. 53%; p = 0.03) and disease free interval (83% vs. 58%; p < 0.05) advantage over those with squamous cell carcinoma. After pre-treatment, no difference between the histological subtypes was detected.Regression analysis did not reveal any factors that significantly affected overall survival in node negative patients. However, four factors did significantly influence disease free interval: pre-treatment (HR 3.3 [95% CI 1.2–9.1], p = 0.02); micrometastasis (HR 5.3 [95% CI 1.4–19.7], p = 0.01); UICC stage II vs. 0/I (HR 2.2 [95% CI 1.1–4.4], p = 0.03); and adenocarcinoma (HR 0.3 [95% CI 0.1–0.9], p = 0.03).

Conclusion

The difference in frequency and clinical impact of immunohistochemically detected micrometastasis may indicate that adenocarcinoma and squamous cell carcinoma should not be treated as one entity.     

The prognostic significance of extracapsular lymph node involvement in node positive patients with colonic cancer

Aims

In colonic cancer the prognostic significance of extracapsular lymph node involvement (LNI) is not established and is therefore the objective of this study.

Methods

Between January 1994 and May 2005, all patients who underwent resection for primary colonic cancer with lymph node metastasis were reviewed. All resected lymph nodes were re-examined to assess extracapsular LNI. In uni- and multivariate analysis disease-free survival (DFS) was correlated with various clinicopathologic factors.

Results

One hundred and eleven patients were included. In 58 patients extracapsular LNI was identified. Univariate analysis revealed that pN-stage (5-year DFS pN1 vs. pN2: 65% vs. 14%, p < 0.001), extracapsular LNI (5-year DFS intracapsular LNI vs. extracapsular LNI: 69% vs. 41%, p = 0.003), and lymph node ratio (5-year DFS <0.176 vs. ≥0.176: 67% vs. 42%, p = 0.023) were significant prognostic indicators. Among these variables pN-stage (hazard ratio 3.5, 95% confidence interval [CI]: 1.72–7.42) and extracapsular LNI (hazard ratio 1.98, 95% CI: 1.00–3.91) were independent prognostic factors. Among patients without extracapsular LNI, those receiving adjuvant chemotherapy had a significantly better survival (p = 0.010). In contrast, chemotherapy did not improve DFS in patients with extracapsular LNI.

Conclusion

Together with pN2 stage, extracapsular LNI reflects a particularly aggressive behaviour and has significant prognostic potential.     

Staging and management of axillary lymph nodes in patients with local recurrence in the breast or chest wall after a previous negative sentinel node procedure

Objective

To evaluate axillary staging and management in patients with local recurrence (LR) after a previous negative sentinel lymph node biopsy (SNB).

Methods

Between 1999 and 2008, 130 patients with previous negative SNB developed a LR of breast or chest wall. After examination of clinical records, 70 patients met the inclusion criteria and remained available for analysis.

Results

Thirty-seven patients were treated with axillary lymph node dissection (ALND), followed by axillary radiotherapy in 9 cases. In 26 of these 37 patients no positive axillary lymph nodes were found. Nineteen patients received no treatment of the axilla at all. Of those, 9 were older than 70 years of age at diagnosis of LR. In 13 patients a second SNB was attempted, but was successful in only 5 cases. Eight patients underwent a complementary ALND. Overall, positive lymph nodes were detected in 13 of the 50 patients who underwent axillary staging, either by SNB or ALND. The median length of follow-up of the 70 patients following their diagnosis of LR was 24 months (range 2–81 months). During this follow-up period one patient developed an axillary recurrence. This was a patient who refused to undergo ALND but was given locoregional radiotherapy instead.

Conclusions

In the absence of guidelines for staging and management of the axilla at time of LR of breast or chest wall, many different strategies are being used. Considering the high rate of positive axillary lymph nodes in these patients, repeat surgical staging is appropriate.     

Prediction of non-sentinel lymph node metastasis in early breast cancer by assessing total tumoral load in the sentinel lymph node by molecular assay

Introduction

The one-step nucleic acid amplification (OSNA) is a molecular procedure that yields a semiquantitative result for detection of nodal metastasis. Size of metastasis in the sentinel lymph node (SLN) by conventional histology has been described as a predictive factor for additional axillary metastasis. The objective of this study is to quantify intraoperatively the total tumoral load (TTL) in the positive SLNs assessed by OSNA and to determine whether this TTL predicts non-SLN metastasis in patients with clinically node negative early stage breast cancer.

Methods

306 patients with cT1-3N0 invasive breast cancer who had undergone intraoperative SLN evaluation by OSNA were included. TTL was defined as the addition of CK19 mRNA copies of each positive SLN (copies/μL).

Results

TTL was a predictive factor of additional non-SLN metastasis in the complete axillary lymph node dissection (cALND) (OR, 1.67; 95% CI, 1.18–2.35). In the multivariate analysis, the TTL was a predictor of non-SLN metastasis in HR positive patients (OR, 1.69; 95% CI, 1.19–2.41). In our cohort of patients, with a TTL ≤1.2 × 10⁵ copies/μL, there was a specificity of 85.3% and negative predictive value (NPV) of 80%. If we consider only the HR positive patients, with a TTL ≤5 × 10⁵ copies/μL there was a specificity of 86.7% and NPV of 83.7%.

Conclusions

TTL assessed by OSNA assay predicts for additional non-SLN metastasis and this intraoperative tool can help guiding decisions on performing a cALND in breast cancer patients.     

The analysis of the outcomes and factors related to iliac–obturator involvement in cutaneous melanoma patients after lymph node dissection due to positive sentinel lymph node biopsy or clinically detected inguinal metastases

Background

We assessed clinical–pathological features and outcomes of cutaneous melanoma patients after ilio-inguinal lymph node dissection (LND) in relation to the presence of metastases in iliac–obturator nodes.

Methods

We analyzed 390 consecutive patients who underwent ilio-inguinal therapeutic LND [TLND] (237) due to clinical/cytologically detected metastases or after completion LND [CLND] (153) due to positive SLN biopsy (in one cancer centre 1994–2009). Median follow-up time was 60 months.

Results

The 5-year overall survival (OS) rate was 49% and median OS – 52 months in the entire group of patients. According to univariate analysis following factors had significant negative influence on OS: presence of metastases to iliac–obturator nodes (5-year OS for positive versus negative: 54.5% and 32%, respectively), macrometastases, higher Breslow thickness, ulceration, higher Clark level, male gender, number of metastatic lymph nodes, extracapsular extension, and, additionally in the CLND group – micrometastases size ≥0.1 mm according to the Rotterdam criteria and non-subcapsular location of micrometastases. Iliac–obturator involvement was also negative factor for OS in multivariate analysis. The presence of iliac–obturator nodal metastases correlated with the following factors: type of LND–CLND versus TLND (15% versus 27.5%) of iliac–obturator involvement, respectively), higher Breslow thickness, extracapsular extension of nodal metastases, male gender. We have not identified any metastases in iliac–obturator nodes in group of patients with micrometastases size ≤1.0 mm and primary tumour Breslow thickness <4.0 mm or no ulcerated primary tumours.

Conclusions

Metastases to iliac–obturator nodes have additional negative prognostic value for melanoma patients with inguinal basin involvement. We are able to identify the subgroup of patients after positive SLN biopsy without metastases to iliac–obturator nodes, probably requiring only inguinal LND.     

Prognostic value of lymph node metastases and lymph node ratio in esophageal squamous cell carcinoma

Aims

Although the positive lymph node (LN) metastasis in patients with thoracic esophageal squamous cell carcinoma carcinoma (SCC) has been reported to be a risk factor to reduce long-term survival, only a few studies have so far evaluated the lymph node metastasis among this group of patients. The purpose of this study was to evaluate the impact of lymph node positivity and ratio on survival of esophageal SCC.

Methods

All patients undergoing esophagectomy at the Forth Hospital of Hebei Medical University between January 1986 and December 2002 were reviewed. Survival curves were estimated using the Kaplan-Meier method.

Results

Of 1325 patients with invasive cancer, had squamous cell cancer of the esophagus. Median overall survival (OS) of the entire group was 36.7 months and 5-year OS was 39.3%. The most significant prognostic factor for overall survival was the presence of positive LN (P < 0.01). Additionally, patients with zero involved LN had a 5-year survival of 49.1%, while patients with 1–3 positive LN and >3 positive LN had 5-year survival of 19.5% and 11.0%, respectively (P < 0.01). Finally, an increasing ratio of positive to examined LN was linearly associated with a worsening 5-year survival, patients with <25%, 25%–50% and >50% positive LN had 5-year survival of 47.53%, 14.6% and 8.9%, respectively (P < 0.01).

Conclusion

Increasing number of positive LN in patients with esophageal cancer and increasing ratio of metastatic to examine LN portend a poor prognosis. These factors should play an important role in predicting prognosis of patients.     

Evaluation of EGFR protein expression by immunohistochemistry using H-score and the magnification rule: Re-analysis of the SATURN study

Introduction

The phase III SATURN study demonstrated that first-line maintenance erlotinib extended progression-free survival (PFS) and overall survival (OS) versus placebo in patients with advanced non-small cell lung cancer (NSCLC). Analysis of epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) found no significant interaction between EGFR IHC status and PFS (p = 0.63) or OS (p = 0.52). The FLEX study of first-line cetuximab plus chemotherapy demonstrated that EGFR IHC expression was predictive of improved OS with cetuximab when assessed by H-score with a magnification rule. This novel method was used to reassess samples from SATURN.

Methods

The H-score method assigned a score of 0–300 to each patient, based on the percentage of cells stained at different intensities viewed at various magnifications. The discriminatory threshold was set at 200, per the FLEX study, and existing samples were re-read and classed as low (H-score < 200) or high (≥200) EGFR expression. PFS and OS were re-analyzed based on these new classifications.

Results

In the overall and EGFR wild-type populations, erlotinib provided a consistent survival benefit versus placebo. Hazard ratios (HRs) in the overall population were similar between EGFR IHC-positive and -negative patients for median PFS (HR 0.68 [95% confidence interval (CI) 0.53–0.86] and 0.76 [95% CI 0.62–0.93], respectively) and OS (HR 0.80 [95% CI 0.62–1.05] and 0.80 [95% CI 0.64–1.01] for IHC-positive and IHC-negative, respectively). In the EGFR wild-type population, HRs were again similar between EGFR IHC-positive and -negative subpopulations for PFS (HR 0.69 [95% CI 0.51–0.95] and 0.84 [95% CI 0.63–1.12], respectively) and OS (HR 0.78 [95% CI 0.55–1.10] and 0.76 [95% CI 0.55–1.05], respectively).

Conclusions

These data suggest that EGFR IHC does not have value as a marker to predict erlotinib benefit in the first-line maintenance setting for advanced NSCLC.     

Prognosis following local recurrence after breast conserving treatment in young women with early breast cancer

Background

Few studies have focussed on the prognosis of young women with local recurrence (LR) after breast-conserving therapy and the factors that can be used to predict their prognosis.

Methods

We studied the outcome and related prognostic factors in 124 patients with an isolated local recurrence in the breast following breast-conserving surgery and radiotherapy for early stage breast cancer diagnosed at the age of 40 years or younger.

Results

The median follow-up of the patients after diagnosis of LR was 7.0 years. At 10 years from the date of salvage treatment, the overall survival rate was 73% (95% CI, 63–83), the distant recurrence-free survival rate was 61% (95% CI, 53–73), and the local control rate (i.e. survival without subsequent LR or local progression) was 95% (95% CI, 91–99). In the multivariate analysis, the risk of distant metastases also tended to be higher for patients with LR occurring within 5 years after BCT, as compared to patients with LR more than 5 years after BCT (Hazard ratio [HR], 1.89; p = 0.09). A worse distant recurrence-free survival was also observed for patients with a LR measuring more than 2 cm in diameter, compared to those with a LR of 2 cm or smaller (HR, 2.88; p = 0.007), and for patients with a LR causing symptoms or suspicious findings at clinical breast examination, compared to those with a LR detected by breast imaging only (HR 3.70; p = 0.03).

Conclusions

These results suggest that early detection of LR after BCT in young women can improve treatment outcome.     

Prognosis for gastric carcinomas with an insufficient number of examined negative lymph nodes

Background

The optimal system for lymph node (LN) staging in gastric cancer is still a subject of debate. The aim of our study was to analyse the probability of error in negative LN (pN0) gastric carcinomas when a low number of LNs were harvested using a probabilistic model.

Methods

Patients with gastric carcinoma who underwent R0 resection at three university hospitals between 2004 and 2009 were retrospectively included. A Bayesian model was used to analyse the probability of error for negative LNs (pN0) gastric carcinomas. Kaplan–Meier survival curves and the log-rank test were used to compare the overall and specific mortality of prognosis groups.

Results

Of the 291 patients included, 123 were classified as pN0 (42%). A significant correlation was found between the extent of the LN dissection performed and the number of the LNs retrieved. According to the Bayesian model the carcinomas with 9 or fewer negative lymph nodes were considered to have a high risk (HR) of misclassification, whereas patients with 10–25 LNs analysed and those with more than 26 negative lymph nodes were considered to have a moderate risk (MR) and low risk (LR), respectively. The log-rank test showed a significant improvement in the disease-specific survival for the MR pN0 (p < 0.001) and LR pN0 (p < 0.04) but not for the HR pN0 patients compared to pN1 patients.

Conclusions

The proposed probabilistic model is clinically useful for differentiating the prognosis in pN0 gastric carcinomas when an insufficient number of negative lymph nodes are retrieved.     

Long-term survival after combined modality treatment in metastatic bladder cancer patients presenting with supra-regional tumor positive lymph nodes only

Aims

To evaluate if combined treatment should be offered to bladder cancer patients presenting with supra-regional lymph node metastases only and a clinical complete or partial response after chemotherapy.

Patients and methods

We identified 14 patients with supra-regional lymph node metastases out of 394 patients with transitional cell carcinoma (TCC) treated in our institute with cystectomy and regional and supra-regional lymph node dissection between 1987 and 2007. Prior to cystectomy, neoadjuvant chemotherapy had been given. The patients received a total of four cycles of platinum-based chemotherapy.

Results

Five patients had a CR, nine patients had a PR after neoadjuvant chemotherapy. Histopathological proof of complete response in the bladder was confirmed in all five cases. One of these five patients had a CR in the bladder but pelvic lymph nodes still contained vital tumor. Five patients had no tumor in the lymph nodes, whereas four had tumor in the lymph nodes. Eleven patients died due to bladder cancer, seven of them within 1 year after cystectomy. The 3- and 5-year disease-specific survival rates were 36% (95% CI: 10–60%) and 24% (95% CI: 0–49%). Mean follow-up was 2.5 years.

Conclusions

Combination therapy consisting of neoadjuvant chemotherapy and surgery in selected patients with tumor positive supra-regional lymph nodes only can result in durable long-term survival rates (24% 5-year survival). Response evaluation after neoadjuvant chemotherapy might play a decisive role in the selection of patients undergoing subsequent surgical removal of all known tumor sites.     

Lymph node size and metastatic infiltration in adenocarcinoma of the pancreatic head

Background

Preoperative lymph node staging of pancreatic cancer by CT relies on the premise that malignant lymph nodes are larger than benign nodes. In imaging procedures lymph nodes >1 cm in size are regarded as metastatic nodes. The extend of lymphadenectomy and potential application of neoadjuvant therapy regimens could be dependent on this evaluation.

Patients and methods

In a morphometric study regional lymph nodes from 52 patients with pancreatic cancer were analyzed. The lymph nodes were counted, the largest diameter of each node was measured, and each node was analyzed for metastatic involvement by histopathological examination. The frequency of metastatic involvement was calculated and correlated with lymph node size.

Results

A total of 636 lymph nodes were present in the 52 specimens examined for this study (12.2 lymph nodes per patient). Eleven patients had a pN0 status, whereas 41 patients had lymph nodes that were positive for cancer. Five-hundred-twenty (82%) lymph nodes were tumor-free, while 116 (18%) showed metastatic involvement on histopathologic examination. The mean (±SD) diameter of the nonmetastatic nodes was 4.3 mm, whereas infiltrated nodes had a diameter of 5.7 mm (p = 0.001). Seventy-eight (67%) of the infiltrated lymph nodes and 433 (83%) of the nonmetastatic nodes were ≤5 mm in diameter. Of 11 pN0 patients, 5 (45%) patients had at least one lymph node ≥10 mm, in contrast only 12 (29%) out of 41 pN1 patients had one lymph node ≥10 mm.

Conclusion

Lymph node size is not a reliable parameter for the evaluation of metastatic involvement in patients with pancreatic cancer.     

Lymph Node Ratio Predicts Recurrence in Papillary Thyroid Cancer

Background.

Lymph node metastasis occurs in 20%–50% of patients presenting for initial treatment of papillary thyroid cancer (PTC). The significance of lymph node metastases remains controversial, and the aim of this study is to determine how the lymph node ratio (LNR) may predict the likelihood of disease recurrence.

Methods.

We conducted a retrospective review of patients undergoing total thyroidectomy for PTC at our institution from 2005 to 2010. A total LNR (positive nodes to total nodes) and central lymph node ratio (cLNR) was calculated. Regression was used to determine a threshold LNR that best predicted recurrence. Multivariate logistic regression then determined the influence of LNR on recurrence while accounting for other known predictors of recurrence. Kaplan-Meier analysis and the log-rank test were used to compare differences in disease-free survival.

Results.

Of the 217 patients undergoing total thyroidectomy for PTC, 69 patients had concomitant neck dissections. Sixteen (23.2%) patients developed disease recurrence. When disease-free survival functions were compared, we found that patients with a total LNR ≥0.7 (p < .01) or a cLNR ≥0.86 (p = .04) had significantly worse disease-free survival rates than patients with ratios below these threshold values. Considering other known predictors of recurrence, we found that LNR was significantly associated with recurrence (odds ratio: 19.5, 95% confidence interval: 4.1–22.9; p < .01).

Conclusions.

Elevated total LNR and cLNR are strongly associated with recurrence of PTC after initial operation. LNR in PTC is a tool that can be used to determine the likelihood of the patient developing recurrent disease and inform postoperative follow-up.     

Sentinel lymph node biopsy in patients with microinvasive breast cancer: A systematic review and meta-analysis

Background

The aim of this meta-analysis is to evaluate the role of sentinel lymph node biopsy (SLNB) in patients with microinvasive breast cancer.

Methods

We searched MEDLINE and ISI Web of Science to identify studies including patients with microinvasive breast cancer who underwent SLNB and reported the rate of sentinel-node positivity. We performed proportion meta-analysis using either fixed or random-effects model based on the between-study heterogeneity.

Findings

A total of 24 studies including 968 patients met the eligibility criteria. The summary estimate for the sentinel-node (SN) positivity rate was 3.2% (95% Confidence Interval (CI): 2.1%–4.6%), 4.0% (95% CI 2.7%–5.5%), and 2.9% (95% CI: 1.6%–4.6%) for macrometastasis, micrometastasis and isolated tumor cells (ITC) respectively. Significant between-study heterogeneity was observed only in the meta-analysis of ITC positivity rate.

Interpretation

The amount of positive sentinel node in patients with proven microinvasive breast cancer is relatively low. As a result, the indications for SLNB in these patients should be probably individualized.     

The prognostic value of tumour-stroma ratio in triple-negative breast cancer

Background

Triple-negative cancer constitutes one of the most challenging groups of breast cancer given its aggressive clinical behaviour, poor outcome and lack of targeted therapy. Until now, profiling techniques have not been able to distinguish between patients with a good and poor outcome. Recent studies on tumour-stroma, found it to play an important role in tumour growth and progression.

Objective

To evaluate the prognostic value of the tumour-stroma ratio (TSR) in triple-negative breast cancer.

Methods

One hundred twenty four consecutive triple-negative breast cancer patients treated in our hospital were selected and evaluated. For each patient the Haematoxylin-Eosin (H&E) stained histological sections were evaluated for percentage of stroma. Patients with less than 50% stroma were classified as stroma-low and patients with ≥50% stroma were classified as stroma-high.

Results

Of 124 triple-negative breast cancer patients, 40% had a stroma-high and 60% had a stroma-low tumour. TSR was assessed by two investigators (kappa 0.74). The 5-years relapse-free period (RFP) and overall survival (OS) were 85% and 89% in the stroma-low and 45% and 65% in the stroma-high group. In a multivariate cox-regression analysis, stroma amount remained an independent prognostic variable for RFP (HR 2.39; 95% CI 1.07–5.29; p = 0.033) and OS (HR 3.00; 95% CI 1.08–8.32; 0.034).

Conclusion

TSR is a strong independent prognostic variable in triple-negative breast cancer. It is simple to determine, reproducible and can be easily incorporated into routine histological examination. This parameter can help optimize risk stratification and might lead to future targeted therapies.     

Lower survival after right-sided versus left-sided colon cancers: Is an extended lymphadenectomy the answer?

Introduction

Tumour location may affect oncologic outcomes for colon adenocarcinoma due to different levels of vascular ligation and nodal harvest, but the data are equivocal. The objective of this study is to determine the effect of tumor location and lymph node yield on overall survival(OS) in stage I-III colon adenocarcinoma.

The significance of immunohistochemistry positivity in sentinel nodes which are negative on haematoxylin and eosin in breast cancer

Introduction

Sentinel lymph node (SLN) biopsy allows a more detailed examination of a smaller number of lymph nodes in patients with clinically node negative breast cancer. Immunohistochemistry detects small tumour burden not routinely seen on haematoxylin and eosin (H&E). The significance of such findings remains to be fully elucidated.

Aim

To assess the axillary disease burden of patients in whom the sentinel lymph node biopsy was positive on immunohistochemistry and negative on H and E.

Methods

An analysis of patients who underwent SLN mapping for breast cancer at St Vincent's University Hospital from January 1st, 2000 to December 31st, 2006 was conducted. All SLNs were assessed by serial H&E and IHC sections. Patients with micrometastases (0.2–2 mm) underwent a completion axillary lymph node dissections (CLND). Patients with ITC (<0.2 mm) were individually discussed and a CLND was performed selectively based on additional clinicopathological criteria and patient preference. Analysis of the additional nodes from CLND was performed. Patients were followed for a median of 27 months (range 12–72 months).

Results

1076 patients who underwent SLN were included for analysis. 211 (20%) had a positive SLN biopsy using H&E. Forty-nine patients (5%) had a negative SLN on H&E which was positive on IHC. Of these, 15 had micrometastases and underwent a CLND. Two had further axillary nodal disease. ITC were found in the remaining 34 patients. Sixteen of these patients underwent a CLND. Five of this group had further nodal disease.

Conclusion

Micrometastases and isolated tumour cells, detected only by immunohistochemical analysis of sentinel lymph nodes, are associated with further positive nodes in the axilla in up to 15% of patients. This upstaging of disease may impact upon patient outcome.