Solitary Nodal Recurrence in the Dorsal Area of the Thoracic Aorta After a Curative Resection of Esophageal Cancer: Report of Two Cases

Although locoregional recurrence is often observed in the cervicothoracic area even after an esophagectomy with three-field lymph node dissection (3FL), recurrence in the mediastinal lymph nodes is relatively rare. We experienced two cases of solitary recurrence in a posterior mediastinal node (No 112-ao) after a curative resection for thoracic esophageal cancer. The lymph node recurrence was located in the connective tissue adjacent to the left posterior wall of the thoracic aorta, and thus could not have been removed by the conventional approach of an esophagectomy through a right thoracotomy. These two patients underwent surgical removal of the tumor through left thoracotomy, and survived for 5 years and 1 year without recurrence, respectively. Because the rate of metastasis in this area appears to be low, it is not always necessary to perform complete nodal dissection of the left side of the descending aorta at the initial surgery in cases of thoracic esophageal cancer. However, our experience suggests the importance of periodic computed tomography scans to check for any nodal recurrence in this area, since a surgical resection may be effective when the recurrence is detected as a solitary metastasis.     

Long-term Results after Dissection of Positive Thoracic Lymph Nodes in Patients with Esophageal Squamous Cell Carcinoma

Background Although thoracic lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma (SCC) has been reported to be a negative risk factor for long-term survival, only a few studies have evaluated the clinicopathologic difference between the impact of metastasis to the paraesophageal lymph nodes and to the nonparaesophageal lymph nodes. The purpose of this study was to evaluate surgical outcome after the clearance of metastatic thoracic lymph nodes. Methods Retrospectively reviewed were 164 consecutive patients with thoracic esophageal SCC who had not had preoperative treatment and underwent surgery from 1980 to 2005 and were found to have thoracic lymph node metastases. Of these patients, 83 underwent surgery from 1980 to 1994 and 81 from 1995 to 2005. Univariate and multivariate analyses were performed to evaluate the impact of nonparaesophageal lymph node metastasis on survival. Results Univariate analysis revealed that T3/T4 tumors and the presence of nonparaesophageal node metastases were associated with only a 20% overall five-year survival rate. The overall five-year survival for the most recent period was significantly better than for the former period (42% vs. 13%, p < 0.01). Based on a multivariate analysis of prognostic impact of each nonparaesophageal node, the presence of metastatic subcarinal and/or posterior mediastinal nodes was an independent risk factor for reduced survival. Conclusion Surgical outcome for patients with thoracic esophageal cancer and metastatic thoracic lymph nodes has improved during the last 25 years. Although postoperative chemotherapy might improve survival, the presence of T3/T4 tumors and/or metastatic nonparaesophageal nodes were unfavorable factors for survival.     

Prediction of Lymph Node Metastasis with Use of Artificial Neural Networks Based on Gene Expression Profiles in Esophageal Squamous Cell Carcinoma

Background: The aim of the study was (1) to detect candidate genes involved in lymph node metastasis in esophageal cancers and (2) to investigate whether we can estimate and predict occurrence of lymph node metastasis by analyzing artificial neural networks (ANNs) using these gene subsets.Methods: Twenty-eight primary esophageal squamous cell carcinomas were used. Gene expression profiles of all primary tumors were obtained by cDNA microarray. Lymph node metastasis–related genes were extracted with use of Significance Analysis of Microarrays (SAM). Predictive accuracy for lymph node metastasis was calculated by evaluation of 28 cases by ANNs with leave-one-out cross-n. The results were compared with those of other analyses such as clustering or predictive scoring (LMS).Results: Our ANN model could predict lymph node metastasis most accurately with 60 clones. The highest predictive accuracy for lymph node metastasis by ANN was 10 of 13 (77%) in newly added cases that were not used for gene selection by SAM and 24 of 28 (86%) in all cases (sensitivity: 15/17, 88%; specificity: 9/11, 82%). Predictive accuracy of LMS was 9 of 13 (69%) in newly added cases and 24 of 28 (86%) in all cases (sensitivity: 17/17, 100%; specificity: 7/11, 67%). It was difficult to extract useful information for the prediction of lymph node metastasis by clustering analysis.Conclusions: ANN had superior potential in comparison with other methods of analysis for the prediction of lymph node metastasis. This systematic analysis combining SAM with ANN was very useful for the prediction of lymph node metastasis in esophageal cancers and could be applied clinically in the near future.     

Expression and Prognostic Value of MG7-Ag in Patients With Surgically Resectable Esophageal Squamous Cell Carcinoma

Purpose MG7-Ag is a human gastric-carcinoma-associated antigen. The expression of MG7-Ag was found to increase gradually with the development and progression of gastric cancer. Moreover, a poorer prognosis was found in MG7-Ag positive gastric-carcinoma patients than in MG7-Ag negative patients. However, neither MG7-Ag expression nor its clinical significance has been previously examined in squamous cell carcinoma (SCC) of the esophagus. In this study, we examined the expression of MG7-Ag in esophageal squamous cell carcinomas to assess its value as a prognostic indicator. Methods The expression of MG7-Ag was detected in 112 cases of esophageal squamous cell carcinoma (SCC) by immunohistochemical analysis. The relation of MG7-Ag staining with various clinicopathological features was statistically analyzed. Results The staining of MG7-Ag was detected in SCC, while not in normal epithelial cells. In esophageal SCC, MG7-Ag was found significantly correlated with depth of invasion (P = .012), in T4, T3 carcinomas but not in T2, T1 carcinomas, lymph node metastases (P = .029), pathological stage (P = .005). Consistently, the survival rate tended to be statistically lower in patients with MG7-Ag positive SCCs than in MG7-Ag negative SCCs (P = .005). However, no significant difference was observed between MG7-expression and patient age, sex, tumor location, differentiation, distant metastasis, and lymphatic invasion. Conclusion MG7-Ag might play a positive role in the process of carcinogenesis and progression of esophageal SCC, and it could be considered as one valuable prognostic indicator in esophageal SCC.     

Thoracic Duct Resection During Esophagectomy Does Not Contribute to Improved Prognosis in Esophageal Squamous Cell Carcinoma: A Propensity Score Matched-Cohort Study

Purpose

Esophagectomy with extended lymphadenectomy remains the mainstay of treatment for localized esophageal squamous cell carcinoma (ESCC). Thoracic duct (TD) resection has been recommended as part of extended lymphadenectomy, although its merits are unclear. The aim of this two-institutional, matched-cohort study is to clarify whether TD resection improves prognosis in esophagectomy for ESCC.

Patients and Methods

In this two-institutional, matched-cohort study of 399 patients with ESCC who underwent McKeown esophagectomy between 2010 and 2014, the primary outcomes were overall survival (OS), disease-free survival (DFS), and cause-specific survival (CSS). Secondary outcomes were perioperative results and recurrence patterns.

Results

Based on a propensity score, 122 TD-resected or 122 TD-preserved patients in all stages were selected (median follow-up 4.5 years). The 5-year OS, DFS, and CSS rates in the TD-resected versus TD-preserved groups were 49% versus 60%, 53% versus 57%, and 58% versus 70%, respectively, without any significant differences. Operative time for the thoracic procedure was significantly longer and the number of retrieved mediastinal nodes was significantly higher in the TD-resected group (P = 0.009 and 0.005, respectively). The rates of chylothorax and left recurrent laryngeal nerve (RLN) palsy were significantly higher in the TD-resected group (P = 0.041 and 0.018, respectively). There were no significant differences in rates of local or distant metastases between the two groups.

Conclusions

TD resection does not contribute to improve OS, DFS, or CSS in ESCC but increases incidence of chylothorax and left RLN palsy. Prophylactic TD resection should be avoided in esophagectomy for ESCC.

     

SnoN Overexpression is Predictive of Poor Survival in Patients with Esophageal Squamous Cell Carcinoma

Background  Earlier studies have identified the minimal overlapping region of amplification at 3q26 in esophageal squamous cell carcinoma (ESCC) by comparative genomic hybridization (CGH) analysis. These include PIK3CA which encodes the p110α catalytic subunit of phosphatidylinositol (PI) 3-kinase, a telomerase RNA component (TERC), a squamous cell carcinoma-related oncogene (SCCRO), ecotropic viral integration site-1 (EVI-1), and a Ski-related novel oncogene (SnoN). In the present study, we investigated the mRNA levels of four candidate genes (TERC, SCCRO, EVI-1, and SnoN) to determine whether genes other than PIK3CA are targets for amplification at 3q26 in ESCC. And also, we examined SnoN expression in ESCC samples. Methods  Fifty-nine representative cases with ESCC were selected from our archives. We performed quantitative RT-PCR of four candidate genes (TERC, SCCRO, EVI-1, and SnoN) and immunohistochemistry for SnoN. Finally, we correlated these findings with the clinicopathological characteristics to determine their interrelationship. Results  Among the four genes we tested, only SnoN mRNA was consistently overexpressed in primary ESCC, compared with those in corresponding nontumorous esophageal epithelia (P < 0.001). Immunoreactive SnoN was detectable in 31 of 59 (52.5%) esophageal squamous cell carcinoma specimens. The levels of SnoN expression were found to correlate with the depth of invasion and recurrence (P < 0.05). Furthermore, patients with positive staining for SnoN displayed more unfavorable outcomes than patients with negative staining (P < 0.05). Conclusion   SnoN is likely to be the target of the amplification at 3q26 in ESCC and plays an important role in the development of ESCC, influencing disease-specific survival.     

Dynamic Sentinel Lymph Node Biopsy in Patients with Invasive Squamous Cell Carcinoma of the Penis: A Prospective Study of the Long-Term Outcome of 500 Inguinal Basins Assessed at a Single Institution

Background

Dynamic sentinel node biopsy (DSNB) in combination with ultrasound scan (USS) has been the technique of choice at our centre since 2004 for the assessment of nonpalpable inguinal lymph nodes (cN0) in patients with squamous cell carcinoma of the penis (SCCp). Sensitivity and false-negative rates may vary depending on whether results are reported per patient or per node basin, and with or without USS.

Objective

To determine the long-term outcome of patients undergoing DSNB and USS-guided fine-needle aspiration cytology (FNAC) in our cohort of newly diagnosed cN0 SCCp patients, as well as to analyse any variation in sensitivity of the procedure.

Design, setting, and participants

A series of consecutive patients with newly diagnosed SCCp, over a 6-yr period (2004–2010), were analysed prospectively with a minimum follow-up period of 21 mo. All patients had definitive histology of ≥T1G2 and nonpalpable nodes in one or both inguinal basins. Patients with persistent or untreated local disease were excluded from the study.

Intervention

All eligible patients had DSNB and USS with or without FNAC of cN0 groins.

Outcome measurements and statistical analysis

The primary end point was no nodal disease recurrence on follow-up. The secondary end point was complications after DSNB. Sensitivity of the procedure was calculated per node basin, per patient, with DSNB alone, and with USS with DSNB combined.

Results and limitations

Five hundred inguinal basins in 264 patients underwent USS with or without FNAC and DSNB. Seventy-three positive inguinal basins (14.6%) in 59 patients (22.3%) were identified. Four inguinal basins in four patients were confirmed false negative at 5, 8, 12, and 18 mo. Two inguinal basins had positive USS and FNAC and negative DSNB results. Sensitivity of DSNB with USS, with and without FNAC, per inguinal basin was 95% and per patient was 94%. Sensitivity of DSNB alone per inguinal basin and per patient was 92% and 91%, respectively. The DSNB morbidity rate was 7.6%.

Conclusions

DSNB in combination with USS has excellent performance characteristics to stage patients with cN0 SCCp, with a 5% false-negative rate per node basin and a 6% false-negative rate per patient.     

Salvage Lymphadenectomy of the Right Recurrent Nerve Node with Tracheal Involvement After Definitive Chemoradiation Therapy for Esophageal Squamous Cell Carcinoma: Report of Two Cases

Thoracic esophageal cancers frequently metastasize to the right recurrent nerve nodes (RRNNs). In fact, huge RRNNs invading the trachea sometimes remain after definitive chemoradiation therapy (CRT), despite complete remission of the primary lesion. We performed salvage lymphadenectomy of a large RRNN combined with partial resection of the trachea in two patients. Using an anterior approach, we removed part of the sternum, clavicle, and the first and second costal cartilage; then, we removed the RRNNs with combined resection of the lateral quarter circumference of the trachea, the esophageal wall, and the recurrent nerve. Reconstruction was done with a musculocutaneous patch of major pectoral muscle to cover the tracheal defect. The only minor complication was venous thrombosis in one patient. Thus, combined removal of the RRNN and trachea was performed safely as a salvage operation after definitive CRT for esophageal squamous cell carcinoma.     

Improved Staging of Cervical Metastases in Clinically Node-Negative Patients With Head and Neck Squamous Cell Carcinoma

Background: The management of the N0 neck in oral and oropharyngeal cancer is often determined by the risk of metastases related to features of the primary tumor. Where the risk of metastases is >20%, elective neck dissection (END) has been advocated. This study reviewed clinical staging, surgical staging, pathologic staging, and histopathologic parameters to determine the prediction of nodal metastases and micrometastases in patients with head and neck squamous cell carcinoma.Methods: A prospective series of 61 clinically neck node–negative patients undergoing surgical resection of a T1/2 intraoral or oropharyngeal invasive squamous cell carcinoma and surgical staging of the neck, with sentinel node biopsy (SNB) alone or SNB-assisted END, between June 1998 and March 2002 were included in this study.Results: Pathologic upstaging of the clinically N0 neck occurred in 27 (44%) of 61 patients. Routine pathology with hematoxylin and eosin upstaged disease in 22 of 27 patients (sensitivity of 81%). Five patients with micrometastasis were staged pN1mi after stepped serial sectioning and immunohistochemistry. Tumor thickness, a noncohesive invasive front, and perineural and bone invasion were all histological predictors for cervical metastases. Five patients with micrometastases were staged pN1mi.Conclusions: Both clinical staging and routine pathologic staging underestimate the presence of nodal metastases. Staging with either SNB alone or SNB-assisted END shows promise in the management of the N0 neck by identifying patients with micrometastases (pN1mi).     

Esophageal Cancer With Cirrhosis of the Liver: Results of Esophagectomy in 18 Consecutive Patients

Backgrounds: Patients with cirrhosis of the liver sometimes are candidates for esophagectomy with extensive lymphadenectomy.Materials and Methods: Of 271 patients with primary esophageal carcinoma, 19 patients (7.0%) had pathologically proven cirrhosis of the liver. Among those, 18 patients underwent esophagectomy with extensive lymph node dissection. Clinicopathologic characteristics of these 18 patients were retrospectively investigated.Results: Pathological T stages were pT1 in 3 patients, pT2 in 9 patients, pT3 in 2 patients, and pT4 in 4 patients. Hepatitis C virus antibody was positive in 1 patient, and 14 patients were alcoholics. Three patients had cryptogenic cirrhosis. Seven patients were classified as Child- Turcotte B and 11 were Child-Turcotte A. Three patients had ICG-R 15 over 30%. Fifteen patients (83.3%) developed a total of 35 postoperative complications. Three patients currently are alive without recurrence. Fifteen patients have died: 7 from cancer recurrence; 5 of causes unrelated to esophageal cancer; and 3 of operative death (operative mortality: 16.7% in 18 cirrhotic patients vs. 5.7% in 227 non-cirrhotic patients; P 5 .102). The 1- and 3-year survival rates for 18 resected cirrhotic patients were 50% and 21%, respectively, and those for 227 resected non-cirrhotic patients were 67% and 42%, respectively (P 5 .051). When operative deaths were excluded from the analysis, the 1- and 3-year survival rates for 15 cirrhotic patients were 60% and 25%, respectively, whereas those for 214 non-cirrhotic patients were 68% and 43%, respectively (P 5 .271).Conclusion: Although cirrhosis has a high morbidity and mortality rate, Child-Turcotte A and B cirrhosis may not contraindicate curative esophagectomy for esophageal carcinoma. However, these patients need meticulous perioperative care to avoid postoperative complications.     

Multivariate Analysis of the Pathologic Features of Esophageal Squamous Cell Cancer: Tumor Budding Is a Significant Independent Prognostic Factor

Absract Background  Tumor budding has been suggested to be a prognostic factor in various cancers but has never been studied in esophageal cancer. Methods  In this study, the microscopic finding of tumor budding in esophageal squamous cell carcinoma was correlated with outcome after esophagectomy. One hundred and thirty-six patients undergoing a curative esophagectomy were assigned to either a frequent (n = 82) or rare (n = 54) group according to the microscopically observed frequency of tumor budding in the tumor. Results  The 5-year survival rates after esophagectomy were 35.4% for the frequent group and 81.3% for the rare group. Multivariate analysis using the Cox proportional hazards model by a stepwise method identified this morphological variable as a significant independent prognostic factor. Conclusions  Tumor budding in esophageal squamous cell carcinoma reflects the biological activity of the tumor and may be a useful prognostic indicator.     

Radiolocalized Sentinel Lymph Node Biopsy in Squamous Cell Carcinoma of the Oral Cavity and Analysis of Various Parameters

Background Sentinel lymph node (SLN) biopsy seems to be a method that solves the problem of neck management with oral squamous cell carcinoma. Using blue dye methods for detection of neck SLNs from the surface of the operative field seems difficult; therefore, we used radiolocalization alone to detect and extract sentinel nodes. Aside from the various histological and clinical parameters examined in this procedure, we also determined whether they had any clinical significance in relation to the detection of SLNs during the operation. Methods Enrolled subjects had preoperative clinical N0 stage squamous cell carcinoma of the oral cavity and had received an unfiltered ^99mTc sulfur colloid peritumoral injection. Localization of the SLNs was performed by using lymphoscintigraphy and a handheld gamma probe. Results In total, 28 oral squamous cell carcinoma patients were included in this prospective study. Sixty-four SLNs in 27 patients were identified by this method. The identification rate was 96.4%. No false-negative predictions of SLN were noted among any of the patients studied. The numbers of the SLNs found during the operation were larger in patients with positive findings than those with negative findings (P < .05 by the Mann-Whitney U-test). Conclusions SLN radiolocalization provided an acceptable identification rate. The cases of positive findings for metastasis seemed to statistically have more SLNs than did those with negative findings, but more evidence is needed to prove this point. Therefore, SLN biopsies for extracting all possible high-risk nodes may be conducive for oral squamous cell carcinoma surgery.     

Predictors of Cancer-specific Mortality After Disease Recurrence in Patients with Squamous Cell Carcinoma of the Penis

Disease recurrence occurs frequently after surgical treatment for squamous cell carcinoma of the penis (SCCp). We sought to determine prognostic factors that influence cancer-specific mortality (CSM) after disease recurrence in patients with SCCp. We performed a retrospective analysis of 314 patients who experienced disease recurrence after surgical treatment for SCCp between 1949 and 2012. Competing risk regression analysis addressed factors associated with CSM after SCCp recurrence. Median time from surgery to disease recurrence was 10.5 mo (interquartile range [IQR]: 5.9–21.3). Of the recurrences, 165 (53%), 118 (38%), and 31 (9.9%) were local, regional, or distant, respectively. Within a median follow-up of 4.5 yr (IQR: 2.0–6.5), 108 patients died of SCCp and 41 patients died of causes other than SCCp. Shorter time to disease recurrence was found to be significantly associated with a higher risk of CSM (p = 0.0006). Lymph node metastasis at the time of initial treatment (subdistribution hazard ratio [SHR]: 1.96; 95% confidence interval [CI] 1.23– 3.11; p = 0.005) and regional recurrence (SHR: 4.14; 95% CI, 2.16–7.93; p < 0.0001) or distant recurrence (SHR: 5.75; 95% CI, 2.59–12.73; p < 0.0001) were associated with increased risk of CSM after disease recurrence. Inclusion of time to recurrence into risk stratification may help patient counseling and treatment planning.     

Prognostic Impact of Pretreatment Serum CYFRA Status in 1047 Patients with Esophageal Squamous Cell Carcinoma Who Underwent Radical Resection: A Japan Esophageal Society Promotion Research

Purpose: The prognostic significance of pretreatment serum C-terminus of cytokeratin 19 (CYFRA21-1, CYFRA) status was evaluated in the patients with surgically treated esophageal squamous cell carcinoma.Methods: A total of 1047 patients with surgically treated esophageal cancer were enrolled in a multi-institutional study promoted by the Japanese Esophageal Society. This study included an up-front surgery group (n = 412), a neoadjuvant chemotherapy (NAC) group (n = 486), and a neoadjuvant chemoradiation/radiation therapy (NACRT/RT) group (n = 149). The pretreatment CYFRA status was analyzed to assess prognostic significance using multivariate analysis according to treatment modalities.Results: The CYFRA-positive group was significantly associated with deep tumor. Univariate analysis showed that the overall survival of the CYFRA-positive group was significantly worse than that of the CYFRA-negative group, but the difference was not significant in the multivariate analysis. CYFRA was an independent risk factor for poor prognosis just in the NACRT/RT group.Conclusions: The CYFRA-positive group was associated with deep tumor and poor survival. Pretreatment CYFRA was not an independent risk factor for poor prognosis in the up-front surgery group or NAC group. It was an independent risk factor for poor prognosis just in the NACRT/RT group.     

Comparison of Surgical Results of D2 Versus D3 Gastrectomy (Para-Aortic Lymph Node Dissection) for Advanced Gastric Carcinoma: A Multi-Institutional Study

Background Curative gastrectomy is a promising approach for the treatment of gastric cancer; however, the optimal extent of lymph node dissection for advanced cancer remains controversial. The aim of this multi-institutional study was to evaluate the feasibility of D3 gastrectomy (para-aortic lymph node dissection) for advanced gastric cancer. The surgical results of D2 and D3 gastrectomy (para-aortic lymph node dissection) were retrospectively compared. Methods A series of 580 advanced gastric cancer patients were registered between 1992 and 2000. Of these, 430 underwent D2 gastrectomy and 150 underwent D3 gastrectomy. Survival time, prognostic factors, postoperative morbidity/mortality, and pattern of recurrence were compared. Results There was no significant difference in survival time between D2 and D3 patients. However, the survival times of D3 patients with tumor diameters measuring 50 to 100 mm or with pN1 disease were significantly longer than those of the corresponding D2 patients. Analysis of the survival of patients with tumor diameters measuring 50 to 100 mm revealed that D3 gastrectomy conferred a survival advantage only to patients with pN2 disease. The incidence of lymphatic recurrence was lower in D3 patients with 50- to 100-mm tumors than in the corresponding D2 patients. Conclusions D3 gastrectomy might be beneficial in patients with advanced pN2 gastric cancer within the group with tumors measuring 50 to 100 mm. A randomized controlled trial of patients with 50- to 100-mm tumors should be performed to test the validity of this preliminary result.     

Factors Affecting Nodal Status in Invasive Breast Cancer: A Retrospective Analysis of 623 Patients

Abstract: With increasing numbers of early, screen‐detected breast cancers and the emergence of sentinel‐node biopsy, surgical management of the axilla is evolving. In recent years many authors have searched for favorable subcategories of tumors in which it may be possible to avoid axillary lymph node clearance. The aim of this study is to determine preoperative factors that might predict lymph node negative axillae. A retrospective analysis of 623 patients with invasive breast cancer was performed. A number of clinical and pathological variables were analyzed. Uni‐ and multivariate analysis was carried out to determine factors predictive for lymph node metastases. Age, tumor size, grade, histology and lymphovascular invasion were found to be independent predictors of nodal positivity but, contrary to other recent studies, we found no effect of ER/PR (estrogen‐receptor/progesterone‐receptor) or HER‐2 status. The strongest predictor of lymph node metastases was tumor size >50 mm (OR 2.33), followed by the presence of lymphovascular invasion (OR 1.33). Our results could be used for preoperative counseling and planning axillary surgery in patients with invasive breast cancer. We propose that the predictive factors identified in this study could be used in combination with axillary ultrasound to selectively target patients for sentinel‐node biopsy or to target the use of ultrasonographic assessment of the axilla. However, no consistent and reliable markers have been identified to predict patients that can safely avoid axillary surgery.