Extranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC.

We investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC.

LNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1?3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases.

LNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.

The role of surgical resection of melanoma lung metastases (MLM) remains controversial. Some authorities advocate an aggressive surgical approach, while others recommend a conservative strategy. This study sought to identify the clinicopathologic and predictors of outcome after surgical management of MLM in a large series of melanoma patients from a single institution.

All patients undergoing surgical management of MLM between November 1984 and April 2010 were identified and predictors of outcome analyzed.

Of the 292 patients eligible for the study, 112 (38%) had previously undergone surgery for nonpulmonary recurrences. Four patients (1%) died within 30 days of surgery for MLM. The median progression-free survival time was 10 months. The median overall survival and 3- and 5-year survival were 23 months [95% confidence interval (CI) 17?30], 41 and 34%, respectively. Metastasis size >2 cm [hazard ratio (HR) 1.4, 95% CI 1.0?1.8, P = 0.03, HR 1.6, 95% CI 1.2?2.2; P = 0.002] and positive surgical margin (HR 1.5, 95% CI 1.2?1.9, P < 0.001; HR 1.4, 95% CI 1.1?1.7, P = 0.003) were independently associated with poorer progression-free survival and overall survival, respectively. The presence of more than one metastasis (HR 1.4, 95% CI 1.1?1.7, P = 0.013) was independently associated with poorer overall survival.

The results support the role of pulmonary metastasectomy in selected patients with MLM. Patients with small (<2 cm) and solitary tumors that can be completely resected with a negative margin are most likely to experience prolonged survival.

Unsatisfying long-term survival of intrahepatic cholangiocarcinoma (ICC) triggers the clinicians searching for molecular markers, such as K-ras mutation, to tailor management strategy. Additionally, emergence of tyrosine kinase inhibitors (TKIs) brings new hope to palliate advanced ICC; whether the efficacy of TKIs is influenced by k-ras mutation is largely unknown. This study was designed to determine the prevalence of k-ras mutation and its clinical significance in ICC, as well as to pave the reference for future application of TKIs.

A total of 86 patients with ICC who underwent hepatectomy were retrospectively recruited. K-ras mutation was determined by using laser capture microdissection and direct sequencing method. Association among clinicopathological variables and K-ras mutation was analyzed. Prognostic factors of ICC after hepatectomy also were determined.

Nineteen (22%) patients exhibited K-ras mutations. Seventeen had their K-ras mutations occurring at codon 12, and the remaining two occurring at codon 13 and codon 61 in one each. Perineural invasion was exclusively the variable associated with K-ras mutation (odds ratio, 6.9) using logistic regression analysis. Multivariate analysis demonstrated that resection margin, T-status, nodal metastasis, and K-ras mutation were independent prognostic factors. The median survival of ICC patients with K-ras mutation was 5.7 months compared with 19.0 months in those without K-ras mutation (P = 0.002).

The prevalence of K-ras mutations in a considerably large cohort of ICC was 22%. K-ras mutation is strongly associated with perineural invasion phenotypically. K-ras mutation is an independent prognostic factor of ICC after hepatectomy.

Tyrosine kinase inhibitor (TKI) therapy for patients with gastrointestinal stromal tumors (GISTs) has been shown to improve overall outcomes. It remains unclear whether TKIs are delaying tumor recurrence or actually affecting cure rates. We sought to determine whether changes in overall and disease-specific survival (OS and DSS, respectively) for patients with surgically resected gastric GISTs have been observed after the introduction of TKI therapies by using population-based data.

The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with resected gastric mesenchymal tumors before the introduction of TKIs (pre-TKI: 1990?1994) and after their inception (post-TKI: 2002?2003).

Overall, 594 patients with gastric mesenchymal tumors were identified, and 189 and 405 underwent resection in the pre- and post-TKI eras, respectively. Between groups, there were no significant differences in patient demographics. The 1- and 6-year OS improved from 84 and 36 to 93 and 71%, respectively. The 1- and 6-year DSS improved from 92 and 62 to 96 and 90%, respectively. Through 6 years, OS and DSS significantly improved for all stages, tumor sizes, and extent of operation. By using multivariate analysis, undergoing treatment in the pre-TKI era was an independent negative predictor of OS, hazard ratio (HR, 2.98) and DSS (HR, 3.81).

The TKI era is associated with dramatic improvements in OS and DSS for patients with surgically resected gastric GISTs, irrespective of stage, tumor size, and extent of operation through 6 years of follow-up. It remains unclear, however, whether this survival advantage is a change in cure rate or simply a delay in disease progression.

The optimal dosage and frequency of platinum-based chemoradiotherapy (CRT) regimen for treating advanced head and neck squamous cell carcinoma remains unresolved. This study aims to compare the toxicity and efficacy of weekly versus more dose-intensive cisplatin-based CRTs.

We reviewed 155 stage III/IV head and neck squamous cell carcinoma patients with no evidence of distant metastasis treated with one of two CRT regimens from 2000 to 2010 at Greater Baltimore Medical Center. Twice-daily radiation was provided as a split course over a 45-day period. Regimen A consisted of concomitant cisplatin (30 mg/m²/1 h) weekly for 6 cycles; regimen B consisted of concomitant cisplatin (12 mg/m²/1 h) and 5-fluorouracil (600 mg/m²/20 h) on days 1 through 5 and days 29 through 33. Main outcome measures included acute toxicities (myelosuppression, neurotoxicity, nephrotoxicity, gastrointestinal dysfunction), unplanned hospitalizations, and disease control at 12 months.

Patients on regimen A were much less likely to experience ototoxicity due to their treatment (0% vs. 9.8%, P = 0.04). They were more likely to experience thrombocytopenia acutely (46% vs. 26%, P = 0.02), but the toxicity was not limiting (grade 1?2). No significant differences exist in the incidence of other toxicities or unplanned hospitalizations. At 1 year, 97% of patients on A vs. 86% of patients on regimen B were free of disease (P = 0.11).

With concurrent radiotherapy, low-dose, single-agent, weekly cisplatin is less likely than higher-dose daily cisplatin plus 5-fluorouracil provided at the beginning and end of treatment to be associated with ototoxicity. The preliminary data suggest at least equivalent efficacy, but longer follow-up is required.

A 28-year-old woman presented with dyspnea on exertion and elevated testosterone level. A 21 × 19 cm right adrenal mass was found invading the liver and inferior vena cava (IVC); tumor thrombus extended to the right atrium on transthoracic echocardiogram.

Median sternotomy and extended right subcostal incisions were made. Inferior surface of liver was mobilized and vessels to the tumor divided and packed. The IVC was isolated and cardiopulmonary bypass initiated. Tumor was excised from IVC and tumor thrombus extracted. After partial IVC wall resection, the venotomy was closed. The right atrium was explored for remaining thrombus. Segment 7 of the liver was resected with division of right hepatic vein. The patient was removed from bypass, and the cut surface of liver was reinforced with chromic sutures. Intraoperative ultrasound demonstrated no remaining tumor thrombus. Provisional closure was achieved with wound vac, and the next day, the patient?s wound was closed primarily.

On postoperative day 3, the patient was extubated; she was discharged on day 12. Pathology revealed well-differentiated adenocarcinoma weighing 2.3 kg with negative surgical margins. Two months after surgery, she received radiation for suspected lumbar vertebral metastasis and initiated mitotane therapy. Follow-up surveillance scans showed no evidence of disease.

Adrenocortical carcinoma is a rare malignancy presenting frequently in advanced stage with poor prognosis. Chemotherapy is often only moderately effective, while complete surgical resection is potentially curative. In this patient, excellent short-term outcome was achieved through radical surgical resection. We continue to monitor her closely for evidence of recurrence.

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes.

After institutional review board approval, our institutional database spanning the years 1998?2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed.

From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months.

Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients.

Some authors have suggested that patients with very small (<0.1 mm) deposits of metastatic melanoma in sentinel lymph nodes (SLNs) should be considered SLN-negative, whereas others have reported that such patients can have adverse long-term outcomes. The aims of the present study were to determine whether extensive sectioning of SLNs resulted in more accurate categorization of histologic features of tumor deposits and to assess prognostic associations of histologic parameters obtained using more intensive sectioning protocols.

From patients with a single primary cutaneous melanoma who underwent SLN biopsy between 1991 and 2008, those in which the maximum size of the largest tumor deposit (MaxSize) in SLNs was <0.1 mm in the original sections were identified. Five batches of additional sections were cut from the SLN tissue blocks at intervals of 250 ?m. The 1st batch was cut from the blocks without any trimming; these sections were therefore immediately adjacent to the original sections. Each batch included 5 sequential sections, the 1st and 5th stained with hematoxylin-eosin, and the 2nd, 3rd, and 4th stained immunohistochemically with S-100, HMB-45, and Melan-A, respectively. In each batch of sections, the following histologic features of tumor deposit(s) in the SLNs were evaluated: MaxSize; tumor penetrative depth (TPD) (defined as the maximum depth of tumor deposit(s) from the inner margin of the lymph node capsule), and intranodal location (classified as subcapsular if the tumor deposit(s) were confined to the subcapsular zone or parenchymal if there was any involvement of the nodal parenchyma beyond the subcapsular zone). The measured histologic parameters were compared in each batch of sections. The association of histologic parameters with overall survival was assessed for the parameters measured in each batch of sections.

There were 20 eligible patients (15 females, 5 males, median age 60 years). After a median follow-up duration of 40 months, 4 patients had died from melanoma and 2 patients of unknown causes. Completion lymph node dissection (CLND) was performed in 13 cases (65%) and was negative in all cases. Relative to the measured values on the original sections, all 3 parameters were upstaged in subsequent batches of sections, but no further upstaging of MaxSize, TPD, or location was seen beyond batch 3, batch 4, and batch 2, respectively. Increasing MaxSize was associated with significantly poorer overall survival in batches 1, 2, and 3. Parenchymal involvement was significantly associated with poorer survival in batches 2?5. TPD was not significantly associated with overall survival.

The results of this study indicate that very small (<0.1 mm) deposits of melanoma in SLNs may be associated with adverse clinical outcomes and that this is due, at least in part, to the underestimation of SLN tumor burden in the initial sections. Our evidence does not support clinical decision-making on the assumption that patients with very small melanoma deposits in SLNs have the same outcome as those who are SLN-negative.

The determining risk factors for patients with squamous cell carcinoma of the hard palate are not well verified.

Medical records from our facility of all patients with squamous cell carcinoma of the hard palate receiving curative surgery between March 2003 and May 2009 were reviewed.

Seventy-eight patients were enrolled in the study. The 5 year disease-free and overall survival rates were 49.8 and 49.7%, respectively. The 5 year disease-free and overall survival rates were statistically different between positive/close margins and negative margins (24.6% vs. 65.4%, P = 0.02; 20.1% vs. 63.1%, P = 0.001, respectively), with and without soft palate invasion (38.8% vs. 68.9%, P = 0.02; 27.4% vs. 77.5%, P = 0.001, respectively), and soft palate invasion patients with and without perineural invasion (10.4% vs. 52.8%, P = 0.02; 0% vs. 38.1%, P = 0.008, respectively). The rate of positive nodal metastasis for T3 and T4 tumors was 44%. For the tumor with soft palate invasion, the rate of positive nodal metastasis was 29%. After multivariate analyses, soft palate invasion and positive/close margins were the determining risk factors for disease-free and overall survival.

Soft palate invasion and positive/close margins were the determining risk factors for disease-free and overall survival in patients with squamous cell carcinoma of the hard palate. Elective neck dissection is suggested for advanced primary tumors (T3 or T4) or tumors with soft palate invasion.

Magnetic resonance imaging (MRI) is increasingly being used for rectal cancer staging. The purpose of this study was to determine the accuracy of phased array MRI for T category (T1?2 vs. T3?4), lymph node metastases, and circumferential resection margin (CRM) involvement in primary rectal cancer.

Medline, Embase, and Cochrane databases were searched using combinations of keywords relating to rectal cancer and MRI. Reference lists of included articles were also searched by hand. Inclusion criteria were: (1) original article published January 2000?March 2011, (2) use of phased array coil MRI, (3) histopathology used as reference standard, and (4) raw data available to create 2 × 2 contingency tables. Patients who underwent preoperative long-course radiotherapy or chemoradiotherapy were excluded. Two reviewers independently extracted data. Sensitivity, specificity, and diagnostic odds ratio were estimated for each outcome using hierarchical summary receiver?operating characteristics and bivariate random effects modeling.

Twenty-one studies were included in the analysis. There was notable heterogeneity among studies. MRI specificity was significantly higher for CRM involvement [94%, 95% confidence interval (CI) 88?97] than for T category (75%, 95% CI 68?80) and lymph nodes (71%, 95% CI 59?81). There was no significant difference in sensitivity between the three elements as a result of wide overlapping CIs. Diagnostic odds ratio was significantly higher for CRM (56.1, 95% CI 15.3?205.8) than for lymph nodes (8.3, 95% CI 4.6?14.7) but did not differ significantly from T category (20.4, 95% CI 11.1?37.3).

MRI has good accuracy for both CRM and T category and should be considered for preoperative rectal cancer staging. In contrast, lymph node assessment is poor on MRI.