Impact of <Emphasis Type="Italic">KRAS</Emphasis> and <Emphasis Type="Italic">EGFR</Emphasis> Gene Mutations on Recurrence and Survival in Patients with Surgically Resected Lung Adenocarcinomas

Background

Oncogenic gene mutations observed in lung adenocarcinomas, such as epidermal growth factor receptor (EGFR) and KRAS, have some predictive value for chemotherapeutic drugs or EGFR–tyrosine kinase inhibitors. However, the influence of these gene alterations on patients’ prognosis remains controversial.

Methods

We retrospectively analyzed the tumors of 180 patients with completely resected pathological stage I–III lung adenocarcinoma which harbored either KRAS codon 12 mutation or EGFR gene mutations within exons 18–21 to investigate the impact of these gene mutations on the patients’ survival. Gene mutations were detected by established methods.

Results

Of 180 patients, 32 had KRAS codon 12 mutations (KRAS group), 148 had EGFR mutations within exon 18–21 (EGFR group). Pathological stage and operation mode were independent factors for disease-free survival. However, the EGFR group had better overall survival than the KRAS group (P = 0.0271). Cox proportional hazard model revealed pathological stage (P = 0.0001) and presence of EGFR gene mutations (P = 0.0408) were independent factors for overall survival. In survival after tumor recurrence, the EGFR group had a better median survival time (46.7 months) after recurrence than the KRAS group (26.0 months).

Conclusions

In patients with completely resected lung adenocarcinomas, KRAS and EGFR gene mutation status of tumors was not associated with disease-free survival. However, the presence of an EGFR gene mutation boded well for the patient’s overall survival, and thus patients with EGFR mutations have a better prognosis than those with KRAS mutations.

     

Higher Expression of Receptor Tyrosine Kinase Axl,and Differential Expression of its Ligand,Gas6, Predict Poor Survival in Lung Adenocarcinoma Patients

Background

Downstream activation through receptor tyrosine kinases (RTKs) plays important roles in carcinogenesis. In this study, we assessed the clinical involvement of Axl, an RTK, and its ligand, Gas6, in surgically treated lung adenocarcinoma.

Methods

Axl and Gas6 mRNA and protein expression levels were quantified using quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, in completely resected lung adenocarcinoma tissues (n = 88) and were evaluated for correlation with clinicopathologic features and patient survival.

Results

Higher expressions of Axl mRNA/protein and Gas6 protein were significantly related to worse clinicopathological features and prognosis (5-year overall survival rates: Axl mRNA low: 72.3 %, high: 49.7 %, P = 0.047; Axl protein low: 77.5 %, high: 38.6 %, P < 0.001; and Gas6 protein low: 70.5 %, high: 48 %, P = 0.042). On the contrary, higher Gas6 mRNA expression was related to better clinicopathological features and prognosis (5-year overall survival rates: Gas6 mRNA low: 59.2 %, high: 81.8 %, P = 0.054). Multivariate analysis suggests that high Axl mRNA expression may be an independent factor for poor patient prognosis (P = 0.04).

Conclusions

In lung adenocarcinoma, Axl and Gas6 expression levels were associated with tumor advancement and patient survival, thus rendering them as reliable biomarkers and potential targets for treatment of lung adenocarcinoma.

     

Lumican and Versican Are Associated with Good Outcome in Stage II and III Colon Cancer

Background

Tumor stroma plays an important role in the progression and metastasis of colon cancer. The glycoproteins versican and lumican are overexpressed in colon carcinomas and are associated with the formation of tumor stroma. The aim of the present study was to investigate the potential prognostic value of versican and lumican expression in the epithelial and stromal compartment of Union for International Cancer Control (UICC) stage II and III colon cancer.

Methods

Clinicopathological data and tissue samples were collected from stage II (n = 226) and stage III (n = 160) colon cancer patients. Tissue microarrays were constructed with cores taken from both the center and the periphery of the tumor. These were immunohistochemically stained for lumican and versican. Expression levels were scored on digitized slides. Statistical evaluation was performed.

Results

Versican expression by epithelial cells in the periphery of the tumor, i.e., near the invasive front, was correlated to a longer disease-free survival for the whole cohort (P = 0.01), stage III patients only (P = 0.01), stage III patients with microsatellite-instable tumors (P = 0.04), and stage III patients with microsatellite-stable tumors who did not receive adjuvant chemotherapy (P = 0.006). Lumican expression in epithelial cells overall in the tumor was correlated to a longer disease-specific survival in stage II patients (P = 0.05) and to a longer disease-free survival and disease-specific survival in microsatellite-stable stage II patients (P = 0.02 and P = 0.004).

Conclusions

Protein expression of versican and lumican predicted good clinical outcome for stage III and II colon cancer patients, respectively.

     

Prognostic role of ERCC1 protein expression in upper tract urothelial carcinoma following radical nephroureterectomy with curative intent

Background

Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients.

Methods

Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models.

Results

ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively).

Conclusions

ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy.

     

Expression of BRCA1, a factor closely associated with relapse-free survival,in patients who underwent neoadjuvant chemotherapy with docetaxel,cisplatin, and fluorouracil for squamous cell carcinoma of the esophagus

Purpose

The aim of this study was to identify the biomarkers associated with chemotherapeutic efficacy and long-term survival for patients with advanced squamous cell carcinoma of the esophagus (SCCE) who had received neoadjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil (NAC-DCF).

Methods

This study included 45 patients with advanced SCCE who received NAC-DCF between 2008 and 2012. The NAC-DCF was conducted as a phase II study (UMIN000007408). The expressions of excision repair cross-complementing-1 (ERCC1), class III beta-tubulin, breast cancer susceptibility gene I (BRCA1), and thymidylate synthase were investigated simultaneously in the pre-treatment endoscopic tumor biopsy samples.

Results

A multivariate logistic regression analysis indicated that pathological responses were significantly associated with tumors with low ERCC1 expression (P = 0.016) and with tumors with high BRCA1 expression (P = 0.030). The multivariate Cox proportional hazard model analysis for relapse-free survival revealed high BRCA1 expression (P = 0.031, hazards ratio 4.39) as the factor associated with survival.

Conclusions

Low ERCC1 expression and high BRCA1 expression in patients with SCCE were associative biomarkers for chemotherapeutic efficacy. High BRCA1 expression was considered the factor associated with survival. These findings may be helpful for tailoring chemotherapy.

     

Tumor diameter accurately predicts perioperative outcomes in T1 renal cancer treated with robot-assisted partial nephrectomy

Purpose

To compare diameter as a continuous variable with categorical R.E.N.A.L. nephrometry score (RNS) in predicting surgical outcomes of robotic partial nephrectomy (RPN).

Methods

We retrospectively reviewed consecutive patients receiving RPN at our institution between July 2007 and June 2014 (n = 286). Three separate multivariate analyses were performed to assess the relationship between RNS components (R = radius, E = endophyticity, N = nearness to collecting system, L = location relative to polar lines), total RNS, and diameter as a continuous variable with operating time, warm ischemia time (WIT), and estimated blood loss (EBL). Each linear regression model’s quality of fit to the data was assessed with coefficients of determination (R ²).

Results

Continuous tumor diameter and total RNS were each significantly correlated to operative time, EBL, and WIT (p < 0.001). Categorical R related to operative time (R = 2 vs. R = 1, p = 0.001; R = 3 vs. R = 1, p = 0.001) and WIT (R = 2 vs. R = 1, p = 0.003; R = 3 vs. R = 1, p = 0.016), but not to EBL. For each of these outcomes, diameter outperformed both R and total RNS, as assessed by R ². Age, body mass index, Charlson Comorbidity Index, and anterior versus posterior location did not correlate with surgical outcomes.

Conclusions

In this series of RPN from a high-volume center, surgical outcomes more closely related to tumor diameter than RNS. While RNS provides surgeons a standardized tool for preoperative planning of renal masses, tumor size may be employed as a more familiar measurement when counseling patients on potential outcomes.

     

The oncological outcomes of segmentectomy in clinical-T1b lung adenocarcinoma with a solid-dominant appearance on thin-section computed tomography

Purpose

We investigated the surgical outcomes of clinical-T1b lung adenocarcinomas patients whose tumors had a solid-dominant radiological appearance and who were treated with segmentectomy or lobectomy.

Methods

We examined 154 surgically resected clinical-T1b lung adenocarcinomas with a “solid-dominant” appearance on thin-section computed tomography (CT). The preoperative thin-section CT images of all cases were reviewed. “Solid-dominant” was defined as 0.5≤ consolidation/tumor ratio (CTR) <1.0.

Results

Pathological nodal metastasis, lymphatic invasion, vascular invasion, and pleural invasion were found in 7 (4.5 %), 27 (18 %), 21 (14 %), and 15 (10 %) patients with clinical-T1b solid-dominant lung adenocarcinoma, respectively. Lobectomy and segmentectomy were performed in 123 (80 %) and 31 (20 %) cases, respectively. The 3-year overall survival (OS) and relapse-free survival (RFS) of patients with clinical-T1b solid-dominant lung adenocarcinoma were 95.5 and 92.4 %, respectively. The 3-year RFS and OS did not differ significantly between the patients who underwent lobectomy or segmentectomy (3-year RFS, 92.3 vs. 93.4 %, p = 0.8713; 3-year OS, 95.3 vs. 96.6 %, p = 0.7603). Segmentectomy was not found to be a prognostic factor for RFS (p = 0.8714), or OS (p = 0.7613).

Conclusions

Segmentectomy can achieve acceptable oncological outcomes (both in terms of OS and RFS), which are similar to those achieved with standard lobectomy, in patients with clinical-T1b solid-dominant lung adenocarcinoma.

     

Oncologic outcomes of patients with positive surgical margin after partial nephrectomy: a 25-year single institution experience

Purpose

To evaluate oncologic outcomes and management of patients with microscopic positive surgical margin (PSM) after partial nephrectomy (PN) for renal cell carcinoma (RCC).

Methods

We reviewed our database to identify patients who underwent PN between 1990 and 2015 for RCC and had PSM on final pathology. A 1:3 matching was performed to a negative surgical margin (NSM) cohort. Kaplan–Meier method and log-rank test were used to estimate survival and differences in outcomes, respectively. Cox proportional hazards models were conducted to estimate the Hazards ratio.

Results

A total of 2297 patients underwent PN at our institution, of which 1863 (81%) had RCC. Microscopic PSM was found in 34 (1.8%) RCC patients who were matched to 100 patients with NSM. Of these 34 patients, local recurrence (n = 4), distant kidney recurrences (n = 4), and metastases (n = 5) developed during a median follow-up of 62 months. Bilateral tumors/tumors in a solitary kidney (n = 12/13, 92%), and multifocal tumors (n = 7/13, 54%) were found in patients who developed recurrence/metastasis. PSM patients were at a higher risk of shorter overall survival (p = 0.001), local recurrence-free survival (p = 0.003), distant recurrence-free survival (p = 0.032) and metastasis-free survival (p = 0.018). There was statistically significant association between PSM and bilateral tumors, prior treated RCC at presentation and higher nephrometry score in multivariable model.

Conclusions

There was a low rate of microscopic PSM in our large cohort of patients undergoing PN despite tumor complexity. Higher nephrometry score, bilateral tumors, and prior treated RCC independently predicted PSM which showed worse survival, recurrence and metastasis compared to patients with NSM.

     

CD133 Expression at the Metastatic Site Predicts Patients’ Outcome in Colorectal Cancer with Synchronous Liver Metastasis

Background

CD133 is a transmembrane protein that is proposed to be a stem cell marker of colorectal cancer (CRC); however, the correlation between CD133 expression and survival of CRC patients with liver metastasis has not been fully examined.

Methods

CD133 expression was evaluated immunohistochemically, both in primary tumors and synchronous liver metastases of 88 consecutive CRC patients, as well as recurrent lesions in the remnant liver of 27 of these 88 patients. The relationship between CD133 expression and clinicopathological characteristics, recurrence-free survival, and overall survival (OS) was analyzed.

Results

CD133 expression in liver metastases (mCD133) was detected in 50 of 88 patients (56.8 %), and had significant correlation with CD133 expression in primary lesions (pCD133) (p < 0.001). CD133 expression in liver recurrent lesions (recCD133) also had a significant correlation with mCD133 (p < 0.001). mCD133+ patients had significantly longer disease-free survival (p = 0.043) and OS (p = 0.014) than mCD133? patients. In addition, mCD133+ patients had a significantly lower rate of extrahepatic recurrence (p < 0.001).

Conclusions

Patients without CD133 expression in liver metastasis had significantly shorter survival, perhaps because mCD133? patients had a significantly higher rate of extrahepatic recurrence.

     

Collapsin Response Mediator Protein 4 Expression is Associated with Liver Metastasis and Poor Survival in Pancreatic Cancer

Background

Pancreatic cancer is an aggressive malignancy with one of the worst mortality rates of all cancers. Recently, collapsin response mediator proteins (CRMPs) were reported to be associated with proliferation, apoptosis, differentiation, and invasion in several cancers. However, CRMP expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer.

Methods

Expression of crmp genes in 11 pairs of pancreatic cancer and corresponding noncancerous pancreas tissues were examined by real-time RT-PCR. Knockdown of CRMP4 expression using siRNA was examined in pancreatic cancer cell lines to determine whether CRMP4 regulates cell proliferation and invasion in vitro. Furthermore, CRMP4 protein levels in primary tumors of pancreatic cancer (n = 53) were examined by immunohistochemistry and compared with the clinicopathological features of the tumors.

Results

Of all the CRMPs, only CRMP4 was differentially expressed in pancreatic cancer tissues (p = 0.008). CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. The expression of CRMP4 was detected immunohistochemically in 34 (64.2 %) of the 53 pancreatic cancer samples, and CRMP4 expression was correlated with severe venous invasion (p = 0.044), stage (p = 0.019), and liver metastasis (p = 0.021). Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival.

Conclusions

Our results suggested that CRMP4 is significantly associated with poor prognosis by promoting liver metastasis and can serve as a novel therapeutic target for pancreatic cancer.

     

Coexistent Loss of the Expressions of BRCA1 and p53 Predicts Poor Prognosis in Triple-Negative Breast Cancer

Background

To investigate the prognostic significance of altered breast cancer susceptibility gene 1 (BRCA1) and p53 expression in triple-negative breast cancer (TNBC).

Methods

Immunohistochemical expression of BRCA1 and p53 was examined in the tumor tissues of 465 TNBC cases and relations were sought with clinicopathological features and patient survival.

Results

Loss of BRCA1 expression was found in 29.5% (137/465) of TNBCs. Positive expression of p53 was observed in 49.9% (232/465). Patients with loss of BRCA1 expression had a tendency to have higher rate of lymph node metastasis (p = 0.075). An association between p53 expression and high histological grade was observed (p = 0.039). TNBC patients with loss of BRCA1 expression had a tendency to have poorer overall survival (OS) than those positive for BRCA1 (p = 0.09). TNBC patients with positive p53 expression showed better OS than those with p53 negativity (p = 0.001). In terms of combined expression patterns, significantly poorer overall survival (OS) was observed for BRCA1-negative/p53-negative TNBCs and best OS for BRCA1-positive/p53-positive TNBCs (p = 0.005).

Conclusions

Combined expression patterns of BRCA1 and p53 could serve as useful prognostic markers in TNBC.

     

DOK2 as a Marker of Poor Prognosis of Patients with Gastric Adenocarcinoma After Curative Resection

Background

DOK2 is known as the substrate of chmeric p210bcr/abl oncoprotein characterizing chronic myelogenous leukemia with Philadelphia chromosome. Reduced DOK2 expression was recently reported in lung adenocarcinoma, suggesting that this protein acts as a tumor suppressor in solid tumors. The purpose of this study was to determine the significance of DOK2 in gastric cancer.

Methods

The study subjects were 118 patients who underwent curative surgery for gastric cancer, as well as 7 gastric cancer cell lines. The tissues and cell lines were analyzed for DOK2 gene and protein expressions by histopathology and immunohistochemistry, and also using a microsatellite marker for loss of heterozygosity. Correlation of survival with clinicopathological parameters was investigated by univariate and multivariate analyses.

Results

DOK2 expression was confirmed in the normal gastric mucosa. Considerable differences in the gene expression were noted among the gastric cell lines. Positive DOK2 expression was noted in the noncancerous regions of all pathological specimens, whereas 59 (50.0%) specimens of 118 patients were negatively stained in the tumor. Loss of heterozygosity was observed in 54.5% of DOK2(?) cases. DOK2(?) patients were more likely to develop recurrence than DOK2(+) and showed poorer 5-year overall survival (59.1%) than DOK2(+) (76.4%, P = .0403). Multivariate analysis identified pT (hazard ratio [HR] = 2.748, 95% confidence interval [95% CI] = 1.061–8.927, P = .0361), pN (HR = 2.486, 95% CI = 1.264–4.932, P = .0086), and DOK2(?) (HR = 2.343, 95% CI = 1.211–4.727, P = .0112) as significant and independent determinants of poor survival.

Conclusions

Our data suggest the potential usefulness of DOK2 as a marker of poor prognosis in patients with gastric cancer after curative resection.

     

Primary Tumor Resection Following Favorable Response to Systemic Chemotherapy in Stage IV Pancreatic Adenocarcinoma with Synchronous Metastases: a Bi-institutional Analysis

Introduction

Patients with metastatic pancreatic adenocarcinoma have traditionally been offered palliative chemotherapy alone, and the role of surgery in these patients remains unknown.

Methods

A bi-institutional retrospective review was performed for patients with metastatic pancreatic adenocarcinoma who underwent resection of the primary tumor from 2008 to 2013. The primary outcome measured was postoperative overall survival. Secondary outcomes included postoperative disease-free survival and overall survival from the time of diagnosis.

Results

Twenty-three patients were identified who met the study criteria with a median follow-up of 30 months. Metastatic sites included the liver (n?=?16), the lung (n?=?6), and the peritoneum (n?=?2). Chemotherapy included FOLFIRINOX (n?=?14) and gemcitabine-based regimens (n?=?9), with a median of 9 cycles (range 2–31) prior to surgical treatment. Median time from diagnosis to surgery was 9.7 months (IQR 5.8–12.8). Median overall survival (OS) from surgery, disease-free survival, and OS from diagnosis were 18.2 months (95 % CI 11.8–35.5), 8.6 months (95 % CI 5.2–16.8), and 34.1 months (95 % CI 22.5–46.2), respectively. The 1- and 3-year OS from surgery were 72.7 % (95 % CI 49.1–86.7) and 21.5 % (95 % CI 4.3–47.2), respectively.

Conclusion

Resection of the primary tumor in patients with metastatic pancreatic adenocarcinoma may be considered in highly selected patients with favorable imaging and CA 19-9 response following chemotherapy at high-volume centers providing multidisciplinary care. These patients should be enrolled in prospective clinical trials or institutional registries to better quantify the potential benefits of such a strategy.

     

Different Expression Patterns of CEACAM1 and its Impacts on Angiogenesis in Gastric Nonneoplastic and Neoplastic Lesions

Objective

This study was designed to investigate the expression patterns of CEACAM1 and its relationship with angiogenesis in nonneoplastic and neoplastic gastric lesions.

Methods

CEACAM1 and TGF-β expression was detected by immunohistochemical staining and dual-labeling immunohistochemical staining in neoplastic and nonneoplastic lesions. MVD-CD31 and MVD-CD105 were counted in CEACAM1-positive areas by dual-labeling immunohistochemistry.

Results

There was no expression of CEACAM1 in normal gastric mucosa. In IM and GIN, CEACAM1 was mainly expressed with membranous pattern. CEACAM1 was expressed with membranous pattern in well-differentiated adenocarcinoma, with cytoplasmic pattern in poorly differentiated adenocarcinoma, and with cytoplasmic and membranous pattern mixed together in intermediately adenocarcinoma. The expression patterns of CEACAM1 showed a significant difference (P < 0.05) in nonneoplastic and neoplastic lesions. Coexpression of CEACAM1 and TGF-β was elevated and significantly different from nonneoplastic to neoplastic lesions (P < 0.05). Moreover, CEACAM1 and TGF-β coexpression were related to carcinoma progression (r = 0.35; P < 0.05). MVD-CD31 and MVD-CD105 showed significant differences from nonneoplastic to neoplastic lesions (P < 0.05).

Conclusions

CEACAM1 has different expression patterns in nonneoplastic and neoplastic lesions. The coexpression of CEACAM1 and TGF-β increased from nonneoplastic to neoplastic lesions and may be related with tumor progression via promoting tumorous angiogenesis.

     

Use of Preoperative Magnetic Resonance Imaging for Invasive Lobular Cancer: Good,Better, but Maybe not the Best?

Background

Invasive lobular cancer (ILC) of the breast is difficult to diagnose clinically and radiologically. It is hoped that preoperative magnetic resonance imaging (MRI) can improve evaluation of extent of disease.

Methods

Patients diagnosed with ILC at a single institution from 2001 to 2008 who underwent clinical breast examination (CBE), mammography, ultrasound, and MRI were studied retrospectively. Concordance between tumor size on imaging/CBE and pathologic size was defined as size within ±0.5 cm. Pearson correlation coefficients (R) were calculated for each modality. Local recurrence and reexcision rates were compared with those patients with ILC who did not undergo preoperative MRI.

Results

Seventy patients with ILC had all imaging modalities, including CBE, performed preoperatively. The sensitivity for detection of ILC by MRI was 99%. MRI-based tumor size was concordant with pathologic tumor size in 56% of tumors. MRI overestimated tumor size by >0.5 cm in 31% of tumors. Correlation of tumor size on imaging with final pathology was better for MRI (R = 0.75) than for mammography (R = 0.65), CBE (R = 0.63), or ultrasound (R = 0.45, all P < 0.01). Preoperative MRI was associated with lower reoperation rates for close/positive margins (P > 0.05).

Conclusions

For ILC, MRI has better sensitivity of detection and correlation with tumor size at pathology than CBE, mammography, or ultrasound. However, 31% of cases are overestimated by MRI, and correlation remains only at 0.75. The select use of MRI for preoperative estimation of tumor size in ILC is supported by our data, but the need for improvement and refinement of imaging remains.

     

Liver transplantation for advanced hepatocellular carcinoma in patients with Child-Pugh A and B

Purpose

To investigate the outcomes of living donor liver transplantation for advanced hepatocellular carcinoma in Child-Pugh A/B patients and the usefulness of our expanded selection criteria, the Kyoto criteria.

Methods

A total of 82 recipients with a Child-Pugh class A (n = 27) or B (n = 55) status having either multiple hepatic nodules or solitary tumors ≥5 cm in size treated between February 1999 and August 2012 were enrolled in this study.

Results

The overall recurrence rate was significantly less for the Child-Pugh B patients than for the Child-Pugh A patients (P = 0.042), while the survival rates did not differ. In the Child-Pugh A and B patients, the survival rate was significantly greater, while the recurrence rate was lower among the patients meeting the Kyoto criteria than those exceeding these criteria (P = 0.006, P = 0.001, P = 0.032 and P < 0.001, respectively). In the Child-Pugh B patients, the overall survival and recurrence rates did not differ between the patients treated with and without pretreatment for hepatocellular carcinoma. In the Child-Pugh B patients treated with pretreatment, the overall survival rate was significantly greater, while the recurrence rate was lower among the patients meeting the Kyoto criteria than those exceeding these criteria (P < 0.001, P < 0.001, respectively).

Conclusions

Living donor liver transplantation performed within the Kyoto criteria achieves excellent overall survival and recurrence rates, especially for Child-Pugh B patients, even those with advanced hepatocellular carcinoma.

     

The Outcomes of a Limited Resection for Non-Small Cell Lung Cancer Based on Differences in Pathology

Objective

A precise preoperative diagnosis of in situ or minimally invasive carcinoma may identify patients who can be treated by limited resection. Although some clinical trials of limited resection for lung cancer have started, it will take a long time before the results will be published. We have already reported a large-scale study of limited resection. We herein report the data for a subclass analysis according to differences in pathology.

Methods

Data from multiple institutions were collected on 1710 patients who had undergone limited resection (segmentectomy or wedge resection) for cT1N0M0 non-small cell carcinoma. The disease-free survival (DFS) and recurrence-free proportion (RFP) were analyzed. Small cell carcinomas and carcinoid tumors were excluded from this analysis. Adenocarcinomas were sub-classified into four groups using two factors, the ratio of consolidation to the tumor diameter (C/T) and the tumor diameter alone.

Results

The median patient age was 64 (20–75) years old. The mean maximal diameter of the tumors was 1.5 ± 0.5 cm. The DFS and RFP at 5 years based on the pathology were 92.2 and 94.7 % in adenocarcinoma (n = 1575), 76.3 and 82.4 % in squamous cell carcinoma (SqCC) (n = 100), and 73.6 and 75.9 % in patients with other tumors (n = 35). The prognosis of adenocarcinoma in both groups A (C/T ≤0.25 and tumor diameter ≤2.0 cm) and B (C/T ≤0.25 and tumor diameter >2.0 cm) was good. In SqCC, only segmentectomy was a favorable prognostic factor. In the groups with other pathologies, large cell carcinomas were worse in prognosis (the both DFS and RFP: 46.3 %).

Conclusion

Knowing the pathological diagnosis is important to determine the indications for limited resection. Measurement of the tumor diameter and C/T was useful to determine the indications for limited resection for adenocarcinoma. Limited resection for adenocarcinomas is similar with a larger resection, while the technique should be performed with caution in squamous cell carcinoma and other pathologies.