The Significance of MMP-9 Over MMP-2 in HCC Invasiveness and Recurrence of Hepatocellular Carcinoma After Curative Resection

Background

The extracellular matrix metalloproteases MMP-9 and MMP-2 are critical for the invasive potential of tumors. However, it is not clear which of the two plays the predominant role in tumor invasion and progression. In the present study, we compared the clinical efficacy of MMP-9 and MMP-2 overexpression for predicting tumor recurrence and survival after surgical resection in HCC patients.

Materials and Methods

MMP-9 and MMP-2 expression in HCC cell lines and in vitro HCC invasion model were detected by quantitative RT-PCR and immunofluorescence. The expression levels of MMP-9 and MMP-2 were assessed by immunohistochemistry in HCC tissue microarrays from HCC patients (study set) who underwent curative resection. The clinicopathological data were retrospectively analyzed. The results were further verified in an independent cohort of 92 HCC patients (validation set).

Results

Univariate analysis demonstrated that high expression of MMP-9 was associated with both time to recurrence (TTR, P = .015) and overall survival (OS, P = .024), whereas high expression of MMP-2 was only correlated with TTR (P = .041). Multivariate analysis confirmed that MMP-9 expression was an independent predictor of TTR and OS. The coindex of MMP-9 and preoperative serum AFP levels was significantly correlated with TTR and OS (P = .036 and P = .040), but the coindex of MMP-2 and AFP did not show prognostic significance for either TTR or OS (P = .067 and P = .053). The prognostic value of MMP-9 overexpression was validated in the independent data set.

Conclusion

MMP-9 is superior to MMP-2 for the prediction of tumor recurrence and survival in HCC patients after surgical resection.

     

Prognosis of Fibrolamellar Carcinoma Compared to Non-cirrhotic Conventional Hepatocellular Carcinoma

Background

Fibrolamellar carcinoma (FLC) and conventional hepatocellular carcinoma (HCC) share the same American Joint Committee on Cancer (AJCC) staging. The worse survival with HCC is attributed to the underlying cirrhosis.The aim of this study was to compare stage-matched prognosis after resection of FLC and non-cirrhotic HCC.

Methods

Outcomes after resection of 65 consecutive patients with FLC and 158 non-cirrhotic patients with HCC were compared. Patients were staged according to the 7th edition AJCC staging.

Results

The AJCC stage distributions for FLC and HCC demonstrated a predominance of stage IV disease in FLC and stage I in HCC (FLC stage I—23 %, II—15 %, III—15 %, IV—46 % vs. HCC stage I—42 %, II—32 %, III—20 %, IV—6 %, p?<?0.001). Among stage IV FLC patients, 81 % had isolated nodal metastases, which did not affect overall survival (OS) or recurrence-free survival (RFS). In FLC, OS was significantly affected by the number of tumors and vascular invasion (p?<?0.05). Recurrent disease developed in 56 (86 %) FLC patients and was treated with repeat surgical resection in 25 (45 %) patients. Vascular invasion was associated with recurrent FLC, with 3-year RFS rates of 9 % and 35 %, with and without vascular invasion (p?=?0.034). With respect to RFS, the AJCC staging did not stratify FLC patients, compared to non-cirrhotic HCC.

Conclusions

When compared to non-cirrhotic HCC, patients with FLC are not adequately stratified by AJCC staging with respect to RFS. Our results support classifying lymph node metastases in FLC as regional disease, rather than systemic disease. Important prognostic factors in FLC are the number of tumors and vascular invasion.

     

Elevated Serum Carcinoembryonic Antigen Is Associated with a Worse Survival Outcome of Patients After Liver Resection for Hepatocellular Carcinoma: a Propensity Score Matching Analysis

Background

The relationship between serum carcinoembryonic antigen (CEA) and postoperative prognosis in hepatocellular carcinoma (HCC) has not been reported.

Methods

Data of 5410 consecutive HCC patients who underwent hepatectomy was retrospectively reviewed. Survival curves for overall survival (OS) and tumor recurrence (TR) were depicted using the Kaplan-Meier method and compared using the log-rank test. Independent risk factors of OS and TR were analyzed with Cox hazard regression model. Besides, a one-to-one propensity score-matched (PSM) subset was performed to reduce selection bias. Subgroup analysis was done according to hepatitis B virus (HBV) infection or not.

Results

Serum CEA ≥5.1 μg/L was an independent risk factor of OS and TR in the entire cohort and PSM subset (OS—hazard ratio?=?1.218, 95 % confidence interval?=?1.060–1.400; 1.383, 1.133–1.688, respectively; TR—1.256, 1.114–1.417; 1.258, 1.067–1.484, respectively). Subgroup analysis showed that CEA ≥5.1 μg/L was an independent risk factor of OS and TR in the HBV infection group (OS—1.234, 1.065–1.429; TR—1.231, 1.083–1.399) but not in the non-HBV infection group (OS—1.376, 0.895–2.117; TR—1.437, 0.989–2.088).

Conclusion

Serum CEA ≥5.1 μg/L was an independent risk factor of OS and TR of HCC patients, and patients with CEA ≥5.1 μg/L had poorer prognosis, especially for HCC patients with HBV infection.

     

Hepatic Hemodynamic Changes Following Stepwise Liver Resection

Aim

Extended liver resection has increased during the last decades. However, hepatic hemodynamic changes after resection and the consequent complications like post hepatectomy liver failure are still a challenging issue. The aim of this study was to systematically evaluate the role of stepwise liver resection on hepatic hemodynamic changes.

Methods

To evaluate this effect we performed 25, 50, and 75 % sequential liver resections in 10 pigs. Before and after each resection, the hepatic artery flow and portal vein flow in relation to the remnant liver volume (RLV) as well as hepatic vascular pressures were measured and compared between the groups.

Results

Following sequential liver resection, the hepatic artery flow /100 g decreases and the portal vein flow increases up to 17 and 167 % following extended liver resection (75 %), respectively. Also, during stepwise liver resection, the portal vein pressure increases gradually up to 33 % following extended hepatectomy (75 %).

Conclusion

Sequential decrease in the RLV decreases the hepatic artery flow /100 g and increases the portal vein flow /100 g and portal vein pressure. As the consequence, the liver goes under more poor-oxygenated blood supply and higher pressure. This may be one of the most important mechanisms of the post hepatectomy liver failure in case of extended liver resection.

     

Recurrence and Poor Prognosis Following Resection of Small Hepatitis B-Related Hepatocellular Carcinoma Lesions Are Associated with Aberrant Tumor Expression Profiles of Glypican 3 and Osteopontin

Background

Early detection and following appropriate treatments of hepatocellular carcinoma (HCC) is still the gold standard for favored outcome of HCC patients; nevertheless, a small portion of hepatitis B virus (HBV)-related small HCC (<5 cm) patients got poor prognosis. Furthermore, the study for small HBV–HCC was limited. Therefore, the aim of this study was to explore the potential genetic signature for HBV-related small HCC as novel prognostic factors.

Methods

We examined expression profiles of HBV-related small HCC using an Affymetrix U133A GeneChip, evaluated differential gene expression by quantitative real-time polymerase chain reaction (qRT-PCR), and finally validated these expression patterns by immunohistochemistry (IHC).

Results:

A total of 57 genes were differentially expressed between tumor and normal parts (n = 20 pairs) using Affymetrix U133A chip, and 16 genes were further evaluated by qRT-PCR. The result was compatible with the finding of oligonucleotide microarray (Pearson’s correlation, r = 0.87). Furthermore, the expression pattern in HCC tissue by IHC in another group of small HBV–HCC (n = 100) showed overexpression of either osteopontin (OPN) or glypican 3 (GPC3) is an independent prognostic factor for disease-free survival (DFS) in HBV-positive small HCC (P < 0.01 and 0.03, respectively). Long-term DFS and overall survival (OS) for small HBV–HCC patients with high risk (both elevated GPC3⁺/OPN⁺) were DFS 0%, OS 0%, respectively; on the other hand, DFS and OS in patients with moderate (only 1 gene elevated) or low (OPN^?/GPC3^?) risk were 35.0 and 46.5%, respectively.

Conclusions

Elevation of both OPN and GPC3 may act as an adverse indicator for HBV-related small HCC patients after curative resection.

     

Risk Factors for Early Recurrence of Single Lesion Hepatocellular Carcinoma After Curative Resection

Background and objectives

Hepatic resection is established as the treatment for HCC. However, patients sometimes experience early recurrence of HCC (ER HCC) after curative resection.

Methods

A retrospective analysis was conducted for 193 patients with single HCC who underwent curative liver resection in our medical center between April 2000 and March 2013. We divided the cohort into two groups; early recurrence group (ER G) which experienced recurrence within 6 months after resection, and non-early recurrence group (NER G). Risk factors for ER HCC were analyzed.

Results

Thirty-nine out of 193 (20.2 %) patients had ER HCC. Univariate analysis showed Glasgow prognostic score (GPS, p = 0.036), neutrophil to lymphocyte ratio (NLR, p = 0.001), level of PIVKA-II (p = 0.0001), level of AFP (p = 0.0001), amounts of blood loss (p = 0.001), operating time (p = 0.002), tumor size (p = 0.0001), stage III and IV (p = 0.0001), and microvascular invasions (portal vein: p = 0.0001 and hepatic vein: p = 0.001) to be associated with ER HCC. By multivariate analysis, there were significant differences in high NLR (p = 0.029) and high AFP (p = 0.0001) in patients with ER HCC.

Conclusions

Preoperative high AFP (more than 250 ng/ml) and high NLR (more than 1.829) were independent risk factors for ER HCC.

     

Clinical factors that affect the outcomes after anatomical versus non-anatomical resection for hepatocellular carcinoma

Purpose

For hepatocellular carcinoma (HCC), the superiority of anatomical resection (AR) over non-anatomical resection (NR) is still controversial. In this study, we assessed the potential benefits of AR for HCC.

Methods

We enrolled 173 consecutive patients with HCC who underwent hepatectomy in our hospital from August 2003 to May 2013 and compared the outcomes for the AR group (n = 125) with those for the NR group (n = 48).

Results

The median observational period was 790 days. The 1- and 2-year overall survival (OS) rates were 92.1 and 85.8 %, respectively; the 1- and 2-year disease-free survival (DFS) rates were 78.2 and 63.0 %, respectively. The AR and NR groups did not significantly differ in the OS or DFS. However, the 2-year DFS was significantly better for the AR group than the NR group among HCV patients (68.2 vs. 32.2 %; P = 0.004) and patients with alpha-fetoprotein (AFP) within the normal range (<20 ng/ml; 76.7 vs. 60.9 %; P = 0.031), total bilirubin <0.8 mg/dl (70.8 vs. 47.0 %; P = 0.034), and tumors 2–5 cm in diameter (82.0 vs. 62.5 %; P = 0.025).

Conclusions

If a patient is HCV-negative, has low AFP, low total bilirubin, or a tumor diameter of 2–5 cm, AR is recommended.

     

Effect of postoperative major complications on prognosis after pancreatectomy for pancreatic cancer: a retrospective review

Purpose

To investigate the impact of postoperative complications on survival after curative resection for pancreatic cancer.

Methods

We reviewed retrospectively the medical records of 122 patients who underwent curative R0 resection for pancreatic cancer. Major complications included pancreatic fistula and hemorrhage of grade B or C according to the International Study Group of Pancreatic Fistula or Surgery criteria, and other complications of grade ≥III according to the Clavien–Dindo classification.

Results

Thirty-eight patients (31 %) suffered major postoperative complications and 40 patients (33 %) suffered minor complications only. Univariate survival analysis showed that patients with major complications had a significantly worse prognosis than those without major complications, with regard to recurrence-free survival (RFS) (P < 0.01) and overall survival (OS) (P < 0.01), whereas minor complications did not affect survival. Major complications significantly inhibited or delayed adjuvant chemotherapy. Multivariate survival analysis showed that the absence of postoperative major complications was an independent favorable factor for RFS (hazard ratio 0.48; 95 % confidence interval: 0.28–0.85) and OS (hazard ratio 0.47; 95 % confidence interval 0.27–0.81).

Conclusions

Postoperative major complications after pancreatectomy for pancreatic cancer affect the prognosis.

     

Predictors of Futile Liver Resection for Patients with Barcelona Clinic Liver Cancer Stage B/C Hepatocellular Carcinoma

Background

There is little information concerning futile liver resection for patients with Barcelona Clinic Liver Cancer (BCLC) stage B/C hepatocellular carcinoma (HCC). This study aimed to establish a predictive model of futile liver resection for patients with BCLC stage B/C HCC.

Methods

The outcomes of 484 patients with BCLC stage B/C HCC who underwent liver resection at our centre between 2010 and 2016 were reviewed. Patients were randomised and divided 2:1 into training and validation sets. A novel risk-scoring model and prognostic nomogram were developed based on the results of multivariate analysis.

Results

Fifty-seven futile operations were observed. Multivariate analyses revealed tumour numbers > 3, Vp4 portal vein tumour thrombosis (PVTT) and alpha-fetoprotein (AFP) > 400 ng/ml independently associated with futile liver resection. A risk-scoring model based on the above-mentioned factors was developed (predictive risk score = 1 × (if AFP > 400 ng/ml) + 2 × (if tumour number > 3) + 3 × (if with Vp4 PVTT)). The area under the receiver-operating characteristic curve of this model was 0.845, with a sensitivity of 60.0% and a specificity of 94.8%. A prognostic nomogram was also developed and achieved a C-index of 0.831. The validation studies optically supported these results.

Conclusion

A risk-scoring model and predictive nomogram for futile liver resection were developed in the present study. T`he BCLC stage B/C HCC patients with a high risk obtained no benefit from liver resection.

     

Perioperative allogenic blood transfusion is a poor prognostic factor after hepatocellular carcinoma surgery: a multi-center analysis

Purpose

The influence of allogenic blood transfusion on the postoperative outcomes of hepatocellular carcinoma (HCC) surgery remains controversial. This study aims to clarify the clinical impacts of perioperative allogenic blood transfusion on liver resection outcome in HCC patients.

Methods

We analyzed data collected over 5 years for 642 patients who underwent hepatectomy for HCC at one of the five university hospitals. We investigated the impact of allogenic blood transfusion on postoperative outcome after surgery in all patients and in 74 matched pairs, using a propensity score.

Results

Of the 642 patients, 198 (30.8%) received perioperative allogenic blood transfusion (AT group) and 444 (69.2%) did not (non-AT group). Overall survival was lower in the AT group than in the non-AT group in univariate (P < 0.001) and multivariate analyses (risk ratio 1.521, P = 0.011). After matching the different distributions using propensity scores, perioperative blood transfusion was found to be a poor prognostic factor for HCC patients.

Conclusions

In this multi-center study, perioperative blood transfusion was an independent factor for poor prognosis after curative surgery for primary HCC in the patient group and in pairs matched by propensity scores.

     

New macroscopic classification and back-flow thrombectomy for advanced hepatocellular carcinoma with portal vein tumor thrombus invading the contralateral second portal branch

Purpose

Patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) invading the portal trunk (Vp4) are poor surgical candidates because of the technical difficulties involved. To overcome the limitations, we developed a technique of back-flow thrombectomy (BFT) based on the inherent portal hemodynamics and the macroscopic form of PVTT.

Methods

Forty-six patients with multiple HCC and Vp4 PVTT underwent hepatectomy with tumor thrombectomy. We used the BFT to treat 24 patients, 18 of whom had PVTT in the contralateral second portal branch. The form of PVTT was classified macroscopically into the floating and expansive types.

Results

The rate of complete removal by BFT of PVTT in the contralateral second portal branch was 89%. The patency rates at the thrombectomy site in all 46 patients and in the 24 BFT patients, 3 months after hepatectomy were 93 and 90%, respectively. The median OS of all 46 patients was 15 months, with 1- and 3-year OS rates of 58.5 and 17.1%, respectively. The median OS of the 24 patients treated with BFT vs. the 22 not treated with BFT was 14 and 15 months, respectively.

Conclusions

BFT can expand the therapeutic time window for patients with HCC and deep-seated PVTT and may improve their survival.

     

Prognostic Analysis of Surgical Resection for Pulmonary Metastasis from Hepatocellular Carcinoma

Introduction

Pulmonary metastases are the most common among extrahepatic recurrences from hepatocellular carcinoma (HCC). It causes high risk of HCC-related death, despite recent progress in therapeutic options. However, a role of pulmonary metastasectomy as well as prognostic factors after metastasectomy has not been well established. We aimed to investigate survival outcomes and prognostic factors after pulmonary resection for metastases from HCC.

Methods

A series of 93 patients who underwent pulmonary resections for metastases from HCC between June 1990 and July 2013 from multi-institutional database were retrospectively evaluated. Perioperative clinicopathological data and their association with prognosis were investigated.

Results

Of 93 patients, 77 had one pulmonary metastasis, and 16 had two or more. Recurrence after pulmonary resection was noted in 60 patients (64.5 %). The estimated 5-year overall survival rate was 41.4 % with median survival time after pulmonary metastatectomy of 39.0 months. Univariate prognostic analysis showed that disease-free interval of ≥12 months was significantly associated with favorable outcomes in both overall survival (5-year rate, 59.3 vs. 28.7 %, p = 0.026) and disease-specific survival (5-year rate, 62.5 vs. 36.2 %; p = 0.038) after pulmonary metastatectomy. A multivariate analysis revealed that disease-free interval was an independent prognostic factor (HR = 2.020, 95 % CI, 1.069–3.816, p = 0.030).

Conclusion

We have shown that a disease-free interval was an independent prognostic factor in patients who underwent pulmonary resection for metastasis from HCC. Also, pulmonary metastasectomy can be one of the therapeutic choices for select patients.

     

Patient Adherence and Experience with Extended Use of Prophylactic Low-Molecular-Weight Heparin Following Pancreas and Liver Resection

Background

Guidelines recommend 28 days venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) following major abdominal surgery for cancer. Overall adherence with these recommendations is poor, but little is known about feasibility and tolerability from a patient perspective.

Methods

An institution-wide policy for routine administration of 28 days of post-operative LMWH following major hepatic or pancreatic resection for cancer was implemented in April 2013. Patients having surgery from July 2013 to June 2015 were approached to participate in an interview examining adherence and experience with extended duration LMWH.

Results

There were 100 patients included, with 81.4 % reporting perfect adherence with the regimen. The most frequent reasons for non-adherence were that a healthcare provider stopped the regimen or because of poor experience with injections. Most patients were able to correctly recall the reason for being prescribed LMWH (82.6 %), and 78.4 % of patients performed all injections themselves. Over half the patients (55.7 %) did not find the injections bothersome.

Conclusion

Patients reported high adherence and a manageable experience with post-operative extended-duration LMWH in an ambulatory setting following liver or pancreas resection. These findings suggest that patient adherence is not a major contributor to poor compliance with VTE prophylaxis guidelines.

     

Predicting Individual Survival After Hepatectomy for Hepatocellular Carcinoma: a Novel Nomogram from the “HCC East &amp; West Study Group”

Introductions

Different staging systems have been devised for patients undergoing resection for hepatocellular carcinoma (HCC) with disparate results. The aim of this study was to create a new nomogram to predict individual survival after hepatectomy for HCC.

Methods

Based on the “Hepatocellular Carcinoma: Eastern & Western Experiences Network,” data from 2046 patients who underwent HCC resections at ten centers were reviewed. Patient survival was analyzed with Cox-regression analysis to construct a unique nomogram and contour plots to predict survival.

Results

The nomograms built on the multivariate analyses, which showed that the independent predictors were tumor size, tumor number, vascular invasion, cirrhosis, preoperative bilirubin value, and esophageal varices, showed good calibration and discriminatory abilities with C-index value of 0.62 (95 % CI, 0.59–0.69) and 0.61 (95 % CI, 0.56–0.64) for overall and disease-free survival, respectively. The 5-year survival contour plots showed that the presence of vascular invasion was associated with decreased survival, regardless of the tumor number or size. Cirrhosis and varices were equally associated with decreased survival, according to the tumor number or size.

Conclusions

These nomograms accurately predict individual prognosis after HCC resection and support an expansion of the selection criteria for resection. They offer useful guidance to clinicians for individual survival prediction.

     

Prognosis of Hepatocellular Carcinoma Patients Who Achieved Long-Term Recurrence-Free Survival After Curative Therapy: Impact of the ALBI Grade

Background/Aims

Some patients experience very late recurrence of HCC more than 5 years after initial therapy. We aimed to clarify the predictive factors for very late recurrence of HCC in such cases.

Methods

Among 807 HCC patients undergoing surgical resection or ablative therapy with curative intent, the patients who survived for 5 years without any recurrence were reviewed. The prognosis and possible predictive factors for late recurrence were analyzed retrospectively.

Results

A total of 184 patients survived for more than 5 years without recurrence. Among them, 61 patients experienced recurrence, at a median of 6 years after initial therapy. In univariate analysis, the pre-treatment aspartate aminotransferase, alanine aminotransferase, Child-Pugh class, and ALBI grade were not related to recurrence, but those at 5 years after treatment were significantly related to recurrence. By multivariate analysis, an ALBI grade of 2–3 at 5 years was an independent risk factor for recurrence (P?<?0.0001). Moreover, variation of the ALBI grade over the 5 years after the initial treatment was significantly related to recurrence-free survival.

Conclusions

The ALBI grade is an effective index of the variation in liver function after curative therapy and may be a useful prognostic factor for the long-term recurrence-free survival of HCC patients.

     

Feasibility of Total Gastrectomy with D2 Lymphadenectomy for Gastric Cancer and Predictive Factors for Its Short- and Long-Term Outcomes

Background

The aim of this study was to evaluate the short- and long-term outcomes after total gastrectomy (TG) with D2 lymphadenectomy.

Methods

Patients undergoing TG with D2 lymphadenectomy for gastric cancer between December 2008 and December 2011 were enrolled. Univariate and multivariate analyses were performed to evaluate the risk factors for the short- and long-term outcomes.

Results

A total of 229 patients were analyzed, and 22.3 % developed complications within 30 days of surgery. No patient died within 30 days, while 2.6 % died within 90 days of the operation. In the multivariate analysis, age ≥65 years and cardiopulmonary comorbidities were associated with morbidity, whereas hypoproteinemia and tumor–node–metastasis (TNM) stage III were associated with the disease-free survival (DFS) and overall survival (OS). The number of preoperative risk factors stratified the morbidity from 10.3 % in those without any risk factors to 40.5 % in patients with both risk factors. Similarly, 5-year survival rates decreased from 68.9 % (DFS) and 71.1 % (OS) in those without risk factors to 20.2 % (DFS) and 22.9 % (OS) in patients with both risk factors.

Conclusion

TG with D2 lymphadenectomy has acceptable short- and long-term outcomes. Patient risk stratification may allow for more rational selection of patients and therapeutic strategies for gastric resection.

     

ALPPS for Hepatocellular Carcinoma Is Associated with Decreased Liver Remnant Growth

Background

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been widely described for colorectal liver metastases with insufficient future liver remnant (FLR). However, its role in hepatocellular carcinoma (HCC) remains poorly defined and not widely accepted.

Methods

A retrospective comparison of clinical data, liver volumetry, histological characteristics, and surgical outcomes between nine HCC and four non-HCC patients who underwent ALPPS was performed.

Results

Patients with HCC were more likely to have histological evidence of hepatic fibrosis (HCC vs. non-HCC, 66.7 vs. 0%, p?=?0.049). Baseline demographic and disease characteristics were otherwise comparable between both groups. FLR growth after ALPPS-Stage 1 was significantly less in HCC patients (HCC vs. non-HCC, 154.5 vs. 251.0 ml, p?=?0.012). FLR growth was also significantly decreased in patients with hepatic fibrosis (fibrosis vs. non-fibrosis, 157.5 vs. 247.5 ml, p?=?0.033). There was no difference in post-hepatectomy liver failure (HCC vs. non-HCC, 28.6 vs. 25%, p?=?0.721) or 90-day mortality (HCC vs. non-HCC, 11.1 vs. 0%, p?=?NS).

Discussion

In our study, HCC patients demonstrated significantly less FLR growth after ALPPS-Stage 1 compared to non-HCC patients. Hepatic fibrosis was also found to negatively impact FLR growth. When considering suitability for ALPPS, patients with HCC may benefit from additional pre-operative assessment of fibrosis.

     

Tumor Biology Rather Than Surgical Technique Dictates Prognosis in Colorectal Cancer Liver Metastases

Introduction

The interplay of tumor biology and surgical margin status after resection for colorectal liver metastasis (CRLM) remains controversial. Consequently, we sought to determine the impact of surgical margin status on overall survival (OS) stratified by KRAS mutational status.

Materials and Methods

Four hundred eighty-five patients with known KRAS mutational status were identified. Clinicopathologic and long-term survival data were collected and assessed.

Results

On pathology, most patients (n?=?380; 78.3 %) had an R0 margin, while 105 (21.7 %) had an R1. Roughly two thirds of tumors were KRAS wild type (wtKRAS) (n?=?307, 63.3 %), while 36.7 % (n?=?178) had KRAS mutations (mutKRAS). Median and 5-year OS of the entire cohort was 65.8 months and 53.8 %, respectively. An R1 resection was associated with worse 5-year OS compared with R0 (42.4 % vs. 57.1 %; hazard ratio (HR) 1.82, 95 % CI 1.28–2.57; P?=?0.001). After controlling for KRAS status, the survival benefit associated with an R0 resection persisted only among patients with wtKRAS tumors (HR 2.16, 95 % CI 1.42–3.30; P?<?0.001). In contrast, surgical margin had no impact on OS among patients with mutKRAS tumors (5-year OS R0, 40.7 % vs. R1, 46.7 %; HR 1.34, 95 % CI 0.73–2.48; P?=?0.348).

Conclusion

The impact of margin status differed by KRAS mutation status. An R0 margin only provided a survival benefit to patients with wtKRAS tumors. Tumor biology and not surgical technique determined prognosis.

     

The influence of comorbidity on the postoperative survival in elderly (≥ 75 years old) with lung cancer

Objectives

We conducted a multi-institutional prospective observational study of elderly patients (≥?75 years-old) with resected non-small cell lung cancer. In this report, we have followed the cohorts for 2 years after surgery and examined both the influence of preoperative comorbidity [Adult Comorbidity Evaluation-27 (ACE-27) index] on the postoperative survival and the change in the Karnofsky Performance Status (KPS).

Methods

From March 2014 to April 2015, 264 patients were prospectively registered from 22 hospitals affiliated with the National Hospital Organization. The mean age at the time of surgery was 79.3 years (range 75–90 years), and 41% of the patients were ≥?80 years of age. A total of 26% underwent sublobar resection. The study endpoints were the postoperative overall survival (OS), its prognostic factors, and the changes in the postoperative KPS.

Results

The 2-year OS was 85.3% (95% confidence interval 80.4–89.1%). Male gender, age?≥?80, a smoking history, grade 2 of ACE-27, and an advanced disease stage were significantly poor prognostic factors for the OS in the univariate risk analysis. The multivariate analysis showed that male gender, age?≥?80, an advanced disease stage and sublobar resection were significantly poor prognostic factors for the OS. In comparison with the preoperative KPS, no marked decline was observed in the postoperative chorological change of KPS.

Conclusions

In the surgical treatment of elderly patients, the comorbidity as assessed by the ACE-27 index might affect the postoperative survival, and therefore should be taken into accounts in the preoperative evaluation of the surgical indications.

     

Palliative surgery for colorectal cancer with peritoneal metastasis: a propensity-score matching analysis

Purpose

Peritoneal metastasis (PM) in patients with colorectal cancer (CRC) is associated with poor prognosis. We conducted this study to assess whether palliative resection (PR) of the primary tumor improved the overall survival (OS) of patients with PM-CRC.

Methods

We analyzed retrospectively, data collected prospectively from patients with CRC. PM was categorized into three subgroups according to the Japanese classification of PM. A propensity‐score model was used to compare the outcomes of patients who underwent PR (PR group) and those who did not [non‐resection (NR) group].

Results

Among 1909 patients with metastatic CRC, 309 (16 %) had only peritoneal metastases and 255 of these patients who underwent palliative surgery (R2) were the subjects of our analysis: 161 in the PR group and 94 in the NR group. Median OS was significantly longer in the PR group than in the NR group (23 vs. 11 months, P < 0.001). Patients in the PR group had less extensive PM and a higher rate of receiving palliative chemotherapy than those in the NR group (P < 0.001). In a Cox multivariate analysis of 69 propensity‐score matched pairs, PR resulted in significantly longer OS than NR (hazard ratio 0.496, 95 % confidence interval 0.268–0.919, P = 0.025).

Conclusions

Our results show that PR resulted in better OS than NR for patients with PM-CRC, when their overall condition permitted a more aggressive approach.