Prognosis After Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma Originating from Non-cirrhotic Liver

Background

Long-term prognosis after resection of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) originating from non-cirrhotic liver is not fully clarified.

Methods

A total of 183 patients who underwent curative hepatectomy for HCC without cirrhosis were classified into two groups: HBV infection group (n = 124) and non-HBV infection group (n = 59). Long-term postoperative outcomes were compared between the two groups.

Results

The 5-year postoperative overall survival (OS) and disease-free survival (DFS) were 42.6 and 39.0 %, respectively, in the HBV infection group versus 52.3 and 46.5 % in the non-HBV infection group (both p > 0.05). When patients were subdivided according to TNM stages, OS in stages II or III HCC patients was similar between the two groups. In contrast, OS and DFS were significantly worse in stage I patients with HBV infection than those in stage I patients without HBV infection (p = 0.041 and 0.038, respectively). Preoperative serum HBV DNA >4 log₁₀ copies/mL and vascular invasion were independent factors associated with poor prognosis (p = 0.034 and 0.017, respectively) for patients with HBV infection.

Conclusions

After hepatic resection for HCC in non-cirrhotic liver, patients with HBV infection with early-stage tumors had worse prognosis than patients without HBV infection, possibly due to the carcinogenetic potential of viral hepatitis in the remnant liver. Antiviral therapy should be considered after hepatectomy in patients with high HBV DNA levels.     

Adjuvant Hepatic Intra-arterial Iodine-131-Lipiodol Following Curative Resection of Hepatocellular Carcinoma: A Prospective Randomized Trial

Background

The purpose of the present study was to determine whether intrahepatic injection of ¹³¹I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC).

Methods

From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4–6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan–Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong.

Results

The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46–1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51–1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by ¹³¹I-lipiodol and hepatic artery dissection during angiography.

Conclusions

The randomized trial provides insufficient evidence to recommend the routine use of ¹³¹I-lipiodol in these patients.     

Infection with Hepatitis C Virus is an Adverse Prognostic Factor after Liver Resection for Early-stage Hepatocellular Carcinoma

Introduction

Recent data support liver resection (LR) as first-line approach in patients with preserved liver function who have resectable/transplantable hepatocellular carcinoma (HCC). This study was designed to evaluate the outcome of LR in patients with transplantable HCC.

Methods

Between 1998 and 2009, 75 patients (65 men, mean age 61 ± 11 years) with HCC eligible for liver transplantation (LT) underwent LR. The underlying hepatic disease was related to hepatitis C (HCV) in 30 (40 %) patients, hepatitis B (HBV) in 15 (20 %) patients, alcohol abuse in 26 patients (36 %) and other in 10 patients (13 %). Fifty-five (73 %) patients had cirrhosis. Intermittent clamping of the hepatic pedicle was used in 41 (55 %) patients. Treatment of recurrence by salvage LT was performed in 6 (8 %) patients.

Results

Operative morbidity and mortality rates were 37 and 5  % respectively. At 1, 3, and 5 years, overall (OS) and disease-free (DFS) survival rates were 81, 69,55 and 56, 31, and 21 %, respectively. On multivariate analysis, HCV infection was the only independent factor associated with decreased OS (p = 0.02). On multivariate analysis, HCV infection (p = 0.05) and intermittent hepatic pedicle clamping (p = 0.003) were associated with decreased DFS. The 1-, 3-, and 5-year OS and DFS rates in patients with HCV-related HCC were 69, 53, 38 and 50, 18, and 9% respectively.

Conclusions

Overall and disease-free survival after liver resection in patients with HCV-related HCC and preserved liver function is poor. Primary LT should be offered to these patients.     

Recurrence Patterns and Prognostic Factors in Patients with Hepatocellular Carcinoma in Noncirrhotic Liver: A Multi-Institutional Analysis

Background

Hepatocellular carcinoma (HCC) primarily affects patients with a cirrhotic liver. Reports on the characteristics of patients with HCC in noncirrhotic liver, as well as predictors of recurrence and survival, are scarce.

Methods

Between 1992 and 2011, 334 patients treated for HCC in noncirrhotic liver were identified from three major hepatobiliary centers. Clinicopathological characteristics were analyzed and independent predictors of recurrence and overall survival were identified using Cox proportional hazards models.

Results

Median patient age was 58 years and 77 % were male. Most patients had a solitary (81 %) and poorly or undifferentiated tumor (56 %); median size was 6.5 cm. The majority of patients (96 %) underwent liver resection (microscopically negative margins in 94 %), whereas a few had transarterial chemoembolization or transplantation (4 %). Median recurrence-free survival (RFS) was 2.5 years, and 1- and 5-year RFS was 71.1, and 35 %, respectively. Elevated alkaline phosphatase levels [hazards ratio (HR) = 1.82], poor tumor differentiation (HR = 1.4), macrovascular invasion (HR = 2.18), and the presence of satellite lesions (HR = 1.9), or intrahepatic metastases (HR = 2.59) were independently associated with shorter RFS; in contrast, an intact tumor capsule independently prolonged RFS (HR = 0.46). Median overall survival was 5.9 years, and 1- and 5-year overall survival was 86.9, and 54.5 %, respectively. Tumor size ≥5 cm (HR = 2.27), macrovascular (HR = 2.72) or adjacent organ invasion (HR = 3.34), and satellite lesions (HR = 2.18) were independently associated with shorter overall survival, whereas an intact tumor capsule showed a protective effect (HR = 0.51).

Conclusions

Following resection of HCC in the setting of no cirrhosis, more than one-half of patients were alive after 5 years. However, even among patients with no cirrhosis, recurrence was common. Factors associated with RFS and overall survival included tumor characteristics, such as tumor capsule, satellite lesions, and vascular invasion.     

Liver Transplantation in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma: The Influence of Viral Characteristics on Clinical Outcome

Background

Hepatitis B virus (HBV) relapse and/or hepatocellular carcinoma (HCC) recurrence remains a major concern for patients who undergo liver transplantation (LT) because of HBV-related HCC. This study investigates the correlation between HBV relapse and HCC recurrence and it explores factors that affect patient outcomes after LT.

Methods

Between September 2002 and August 2009, 78 consecutive patients who underwent LT because of HBV-related HCC were enrolled in this study. Serum samples obtained before LT were assayed both for virological factors associated with HBV DNA and for genotypic characteristics of the virus. All patient clinicopathological features and virological factors were assessed further by univariate and multivariate analyses to determine prognostic factors.

Results

During a median follow-up period of 29.4 months, 13 (16.6 %) patients experienced HCC recurrence and 18 (23.1 %) patients experienced HBV relapse. HBV relapse exhibited a close association with HCC recurrence (p = 0.004) and led to unfavorable overall survival after LT. Multivariate analysis of prognostic factors showed that the basal core promoter (BCP) mutation independently predicted a shorter survival period free from HBV relapse (p = 0.036). Moreover, with the exception of unfavorable tumor characteristics, the BCP mutation was found to be an important prognostic factor that affected HCC recurrence after LT (p = 0.042).

Conclusions

In this study, the HBV–BCP mutation was identified as an important predictor of post-LT clinical outcomes in patients with HBV-related HCC. Therefore, we recommend that aggressive antiviral treatment may be considered for patients associated with this risk factor.     

Limitations of Lymph Node Ratio, Evidence-Based Benchmarks, and the Importance of a Thorough Lymph Node Dissection in Melanoma

Background

Stage III melanoma is currently stratified by number of lymph nodes (LNs) involved. However, given the variability of LN retrieval counts we hypothesize that lymph node ratio (LNR) may also provide prognostic information.

Methods

Retrospective cohort study of 411 patients with stage III melanoma were divided into two groups based on LNR (<0.15, n = 291 and ≥0.15, n = 120).

Results

In multivariate analysis N stage (N3 vs. N1, hazard ratio [HR] = 2.13, p < 0.001), extranodal extension (HR = 1.92, p = 0.002), macrometastasis (HR = 1.70, p = 0.005), non-SLN involvement (HR = 1.65, p = 0.005), risk of N2 disease exceeding 35 % (HR = 1.51, p = 0.03), and LNR ≥0.15 (HR = 1.46, p = 0.03) were associated with overall survival (OS). LNR failed to further stratify stage III melanoma; however, the number of LNs examined was an independent prognostic factor. Patients who had >8 inguinal, >15 axillary, or >20 cervical LNs examined had fewer same nodal basin recurrences (26 [8 %] vs. 20 [20 %], p = 0.0009) and for N1 patients an improved OS (3-year OS 84 % vs. 76 %, 10-year OS 53 % vs. 34 %, p = 0.06) compared with N1 patients who had fewer LNs examined.

Conclusions

LNR is an important prognostic factor in stage III melanoma; however, it was not independent over the current AJCC TNM staging system. Diligence by the surgeon and pathologist to retrieve and examine >8 inguinal, >15 axillary, or >20 cervical LNs is associated with fewer same nodal basin recurrences and improved survival and is critical to reliable prognostication.     

Selection Criteria for Postmastectomy Radiotherapy in T1–T2 Tumors with 1 to 3 Positive Lymph Nodes

Background

Postmastectomy radiotherapy (PMRT) is well established in patients with ≥4 positive axillary lymph nodes (ALN); indications in 1 to 3 positive ALN remains controversial. We examined clinicopathologic criteria used for PMRT selection and compared locoregional recurrence (LRR), recurrence-free survival (RFS), and overall survival (OS) among patients with and without PMRT.

Methods

Between 1995 and 2006, a total of 1,331 patients with T1–T2 tumors and 1 to 3 positive ALN underwent mastectomy. We excluded T3/T4 tumors and neoadjuvant chemotherapy; we analyzed 1,087 patients (924 without PMRT, 163 with PMRT). Chi square testing compared clinicopathologic features between groups. The Kaplan–Meier method and Cox regression analysis examined the association between PMRT and LRR, RFS, and OS.

Results

PMRT patients were more likely to be ≤50 years old (p = 0.001) and to have larger tumors (p = 0.01), disease of a higher histologic grade (p = 0.03), lymphovascular invasion (LVI) (p < 0.0001), a greater number of positive ALN (p < 0.0001), extranodal invasion (p < 0.0001), and macroscopic ALN metastases (p < 0.0001). With a median follow-up of 7 years, PMRT and no-PMRT groups were similar in LRR (p = 0.57), RFS (p = 0.70), and OS (p = 0.28). On multivariate analysis of the no-PMRT group, age ≤50 years (p = 0.002) and presence of LVI (p < 0.0001) were associated with LRR. Stratified by age and LVI, patients ≤50 years old and with LVI had the highest 5-year LRR, 10.1 versus 1.1 %, than in patients >50 years old without LVI (p < 0.001).

Conclusions

By using clinicopathologic features, clinicians delivered PMRT to a select group of patients with T1–T2 tumors and 1 to 3 positive ALN, resulting in similarly low rates of 5-year LRR. Among patients not receiving PMRT, age ≤50 years and LVI were associated with increased LRR rates and warrant PMRT consideration.     

Combination of Osteopontin with Peritumoral Infiltrating Macrophages is Associated with Poor Prognosis of Early-Stage Hepatocellular Carcinoma after Curative Resection

Background

Crosstalk between a tumor and the microenvironment plays a key role in tumor progression and metastasis. This study was performed to elucidate the prognostic significance of combining tumor-secreted osteopontin (OPN) with microenvironment-associated peritumoral macrophages (PTMs) in hepatocellular carcinoma (HCC), especially for those with early-stage disease.

Methods

Tissue microarray-based immunohistochemistry was used to investigate OPN and PTMs expression in two independent cohorts consisting of 374 patients with HCC who underwent radical resection. The prognostic value for the two factors alone or in combination was investigated in these patients.

Results

OPN combined with PTMs was an independent prognostic factor for both overall survival (OS; p < 0.0001) and time to recurrence (TTR; p = 0.003) from the learning cohort (n = 96). Their combined value for prognosis was validated in early-stage HCCs using another independent cohort (n = 278; OS, p < 0.001; TTR, p = 0.001). This combination remained significant in HCCs with low α-fetoprotein levels in both cohorts, and was predictive for early recurrence/death risk (<2 years) compared with a single marker. Only OPN+HCCs had a significant correlation of PTMs levels with OS (p = 0.01) or TTR (p = 0.011).

Conclusions

Tumor OPN combined with PTMs is a promising predictor of tumor recurrence and survival in patients with HCC, especially for those with early-stage disease. The interplay of OPN and PTMs represents a new insight into tumor progression and therapeutic targets for HCC.     

Impact of Molecular Subtype on Locoregional Recurrence in Mastectomy Patients with T1–T2 Breast Cancer and 1–3 Positive Lymph Nodes

Background

Postmastectomy radiation (PMRT) in T1–T2 tumors with 1–3 positive axillary lymph nodes (ALNs) is controversial. Impact of molecular subtype (MST) on locoregional recurrence (LRR) and PMRT benefit is uncertain. We examined the association between MST and LRR, recurrence-free survival (RFS), and overall survival (OS), in T1–T2 tumors with 1–3 positive ALNs.

Methods

From an institutional database, we identified mastectomy patients with 1–3 positive ALNs between 1995 and 2006. Patients who received neoadjuvant chemotherapy, had T3–T4 tumors, or ≥4 positive ALNs were excluded. MST was defined as: hormone receptor (HR)+/HER2?(luminal A/B), HR+/HER2+(luminal HER2), HR?/HER2+(HER2), and HR?/HER2?(basal). Kaplan–Meier method and Cox regression analysis were used to examine association between MST and LRR, RFS, and OS.

Results

This study included 884 patients (700 no PMRT, 141 PMRT): 72.8 % luminal A/B, 7.8 % luminal HER2, 6.8 % HER2, and 12.6 % basal. Median follow-up was 6.3 years; 39 LRRs occurred. Luminal A/B subtype had the smallest tumors (p = 0.03), lowest intraductal component (p = 0.01), histologic grade (p < 0.0001), lymphovascular invasion (LVI) (p = 0.008), and multifocality/multicentricity (p = 0.02). On univariate analyses, there was no association between MST and LRR. MST was associated with RFS and OS; the basal and HER2 subtype had the lowest RFS (p = 0.0002) and OS (p < 0.0001). On multivariate analysis, only age ≤50 years (p = 0.003) and presence of LVI (p = 0.0003) were predictive of LRR; MST was not (p = 0.38).

Conclusion

In patients with T1–T2 breast cancer and 1–3 positive lymph nodes who did not receive PMRT, MST was not an independent predictor of LRR and may not be useful in selecting PMRT candidates in that group.     

The impact of immunohistochemical expression of nitric oxide synthases on clinical and pathological features of renal cell carcinoma

Purpose

To evaluate the immunohistochemical expression of nitric oxide synthase (NOS) types 1, 2, and 3 in intratumoral and non-neoplastic samples of renal cell carcinoma (RCC) and correlate it with the clinical and pathological features of this malignancy.

Methods

We analyzed 110 patients with RCC underwent radical nephrectomy (RN) or partial nephrectomy (PN) by streptavidin–biotin peroxidase method, tissue microarray, and digital microscopy. As endpoints, NOS expression was correlated with pathological features, overall survival (OS), and cancer-specific survival (CSS).

Results

Non-neoplastic samples had higher NOS3 and lower NOS 2 levels than RCC tissues. Greater expression of all NOS isoforms was associated with larger tumors. High NOS1 expression correlated with microscopic venous invasion (MVI) (p = 0.046) and lymph node metastases (p = 0.007). High NOS2 expression was linked to MVI, more RN performed, and male gender (p = 0.035, p = 0.003, and p =  0.027, respectively). High NOS3 expression correlated with lymph node metastases (p = 0.039), microlymphatic invasion (p = 0.029), invasion of the renal pelvis and ureter (p = 0.004), RN (p = 0.003), and shorter OS (58.1 vs. 79.4 % respectively, p = 0.033) by univariate analysis. DFS was not influenced by any NOS isoform. By multivariate analysis, the risk factors for death were TNM stages III and IV (hazard ratio [HR] = 4.5), high Fuhrman’s grade (HR = 2.9), Karnofsky performance status ≤80 (HR = 2.5), progression (HR = 5.5), and recurrence (HR = 6.3). Stage III disease was an independent risk factor for recurrence (HR = 9.5).

Conclusions

High NOS expression in RCC is associated with a poor prognosis and larger tumors. NOS3 influences OS by univariate analysis.     

Video-Assisted Thoracoscopic Surgical Thymectomy to Treat Early Thymoma: A Comparison with the Conventional Transsternal Approach

Background

For thymoma, the feasibility of resection via video-assisted thoracoscopic surgery (VATS) remains controversial. The objective of our study was to compare the outcomes of VATS and transsternal thymectomy in order to evaluate the efficacy of the VATS method for treatment of early stage thymoma.

Methods

This study is a retrospective study of 120 patients who underwent thymectomy of early stage thymoma (Masaoka stage I and II) in a single medical center from 1991 to 2010. Of these patients, 76 patients underwent VATS thymectomy (VATS group) and 44 patients underwent the conventional transsternal approach (sternotomy group). We applied the Kaplan–Meier method to estimate overall survival (OS), recurrence-free survival (RFS), and time to tumor recurrence (TTR) of these two groups.

Results

The mean follow-up time was 61.9 months in the VATS group and 69.7 months in the sternotomy group. There was no surgery-related mortality or major complication. The VATS group had smaller specimen size (p < 0.05) and tumor size (p < 0.01), shorter length of stay (LOS) in the hospital (p < 0.01), and shorter duration of chest tube drainage (p < 0.05) than the sternotomy group. There were no significant differences between the two groups for OS, RFS, and TTR.

Conclusions

In early stage thymoma, VATS thymectomy associated with shorter hospital LOS and shorter duration of pleural drainage compared with the conventional transsternal approach. Otherwise, the two approaches had similar oncologic outcomes during the mean 60-month follow-up period.     

Japanese D3 Lymph Node Dissection in Low Rectal Cancer with Inferior Mesenteric Lymph Node Metastases

Background

There is currently no consensus on the significance of Japanese D3 lymph node dissection in low rectal cancer with inferior mesenteric lymph node (IMLN) metastasis. This is partly because, despite a number of studies on the subject, cases of IMLN metastasis are relatively rare, and there are few cases of curative resection because of metastasis to other organs. A retrospective study involving a large number of patients was conducted.

Methods

The subjects were 2,743 patients registered in the national registry of the Japanese Society for Cancer of the Colon and Rectum. The data were analyzed for (1) prognostic factors for IMLN metastasis, and (2) outcomes in R0 cases with IMLN metastasis.

Results

In the control group, 67 patients (2.7 %) were considered positive for IMLN metastasis. The outcomes in the 35 R0 cases with IMLN metastasis were 50.8 % for 5-year relapse-free survival (RFS) and 61.9 % for 5-year overall survival (OS), which were each better than for R1+R2 cases (5-year RFS 16.1 %, p = 0.0001; 5-year OS 26.7 %, p = 0.0002). The outcomes for R0 cases (total metastatic lymph nodes ≥7) with IMLN metastasis (5-year RFS 53.9 %, 5-year OS 68.8 %) did not differ significantly from those for IMLN(?) cases (5-year RFS 54.6 %, 5-year OS 57.1 %) (RFS: p = 0.9515, OS: p = 0.4621).

Conclusions

It was confirmed that cases of IMLN metastasis in low rectal cancer tend to have a large total number of metastatic lymph nodes, but if curative resection can be performed, a good prognosis can be expected. These results demonstrate the value of radical Japanese D3 lymph node dissection in low rectal cancer with IMLN metastasis.     

HBV DNA and HBsAg Levels as Risk Predictors of Early and Late Recurrence after Curative Resection of HBV-related Hepatocellular Carcinoma

Background

Recent studies have shown that high hepatitis B virus (HBV) load is associated with increased risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). The aim of our study was to investigate the predictive role of HBV DNA and hepatitis B surface antigen (HBsAg) levels in early and late recurrence of HCC after curative resection in patients with HBV-related HCC.

Methods

From January 2008 to December 2010, a total of 248 patients underwent curative resection for HBV-related early-stage HCC (solitary tumor; < 5 cm in diameter or multinodular tumor; number of tumors ≤3 and diameter < 3 cm). We analyzed the predictive factors including HBV DNA and HBsAg levels for early recurrence (within 2 years) and late recurrence (after 2 years) of HCC after curative resection.

Results

The median follow-up duration was 33.3 months. Cumulative recurrence rates after resection at 1, 3, and 5 years were 16.6, 34.0, and 46.7 %, respectively. The multivariate analysis showed that risk factors for early recurrence were the presence of microvascular invasion (hazard ratio [HR] 3.86; p < 0.001), preoperative HBV DNA levels ≥ 20,000 IU/mL (HR 2.77; p < 0.001), and des-γ-carboxy prothrombin level ≥ 40 mAU/mL (HR 1.76; p = 0.045). Although, the risk factors for late recurrence by multivariate analysis were preoperative HBsAg levels ≥ 4,000 IU/mL (HR 2.80; p = 0.023) and age at resection ≥ 50 years (HR 3.22; p = 0.032).

Conclusion

The HBV DNA levels were associated with early recurrence, whereas HBsAg levels were associated with late recurrence after curative resection in HBV-related HCC.     

Cutaneous Angiosarcoma: A Single-Institution Experience

Background

Cutaneous angiosarcoma (CAS) is a rare, aggressive vascular sarcoma with a poor prognosis, historically associated with 5-year overall survival (OS) rates between 10 and 30 %.

Methods

This is a single-institution retrospective review of patients treated for CAS from 1999–2011. Demographics, primary tumor characteristics, treatment, and outcomes were analyzed.

Results

A total of 88 patients were identified (median age 70 years and 57 % female). Median tumor size was 3 cm. Median follow-up was 22 months. The 5-year OS and recurrence-free survival (RFS) were 35.2 and 32.3 %, respectively; median was 22.1 months. Also, 36 patients (41 %) received surgery alone, 7 (8 %) received XRT alone, and 41 (47 %) received surgery and XRT. Of the 67 of 88 patients who were disease-free after treatment, 33 (50 %) recurred (median of 12.3 months). Surgery alone had the highest 5-year OS (46.9 %) and RFS (39.9 %) (p = ns). Four presentation groups were identified: (1) XRT-induced, n = 30 (34 %), 26 of 30 occurred in females with a prior breast cancer, (2) sporadic CAS on head and neck (H/N), n = 38, (3) sporadic CAS on trunk/extremities, n = 13, and (4) Stewart–Treves n = 7. Those with trunk/extremity CAS had the highest 5-year OS (64.8 %), with H/N CAS having the worst 5-year OS (21.5 %). On MV analysis, only tumor size <5 cm correlated with improved OS (p = 0.014).

Discussion

In this large series, there appears to be a better overall prognosis than historically reported, especially in Stewart–Treves and CAS on trunk or extremities. While surgery alone was associated with better OS and RFS compared with other treatment modalities, this was not statistically significant. Tumor size was a significant prognostic factor for OS.     

Factors Influencing the Length of Stay after Radical Cystectomy: Implications for Cancer Care and Perioperative Management

Introduction

Although radical cystectomy (RC) is the gold standard treatment for muscle invasive bladder cancer it is associated with perioperative complications, readmissions, and a prolonged length of hospital stay (PLOS). We explored the perioperative factors associated with a PLOS after RC and subsequent long-term outcomes.

Material and Methods

Consecutive patients with urothelial bladder cancer undergoing RC with curative intent at our institution were classified into two groups: LOS <12 days and PLOS ≥12 days. Clinicopathological variables were compared on univariate and multivariable analysis. Complications, re-admissions, adjuvant chemotherapy use, recurrence free survival (RFS), and overall survival (OS) were compared between the two groups. Competing risk analysis was performed for bladder cancer specific mortality (BCSM).

Results

330 patients were included in the analysis (median LOS = 9 days [IQR = 8–11]) of which, 274 patients (83 %) had a LOS <12 days (median = 8 days [IQR = 7–10]) and 56 patients (17 %) had a PLOS ≥12 days (median = 16 days [IQR = 13–21.5]). Only female gender, older age, and perioperative complications were associated with a PLOS. 90 day readmission rates were similar (p = 0.75). No difference was seen for BCSM, RFS, or adjuvant chemotherapy usage between the two groups. However, OS was significantly worse for PLOS (median OS = 27.7 vs. 45.6 months [p = 0.046]; HR = 1.53 [95 % CI = 1.01–2.33]).

Conclusion

Both female and elderly patients should receive preoperative counseling about their increased risk of a PLOS after RC. Patients who experience a PLOS are at greater risk for subsequent all-cause mortality. These patient groups may benefit from proactive interventions.     

Assessment of ISGLS Definition of Posthepatectomy Liver Failure and Its Effect on Outcome in Patients with Hepatocellular Carcinoma

Background

Posthepatectomy liver failure (PHLF) is a major complication after hepatectomy. As there was no standardized definition, the International Study Group of Liver Surgery (ISGLS) defined PHLF as increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5 in 2010. We evaluated the impact of the ISGLS definition of PHLF on hepatocellular carcinoma (HCC) patients.

Methods

We retrospectively analyzed 210 consecutive HCC patients who underwent curative hepatectomy at our facility from 2005 to 2010. The median follow-up period after hepatectomy was 35.2 months.

Results

Thirty-nine (18.6 %) patients fulfilled the ISGLS definition of PHLF. Overall survival (OS) rates at 1, 3, and 5 years in patients with/without PHLF were 69.1/93.5, 45.1/72.5, and 45.1/57.8 %, respectively (P?=?0.002). Recurrence-free survival (RFS) rates at 1, 3, and 5 years in patients with/without PHLF were 40.9/65.9, 15.7/38.3, and 15.7/20.3 %, respectively (P?=?0.003). Multivariate analysis revealed that PHLF was significantly associated with both OS (P?=?0.047) and RFS (P?=?0.019). Extent of resection (P?<?0.001), intraoperative blood loss (P?=?0.002), and fibrosis stage (P?=?0.040) were identified as independent risk factors for developing PHLF.

Conclusion

The ISGLS definition of PHLF was associated with OS and RFS in HCC patients, and long-term survival will be improved by reducing the incidence of PHLF.     

Assessing Prognostic Significance of Preoperative Alpha-Fetoprotein in Hepatitis B-Associated Hepatocellular Carcinoma: Normal is not the New Normal

Background

Hepatitis B (HBV)-associated hepatocellular carcinoma (HCC) is often associated with alpha-fetoprotein (AFP) production. Although serum AFP has been demonstrated to be a prognostic factor for patient survival, optimal cutoff levels remain unclear.

Methods

Patients with HBV-associated HCC treated by primary liver resection were prospectively followed at a single institution between 1995 and 2008. AFP level was categorized into quintiles for Kaplan–Meier analysis and multivariable Cox proportional hazards regression models.

Results

Best 5-year survival after surgery was observed for patients with AFP in the first quintile (1.4–4.1 ng/mL), with progressively worse outcomes for patients in each increasing quintile. AFP was associated with overall survival (HR = 1.61; 95 % CI 1.30–1.98), disease-free survival (HR = 1.26; 95 % CI 1.10–1.44), and 2-year recurrence (HR = 1.30; 95 % CI 1.07–1.57) in multivariate analysis. Noncirrhotic patients (Ishak 1–5) with AFP in quintile 1 had 94 % 5-year survival, compared with 0 % survival for patients with AFP in quintile 5 (2,332.7–327,560.0 ng/mL) and Ishak stage 6 cirrhosis.

Conclusions

Preoperative serum AFP is an independent predictor of prognosis among HBV-HCC patients following surgical resection. Categorizing AFP into quintiles creates the opportunity to observe differences in outcomes even at low serum levels within the normal range. Additionally, combining AFP quintiles and fibrosis staging provides a predictive model of prognosis for HCC. Thus, even small differences in AFP within the normal range may impact prognosis and disease progression for HBV-HCC.     

Utility of the Proximal Margin Frozen Section for Resection of Gastric Adenocarcinoma: A 7-Institution Study of the US Gastric Cancer Collaborative

Background

The proximal gastric margin dictates the extent of resection for gastric adenocarcinoma (GAC). The value of achieving negative margins via additional gastric resection after a positive proximal margin frozen section (FS) is unknown.

Methods

The US Gastric Cancer Collaborative includes all patients who underwent resection of GAC at seven institutions from 2000–2012. Intraoperative proximal margin FS data and final permanent section (PS) data were classified as R0 or R1, respectively; positive distal margins were excluded. The primary aim was to evaluate the impact on local recurrence of converting a positive proximal FS-R1 margin to a PS-R0 final margin by additional resection. Secondary endpoints were recurrence-free survival (RFS) and overall survival (OS).

Results

Of 860 patients, 520 had a proximal margin FS and 67 were positive. Of these, 48 were converted to R0 on PS by additional resection. R0 proximal margin was achieved in 447 patients (86 %), PS-R1 in 25 (5 %), and converted FS-R1-to-PS-R0 in 48 (9 %). The median follow-up was 44 months. Local recurrence was significantly decreased in the converted FS-R1-to-PS-R0 group compared to the PS-R1 group (10 vs. 32 %; p = 0.01). Median RFS was similar between the FS-R1-to-PS-R0 and PS-R1 cohorts (25 vs. 20 months; p = 0.49), compared to 37 months for the PS-R0 group. Median OS was similar between the FS-R1-to-PS-R0 conversion and PS-R1 groups (36 vs. 26 months; p = 0.14) compared to 50 months for the PS-R0 group. On multivariate analysis, increasing T-stage and N-stage were associated with worse OS; the FS-R1-to-PS-R0 proximal margin conversion was not significantly associated with improved RFS (p = 0.68) or OS (p = 0.44).

Conclusion

Conversion of a positive intraoperative proximal margin frozen section during gastric cancer resection may decrease local recurrence, but it is not associated with improved RFS or OS. This may guide decisions regarding the extent of resection.     

Pretreatment Clinical Mediastinal Nodal Bulk and Extent do not Influence Survival in N2-Positive Stage IIIA Non-small Cell Lung Cancer Patients Treated with Trimodality Therapy

Background

Treatment for patients with N2-positive stage IIIA non-small cell lung cancer has been a controversial issue. The current study evaluated the outcomes in patients treated with trimodality therapy, which consisted of neoadjuvant radiation therapy concurrent with chemotherapy followed by surgical resection, with emphasis on clinical and pathologic nodal status.

Methods

We reviewed the records of 355 patients who were treated with trimodality therapy between 1997 and 2011.

Results

After completion of neoadjuvant chemoradiation, overall down-staging and complete response rates were 50.4 % (179 patients), and 13.2 % (47 patients), respectively. With median follow-up of 35.3 months, median times of progression-free survival (PFS) and overall survival (OS) were 16.3 months and 45.5 months, respectively. Seventeen patients (4.8 %) died of postoperative complications, and the remaining 338 patients were analyzed on prognostic factors. Old age (p = 0.032), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were found to be the significant prognosticators for worse PFS, and old age (p = 0.013), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were related to worse OS. Clinical N2 status did not influence either OS or PFS: the number of involved stations (single station vs. multi-station; p = 0.187 for PFS; p = 0.492 for OS), and bulk (clinically evident vs. microscopic; p = 0.902 for PFS; p = 0.915 for OS).

Conclusion

ypN stage was the most important prognosticator for both PFS and OS; however, neither initial bulk nor extent of cN2 disease influenced prognosis. Surgery following neoadjuvant chemoradiation should have contributed to improved clinical outcomes regardless of clinical nodal bulk and extent.