Survival analysis and prognostic nomogram for patients undergoing resection of extrahepatic cholangiocarcinoma

BackgroundTumor location of extrahepatic cholangiocarcinoma (CCA) might influence survival after resection.MethodsA consecutive series of 175 patients who had undergone a potentially curative resection of extrahepatic CCA was analyzed. We calculated concordance indices of different constructed prognostic models for survival including TNM (tumour–node–metastasis) staging and developed a nomogram of the most sensitive model.ResultsOverall cancer-specific survival rates were 83%, 58%, and 26% at 1, 2, and 5 years, respectively. Cancer-specific survival according to location was 42% for proximal, 23% for mid, and 19% for distal CCA after 5 years. Tumor location was not an independent significant predictor (P = 0.06). A prognostic model using all potential prognostic variables predicted survival better compared with TNM staging (concordance index 0.65 versus 0.63). A reduced model containing only lymph node status, microscopically residual tumor status, and tumor differentiation grade, also outperformed TNM staging (concordance index 0.66).ConclusionsTumor location of extrahepatic CCA does not independently predict cancer-specific survival after resection. We developed a nomogram, based on a prognostic model with lymph node status, microscopically residual tumor status of resection margins, and tumor differentiation grade, that predicted survival better than TNM staging.     

A new histological classification for intra-operative histological examination of the ductal resection margin in cholangiocarcinoma

The purpose of this study was to establish a standard histological classification for intra‐operative histological examination of ductal resection margins in cholangiocarcinoma to distinguish between epithelial and intramural lesions and to clarify correlations between the new classification and clinical outcomes. Intra‐operative diagnosis of ductal margins was performed for 357 stumps from 216 patients undergoing surgical resection of cholangiocarcinoma at the National Cancer Center, Japan. Three expert pathologists reviewed the materials and established a histological classification defined by grade of atypia. The new classification comprised four categories: ‘insufficient’, insufficient for diagnosis due to distortion of specimen; ‘negative for malignancy’, no atypia suggestive of neoplasia; ‘undetermined lesion’, specimen showing either cellular or structural atypia; and ‘positive for malignancy’, specimen showing both cellular and structural atypia. Each category was defined to distinguish between epithelial and intramural lesions. Validity and reproducibility of the proposed classification were found to be moderate to substantial. Multivariate analyses using the clinicopathological factors identified to be associated with overall survival by univariate analyses indicated that patients diagnosed with ‘positive for malignancy’ in intramural lesions of the proximal margin displayed significant poor prognosis. Meanwhile, in patients diagnosed with ‘positive for malignancy’ or ‘undetermined lesion’ in epithelial lesions of the proximal margin, no difference in overall survival was apparent compared to patients diagnosed with ‘negative for malignancy’. We propose new histological classification for intra‐operative histological examination of ductal resection margins in cholangiocarcinoma that shows a correlation with patients’ prognosis and should facilitate the determination of ductal resection margin status for cholangiocarcinoma. (Cancer Sci 2009; 100: 255–260)     

Predictors of undergoing multivisceral resection,margin status and survival in Dutch patients with locally advanced colorectal cancer

BackgroundThe aim of this nationwide observational study was to evaluate factors associated with multivisceral resection (MVR), margin status and overall survival in locally advanced colorectal cancer (CRC).Material and methodsPatients with (y)pT4, cM0 CRC between 2006 and 2017 were selected from the Netherlands Cancer Registry. Cox-proportional hazards modelling was used for survival analysis, stratified for T4a and T4b. Annual hospital volume cut-off was 75 for colon and 40 for rectal resections.ResultsA total of 11.930 patients were included and 2410 patients (20.2%) underwent MVR. Factors associated with MVR for colon and rectal cancer besides cT4 category were more recent diagnosis (OR 3.61, CI 95% 3.06–4.25 (colon) and OR 2.72, CI 95% 1.82–4.08 (rectum)) and high hospital volume (OR 1.20, CI 95% 1.05–1.38 (colon) and OR 2.17, CI 95% 1.55–3.04 (rectum)). Patients ≥70 year were less likely to undergo MVR for colon cancer (OR 0.80, 95% CI 0.70–0.90). Risk factors for incomplete resection were cT4 (OR 3.08, CI 95% 2.35–4.04 (colon) and OR 1.82, CI 95% 1.13–2.94 (rectum)) and poor/undifferentiated tumors (OR 1.41, CI 95% 1.14–1.72 (colon) and OR 1.69, CI 95% 1.05–2.74 (rectum)). More recent diagnosis was independently associated with less incomplete resections in colon cancer (OR 0.58, CI 95% 0.40–0.76). Independent predictors of survival were age, resection margin, nodal status and adjuvant chemotherapy, but not MVR.ConclusionTreatment of locally advanced CRC with MVR at population level was influenced by year of diagnosis and hospital volume. Margin status in colon cancer improved substantially over time.     

Alteration of p53-binding protein 1 expression as a risk factor for local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma

P53-binding protein 1 (53BP1) is an early DNA damage response-protein that is rapidly recruited to sites of DNA double-strand breaks. The presence of 53BP1 nuclear foci can be considered as a cytologic marker for endogenous double-strand breaks reflecting genomic instability. This study aimed to clarify the early DNA damage response mediated by 53BP1 in tumor specimens of ductal resection margins and to elucidate its predictive value for clinically evident local recurrence at ductal stumps in 110 patients undergoing resection for extrahepatic cholangiocarcinoma. The ductal resection margin status was classified as negative (85 patients), positive with carcinoma in situ (14 patients), or positive with invasive carcinoma (11 patients). The nuclear staining pattern of 53BP1 was evaluated by immunofluorescence. TUNEL analysis was used to calculate apoptotic index. Ductal margin status was the only independent risk factor for local recurrence (P=0.001). The cumulative probability of local recurrence at 5 years was 10%, 40% and 100% in patients with negative ductal margins, positive with carcinoma in situ and positive with invasive carcinoma, respectively (P<0.001). Of the 14 tumor specimens of carcinoma in situ, 10 showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and 4 showed discrete nuclear foci of 53BP1 (53BP1 activation). All 11 tumor specimens of invasive carcinoma showed 53BP1 inactivation. Apoptotic index was markedly decreased in tumor specimens with 53BP1 inactivation compared to those with 53BP1 activation (median index, 0% vs. 22%; P<0.001). Among 14 patients with residual carcinoma in situ, the cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation (60% vs. 0% at 5 years; P=0.020). In conclusion, after resection for extrahepatic cholangiocarcinoma, clinically evident local recurrence at ductal stumps is closely associated with 53BP1 inactivation and decreased apoptosis.     

Impact of COPD on pulmonary complications and on long-term survival of patients undergoing surgery for NSCLC

PURPOSE: The purpose of our study was to determine the incidence of various types of postoperative pulmonary complications and to evaluate the impact of chronic obstructive pulmonary disease (COPD) on the long-term survival of patients with non-small cell lung cancer (NSCLC) undergoing pulmonary resection. METHODS: We performed a retrospective chart review of 244 patients who had undergone lung resection for NSCLC at Indiana University. COPD, defined as predicted forced expiratory volume in 1 s (FEV1)< or =70% and FEV1/FVC< or =70%, was determined based on preoperative pulmonary function testing in 78 of 244 patients (COPD group). The remaining 166 patients were classified as non-COPD. The incidence of postoperative complications, which included air leak of > or=10 days, atelectasis, pneumothorax, pneumonia, bronchopleural fistula, empyema, acute respiratory distress syndrome, mechanical ventilation of > or =7 days, and outpatient oxygen supplementation were compared between the two groups. Long-term survival and mortality due to respiratory failure were analyzed between the two groups using the Kaplan-Meier method and log rank test. RESULTS: All of the above-stated postoperative pulmonary complications occurred more frequently in the COPD than in the non-COPD patients (all P<0.01). The overall 5-year survival rate was 36.2% in the COPD and 41.2% in the non-COPD patients (P=0.1023). Five-year cancer related survival was 43.2% in the COPD and 47.7% in the non-COPD patients (P=0.357). There was no significant difference in survival among patients with different stages of lung cancer. However, the intercurrent survival, which is associated with non-cancer related death, was 60.1% in patients with COPD and 86.2% in patients without COPD at 5 years (P<0.0001). The major cause of non-cancer related death in the COPD group was respiratory failure (P=0.0008). CONCLUSION: The presence of COPD is an acceptable predictor of postoperative pulmonary complications in patients with NSCLC. COPD is also a significant risk factor for development of respiratory-related complications, which may explain the poor long-term survival in these patients.     

Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma

Purpose

We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC).

Methods/patients

A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0 + S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1 + CCRT group, n = 19) or adjuvant radiation therapy (RT) alone (R1 + RT group, n = 13).

Results

During the median follow-up period of 26 months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0 + S group; 71.8, 57.8, and 57.9% for R1 + CCRT group; and 16.8, 9.6, and 15.4% for R1 + RT group, respectively. Multivariate analysis revealed that the R1 + CCRT group did not show any significant difference in survival rates compared with the R0 + S group. The R1 + RT group had lower LRRFS [hazard ratio (HR) 3.008; p = 0.044], DFS (HR 2.364; p = 0.022), and OS (HR 2.417; p = 0.011) when compared with the R0 + S and R1 + CCRT group.

Conclusions

A lack of significant survival difference between R0 + S group and R1 + CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor.

     

Meta-analysis and cost effective analysis of portal-superior mesenteric vein resection during pancreatoduodenectomy: Impact on margin status and survival

Introduction

The benefit of portal-superior mesenteric vein resection (PSMVR) with pancreatoduodenectomy (PD) remains controversial. This study assesses the impact of PSMVR on resection margin status and survival.

Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas

The aim of the present study was to examine the relationship between the clinicopathological status, the pre- and postoperative systemic inflammatory response and survival in patients undergoing potentially curative resection for ductal adenocarcinoma of the head of the pancreas. Patients (n = 65) who underwent resection of ductal adenocarcinoma of the head of pancreas between 1993 and 2001, and had pre- and postoperative measurements of C-reactive protein, were included in the study. The majority of patients had stage III disease (International Union Against Cancer Criteria, IUCC), positive circumferential margin involvement (R1), tumour size greater than 25 mm with perineural and lymph node invasion and died within the follow-up period. On multivariate analysis, tumour size (hazard ratio (HR) 2.10, 95% confidence interval (CI) 1.20-3.68, P = 0.009), vascular invasion (HR 2.58, 95% CI 1.48-4.50, P < 0.001) and postoperative C-reactive protein (HR 2.00, 95% CI 1.14-3.52, P = 0.015) retained independent significance. Those patients with a postoperative C-reactive protein < or = 10 mg l(-1) had a median survival of 21.5 months compared with 8.4 months in those patients with a C-reactive protein >10 mg l(-1) (P < 0.001). The results of the present study indicate that, in patients who have undergone potentially curative resection for ductal adenocarcinoma of the head of pancreas, the presence of a systemic inflammatory response predicts poor outcome.     

Impact of chemotherapy-related prognostic factors on long-term survival in patients with stage III colorectal cancer after curative resection

Background

This retrospective study evaluated the prognostic factors of chemotherapy in stage III colorectal cancer after curative resection.

Methods

From 1996 to 2001, 1,054 patients with primary single colorectal cancer underwent curative resection. Seven hundred sixteen patients received various 5-fluorouracil (FU)-based adjuvant chemotherapy regimens, including oral and intravenous treatments. The chemotherapy-related parameters examined included therapeutic duration, frequency, route of administration, composition of combination therapies, and postoperative time interval from the operation to the start of chemotherapy.

Results

The therapeutic duration and postoperative time interval of starting therapy were independent prognostic factors, in addition to clinicopathological factors. The 8-year cancer-specific/overall survival rates in patients who received chemotherapy for >4 months (63.0/58.6%) were significantly higher than the rates in patients who received no chemotherapy (56.7/37.7%, P < 0.01) and those who remained on chemotherapy for 1–4 months (49.4/41.9%, P < 0.05). The 8-year cancer-specific/overall survival rates in patients who waited 1–5 weeks after surgery to receive chemotherapy (62.9/58.5%) were significantly higher versus rates in those who did not receive chemotherapy (56.7/37.7%) and those who did not receive chemotherapy until >5 weeks after surgery (52.3/45.9%) (both P < 0.05). Survival rates did not differ between patients who did not undergo chemotherapy, those for whom chemotherapy lasted 1–4 months, and patients who did not receive chemotherapy until >5 weeks after surgery.

Conclusions

The appropriate duration of therapy and early chemotherapy after surgery were 2 of the most important factors in eradicating occult cancer and effecting long-term survival benefits in patients with stage III colorectal cancer.     

肝细胞癌手术切缘对患者术后复发与生存的影响

目的 比较不同的手术切缘对肝癌患者术后复发及生存的影响,为肝癌患者手术中选择合理切缘提供参考。方法 将152例初治的可手术切除肝癌患者随机分为两组,分别按以下标准手术：74例宽切缘组患者按门静脉血流方向远端距肿瘤边缘2cm,近端距肿瘤边缘1cm完整切除;78例窄切缘组患者切除范围距离肿瘤〈1cm,切缘无癌残留。应用Kaplan-Meier法进行生存分析,用Log rank检验分别比较两组的无瘤生存期和总生存期。结果 宽切缘组患者平均无瘤生存期为35．5个月,平均总生存期为42．0个月;窄切缘组患者平均无瘤生存期为28．8个月,平均总生存期为37．5个月,两组无瘤生存期（t=6．01,P=0．0142）和总生存期（t=6．23,P=0．0125）比较,差异均有统计学意义。结论 按门静脉血流方向远端距肿瘤2cm,近端距肿瘤1cm切除为标准的手术范围可较合理地延长肝癌患者术后无瘤生存期和总生存期。     

Impact of systemic inflammation on outcome following resection for intrahepatic cholangiocarcinoma

AIMS: To analyse the results and prognostic factors affecting disease-free and overall survival following potentially curative resection for intrahepatic cholangiocarcinoma (IHCC). METHODS: Patients undergoing resection for IHCC from January 1996 to December 2006 were included. Data analysed included demographics, clinical and histopathology data. RESULTS: Twenty-seven patients were identified with a median age of 57 (32-84) years. The 1-, 3- and 5-year overall and disease-free survival rates were 74%, 16% and 16%, and 44%, 15% and 15%, respectively. On univariate analysis, age <65 years, female gender, neutrophil to lymphocyte ratio (NLR) >or= 5, micro-vascular invasion and lymph node involvement were predictors of poorer overall survival. Multivariate analysis did not identify any independent predictors of overall survival. A NLR >or= 5 was the only adverse predictor of disease-free survival. The median disease-free survival of patients with NLR >or= 5 was 6 months compared to 18 months for those with NLR < 5. There was a significant association between patients with a NLR >or= 5 and larger tumour size, satellite lesions, micro-vascular invasion and lymph node involvement. CONCLUSION: Long-term outcome following resection of IHCC is poor. A pre-operative NLR >or= 5 was an adverse predictor of disease-free survival and was associated with an aggressive tumour biology profile.