Hepatic epithelioid haemangioendothelioma: is transplantation the only treatment option?

Background

Hepatic epithelioid haemangioendothelioma (HEH) is a rare vascular neoplasm with unpredictable clinical behaviour.

Aim

To compare overall survival (OS) and disease-free survival (DFS) between liver resection (LR) and orthotopic liver transplantation (OLT) for the treatment of HEH.

Methods

Retrospective review of 30 patients with HEH treated at Mayo Clinic during 1984 and 2007.

Results

Median age was 46 years with a female predominance of 2 : 1. Treatment included LR (n = 11), OLT (n = 11), chemotherapy (n = 5) and no treatment (n = 3). LR was associated with a 1-, 3- and 5-year OS of 100%, 86% and 86% and a DFS of 78%, 62% and 62%, respectively. OLT was associated with a 1-, 3- and 5-year OS of 91%, 73% and 73% and a DFS 64%, 46% and 46%, respectively. Metastases were present in 37% of patients but did not significantly affect OS. Important predictors of a favourable OS and DFS were largest tumour ≤ 10 cm and multifocal disease with ≤10 nodules.

Conclusion

LR and OLT achieve comparable results in the treatment of HEH. LR is appropriate for patients with resectable disease and favourable prognostic factors. OLT is appropriate for patients with unresectable disease and possibly those with unfavourable prognostic factors. Metastases may not be a contraindication to surgical treatment.     

Impact of peri-operative bevacizumab on survival in patients with resected colorectal liver metastases: an analysis of the LiverMetSurvey

Background

Peri-operative chemotherapy is recommended for the management of colorectal liver metastases (CRLM). The aim of this study was to examine the impact of peri-operative bevacizumab on survival in patients with resected CRLM.

Methods

A multicentre retrospective cohort of patients with resected CRLM was analysed from the LiverMetSurvey Registry. Patients who received peri-operative FOLFOX (group A) were compared with those who received peri-operative FOLFOX and bevacizumab (group B).

Results

In total, 501 patients were compared (A, n = 384; B, n = 117). Group A was older (68.3 versus 62.5 years, P < 0.01), had more rectal cancers (30.7 versus 18.8%, P < 0.01) and higher carcinoembryonic antigen (CEA) levels at diagnosis (17.0 versus 9.7 ng/ml, P = 0.043). No difference was observed regarding primary tumour stage, synchronicity and the number or size of metastases. Post-operative infections were more frequent in group B (4.7% versus 12.8%, P < 0.01). Peri-operative bevacizumab had no effect on 3-year overall survival (OS) (76.4% versus 79.8%, P = 0.334), or disease-free survival (DFS) (7.4% versus 7.9%, P = 0.082). DFS was negatively associated with primary tumour node positivity (P = 0.011) and synchronicity (P = 0.041).

Conclusions

The addition of bevacizumab to standard peri-operative chemotherapy does not appear to be associated with improved OS or DFS in patients with resected CRLM.     

A simplified prognostic system for resected pancreatic neuroendocrine neoplasms

Background:

A number of prognostically relevant clinicopathological variables have been proposed for pancreatic neuroendocrine neoplasms. However, a standardized prognostication system has yet to be established for patients undergoing potentially curative tumour resection.

Methods:

We examined a prospectively maintained, single-institution database to identify patients who underwent potentially curative resection of non-metastatic primary pancreatic neuroendocrine neoplasms. Patient, operative and pathological characteristics were analysed to identify variables associated with disease-specific and disease-free survival.

Results:

Between 1991 and 2007, 43 patients met inclusion criteria. After a median follow-up of 68 months, 5-year disease-specific survival was 94% and 5-year disease-free survival was 72%. Tumours sized ≥5 cm and vascular invasion were associated with worse disease-specific survival. Tumours sized ≥5 cm, nodal metastases, positive resection margins and perineural invasion were associated with worse disease-free survival. A scoring system consisting of tumour size ≥5 cm, histological grade, nodal metastases and resection margin positivity (SGNM) permitted stratification of disease-specific (P= 0.006) and disease-free (P= 0.0004) survival. This proposed scoring system demonstrated excellent discrimination of individual disease-specific and disease-free survival outcomes as reflected by concordance indices of 0.814 and 0.794, respectively.

Conclusions:

A simple scoring system utilizing tumour size, histological grade, nodal metastases and resection margin status can be used to stratify outcomes in patients undergoing resection of primary pancreatic neuroendocrine neoplasms.     

Simultaneous pancreatectomy and liver transplantation: a single-institution experience

Background:

There is wide debate among transplant centres regarding the indications for liver transplantation (LT) in malignancy. We report a single-centre experience with simultaneous LT and total pancreatectomy or pancreaticoduodenectomy.

Methods:

We performed a retrospective review of a prospectively established database of patients who underwent simultaneous LT and total pancreatectomy or pancreaticoduodenectomy. We analysed demographics, indications, approach and outcomes.

Results:

Between 1991 and 2006, 11 patients (four male; median age 51 years) underwent simultaneous LT and total pancreatectomy (n = 4) or pancreaticoduodenectomy (n = 7). Indications included metastatic neuroendocrine tumour (n = 5), hepatocellular carcinoma (n = 2), metastatic periampullary adenocarcinoma (n = 1), periampullary adenocarcinoma with end-stage liver disease (ESLD) (n = 2) and intraductal papillary mucinous neoplasm with ESLD (n = 1). The three patients with ESLD had non-alcoholic steatohepatitis, primary sclerosing cholangitis or cryptogenic cirrhosis. Median postoperative length of stay was 31 days (21–110 days). Overall median survival was 101 months (95% confidence interval 70.6–131.4). One-year survival was 91%, 2-year 90%, 5-year 67% and 10-year 33%. Postoperative complications included: re-operation (n = 4); anastamotic leak (n = 2); abdominal abscess (n = 3), and organ rejection (n = 1).

Conclusions:

We report a series of pancreatectomy or pancreaticoduodenectomy and simultaneous LT in patients with extensive malignancy or impending liver failure that prevented pancreatectomy. This series provides evidence that combined pancreatic resection and LT can be a strategy in both radical resections and cases with ESLD that would otherwise preclude operative intervention.     

Long-term survival after surgical management of neuroendocrine hepatic metastases

Background:

Surgical cytoreduction and endocrine blockade are important options for care for neuroendocrine liver metastases. We investigated the long-term survival of patients surgically treated for hepatic neuroendocrine metastases.

Methods:

Patients (n= 172) undergoing operations for neuroendocrine liver metastases from any primary were identified from a prospective liver database. Recorded data and medical record review were used to analyse the type of procedure, length of hospital stay, peri-operative morbidity, tumour recurrence, progression,and survival.

Results:

The median age was 56.8 years (range 11.5–80.7 years). 48.3% of patients were female. Median overall survival was 9.6 years (range 89 days to 22 years). On multivariate analysis, lung/thymic primaries were associated with worse survival [hazard ratio (HR): 15.6, confidence interval (CI): 4.3–56.8, P= 0.002]. Severe post-operative complications were also associated with worse long-term survival (P < 0.001). A positive resection margin status (R1) was not associated with a worse overall survival probability (P∼ 0.8).

Discussion:

Early and aggressive surgical management of hepatic metastases from neuroendocrine tumours is associated with significant long-term survival rates. Radiofrequency ablation is a reasonable option if a lesion is unresectable. R1 resections, unlike many other cancers, are not associated with a worse overall survival.     

Distal pancreatectomy: what is the standard for laparoscopic surgery?

Background/aims:

Distal pancreatectomy (DP) is performed for a range of benign and malignant lesions. Accurate pre-operative diagnosis can be unreliable and morbidity remains high. This study evaluates a 12-year, single-centre experience with open DP to review indications, diagnoses and associated morbidity.

Methods:

Retrospective review of patients who underwent DP at a UK-based tertiary referral centre between 1994 and 2006.

Results:

Sixty-five patients (mean age 49.9 years) had final diagnoses of chronic pancreatitis ± pseudocyst (n= 22), benign cystadenoma (n= 15), neuroendocrine tumour (n= 8), primary pancreatic carcinoma (n= 6) and 14 other conditions. DP performed for presumed cystic neoplasm (n= 24) revealed a correct pre-operative diagnosis in 71% of patients. Histological examination confirmed that 59% of resected cystic tumours were either malignant or had malignant potential. When DP was undertaken for presumed pseudocyst (n= 12), 83% of cases were correctly diagnosed pre-operatively. Overall mortality and morbidity rates were 3% and 39%, respectively, with five patients (8%) developing a clinically significant pancreatic fistula. Ten (17%) patients developed diabetes mellitus and nine (14%) required long-term pancreatic exocrine supplementation.

Conclusions:

Open DP can be performed with acceptable morbidity, low mortality and preservation of pancreatic function in the majority of cases, setting the standard for laparoscopic techniques.     

Longterm survival after pancreaticoduodenectomy for periampullary adenocarcinomas

Objectives

The aim of this study was to identify predictors for longterm survival following pancreaticoduodenectomy (PD) for pancreatic and other periampullary adenocarcinomas.

Methods

Clinicopathological factors were compared between short-term (<5 years) and longterm (≥5 years) survival groups. Rates of actual 5-year and actuarial 10-year survival were determined.

Results

There were 109 (21.8%) longterm survivors among a sample of 501 patients. Patients with ampullary adenocarcinoma represented 76.1% of the longterm survivors. Favourable factors for longterm survival included female gender, lack of jaundice, lower blood loss, classical PD, absence of postoperative bleeding or intra-abdominal abscess, non-pancreatic primary cancer, earlier tumour stage, smaller tumour size (≤2 cm), curative resection, negative lymph node involvement, well-differentiated tumours, and absence of perineural invasion. Independent factors associated with longterm survival were diagnosis of primary tumour, jaundice, intra-abdominal abscess, tumour stage, tumour size, radicality, lymph node status and cell differentiation. The prognosis was best for ampullary adenocarcinoma, for which the rate of actual 5-year survival was 32.8%, and poorest for pancreatic head adenocarcinoma, for which actual 5-year survival was only 6.5%.

Conclusions

The majority of longterm survivors after PD for periampullary adenocarcinomas are patients with ampullary adenocarcinoma. The longterm prognosis in pancreatic head adenocarcinoma remains dismal.     

Prognostic determinants for survival after resection/ablation of a large hepatocellular carcinoma

Background:

Liver resection of large hepatocellular carcinomas (HCC), measuring at least 10 cm remains a controversial debate. Multiple studies on HCCs treated with surgical resection and/or ablation had shown variable results with 5-year survival rates ranging from 0% to 54.0%. The aim of this study was to evaluate the survival of patients with HCCs measuring at least 10 cm and to identify the potential prognostic variables affecting the outcome.

Methods:

Retrospective analysis was performed on the prospectively updated HCC database. A total of 44 patients with tumours measuring 10 cm or more were ‘curatively’ treated with surgical resection with or without ablation. Patient demographics, clinical, surgical, pathology and survival data were collected and analysed.

Results:

Thirty-one patients received surgical resection alone. Thirteen other patients were treated with a combination of surgical resection and ablation. The median follow-up duration was 14.5 months. The overall median survival at 1, 3 and 5 years were 66.4%, 38.1% and 27.8%, respectively. The median time to tumour recurrence was 10.7 months and the 1, 3 and 5-year disease-free survival were 49.6%, 23.9% and 19.1%, respectively.Univariate analysis demonstrated cirrhosis, microvascular invasion, poor tumour differentiation and ethnicity to adversely affect survival. For overall survival, only cirrhosis, poor tumour differentiation and ethnicity were significant on multivariate analysis. Portal vein tumour thrombus, microvascular invasion and ethnicity were identified on univariate analysis to significantly affect disease-free survival.

Conclusion:

Surgical treatment offers good survival to patients with large HCCs (≥10 cm). Both cirrhosis and poor tumour differentiation are independent variables prognostic of adverse survival.     

Actual 10-year survival following hepatectomy for hepatocellular carcinoma

Objectives

This study was conducted to compare 10-year survivors with patients who survived <10 years in a large Western series of patients submitted to hepatectomy for hepatocellular carcinoma (HCC).

Methods

A retrospective review of a series of hepatic resections conducted in a referral centre for HCC between January 1987 and October 2002 was conducted.

Results

A total of 176 patients were analysed. Twenty-eight patients survived ≥ 10 years (Group A) and were compared with the 148 patients who did not (Group B). Group A had smaller tumours (5.7 cm versus 8.2 cm; P = 0.001) and a lower incidence of microvascular invasion (18.5% versus 37.1%; P = 0.004). Recurrence did not differ significantly (Group A 18/28, 64.3% versus Group B 94/148, 63.5%). Median time to recurrence was longer in Group A (70 months versus 15 months; P < 0.0001), and more patients in Group A were able to undergo curative treatment for recurrence (88.8% versus 40.4%; P < 0.0001). Multivariate analysis showed that lack of vascular invasion (P = 0.020), absence of perioperative transfusion (P = 0.014), and recurrence at >2 years after primary resection (P = 0.045) were significantly associated with 10-year survival.

Conclusions

Ten-year survival after liver resection for HCC can be expected in approximately 15% of patients. Recurrence does not preclude longterm survival. Recurrence at >2 years after resection, absence of vascular invasion, and absence of perioperative transfusion are independently associated with 10-year survival.     

A contemporary analysis of survival for resected pancreatic ductal adenocarcinoma

Introduction

Survival after a resected pancreatic ductal adenocarcinoma (PDAC) appears to be improving. Yet, in spite of advancements, prognosis remains disappointing. This study analyses a contemporary experience and identifies features associated with survival.

Methods

Kaplan–Meier analysis was conducted for 424 PDAC resections performed at two institutions (2001–2011). Multivariate analysis was performed to elicit characteristics independently associated with survival.

Results

The median, 1-, and 5-year survivals were 21.3 m, 76%, and 23%, with 30/90-day mortalities of 0.7%/1.7%. 76% of patients received adjuvant therapy. Patients with major complications (Clavien Grade IIIb-IV) survived equivalently to patients with no complications (P = 0.33). The median and 5-year survival for a total pancreatectomy was 32.2 m/49%; for 90 ‘favourable biology’ patients (R0/N0/M0) was 37.3 m/40%; and for IPMN (9% of series) was 21.2 m/46%. Elderly (>75 yo) and nonelderly patients had similar survival. Favorable prognostic features by multivariate analysis include lower POSSUM physiology score, R0 resection, absence of operative transfusion, G1/G2 grade, absence of lymphovascular invasion, T1/T2 stage, smaller tumor size, LN ratio <0.3, and receipt of adjuvant therapy.

Conclusion

This experience with resected PDAC shows decreasing morbidity and mortality rates along with modestly improving long-term survival, particularly for certain subgroups of patients. Survival is related to pathological features, pre-operative physiology, operative results and adjuvant therapy.     

Equivalent survival following liver transplantation in patients with non-alcoholic steatohepatitis compared with patients with other liver diseases

Background

Orthotopic liver transplantation (LT) in non-alcoholic steatohepatitis (NASH) is increasing in parallel with the obesity epidemic.

Methods

This study retrospectively reviewed the clinical outcomes of LTs in NASH (n= 129) and non-NASH (n= 775) aetiologies carried out at a single centre between 1999 and 2009.

Results

Rates of 1-, 3- and 5-year overall survival in NASH (90%, 88% and 85%, respectively) were comparable with those in non-NASH (92%, 86% and 80%, respectively) patients. Mortality within 4 months of LT was twice as high in NASH as in non-NASH patients (8.5% vs. 4.2%; P= 0.04). Compared with non-NASH patients, post-LT mortality in NASH patients was more commonly caused by infectious (38% vs. 26%; P < 0.05) or cardiac (19% vs. 7%; P < 0.05) aetiologies. Five-year survival was lower in NASH patients with a high-risk phenotype (age >60 years, body mass index >30 kg/m², with hypertension and diabetes) than in NASH patients without these characteristics (72% vs. 87%; P= 0.02). Subgroup analyses revealed that 5-year overall survival in NASH was equivalent to that in Laennec''s cirrhosis (85% vs. 80%; P= 0.87), but lower than that in cirrhosis of cryptogenic aetiology (85% vs. 96%; P= 0.04).

Conclusions

Orthotopic LT in NASH was associated with increased early postoperative mortality, but 1-, 3- and 5-year overall survival rates were equivalent to those in non-NASH patients.     

Spontaneous regression of hepatocellular carcinoma is most often associated with tumour hypoxia or a systemic inflammatory response

Background

Spontaneous regression of hepatocellular carcinoma (HCC) is well documented, although the aetiology of this phenomenon remains unknown.

Methods

A review of the English literature was performed for reports of spontaneous regression of HCC. Reports were classified by mechanism based on the available information.

Results

Spontaenous regression of HCC has been identified in 75 patients. The most common mechanisms of regression identified were tumour hypoxia (n= 21, 28.0%), a systemic inflammatory response (n= 25, 33.3%) and unknown (n= 29, 38.7%). In patients where tumour hypoxia was described as the aetiology, mechanisms included spontaneous hepatic artery thrombosis and sustained systemic hypotension. In patients where a systemic inflammatory response was the aetiology, mechanisms included cholangitis, trauma and elevated cytokine levels.

Discussion

Spontaneous regression of HCC is most commonly associated with tumour hypoxia or a systemic inflammatory response. Determining the aetiology of spontaneous regression may identify potential therapeutic pathways. Tumour hypoxia is already the basis of treatment modalities such as hepatic artery embolization and the anti-angiogenic agent sorafenib. However, treatment modalities for HCC do not currently include immune-directed therapies; this may prove to be a worthy target for future research.     

Preoperative body composition is influenced by the stage of operable pancreatic adenocarcinoma but does not predict survival after Whipple's procedure

Objectives:

Cachexia is common in pancreatic cancer and may have an influence on longterm survival but few studies have investigated this in patients with operable tumours. Therefore, this study was carried out to document body composition status in patients with pancreatic adenocarcinoma (PCa) presenting for a Whipple''s procedure (WP) and to relate the findings to histopathology and longterm survival.

Methods:

Body composition was measured 1 day before a WP for ductal PCa in 36 patients (15 men, 21 women) aged 41–81 years. Results for total body nitrogen (TBN), nitrogen index (NI), total body water (TBW), fat mass (FM) and total body potassium (TBK) were compared with results in 73 age- and sex-matched controls. Patients'' survival and details from histopathology synoptic reports were documented.

Results:

Patients undergoing WPs had low TBK values (P < 0.001) and females had lower body fat (P= 0.007) compared with controls. Five of 36 presented with significant protein deficiency, but this was not associated with a prolonged length of stay or reduced survival. The 12 patients who had involved surgical margins had larger tumours and reduced weight (P= 0.015), FM (P= 0.001), TBN (P= 0.045), TBK (P= 0.014) and survival (P= 0.036). However, multivariate Cox''s regression analysis only included FM along with vascular invasion and margin status as independent predictors of survival.

Conclusions:

PCa patients undergoing a WP have reduced body fat and TBK compared with community controls while those with stage III tumours had greater deficits of fat, TBK and protein stores. However, preoperative body composition was a poor predictor of postoperative survival after pathological data were considered.     

Predicting patient survival after pancreaticoduodenectomy for malignancy: histopathological criteria based on perineural infiltration and lymphovascular invasion

Background:

Accurate and simple prognostic criteria based on histopathology following pancreaticoduodenectomy would be helpful in assessing prognosis and considering and evaluating adjuvant therapy. This study analysed the histological parameters influencing outcome following pancreaticoduodenectomy for periampullary malignancy.

Methods:

A total of 110 pancreaticoduodenectomies were performed from 1998 to 2008. The median age of patients was 69 years (range 20–89 years). The median follow-up was 4.9 years. Of the procedures, 87% (96) were performed for malignancies and the remainder (n= 14) for benign aetiologies. Of the 96 malignancies, 60 were pancreatic adenocarcinoma and the rest were ampullary (14), cholangio (9), duodenal (9) carcinomas and others. Statistical analysis was performed using log-rank and Cox regression multivariate analyses.

Results:

Patients who underwent resection had 1-, 3- and 5-year survival rates of 70%, 46% and 41%, respectively. The 1-, 3- and 5-year survival rates for periampullary cancers other than pancreatic adenocarcinoma were 83%, 69% and 61%, respectively; those for pancreatic adenocarcinoma were 62%, 31% and 27%, respectively (P < 0.003). Poor tumour differentiation (P < 0.02), tumour size >3 cm (P < 0.04), margin ≤2 mm (P < 0.02), nodal involvement (P < 0.003), perineural infiltration (P < 0.0001) and lymphovascular invasion (P < 0.002) were associated with poorer prognosis. In a multivariate analysis, histologically identified perineural infiltration (P < 0.03) and lymphovascular invasion (P= 0.05) were significant factors influencing outcome. Five-year survival was 77% in patients negative for both factors and 15% in patients positive for both (P < 0.0001). In the pancreatic adenocarcinoma subgroup, patients who were negative for both factors had a 5-year survival of 71%, whereas those who were positive for both had a 5-year survival of 16% (P < 0.02).

Conclusions:

The presence of perineural infiltration and lymphovascular invasion on histopathology is highly significant in predicting 5-year outcomes after pancreaticoduodenectomy for periampullary and pancreatic malignancies.     

Factors linked to longterm survival of patients with hepatocellular carcinoma accompanied by tumour thrombus in the major portal vein after surgical resection

Objectives

The prognosis in patients with hepatocellular carcinoma (HCC) accompanied by main portal vein tumour thrombus (MPVTT) is poor. The aim of this study was to clarify the factors linked to survival of >5 years after hepatectomy in HCC patients with MPVTT.

Methods

Twenty-nine HCC patients with MPVTT were divided into two groups comprising, respectively, patients who survived >5 years after hepatectomy (survivors, n = 5) and those who did not (non-survivors, n = 24). The two groups were compared.

Results

Overall survival rates at 1, 3 and 5 years were 62.1%, 24.1% and 17.2%, respectively. Four (80.0%) 5-year survivors had recurrences of HCC in which the number of recurrent nodules was under four. Three (21.4%) of the 14 non-survivors who underwent curative resection experienced recurrences of HCC and all of them demonstrated fewer than four recurrent nodules (P = 0.0114). Local therapy, such as radiofrequency ablation and resection of recurrence, had more often been used in survivors than in non-survivors (P = 0.0364).

Conclusions

Although surgical outcomes in patients with HCC accompanied by MPVTT are unsatisfactory, some patients do enjoy longterm survival. When the number of recurrent nodules is less than four, local therapy should be selected with the aim of achieving 5-year survival.     

Single nucleotide polymorphism in RECQL and survival in resectable pancreatic adenocarcinoma

Background:

RECQL is a DNA helicase involved in DNA mismatch repair. The RECQL polymorphism, 3′ untranslated region (UTR) A159C, was previously associated with overall survival of patients with resectable pancreatic adenocarcinoma treated with neoadjuvant chemoradiation. In the present study, we examined RECQL for somatic mutations and other polymorphisms and compared these findings with the outcome in patients who received adjuvant or neoadjuvant chemoradiation. We hypothesized that RECQL (i) would be mutated in cancer, (ii) would have polymorphisms linked to the 3′UTR A159C and that either or both events would affect function. We also hypothesized that (iii) these changes would be associated with survival in both cohorts of patients.

Material and methods:

We sequenced RECQL''s 15 exons and surrounding sequences in paired blood and tumour DNA of 39 patients. The 3′UTR A159C genotype was determined in blood DNA samples from 176 patients with resectable pancreatic adenocarcinoma treated with adjuvant (53) or neoadjuvant (123) chemoradiation. Survival was calculated using the Kaplan–Meier method, with log rank comparisons between groups. The relative impact of genotype on time to overall survival was performed using the Cox proportional hazards model.

Results:

Somatic mutations were found in UTRs and intronic regions but not in exonic coding regions of the RECQL gene. Two single nucleotide polymorphisms (SNPs), located in introns 2 and 11, were found to be part of the same haplotype block as the RECQL A159C SNP and showed a similar association with overall survival. No short-term difference in survival between treatment strategies was found. We identified a subgroup of patients responsive to neoadjuvant therapy in which the 159 A allele conferred strikingly improved long-term survival.

Discussion:

The RECQL 3′UTR A159C SNP is not linked with other functional SNPs within RECQL but may function as a site for regulatory molecules. The mechanism of action needs to be clarified further.     

Evaluation of peri-operative chemotherapy using a prognostic nomogram for survival after resection of colorectal liver metastases

Introduction:

Nomograms are statistical tools designed to predict outcomes. This study evaluates the effects of peri-operative chemotherapy on the accuracy of a prognostic nomogram for disease-specific survival (DSS) after resection of colorectal liver metastases (CRLM) established at Memorial-Sloan Kettering Cancer Center (MSKCC).

Methods:

An external cohort of 203 patients who underwent resection of CRLM between 1996 and 2006 was used to assess the nomogram.

Results:

After median follow-up of 30.4 months (range 0.33–150), Kaplan–Meier (KM) estimates for 3-, 5- and 8-year post-resection DSS were 56%, 41%, and 32%, respectively; similar to nomogram-predicted probabilities for DSS. The concordance index for the nomogram was higher (0.602) than for the Fong colorectal risk score (CRS; 0.533). KM DSS was longer for patients (n= 50) treated with at least 6 months of peri-operative irinotecan or oxaliplatin compared with all other patients (median 66 vs. 40 months, P= 0.06). KM DSS was greater than nomogram predicted DSS for treated patients and less than nomogram predicted DSS for all other patients.

Conclusions:

The CRLM nomogram was validated by an external cohort and more accurately predicted post-resection survival than the commonly used CRS. Differences in observed and nomogram-predicted survival may reflect the effect of treatment factors, such as peri-operative chemotherapy.     

Neoadjuvant therapy may lead to successful surgical resection and improved survival in patients with borderline resectable pancreatic cancer

Background:

Borderline resectable pancreatic cancers are technically amenable to surgical resection, but are associated with increased risk of locoregional recurrence. Patients with these tumours may be treated with neoadjuvant therapy in an attempt to improve margin-negative resection rates.

Methods:

The University of Cincinnati Pancreatic Cancer Database was retrospectively reviewed. Borderline resectable disease was defined by the following radiographic criteria: (i) short segment occlusion of the superior mesenteric vein (SMV), portal vein (PV) or SMV/PV confluence; (ii) short segment hepatic artery encasement, or (iii) superior mesenteric artery/coeliac artery abutment of <180 degrees. Patients with resectable disease who had questionable metastatic disease or poor performance status were also included.

Results:

Twenty-nine patients met the criteria. Of these, 26 underwent a full course of neoadjuvant therapy. Twelve (46%) underwent surgical resection and 14 had tumour progression or were deemed unresectable at laparotomy. The most common neoadjuvant therapy regimen was gemcitabine-based chemotherapy alone (58%). Of those undergoing surgery, 67% had margin-negative (R0) resections and 42% required venous resection. Median survival was 15.5 months for unresected patients and 23.3 months for resected patients.

Discussion:

Borderline resectable pancreatic tumours can be treated neoadjuvantly, resulting in margin-negative resection and survival rates similar to those in initially resectable disease.     

Lymphovascular and perineural invasion as selection criteria for adjuvant therapy in intrahepatic cholangiocarcinoma: a multi-institution analysis

Objectives

Criteria for the selection of patients for adjuvant chemotherapy in intrahepatic cholangiocarcinoma (IHCC) are lacking. Some authors advocate treating patients with lymph node (LN) involvement; however, nodal assessment is often inadequate or not performed. This study aimed to identify surrogate criteria based on characteristics of the primary tumour.

Methods

A total of 58 patients who underwent resection for IHCC between January 2000 and January 2010 at any of three institutions were identified. Primary outcome was overall survival (OS).

Results

Median OS was 23.0 months. Median tumour size was 6.5 cm and the median number of lesions was one. Overall, 16% of patients had positive margins, 38% had perineural invasion (PNI), 40% had lymphovascular invasion (LVI) and 22% had LN involvement. A median of two LNs were removed and a median of zero were positive. Lymph nodes were not sampled in 34% of patients. Lymphovascular and perineural invasion were associated with reduced OS [9.6 months vs. 32.7 months (P= 0.020) and 10.7 months vs. 32.7 months (P= 0.008), respectively]. Lymph node involvement indicated a trend towards reduced OS (10.7 months vs. 30.0 months; P= 0.063). The presence of either LVI or PNI in node-negative patients was associated with a reduction in OS similar to that in node-positive patients (12.1 months vs. 10.7 months; P= 0.541). After accounting for adverse tumour factors, only LVI and PNI remained associated with decreased OS on multivariate analysis (hazard ratio 4.07, 95% confidence interval 1.60–10.40; P= 0.003).

Conclusions

Lymphovascular and perineural invasion are separately associated with a reduction in OS similar to that in patients with LN-positive disease. As nodal dissection is often not performed and the number of nodes retrieved is frequently inadequate, these tumour-specific factors should be considered as criteria for selection for adjuvant chemotherapy.     

Surgical dilemma: liver resection or liver transplantation for hepatocellular carcinoma and cirrhosis. Intention-to-treat analysis in patients within and outwith Milan criteria

Background:

The optimal role of surgery in the management of hepatocellular carcinoma (HCC) is in continuous evolution.

Objective:

The objective of this study was to analyse survival rates after liver resection (LR) and orthotopic liver transplantation (OLT) for HCC within and outwith Milan criteria in an intention-to-treat analysis.

Methods:

During 1997–2007, 179 patients with cirrhosis and HCC either underwent LR (n= 60) or were listed for OLT (n= 119). Patients with incidental HCC after OLT, preoperative macrovascular invasion before LR, non-cirrhosis and Child–Pugh class C cirrhosis prior to OLT were eliminated, leaving 51 patients primarily treated with LR and 106 patients listed for primary OLT (84 of whom were transplanted) to be included in this analysis. A total of 66 patients fell outwith Milan criteria (26 LR, 40 OLT) and 91 continued to meet Milan criteria (25 LR, 66 OLT).

Results:

The median length of follow-up was 26 months. The mean waiting time for OLT was 7 months. During that time, 21 patients were removed from the waiting list as a result of tumour progression. Probabilities of dropout were 2% and 13% at 6 and 12 months, respectively, for patients within Milan criteria, and 34% and 57% at 6 and 12 months, respectively, for patients outwith Milan criteria (P < 0.01). Tumour size >3 cm was found to be the independent factor associated with dropout (hazard ratio [HR] 6.0). Postoperative survival was slightly higher after OLT, but this was not statistically significant (64% for OLT vs. 57% for LR). Overall survival from time of listing for OLT or LR did not differ between the two groups (P= 0.9); for patients within Milan criteria, 1- and 4-year survival rates after LR were 88% and 61%, respectively, compared with 92% and 62%, respectively, after OLT (P= 0.54). For patients outwith Milan criteria, 1- and 4-year survival rates after LR were 69% and 54%, respectively, compared with 65% and 40%, respectively, after OLT (P= 0.42). Tumour size >3 cm was again found to be an independent factor for poor outcome (HR 2.4) in the intention-to-treat analysis.

Conclusions:

Survival rates for patients with HCC are similar in LR and OLT. Liver resection can potentially decrease the dropout rate and serve as a bridge for future salvage LT, particularly in patients with tumours >3 cm.