Relevance of residual disease after liver resection for incidental gallbladder cancer

Objectives

In patients diagnosed with incidental gallbladder cancer (GC), the benefit and optimal extent of further surgery remain unclear. The aims of this study were to analyse outcomes in patients who underwent liver resection following a diagnosis of incidental GC and to determine factors associated with longterm survival.

Methods

A retrospective analysis of patients diagnosed with incidental GC between June 1999 and June 2010 was performed. Data covering demographics, clinical and surgical characteristics and local pathological stage were analysed.

Results

A total of 24 patients were identified. All patients underwent a resection of segments IVb and V and lymphadenectomy. Histological examination revealed residual disease in 10 patients, all of whom presented with recurrent disease at 3–12 months. Overall 5-year survival was 53%. Increasing T-stage (P < 0.001), tumour–node–metastasis (TNM) stage (P= 0.003), and the presence of residual tumour in the resected liver (P < 0.001) were all associated with worse survival.

Conclusions

Aggressive re-resection of incidental GC offers the only chance for cure, but its efficacy depends on the extent of disease found at the time of repeat surgery. The presence of residual disease correlated strongly with T-stage and was the most relevant prognostic factor for survival in patients treated with curative resection.     

Outcome of radical surgery for stage IV gallbladder carcinoma

Background/Purpose

The role of aggressive surgery for patients with stage IV gallbladder carcinoma was examined.

Methods

Cancers were classified according to the TNM system of the Japanese Society of Biliary Surgery. The survival of 37 patients with stage IV cancer (stage IVa, n = 15; stage IVb, n = 22) treated by surgical resection during the period January 1990 to December 2004 was examined and compared with the survival of 41 patients with stage IV disease not treated by surgical resection during the same period.

Results

The postoperative survival rate was significantly better for patients with resected stage IVa cancer than for patients with resected stage IVb disease and for those with nonresected stage IV disease. Survival in patients with N3 lymph node metastasis, liver metastasis, peritoneal dissemination, or vascular invasion was poor, like that in the nonresected group. Surgical resection without residual tumors (curability A and B) yielded a significantly better outcome than that with residual tumor (curability C). There were three 5-year survivors that were treated successfully by curative resection (curability A and B) and all had T4N0 disease.

Conclusions

These results suggest that surgical resection significantly improves survival even in patients with stage IV gallbladder carcinoma when N3 metastasis, liver metastasis, peritoneal dissemination, and vascular invasion are absent. Curative resection can be expected to produce long-term survival in selected patients with stage IV gallbladder carcinoma.

     

Prognostic significance of lymph node ratio after resection of peri-hilar cholangiocarcinoma

Background

Lymph node (LN) metastases are a major negative prognostic factor for peri-hilar cholangiocarcinoma (PCC). Prognostic significance of the extent of LN dissection, number of metastatic LN and the lymph node ratio (LNR) are still under debate.

Aims

The aims of the present study were to evaluate the prognostic value of the LN status, the total number of LNs evaluated and LNR in PCC.

Methods

Between 1990 and 2008, 62 patients with PCC submitted to surgical resection with curative intent were retrospectively evaluated. Number and status of harvested LN were recorded.

Results

In 53 patients (85.4%) regional lymphadenectomy was performed. Median number of LNs examined was 7 (range 1–25). Median survival was 41.9 months in patients with N0 compared with 22.7 months in 21 patients (39.6%) with N+ (P = 0.03). Median survival was 3, 18.5 and 29 months for patients with 0, 1–3 and >3 LN retrieved, respectively (P < 0.01). Five-year survival for patients above and below the LNR cut-off value of 0.25 was 0% and 22.5%, respectively (P = 0.03).

Conclusions

LN metastases are a major prognostic factor for survival after surgical resection of PCC. The number of LN harvested and LNR showed high prognostic value.     

2564 resected periampullary adenocarcinomas at a single institution: trends over three decades

Objective

This study was carried out to determine relative survival rates and trends in outcomes in patients who underwent resection of periampullary adenocarcinomas (PACs) with curative intent at a single institution over the last three decades.

Methods

From 1980 to 2011, 2564 pancreaticoduodenectomies (PDs) were performed for PACs. Pathological diagnosis, therapy and survival were retrospectively analysed.

Results

The primary sites included the pancreas (66%), ampulla (16%), bile duct (12%) and duodenum (6%). Operation volume increased from 11 per year in the 1980s to 135 per year in the 2000s (P < 0.001). Patients in the 1980s were younger (median age: 64 years; range: 33–90 years) than those in the 1990s (median age: 68 years; range: 31–103 years) and 2000s (median age: 68 years; range: 24–93 years) (P < 0.001). Over time, the frequency of a diagnosis of pancreatic cancer arising from intraductal papillary mucinous neoplasm increased from 2% in the 1980s to 8% in the 2000s (P < 0.001). The rate of 30-day mortality after surgery in the 1980s was 2%, which was similar to rates in the 1990s (1%) and 2000s (1%). Survival in each type of PAC did not change over time. Pancreatic cancer was associated with the worst survival (median survival: 19 months) compared with adenocarcinomas of the ampulla (median survival: 47 months), bile duct (median survival: 23 months) and duodenum (median survival: 54 months) (P < 0.001).

Conclusions

There are significant differences among PACs in longterm survival following PD. Although the numbers of patients undergoing safe resection have increased, overall longterm outcomes have not improved significantly.     

Diffuse large B-cell lymphoma with involvement of the kidney: outcome and risk of central nervous system relapse

Background

Renal involvement is uncommon in diffuse large B-cell lymphoma. Recent data suggest that it is an independent risk factor for central nervous system relapse. We reviewed the clinical features, risk of central nervous system involvement, and survival of patients with diffuse large B-cell lymphoma with involvement of the kidney at diagnosis.

Design and Methods

All patients with diffuse large B-cell lymphoma and renal involvement diagnosed from January 1, 1982 to December 31, 2008 at the British Columbia Cancer Agency were retrospectively identified in the Lymphoid Cancer Database. Patients were included if they were 16 years old or over, had advanced stage disease [stage III/IV, or stage I/II with B symptoms or bulky mass (>10 cm)] and were treated with curative intent. Central nervous system involvement was diagnosed by cerebrospinal fluid cytology, radiology or clinically.

Results

We identified 55/2656 (2%) patients with diffuse large B-cell lymphoma and renal involvement at diagnosis. The male to female ratio was 2:1. The patients’ median age was 58 years. Bilateral renal involvement was present in 24 (44%) and stage IV disease in 50 (91%). The International Prognostic Index score was 3, 4 or 5 in 52 (95%), the glomerular filtration rate was less than 30 mL/min/m² in 9 (16%) and elevated lactate dehydrogenase was recorded in 46 (84%). Twenty-five (46%) patients received CHOP plus rituximab and 30 (54%) received CHOP-like regimens without rituximab. In total, 20 (36%) patients had central nervous system involvement: four at the time of diagnosis and 16 at relapse. The median time to central nervous system relapse was 5.6 months (range, 1.2 months–4.6 years), and was not affected by the addition of rituximab (P=0.547). The 5-year overall and progression-free survival rates for the whole cohort were 29% and 25%, respectively. In patients who received rituximab, there were trends towards improved 5-year overall survival (43% versus 18%, P=0.071) and progression-free survival (40% versus 13%, P=0.057).

Conclusions

There is an exceptionally high incidence of central nervous system relapse in patients with diffuse large B-cell lymphoma and kidney involvement at diagnosis. The addition of rituximab may improve overall survival in this poor-risk population, likely through improved control of systemic disease.     

A 21‐year analysis of stage I gallbladder carcinoma: is cholecystectomy alone adequate?

Objectives

Gallbladder carcinoma (GBC) is a rare disease that is often diagnosed incidentally in its early stages. Simple cholecystectomy is considered the standard treatment for stage I GBC. This study was conducted in a large cohort of patients with stage I GBC to test the hypothesis that the extent of surgery affects survival.

Methods

The National Cancer Institute''s Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients in whom microscopically confirmed, localized (stage I) GBC was diagnosed between 1988 and 2008. Surgical treatment was categorized as cholecystectomy alone, cholecystectomy with lymph node dissection (C + LN) or radical cholecystectomy (RC). Age, gender, race, ethnicity, T1 sub-stage [T1a, T1b, T1NOS (T1 not otherwise specified)], radiation treatment, extent of surgery, cause of death and survival were assessed by log-rank and Cox''s regression analyses.

Results

Of 2788 patients with localized GBC, 1115 (40.0%) had pathologically confirmed T1a, T1b or T1NOS cancer. At a median follow-up of 22 months, 288 (25.8%) had died of GBC. Five-year survival rates associated with cholecystectomy, C + LN and RC were 50%, 70% and 79%, respectively (P < 0.001). Multivariate analysis showed that surgical treatment and younger age were predictive of improved disease-specific survival (P < 0.001), whereas radiation therapy portended worse survival (P = 0.013).

Conclusions

In the largest series of patients with stage I GBC to be reported, survival was significantly impacted by the extent of surgery (LN dissection and RC). Cholecystectomy alone is inadequate in stage I GBC and its use as standard treatment should be reconsidered.     

Portal vein resection using the no-touch technique with a hepatectomy for hilar cholangiocarcinoma

Objectives

To assess the safety and feasibility and discuss the oncological impact of a portal vein resection using the no-touch technique with a hepatectomy for locally advanced hilar cholangiocarcinoma.

Patients and Methods

From 2005 to March 2009, 49 patients with hilar cholangiocarcinoma underwent a major right-sided hepatectomy with curative intent. Portal vein resection was performed using the no-touch technique in 36 patients (PVR group) but the portal vein was not resected in the other 13 patients (NR group). Peri-operative data and histological findings were compared between the two groups. Moreover, tumour recurrence and survival rates after surgery were calculated and compared for each group.

Results

Although the tumours of the patients in the PVR group were more locally advanced, the residual tumour status and tumour recurrence rate were similar and there was no significant difference in long-term survival between the two groups: 5-year survival rates in the PVR and NR groups were 59% and 51%, respectively (P = 0.353). In-hospital mortality was encountered in 2 of the 49 patients.

Conclusion

A portal vein resection using the no-touch technique with a right-sided hepatectomy had a positive impact on survival and is feasible in terms of long-term outcomes with acceptable mortality.     

Impact of preoperative therapy on patterns of recurrence in pancreatic cancer

Background

A theoretical advantage of preoperative therapy in pancreatic adenocarcinoma is that it facilitates the early treatment of micrometastases and reduces postoperative systemic recurrence.

Methods

Medical records of 309 consecutive patients undergoing resection of adenocarcinoma in the head of the pancreas were reviewed. Survival was calculated using the Kaplan–Meier method. Associations between preoperative therapy and patterns of recurrence were determined using chi-squared analysis.

Results

Preoperative therapy was administered to 108 patients and upfront surgery was performed in 201 patients. Preoperative therapy was associated with a significantly longer median disease-free survival of 14 months compared with 12 months in patients submitted to upfront surgery (P = 0.035). The rate of local disease as a component of first site of recurrence was significantly lower with preoperative therapy (11.3%) than with upfront surgery (22.9%) (P = 0.016). Preoperative therapy was associated with a lower rate of hepatic metastasis (21.7%) than upfront surgery (34.3%) (P = 0.026). Preoperative therapy did not affect rates of peritoneal or pulmonary metastasis.

Conclusions

Preoperative therapy for pancreatic cancer was associated with longer disease-free survival and lower rates of local and hepatic recurrences. These data support the use of preoperative therapy to reduce systemic and local failures after resection.     

Clinical parameters predicting survival duration after hepatectomy for intrahepatic cholangiocarcinoma

BACKGROUND:

Currently, the most effective treatment for intrahepatic cholangiocarcinoma (ICC) is complete hepatic tumour excision.

OBJECTIVE:

To identify the clinical parameters associated with survival duration for ICC patients following hepatectomy, and to construct a mathematical model for predicting survival duration.

METHODS:

Demographic data and clinical variables for 102 patients diagnosed with ICC, who underwent exploratory laparotomy at a single centre from July 1998 to December 2000 and were followed for an average of 24 months, were collected in 2011. Patients were randomly assigned into training (n=76) and validation (n=26) groups. Univariate and multivariate analyses were performed to identify factors associated with posthepatectomy survival duration.

RESULTS:

Univariate analysis revealed that more than three lymph node metastases, a serum carbohydrate antigen 19-9 level >37 U/mL, stage IVa tumours, and intra- or perihepatic metastases were significantly associated with decreased survival duration. Curative resection was significantly associated with increased survival duration. A mathematical model incorporating parameters of age, sex, metastatic lymph node number, curative surgery, carbohydrate antigen 19-9 concentration, alpha-fetoprotein concentration, hepatitis B, TNM stage and tumour differentiation was constructed for predicting survival duration. For a survival duration of less than one year, the model exhibited 93.8% sensitivity, 92.3% total accuracy and a positive predictive value of 93.8%; for a survival duration of one to three years, the corresponding values were 80.0%, 69.2% and 57.1%, repsectively.

CONCLUSIONS:

The mathematical model presented in the current report should prove to be useful in the clinical setting for predicting the extent to which curative resection affects the survival of ICC patients, and for selecting optimal postoperative treatment strategies.     

Prognostic significance of the lymph node ratio regarding recurrence and survival in rectal cancer patients treated with postoperative chemoradiotherapy

Background/Aims

To evaluate the prognostic impact of the lymph node ratio (LNR: the ratio of positive lymph nodes to the total number of lymph nodes examined) on disease recurrence and survival among rectal cancer patients who received curative surgery and postoperative chemoradiotherapy (CRT).

Methods

Between 1995 and 2008, 124 patients with pathologic T3-4 or node-positive rectal cancer underwent curative surgery and postoperative CRT. Postoperative radiotherapy was delivered at a median dose of 50.4 Gy (range, 45 to 59.4 Gy) for 6 weeks. Chemotherapy consisted of a bolus injection of 5-fluorouracil and leucovorin in the first and last week of radiotherapy (91.9%) or daily capecitabine during radiotherapy (8.1%). Further adjuvant chemotherapy was administered after chemoradiation.

Results

The median follow-up was 5.1 years. In the multivariate analysis, pathologic N (pN) stage and lymphovascular invasion were significantly associated with disease-free survival and disease-specific survival (p<0.05). However, when the LNR with a cutoff value of 0.2 was included as a covariate in the model, the LNR was highly significant (p<0.001), and the pN stage lost its significance (p>0.05).

Conclusions

The LNR predicts recurrence and survival more accurately than pN stage. The pN stage and the LNR should be considered together when estimating the risk of disease recurrence among rectal cancer patients.     

Sequential intra-arterial therapy and portal vein embolization is feasible and safe in patients with advanced hepatic malignancies

Background

A major hepatic resection for malignancies requires an adequate post-operative liver reserve. Portal vein embolization (PVE) with intra-arterial therapy (IAT) may increase future liver remnant (FLR) hypertrophy. As such, the feasibility, safety and efficacy of IAT+PVE were investigated.

Methods

Between 2000 to 2011, 86 patients with malignancy of the liver were identified from a multi-institutional database. Twenty-nine patients underwent sequential IAT+PVE, 25 had PVE alone and 32 had IAT alone. Clinicopathological data were evaluated.

Results

Most patients had hepatocellular carcinoma (HCC) (65.1%) and 31.4% had secondary metastatic disease. A complete or partial response using European Association for the Study of the Liver (EASLD) criteria was seen in 48.3% of patients undergoing IAT+PVE vs. 56.6% among patients undergoing IAT (P = 0.601). The median increase in percentage FLR volume was comparable in IAT+PVE (7.4%) vs. PVE only (7.9%) (P = 0.203). There were no IAT+PVE-associated deaths and only one complication. Among patients treated with IAT+PVE (n = 29), 27 underwent a subsequent hepatic resection. Peri-operative morbidity and mortality was 29.6% and 7.4%, respectively. Among the patients with HCC who underwent curative intent surgery after IAT+PVE, the median survival was 59.0 months.

Conclusions

Sequential IAT and PVE are feasible and safe. Utilization of IAT+PVE before a resection can lead to long-term survival and should be considered in the treatment of patients with advanced hepatic malignancies.     

Intrahepatic cholangiocarcinoma in a low endemic area: rising incidence and improved survival

Background

To explore trends in the incidence and survival of patients with intrahepatic cholangiocarcinoma (ICC) an unselected population in Western Europe was studied.

Methods

Between 1989 and 2009, all patients newly diagnosed with ICC were selected from the Netherlands Cancer Registry (n = 809). Trends in incidence, treatment and relative survival were calculated according to gender and age. Follow-up for vital status was complete until 1st January 2010.

Results

The incidence rates of ICC increased significantly between 1999 and 2009, especially in the age group 45–59 years [estimated annual percentage change +3.0%, 95% confidence interval (CI) 0.2–5.8]. In the other age groups ICC incidence remained stable. Patients diagnosed with Tumour Lymph Node Metastasis (TNM) stage I mainly underwent surgery (68%), and the majority of the patients with stage II, III and IV received best supportive care (73%). One-year relative survival for patients with ICC increased significantly from 24% in 1989–1994 to 28% in 2005–2009 (P = 0.03), and corresponding 3-year relative survival improved from 4% to 8% (P = 0.02). Three-month and 1-year relative survival for patients with ICC receiving surgery was 91% and 71%, respectively.

Discussion

Between 1999 and 2009, the incidence of ICC rose, especially in the age group 45–59 years, suggesting aetiological influences. Survival rates have improved during the study period.     

Complications following liver resection for colorectal metastases do not impact on longterm outcome

Background

It has been suggested that adverse postoperative outcomes may have a negative impact on longterm survival in patients with colorectal liver metastases.

Objectives

This study was conducted to evaluate the prognostic impact of postoperative complications in patients submitted to a potentially curative resection of colorectal liver metastases.

Methods

A retrospective analysis of outcomes in 199 patients submitted to hepatic resection with curative intent for metastatic colorectal cancer during 1999–2008 was conducted.

Results

The overall complication rate was 38% (n = 75). Of all complications, 79% were minor (Grades I or II). There were five deaths (3%). The median length of follow-up was 39 months. Rates of 5-year overall and disease-free survival were 44% and 27%, respectively. Univariate analysis demonstrated that an elevated preoperative level of carcinoembryonic antigen (CEA), intraoperative blood loss of >300 ml, multiple metastases, large (≥35 mm) metastases and resection margins of <1 mm were associated with poor overall and disease-free survival. In addition, male sex and synchronous metastases were associated with poor disease-free survival. Postoperative complications did not have an impact on either survival measure. The multivariate model did not include complications as a predictive factor.

Conclusions

Postoperative complications were not found to influence overall or disease-free survival in the present series. The number and size of liver metastases were confirmed as significant prognostic factors.     

Factors affecting tumor recurrence after curative surgery for NSCLC: impacts of lymphovascular invasion on early tumor recurrence

Background

Although surgery is potentially curative treatment for non-small cell lung cancer (NSCLC), the risk of postoperative disease recurrence is still high. This study was conducted to assess the factors associated with postoperative tumor recurrence in patients who underwent curative surgery for NSCLC.

Methods

One hundred seventy-one patients who underwent curative surgery for NSCLC were included in this study. Clinicopathological factors of histologic type, pathologic TNM stage, T stage, N stage, lymphovascular invasion (LVI), perineural invasion (PNI), surgical procedure, adjuvant chemotherapy and adjuvant radiotherapy were investigated. Gender, age, and clinicopathologic factors were included in univariate and multivariate analyses using the Kaplan-Meier method and Cox proportional hazards model, respectively. Mann-Whitney U and Kruskal-Wallis tests were used to investigate the significance of differences in recurrence-free interval (RFI) according to clinicopathological factors.

Results

Median RFI was 20 months. Univariate and multivariate analyses for overall recurrence identified T stage, N stage, and LVI as significant factors (P=0.045, 0.044, and <0.001, respectively). Pathologic stage (P=0.005) was the only factor that was significantly associated with locoregional recurrence. T stage (P=0.040) and LVI (P<0.001) were significantly associated with distant recurrence. The difference in 2-year freedom from recurrence between LVI positive and negative groups was significant (14.9% vs. 44.6%, P<0.001). LVI was the only factor that was significantly associated with a shortened mean RFI (P<0.001).

Conclusions

LVI had a significant effect on both overall and distant recurrence rates as well as on early tumor recurrence after curative surgery for NSCLC.     

Pretreatment biopsy for histological diagnosis and induction therapy in thymic tumors

Background

This study was to investigate the value of pretreatment biopsy for histological diagnosis and induction therapies in the management of locally advanced thymic malignancies.

Methods

The clinical pathological data of patients with thymic tumors in the Chinese Alliance for Research in Thymomas (ChART) who underwent biopsy before treatment from 1994 to December 2012 were retrospectively reviewed. The application trend of preoperative histological diagnosis and its influence on treatment outcome were analyzed.

Results

Of 1,902 cases of thymic tumors, 336 (17.1%) had undergone biopsy for histological diagnosis before therapeutic decision was decided. In recent years, percentage of pretreatment histological diagnosis significantly increased in the later ten years than the former during the study period (P=0.008). There was also a significant increase in thoracoscopy/mediastinoscopy/E-BUS biopsy as compared to open biopsy (P=0.029). Survival in Patients with preoperative biopsy for histology had significantly higher stage lesions (P=0.000) and higher grade malignancy (P=0.000), thus a significantly lower complete resection rate (P=0.000) and therefore a significantly worse survival than those without preoperative biopsy (P=0.000). In the biopsied 336 patients, those who received upfront surgery had significantly better survival than those received surgery after induction therapy (P=0.000). In stage III and IVa diseases, the R0 resection rate after induction therapies increased significantly as compared to the surgery upfront cases (65.5% vs. 46.2%, P=0.025). Tumors downstaged after induction had similar outcomes as those having upfront surgery (92.3% vs. 84.2%, P=0.51). However, tumors not downstaged by induction had significantly worse prognosis than those downstaged (P=0.004), and fared even worse than those having definitive chemoradiation without surgery (37.2% vs. 62.4%, P=0.216).

Conclusions

It is crucial to get histological diagnosis for thymoma before surgery or adjuvant treatment and minimally invasive biopsy should be undertaken. Although in our study we could not find the benefit of induction chemotherapy before surgery in survival and recurrence rate, it could increase the R0 resection rate compared with direct surgery in late stage (III and IVa).     

Management of incidental and suspicious gallbladder cancer: focus on early referral to a tertiary centre

Objectives

This study was conducted to assess the management of incidental gallbladder cancer and indeterminate gallbladder lesions. Its secondary aim referred to the devising of a management pathway for these patients.

Methods

Patients referred with incidental gallbladder cancer and indeterminate gallbladder lesions during 2002–2011 were identified from a prospectively maintained database. Collated data included operative findings, histopathological data and survival outcomes.

Results

The study included a total of 104 patients, 40 of whom had incidental gallbladder cancer following cholecystectomy. In this group, the index cholecystectomy was considered curative (T-is/T1a stage) in three patients; 11 patients underwent further resection, and 26 patients were inoperable. One-, 3- and 5-year overall survival rates were 91.1%, 91.0% and 60.7%, respectively, in patients who underwent re-resection. Of the 64 patients with indeterminate gallbladder lesions, 54 patients underwent modified radical cholecystectomy. Seven patients were found to have gallbladder cancer. One-, 3- and 5-year overall survival rates were 85.9%, 43.1% and 42.8%, respectively. Five-year overall survival in patients treated with surgery for gallbladder cancer was 59.9%.

Conclusions

The majority of patients with incidental gallbladder cancer were not amenable to further potentially curative resection. The radiological suspicion of gallbladder cancer should lead to prompt referral to a tertiary hepatobiliary unit for further management.     

Model to predict survival after surgical resection of intrahepatic cholangiocarcinoma: the Mayo Clinic experience

Background

The 7th edition of the American Joint Committee on Cancer (AJCC) staging system has recently been validated and shown to predict survival in patients with intrahepatic cholangiocarcinoma (ICC). The present study attempted to investigate the validity of these findings.

Methods

A single-centre, retrospective cohort study was conducted. Histopathological restaging of disease subsequent to primary surgical resection was carried out in all consecutive ICC patients. Overall survival was compared using Kaplan–Meier estimates and log-rank tests.

Results

A total of 150 patients underwent surgery, 126 (84%) of whom met the present study''s inclusion criteria. Of these 126 patients, 68 (54%) were female. The median length of follow-up was 4.5 years. The median patient age was 58 years (range: 24–79 years). Median body mass index was 27 kg/m² (range: 17–46 kg/m²). Staging according to the AJCC 7th edition categorized 33 (26%) patients with stage I disease, 27 (21%) with stage II disease, five (4%) with stage III disease, and 61 (48%) with stage IVa disease. The AJCC 7th edition failed to accurately stratify survival in the current cohort; analysis revealed significantly worse survival in those with microvascular invasion, tumour size of >5 cm, grade 4 disease, multiple tumours and positive lymph nodes (P < 0.001). A negative resection margin was associated with improved survival (P < 0.001).

Conclusions

The AJCC 7th edition did not accurately predict survival in patients with ICC. A multivariable model including tumour size and differentiation in addition to the criteria used in the AJCC 7th edition may offer a more accurate method of predicting survival in patients with ICC.     

Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia

Background

Reduced intensity conditioning regimens permit the delivery of a potentially curative graft-versus-leukemia effect in older patients with acute myeloid leukemia. Although T-cell depletion is increasingly used to reduce the risk of graft-versus-host disease its impact on the graft-versus-leukemia effect and long-term outcome post-transplant is unknown.

Design and Methods

We have characterized pre- and post-transplant factors determining overall survival in 168 patients with acute myeloid leukemia transplanted using an alemtuzumab based reduced intensity conditioning regimen with a median duration of follow-up of 37 months.

Results

The 3-year overall survival for patients transplanted in CR1 or CR2/CR3 was 50% (95% CI, 38% to 62%) and 44% (95% CI, 31% to 56%), respectively compared to 15% (95% CI, 2% to 36%) for patients with relapsed/refractory disease. Multivariate analysis demonstrated that both survival and disease relapse were influenced by status at transplant (P=0.008) and presentation cytogenetics (P=0.01). Increased exposure to cyclosporine A (CsA) in the first 21 days post-transplant was associated with an increased relapse risk (P<0.0001) and decreased overall survival (P<0.0001).

Conclusions

Disease stage, presentation karyotype and post-transplant CsA exposure are important predictors of outcome in patients undergoing a T-cell depleted reduced intensity conditioning allograft for acute myeloid leukemia. These data confirm the presence of a potent graft-versus-leukemia effect after a T-cell depleted reduced intensity conditioning allograft in acute myeloid leukemia and identify CsA exposure as a manipulable determinant of outcome in this setting.     

Treatment sequencing strategy for hepatic epithelioid haemangioendothelioma

Background

The biology of hepatic epithelial haemangioendothelioma (HEHE) is variable, lying intermediate to haemangioma and angiosarcoma. Treatments vary owing to the rarity of the disease and frequent misdiagnosis.

Methods

Between 1989 and 2013, patients retrospectively identified with HEHE from a single academic cancer centre were analysed to evaluate clinicopathological factors and initial treatment regimens associated with survival.

Results

Fifty patients with confirmed HEHE had a median follow-up of 51 months (range 1–322). There was no difference in 5-year survival between patients presenting with unilateral compared with bilateral hepatic disease (51.4% versus 80.7%, respectively; P = 0.1), localized compared with metastatic disease (69% versus 78.3%, respectively; P = 0.7) or an initial treatment regimen of Surgery, Chemotherapy/Embolization or Observation alone (83.3% versus 71.3% versus 72.4%, respectively; P = 0.9). However, 5-year survival for patients treated with chemotherapy at any point during their disease course was decreased compared with those who did not receive any chemotherapy (43.6% versus 82.9%, respectively; P = 0.02) and was predictive of a decreased overall survival on univariate analysis [HR 3.1 (CI 0.9–10.7), P = 0.02].

Conclusions

HEHE frequently follows an indolent course, suggesting that immediate treatment may not be the optimal strategy. Initial observation to assess disease behaviour may better stratify treatment options, reserving surgery for those who remain resectable/transplantable. Prospective cooperative trials or registries may confirm this strategy.     

Yield of clinical and radiographic surveillance in patients with resected pancreatic adenocarcinoma following multimodal therapy

Background

Following potentially curative resection at this centre, patients with pancreatic adenocarcinoma (PAC) are routinely enrolled in a programme of clinical and radiographic surveillance. This study sought to evaluate its diagnostic yield.

Methods

All patients who underwent pancreaticoduodenectomy for PAC at this institution during 1998–2008 were identified. Patients with asymptomatic recurrence were compared with those with symptomatic recurrence. Factors associated with survival following the detection of recurrence were compared.

Results

A total of 216 of 327 (66.1%) resected patients developed recurrence. Asymptomatic recurrence was detected in 118 (54.6%) patients. Symptomatic recurrence was associated with multifocal disease or carcinomatosis, poor performance status and less frequent subsequent therapy. Median time to recurrence did not differ between groups, but survival after detection was shorter in symptomatic patients (5.1 months vs. 13.0 months; P < 0.001). Treatment was administered more frequently to asymptomatic patients (91.2% vs. 61.4%; P < 0.001). At recurrence, a preserved performance status score of ≤1, further therapy, low CA 19-9, and an isolated site of recurrence were independently associated with longer post-recurrence survival (P < 0.001).

Conclusions

Overall, 54.6% of cases of recurrent PAC were detected prior to the onset of symptoms using a standardized clinical and radiographic surveillance strategy. Although this retrospective analysis limits definitive conclusions associating this strategy with survival, these results suggest the need for further studies of postoperative surveillance.