Hepatocellular Carcinoma
Conditions
Brief summary
The purposes of this prospective study were to evaluate the successful rate of primary culture of hepatocellular carcinoma cells and cancer-associated fibroblasts from the residual specimens in routine fine-needle aspiration of hepatic tumor and the potential application of this method as an additional tool for personalized treatment of hepatocellular carcinoma patients.
Detailed description
Fine-needle aspiration (FNA) cytology or biopsy of hepatic tumor is frequently applied in the collection of specimens because it is considered safe, efficacious, accurate and cost effective. Our previous study from small number of patients showed that specimens obtained from FNA had potential to be applied for primary culture of cancer cells. This study was to modified our method for primary culture of both hepatocellular carcinoma cells and cancer-associated fibroblasts in patients with tumor measuring larger than or equal to 3cm. All patients received one session of aspiration for the diagnosis of hepatic tumor. The aspirated specimens were applied for both cytologic and pathologic examinations at first. After then, 10 mL 0.9% NaCl was aspirated by the same needle connected with the same syringe and injected into 15 mL sterilized centrifugation tube. If the tube contained visible specimens, these specimens were sent for primary culture.
Interventions
None listed
Sponsors
Department of Health, Executive Yuan, R.O.C. (Taiwan)
Kaohsiung Medical University Chung-Ho Memorial Hospital
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
20 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* patients had residual aspirated specimens for primary culture.
Exclusion criteria
* patients did not have residual aspirated specimens for primary culture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between the Growth Speeds of the Cultured Cells and the AJCC TNM Stage (7th Eds) at Entering of the Study. | 28 days after plating of cells | Patients were divided into AJCC TNM staging \< = IIIA and \> = IIIB two groups. The incidences of patients with rapidly proliferative cultured cells in these two groups were compared. Rapidly proliferative group was defined as (1) growth area of cultured cells at the 28th day of primary culture exceeded two times of the growth area measured at the 14th day, or (2) growth area of cultured cells at the 28th day reached \> 70% growth area of the flask. Based on the results from special stain, patients in rapidly proliferative group were further divided into patients with rapid proliferation of HCC cells alone, rapid proliferation of HCC cells with concomitant cancer-associated fibroblasts (CAFs) (HCC + CAFs) and CAFs alone. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | 6 months after plating of cells | 104 Patients with complete follow-up data were further divided into receiving (1) curative treatment of HCC including operative resection and local ablation therapy, (2) palliative transcatheter arterial chemoembolization (TACE), and (3) supportive treatment. |
Countries
Taiwan
Participant flow
Recruitment details
From April 2010 to January 2013 in Cancer Center and Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital
Pre-assignment details
A total of 114 patients signed the inform consents. However, 9 patients were excluded due to negative cytological and pathologic results of malignancy in 4 patients, adenocarcinoma in 2 patients and fungal contamination during the preparation of the specimens in 3 patients.
Participants by arm
| Arm | Count |
|---|---|
| AJCC TNM Staging < = IIIA HCC Patients Tumor stage is based on the AJCC (American Joint Committee on Cancer) TNM staging system (2010, 7th edition) | 76 |
| AJCC TNM Staging > = IIIB HCC Patients Tumor stage is based on the AJCC (American Joint Committee on Cancer) TNM staging system (2010, 7th edition) | 29 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | AJCC TNM Staging < = IIIA HCC Patients | AJCC TNM Staging > = IIIB HCC Patients | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 45 Participants | 11 Participants | 56 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 18 Participants | 49 Participants |
| Age, Continuous | 66.4 years STANDARD_DEVIATION 12 | 59.6 years STANDARD_DEVIATION 14 | 63.1 years STANDARD_DEVIATION 12.7 |
| Sex: Female, Male Female | 14 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Male | 62 Participants | 24 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Correlation Between the Growth Speeds of the Cultured Cells and the AJCC TNM Stage (7th Eds) at Entering of the Study.
Patients were divided into AJCC TNM staging \< = IIIA and \> = IIIB two groups. The incidences of patients with rapidly proliferative cultured cells in these two groups were compared. Rapidly proliferative group was defined as (1) growth area of cultured cells at the 28th day of primary culture exceeded two times of the growth area measured at the 14th day, or (2) growth area of cultured cells at the 28th day reached \> 70% growth area of the flask. Based on the results from special stain, patients in rapidly proliferative group were further divided into patients with rapid proliferation of HCC cells alone, rapid proliferation of HCC cells with concomitant cancer-associated fibroblasts (CAFs) (HCC + CAFs) and CAFs alone.
Time frame: 28 days after plating of cells
Population: Comparison the incidence of patients with rapidly proliferative cultured cells between two groups
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AJCC TNM Staging > = IIIB | Correlation Between the Growth Speeds of the Cultured Cells and the AJCC TNM Stage (7th Eds) at Entering of the Study. | Rapidly proliferative cultured cells | 21 participants |
| AJCC TNM Staging > = IIIB | Correlation Between the Growth Speeds of the Cultured Cells and the AJCC TNM Stage (7th Eds) at Entering of the Study. | Rapid Proliferation of HCC with or without CAFs | 14 participants |
| AJCC TNM Staging > = IIIB | Correlation Between the Growth Speeds of the Cultured Cells and the AJCC TNM Stage (7th Eds) at Entering of the Study. | Rapid Proliferation of CAFs alone | 7 participants |
| AJCC TNM Staging < = IIIA HCC Patients | Correlation Between the Growth Speeds of the Cultured Cells and the AJCC TNM Stage (7th Eds) at Entering of the Study. | Rapidly proliferative cultured cells | 29 participants |
| AJCC TNM Staging < = IIIA HCC Patients | Correlation Between the Growth Speeds of the Cultured Cells and the AJCC TNM Stage (7th Eds) at Entering of the Study. | Rapid Proliferation of HCC with or without CAFs | 9 participants |
| AJCC TNM Staging < = IIIA HCC Patients | Correlation Between the Growth Speeds of the Cultured Cells and the AJCC TNM Stage (7th Eds) at Entering of the Study. | Rapid Proliferation of CAFs alone | 20 participants |
Comparison: Null hypothesis: There is no significant difference in the incidence of patients with rapidly proliferative cultured cells between two groups.p-value: <0.005Chi-squared
Comparison: Null hypothesis: There is no significant difference in the incidence of patients with rapidly proliferative cultured HCC cells with or without concomitant cancer-associated fibroblasts between two groups.p-value: <0.005Chi-squared
Comparison: Null hypothesis: There is no significant difference in the incidence of patients with rapidly proliferative cultured cancer-associated fibroblasts alone between two groups.p-value: >0.1Chi-squared
Secondary
Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells
104 Patients with complete follow-up data were further divided into receiving (1) curative treatment of HCC including operative resection and local ablation therapy, (2) palliative transcatheter arterial chemoembolization (TACE), and (3) supportive treatment.
Time frame: 6 months after plating of cells
Population: Correlation between the growth speeds of cultured cells and worsening of AJCC TNM stages or HCC related death 6 months after plating of cells
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AJCC TNM Staging > = IIIB | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapidly proliferative cultured cells | 10 participants |
| AJCC TNM Staging > = IIIB | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapid growth and worsening stage or death | 0 participants |
| AJCC TNM Staging > = IIIB | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Slow growth and worsening staging or death | 0 participants |
| AJCC TNM Staging > = IIIB | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapid growth of HCC cells and worsening | 0 participants |
| AJCC TNM Staging < = IIIA HCC Patients | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapidly proliferative cultured cells | 15 participants |
| AJCC TNM Staging < = IIIA HCC Patients | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapid growth of HCC cells and worsening | 2 participants |
| AJCC TNM Staging < = IIIA HCC Patients | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapid growth and worsening stage or death | 5 participants |
| AJCC TNM Staging < = IIIA HCC Patients | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Slow growth and worsening staging or death | 2 participants |
| TNM Staging < = IIIA Patients Receiving Supportive Treatment | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapid growth of HCC cells and worsening | 2 participants |
| TNM Staging < = IIIA Patients Receiving Supportive Treatment | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapid growth and worsening stage or death | 3 participants |
| TNM Staging < = IIIA Patients Receiving Supportive Treatment | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Slow growth and worsening staging or death | 1 participants |
| TNM Staging < = IIIA Patients Receiving Supportive Treatment | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapidly proliferative cultured cells | 3 participants |
| TNM Staging > = IIIB Patients Receiving TACE | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapidly proliferative cultured cells | 9 participants |
| TNM Staging > = IIIB Patients Receiving TACE | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapid growth and worsening stage or death | 4 participants |
| TNM Staging > = IIIB Patients Receiving TACE | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapid growth of HCC cells and worsening | 4 participants |
| TNM Staging > = IIIB Patients Receiving TACE | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Slow growth and worsening staging or death | 0 participants |
| TNM Staging > = IIIB Patients Receiving Supportive Treatment | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapid growth of HCC cells and worsening | 8 participants |
| TNM Staging > = IIIB Patients Receiving Supportive Treatment | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Slow growth and worsening staging or death | 2 participants |
| TNM Staging > = IIIB Patients Receiving Supportive Treatment | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapid growth and worsening stage or death | 11 participants |
| TNM Staging > = IIIB Patients Receiving Supportive Treatment | Correlation Between the Growth Speeds of Cultured Cells and Worsening of AJCC TNM Stages or HCC Related Death 6 Months After Plating of Cells | Rapidly proliferative cultured cells | 12 participants |
Comparison: null hypothesis: There is no significant difference in the incidence of change in AJCC TNM stages and survivals 6 months after plating of cells between patients with rapidly and slowly proliferative cultured cells.p-value: 1Fisher Exact
Comparison: Null hypothesis: There is no significant difference in the incidence of change in AJCC TNM stages and survivals 6 months after plating of cells between patients with rapidly and slowly proliferative cultured cells.p-value: 0.032Fisher Exact
Comparison: Null hypothesis: There is no significant difference in the incidence of change in AJCC TNM stages and survivals 6 months after plating of cells between patients with rapidly and slowly proliferative cultured cells.p-value: 0.048Fisher Exact
Comparison: Null hypothesis: There is no significant difference in the incidence of change in AJCC TNM stages and survivals 6 months after plating of cells between patients with rapidly and slowly proliferative cultured cells.p-value: 0.176Fisher Exact
Comparison: Null hypothesis: There is no significant difference in the incidence of change in AJCC TNM stages and survivals 6 months after plating of cells between patients with rapidly and slowly proliferative HCC cultured cells.p-value: 0.021Fisher Exact
Comparison: Null hypothesis: There is no significant difference in the incidence of change in AJCC TNM stages and survivals 6 months after plating of cells between patients with rapidly and slowly proliferative cultured cells.p-value: 0.129Fisher Exact