Carcinoma, Squamous Cell, Malignant Melanoma
Conditions
Keywords
Groin dissection, Axilla (or axillary) dissection, Lymph node dissection, Lymphadenectomy, Seroma, Wound drainage, Fibrin sealant, Malignant melanoma, Squamous cell carcinoma
Brief summary
The purpose of this study is to determine whether the use of fibrin sealant reduces post-operative drainage following groin and axillary lymph node dissection.
Detailed description
Background: Fibrin sealant has been used for many years in clinical practice and has a wide range of applications including the control of lymphatic leaks and haemostasis. The physiological mechanism of action of fibrin was first described by Morawitz in 1905; fibrin sealant was first marketed in 1983. Lymph node dissection is undertaken for the control of malignant disease - frequently malignant melanoma or squamous cell carcinoma. Following groin or axillary dissection, excessive post operative drainage may necessitate the presence of wound drains for 10 days or more. This may prolong hospital stay in some patients, and may be associated with an increased complication rate (such as wound infection). Hypothesis: the use of fibrin sealant prior to wound closure following either groin or axillary dissection may reduce post-operative wound drainage. Comparison: patients who require an elective groin or axillary dissection who either undergo standard wound closure or those who have fibrin sealant instilled into the surgical wound prior to wound closure.
Interventions
DRUGFibrin Sealant (Tisseel) used in the Experimental Arm.
For patients in the Experimental (Treatment) Arm, 4 ml of Tisseel fibrin sealant were instilled into the wound using the Duploject™ spray delivery system prior to wound closure. Tisseel™ fibrin sealant was provided by Baxter Healthcare Ltd., Newbury, Berkshire, UK. For patients in the Active Comparator (Control) Arm, no fibrin sealant was used during wound closure (with the surgical procedure being identical in all other respects).
Sponsors
Baxter Healthcare Corporation
Oxford University Hospitals NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients over 18 years of age * Requiring groin or axillary lymph node dissection for malignant disease.
Exclusion criteria
* Patients under age 18 years. * Patients unable to speak English. * Patients with learning difficulties. * Patients with mental illness. * Prisoners. * Other vulnerable groups.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-operative Wound Drainage. | From date of surgery to date of wound drain removal (typically a period of approximately one week). | The postoperative wound drainage volume was measured from the day of surgery until the the date of removal of the last wound drain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Time Drains Remain in Situ. | From date of surgery until date of wound drain removal. | The duration of postoperative wound drainage was measured from the day of surgery until the the date of removal of the last wound drain. |
| Number of Patients With Post-operative Complications (Excluding Lymphoedema). | Until wound healing complete. | Complications were classified as being either 'Minor' (i.e. (managed without operation, prolonged hospital stay or readmission) or 'Major' (i.e. requiring surgical intervention or readmission to hospital). The number of patients with each 'Minor' and 'Major' complication were recorded. |
| Length of Hospital Inpatient Stay. | From date of surgery until date of discharge from hospital. | The length of hospital stay was calculated from the day of surgery to the day that the patient was discharged from hospital. |
| Disease Recurrence. | From date of surgery until end of study follow-up period (1st June 2010) | This was measured as either: 1. the number of participants with local recurrence; 2. the number of participants with in transit or regional recurrence; or 3. the number of participants with distant metastasis (but alive on 1st June 2010). |
| Death. | From day of surgery until end of study follow-up period (1st June 2010) | Death was recorded as the number of participants who had died by the end of the study follow-up period (1st June 2010). Deaths were recorded as either being related to the primary disease (i.e. due to distant metastasis) or death due to another (unrelated) cause (e.g. myocardial infarction or cerebrovascular accident). |
| Post Operative Pain Score Measured on 1st Post-operative Day. | During the immediate post-operative period. | Pain score was recorded at 24 hours following the completion of surgery using a Visual Analogue Score (using a scale of 1 \[no pain\] to 10 \[very severe pain\]) which the patient was asked to record. |
Participant flow
Recruitment details
Patient recruitment occurred between 1.1.2003 and 31.12.2006. A total of 74 patients were recruited. All patients were followed up until 1.6.2010.
Pre-assignment details
All 74 patients who were enrolled in the trial were followed up until 1.6.10 (unless they died prior to this date).
Participants by arm
| Arm | Count |
|---|---|
| Groin Dissection: Sealant Used. All infrainguinal nodes, including Cloquet's node, were removed in all groin dissection cases. Routine peri-operative antibiotic prophylaxis was used. Diathermy and ligating clips were used as required and the wound bed irrigated with sterile water prior to closure. Closed suction drains were inserted and secured with drain sutures. 4 ml of Tisseel fibrin sealant (containing 1000 IU of human thrombin as the 'fast-set' preparation) were instilled into the wound using the Duploject™ spray delivery system. Firm pressure was applied to the wound for three minutes whilst the sealant set in order to obliterate the dead space, following which the skin was closed in two layers using absorbable sutures and the drains were vacuumed. A dry dressing was applied. | 18 |
| Groin Dissection: no Sealant Used. All infrainguinal nodes, including Cloquet's node, were removed in groin dissection cases. Routine peri-operative antibiotic prophylaxis was used. Diathermy and ligating clips were used as required and the wound bed irrigated with sterile water prior to closure. Closed suction drains were inserted and secured with drain sutures. No Tisseel fibrin sealant was instilled into the wound. The skin was closed in two layers using absorbable sutures and the drains were vacuumed. A dry dressing was applied. | 20 |
| Axillary Dissection: Sealant Used. A level I to III nodal clearance was performed in axillary dissection cases. Routine peri-operative antibiotic prophylaxis was used. Diathermy and ligating clips were used as required and the wound bed irrigated with sterile water prior to closure. Closed suction drains were inserted and secured with drain sutures. 4 ml of Tisseel fibrin sealant (containing 1000 IU of human thrombin as the 'fast-set' preparation) were instilled into the wound using the Duploject™ spray delivery system. Firm pressure was applied to the wound for three minutes whilst the sealant set in order to obliterate the dead space, following which the skin was closed in two layers using absorbable sutures and the drains were vacuumed. A dry dressing was applied. | 18 |
| Axillary Dissection: no Sealant Used. A level I to III nodal clearance was performed in axillary dissection cases. Routine peri-operative antibiotic prophylaxis was used. Diathermy and ligating clips were used as required and the wound bed irrigated with sterile water prior to closure. Closed suction drains were inserted and secured with drain sutures. No Tisseel fibrin sealant was instilled into the wound. The skin was closed in two layers using absorbable sutures and the drains were vacuumed. A dry dressing was applied. | 18 |
| Total | 74 |
Baseline characteristics
| Characteristic | Groin Dissection: no Sealant Used. | Axillary Dissection: Sealant Used. | Groin Dissection: Sealant Used. | Axillary Dissection: no Sealant Used. | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 8 Participants | 6 Participants | 2 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 10 Participants | 12 Participants | 16 Participants | 51 Participants |
| Age Continuous | 58.2 years STANDARD_DEVIATION 18.1 | 64.7 years STANDARD_DEVIATION 18.4 | 57.3 years STANDARD_DEVIATION 17.9 | 57.3 years STANDARD_DEVIATION 14.2 | 58.1 years STANDARD_DEVIATION 17.1 |
| Region of Enrollment United Kingdom | 20 participants | 18 participants | 18 participants | 18 participants | 74 participants |
| Sex: Female, Male Female | 13 Participants | 7 Participants | 9 Participants | 6 Participants | 35 Participants |
| Sex: Female, Male Male | 7 Participants | 11 Participants | 9 Participants | 12 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 20 | 0 / 18 | 0 / 18 |
| serious Total, serious adverse events | 10 / 18 | 12 / 20 | 9 / 18 | 9 / 18 |
Outcome results
Primary
Post-operative Wound Drainage.
The postoperative wound drainage volume was measured from the day of surgery until the the date of removal of the last wound drain.
Time frame: From date of surgery to date of wound drain removal (typically a period of approximately one week).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Groin Dissection: Sealant Used. | Post-operative Wound Drainage. | 892.5 ml |
| Groin Dissection: no Sealant Used. | Post-operative Wound Drainage. | 762.5 ml |
| Axillary Dissection: Sealant Used. | Post-operative Wound Drainage. | 565 ml |
| Axillary Dissection: no Sealant Used. | Post-operative Wound Drainage. | 590 ml |
p-value: 0.704t-test, 2 sided
p-value: 0.217t-test, 2 sided
Secondary
Death.
Death was recorded as the number of participants who had died by the end of the study follow-up period (1st June 2010). Deaths were recorded as either being related to the primary disease (i.e. due to distant metastasis) or death due to another (unrelated) cause (e.g. myocardial infarction or cerebrovascular accident).
Time frame: From day of surgery until end of study follow-up period (1st June 2010)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Groin Dissection: Sealant Used. | Death. | 10 Participants. |
| Groin Dissection: no Sealant Used. | Death. | 12 Participants. |
| Axillary Dissection: Sealant Used. | Death. | 9 Participants. |
| Axillary Dissection: no Sealant Used. | Death. | 9 Participants. |
Comparison: Death from metastatic disease in the groin cohort.p-value: 0.96395% CI: [0.4, 2.58]Regression, Cox
Comparison: Death from an unrelated cause in the groin cohort.p-value: 0.33895% CI: [0.03, 3.2]Regression, Cox
Comparison: Death from metastatic disease in the axillary cohort.p-value: 0.8895% CI: [0.35, 2.47]Regression, Cox
Comparison: Death from an unrelated cause in the axillary cohort.p-value: 0.92395% CI: [0.05, 13.95]Regression, Cox
Secondary
Disease Recurrence.
This was measured as either: 1. the number of participants with local recurrence; 2. the number of participants with in transit or regional recurrence; or 3. the number of participants with distant metastasis (but alive on 1st June 2010).
Time frame: From date of surgery until end of study follow-up period (1st June 2010)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Groin Dissection: Sealant Used. | Disease Recurrence. | 11 Participants. |
| Groin Dissection: no Sealant Used. | Disease Recurrence. | 6 Participants. |
| Axillary Dissection: Sealant Used. | Disease Recurrence. | 5 Participants. |
| Axillary Dissection: no Sealant Used. | Disease Recurrence. | 8 Participants. |
Comparison: Local recurrence in the groin cohort.p-value: 1Fisher Exact
Comparison: In transit or regional recurrence in the groin cohort.p-value: 0.301Fisher Exact
Comparison: Distant metastasis in the groin cohort (with the patient being alive at the end of the study follow-up period on 1.6.10).p-value: 0.474Fisher Exact
Comparison: Local recurrence in the groin cohort.p-value: 0.606Fisher Exact
Comparison: In transit or regional recurrence in the axillary cohort.p-value: 1Fisher Exact
Comparison: Distant metastasis in the axillary cohort (with the patient being alive at the end of the study follow-up period on 1.6.10).p-value: 0.486Fisher Exact
Secondary
Length of Hospital Inpatient Stay.
The length of hospital stay was calculated from the day of surgery to the day that the patient was discharged from hospital.
Time frame: From date of surgery until date of discharge from hospital.
Population: As the length of hospital stay was affected by numerous factors other than those related to the surgery itself (e.g. the patient's social circumstances), the results for this secondary outcome measure have not been presented.
Secondary
Length of Time Drains Remain in Situ.
The duration of postoperative wound drainage was measured from the day of surgery until the the date of removal of the last wound drain.
Time frame: From date of surgery until date of wound drain removal.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Groin Dissection: Sealant Used. | Length of Time Drains Remain in Situ. | 7 Days |
| Groin Dissection: no Sealant Used. | Length of Time Drains Remain in Situ. | 7.5 Days |
| Axillary Dissection: Sealant Used. | Length of Time Drains Remain in Situ. | 7.5 Days |
| Axillary Dissection: no Sealant Used. | Length of Time Drains Remain in Situ. | 9 Days |
p-value: 0.988t-test, 2 sided
p-value: 0.426t-test, 2 sided
Secondary
Number of Patients With Post-operative Complications (Excluding Lymphoedema).
Complications were classified as being either 'Minor' (i.e. (managed without operation, prolonged hospital stay or readmission) or 'Major' (i.e. requiring surgical intervention or readmission to hospital). The number of patients with each 'Minor' and 'Major' complication were recorded.
Time frame: Until wound healing complete.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Groin Dissection: Sealant Used. | Number of Patients With Post-operative Complications (Excluding Lymphoedema). | 12 Participants |
| Groin Dissection: no Sealant Used. | Number of Patients With Post-operative Complications (Excluding Lymphoedema). | 16 Participants |
| Axillary Dissection: Sealant Used. | Number of Patients With Post-operative Complications (Excluding Lymphoedema). | 13 Participants |
| Axillary Dissection: no Sealant Used. | Number of Patients With Post-operative Complications (Excluding Lymphoedema). | 12 Participants |
p-value: 0.351Fisher Exact
p-value: 0.48Fisher Exact
Secondary
Post Operative Pain Score Measured on 1st Post-operative Day.
Pain score was recorded at 24 hours following the completion of surgery using a Visual Analogue Score (using a scale of 1 \[no pain\] to 10 \[very severe pain\]) which the patient was asked to record.
Time frame: During the immediate post-operative period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Groin Dissection: Sealant Used. | Post Operative Pain Score Measured on 1st Post-operative Day. | 1 Units on a scale. |
| Groin Dissection: no Sealant Used. | Post Operative Pain Score Measured on 1st Post-operative Day. | 2 Units on a scale. |
| Axillary Dissection: Sealant Used. | Post Operative Pain Score Measured on 1st Post-operative Day. | 2 Units on a scale. |
| Axillary Dissection: no Sealant Used. | Post Operative Pain Score Measured on 1st Post-operative Day. | 2 Units on a scale. |
p-value: 0.002Wilcoxon (Mann-Whitney)
p-value: 0.4Wilcoxon (Mann-Whitney)