We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Article |

Systemic Leakage and Side Effects of Tumor Necrosis Factor α Administered Via Isolated Limb Perfusion Can Be Manipulated by Flow Rate Adjustment

Patrik Sorkin, MD; Subhi Abu-Abid, MD; Dina Lev, MD; Mordechai Gutman, MD; Dan Aderka, MD; Pinhas Halpern, MD; Aric Setton, MD; Nahman Kudlik, MSc; Jack Bar-On, MSc; Valery Rudich, MD; Isaak Meller, MD; Joseph M. Klausner, MD
Arch Surg. 1995;130(10):1079-1084. doi:10.1001/archsurg.1995.01430100057012.
Text Size: A A A
Published online


Background:  The tolerated systemic dose of recombinant tumor necrosis factor α (rTNF-α) is very limited, since its administration leads to a severe septic shock—like condition. Its implementation in isolated limb perfusion (ILP) for metastatic melanoma or advanced soft-tissue sarcoma confined to the limb facilitates doses of rTNF-α 10 times higher than the systemic tolerated dose. However, with the traditional high flow rate used in ILP, systemic leakage and side effects are not eliminated.

Objective:  To determine if a lower perfusion flow rate would reduce leakage and consequently toxic effects.

Methods:  Isolated limb perfusion was performed for melanoma and soft-tissue sarcoma confined to the limb using a flow rate of 869 ±122 mL/min in nine patients (group 1) and a lower rate of 286±62 mL/min in six patients (group 2).

Results:  The systemic leakage rate was 12.5%±2.9% in group 1, compared with 2.3%±1.0% in group 2 (P=.003). Peak TNF-α levels were 29 000±2700 pg/mL in group 1, higher than 1580±1355 pg/mL in group 2 (P=.02). The tachycardia, hypotension, increased cardiac output, decreased systemic vascular resistance, bilirubinemia, elevation of liver enzyme levels, hypocholestrolemia, thrombocytopenia, and prolongation of prothrombin and partial thromboplastin times all observed in group 1 were significantly attenuated or eliminated in group 2. The limb Po2, Pco2, pH, and viability remained similar in both groups. Also, the tumor response rate remained high and was unaffected by the decrease in flow rate.

Conclusions:  Decreasing perfusion flow rate during ILP results in diminished leakage of TNF-α Consequently, the systemic hemodynamic, metabolic, and hematologic toxic effects are virtually abolished.(Arch Surg. 1995;130:1079-1084)


Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?





Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.