Minimally invasive surgery may result in lower peak levels of circulating vascular endothelial growth factor.

BACKGROUND: Angiogenesis is felt to be a factor in the establishment and progression of cancer and cancer metastasis. Vascular endothelial growth factor (VEGF) is one of the most powerful stimulants of tumor angiogenesis identified. VEGF levels can be affected by physiologic stimuli and measured systemically.
METHODS: Circulating VEGF levels were measured immediately before and after laparoscopic colon surgery in 10 unselected sequential patients with a diagnosis requiring surgical intervention for colon pathology.
RESULTS: Preoperative VEGF ranged from 31.3 pcg/cc to 187 pcg/cc. Postoperative VEGF ranged from 45 pcg/cc to 2228 pcg/cc. Factors of age, weight, diagnosis, length of cumulative skin incisions, and the receipt of preoperative blood products were considered. Data were compared by t test and regression analysis. Although several patients showed variability, some pronounced, in their pre- and postoperative levels, no 1 factor reached statistical significance as the cause of this variability. Utilizing regression analysis, however, considering only those patients in whom a diagnosis of cancer existed and who received blood products, the length of the incision alone accounted for an R2 change of 0.471. That is, in this subset of patients, incision size alone accounted for almost half of the variability in VEGF.
CONCLUSION: The data suggest a possible link between incision size in colon surgery and levels of VEGF. The sample size was insufficient for statistical significance. The study also does not answer whether a systemic release of VEGF at the time of surgery adversely affects the clinical outcome in cases of colon cancer. The data do warrant further investigation with a larger sample size and clinical follow-up.

INTRODUCTION

Recent work in cancer biology has focused on angiogenesis.[1] Although micrometastasis may remain viable in a dormant state for some time, ingrowth of a blood supply may be necessary for a focus of cells to become a growing, detectable, clinically evident metastasis. Vascular endothelial growth factor (VEGF) is, in vitro, an extraordinarily potent stimulator of tumor angiogenesis. It may represent one of the significant factors responsible for the progression of disseminated micrometastasis into stage 4 cancers.

Levels of VEGF have been shown to be elevated after open colon surgery.[2,3] We compare the levels of VEGF of an unselected group of patients in whom laparoscopic colorectal surgery was performed with those published for a group of patients who had open colon surgery[2] and consider the therapeutic implications.[2,3]

METHODS

Over a 2-month period, all patients (N=10) who were to undergo colon surgery had peripheral blood drawn within 1 hour prior to surgery and 1 postoperatively. Specimens were submitted to an off-site laboratory (Quest Diagnostics, Nichol's Institute, San Juan Capistrano, California) for analysis of levels of vascular endothelial growth factor (VEGF) determined by using the ELISA kit (Quantikine, R&D Systems, Minneapolis, Minnesota). All patients were considered for and started with a laparoscopic or laparoscopically assisted approach. Patient data that were considered included: age, weight, diagnosis (including cancer stage, where applicable), the combined size of all the cutaneous incisions (including trocar sites), and whether perioperative transfusions were received.

RESULTS

Pre-operative VEGF ranged from 31.3 pcg/cc to 187 pcg/cc (). Postoperative VEGF ranged from 45 pcg/cc to 2228 pcg/cc. The pre- and postoperative difference ranged from −6 pcg/cc to 2197 pcg/cc (mean 241, median 24.5). Factors of age, weight, diagnosis, cumulative length of skin incisions, and the receipt of preoperative blood products were considered. Data were compared by t test and regression analysis.

Although several patients showed variability, some pronounced, in their pre- and postoperative levels, no 1 factor reached statistical significance as the cause of this variability. Utilizing regression analysis to compare the effects of different variables, it was determined that those patients in whom a diagnosis of cancer existed and who received blood products, the length of the incision alone accounted for an R2 change of 0.471. That is, in this subset of patients, incision size alone accounted for almost half of the variability in VEGF.

DISCUSSION

The data suggest a possible link between incision size in colon surgery and levels of VEGF. Circulating levels of VEGF have recently been shown to be increased in the early postoperative period in patients undergoing colon cancer surgery via the open technique[4] ().

In our group of patients in whom laparoscopic surgery was undertaken, the sample size was insufficient for statistical significance. The study also does not answer whether a systemic release of VEGF at the time of surgery adversely affects the clinical outcome in cases of colon cancer.

A link may exist between the degree of physiologic insult and a short-lived trophic effect on occult micrometastasis that could be reflected in the long-term clinical outcome[4,5] of Stage III patients primarily and that may have implications in choosing between open vs. minimally invasive surgery. The data do warrant further investigation with a larger sample size and clinical follow-up.

Table 1.

Vascular Endothelial Growth Factor (VEGF) Data*

Patient	Age	Procedure	Incision Size (cm)	Diagnosis	VEGF (pg/mL )†Pre/Post
193	76	LARR Status post 6 U FFP	14+Trocars (2.7)	CA B1	lt;31.3/2228
136	77	RC	5+Trocars (2.7)	VA	34/76
140	77	LARR	14+Trocars (2.7)	CA+Obstruction	<313/55
100	85	LARR	8.5	PR	?/148
165	72	HP + midline incision	20 including stoma	Stricture/Obstruction	<31.3/47
236	62	RSF	11	CA B2	31.3/56
174	49	Colotomy	11	FB of rectum	86/121
153‡	72	RVC	8	Status post obstruction	<31/104
145	72	Sigmoid Resection	7.5	PD w/abscess	49/53
193	58	RC Status post 4 U PRBC Walled-off perforated cecum	18	CA stage IV	187/173
149	77	RC Status post 2 U PRBC	12	CA stage C	45/45

CA: Cancer; FB: Foreign body; FFP: Fresh frozen plasma; HP: Hartmann procedure; LARR: Low anterior resection of rectum; PD: Perforated diverticulum; PR: Prolapsed rectum; PRBC: packed red blood cells; RC: Right colectomy; RSF: Resection of splenic flexure; RVC: Reversal of colostomy; VA: Villous adenoma.

VEGF preoperative range: 31-86 pg/mL.

Platelets preop: 318; platelets postop: 308.

Table 2.

Data From Rocca[2] et al

Patients	Platelets (pg/106)	Duke's Stage
Male: 22	Preoperative: 1.32	A: 1
Female: 8	Postoperative day 2: 1.61	B: 12
Median age: 62	Postoperative day 3: 2.43	C: 11
		D: 6