Tumour growth stimulation after partial hepatectomy can be reduced by treatment with tumour necrosis factor α

Slooter, Gerrit D.; Marquet, R. L.; Jeekel, J.; Ijzermans, J. N. M.

doi:10.1002/bjs.1800820144

Cited by 67 publications

(45 citation statements)

References 26 publications

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“…Chemotherapy was continued after each hepatectomy; this was because the growth factors involved in the hypertrophy of the remnant liver induced by the first resection can also boost the growth of the tumor tissue left in place. This phenomenon has been described after liver resection [17][18][19] and after portal embolization 20 and might be amplified by repeat surgeries. 21 Nevertheless, because regeneration is essential to the feasibility of the second-stage resection, an interval of 3 weeks was observed after each hepatectomy to minimize the inhibition of antitumor drugs on liver regeneration.…”

Section: Discussionmentioning

confidence: 91%

Two-Stage Hepatectomy: A Planned Strategy to Treat Irresectable Liver Tumors

et al. 2000

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ObjectiveTo assess feasibility, risks, and patient outcomes in the treatment of colorectal metastases with two-stage hepatectomy. Summary Background DataSome patients with multiple hepatic colorectal metastases are not candidates for a complete resection by a single hepatectomy, even when downstaged by chemotherapy, after portal embolization, or combined with a locally destructive technique. In two-stage hepatectomy, the highest possible number of tumors is resected in a first, noncurative intervention, and the remaining tumors are resected after a period of liver regeneration. In selected patients with irresectable multiple metastases not amenable to a single hepatectomy procedure, two-stage hepatectomy might offer a chance of long-term remission. MethodsOf consecutive patients with conventionally irresectable colorectal metastases treated by chemotherapy, 16 of 398 (4%) became eligible for curative two-stage hepatectomy combined with chemotherapy and adjuvant nonsurgical interventions as indicated. ResultsTwo-stage hepatectomy was feasible in 13 of 16 patients (81%). There were no surgical deaths. The postoperative death rate (2 months or less) was 0% for the first-stage procedure and 15% for the second-stage one. Postoperative complication rates were 31% and 45%, respectively, with only one complication leading to reoperation. The 3-year survival rate was 35%, with four patients (31%) disease-free at 7, 22, 36, and 54 months. Median survival was 31 months from the second hepatectomy and 44 months from the diagnosis of metastases. ConclusionsTwo-stage hepatectomy combined with chemotherapy may allow a long-term remission in selected patients with irresectable multiple metastases and increases the proportion of patients with resectable disease.Liver resection is the only treatment known to provide long-term survival and the possibility of cure in patients with liver metastases. [1][2][3][4][5][6] However, at the time of diagnosis, most patients have irresectable tumors. Systemic chemotherapy, the current standard treatment, offers these patients a limited benefit, with median survivals not exceeding 12 to 18 months. [7][8][9][10] We combine chemotherapy with other therapeutic modalities and offer resection to patients who respond in such a way that surgery again becomes an option.In patients whose initially irresectable metastases are downstaged by neoadjuvant chemotherapy, one-stage resection provides a survival rate similar to that of patients undergoing primary resection. 11 We have also shown that cryosurgery and portal embolization can increase the resectability rate in patients with colorectal metastases. 12,13 In patients with intrahepatic multinodular diffusion of tumor, however, even with these techniques, it is not always possible to perform a resection that would be curative. An incomplete resection is not indicated because there is no significant survival benefit compared with patients who do not undergo surgery.14 We proposed to modify this practice by using a strategy whose overall intention is cu...

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Section: Discussionmentioning

confidence: 91%

Two-Stage Hepatectomy: A Planned Strategy to Treat Irresectable Liver Tumors

et al. 2000

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“…Surgical treatment is the only curative option available for patients. Previous studies suggest that removal of the primary tumour can be associated with an enhanced tumour growth of residual micro-metastases (1). Experimental animal data show that metastatic growth after liver resection is significantly accelerated in the course of hepatic regeneration (2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Increased growth factor expression after hepatic and pancreatic resection

Justinger

Schlüter²,

Oliviera-Frick³

et al. 1994

Oncol Rep

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Abstract. Removal of the primary tumour is suggested to associate with an enhanced tumour growth of residual micrometastases. Recent data focus on growth factors that may be released in response to surgery-stimulating receptors of residual tumour cells. Vascular endothelial (VEGF) and hepatocyte growth factor (HGF) are potent inducers of angiogenesis. The two factors are necessary for wound healing and the promotion of tumour growth. This study was designed to determine growth factor serum levels in patients before, during and after major abdominal surgery. It was recently shown that simultaneous hepatic and pancreatic resection led to poor liver regeneration. As growth factors may be involved in these findings we compared the growth factor levels after liver resection with the levels in patients after pancreatic resection. Forty patients were accrued before hepatopancreatic surgery (hepatic resection n=20 and pancreatic resection n=20). Blood samples were taken from each patient immediately prior to surgery, during the operation and on the postoperative days (POD) 1-3, 5 and 10. To examine the wound fluid, liquid from the wound drains was collected on POD 3. Using ELISA the concentration of the angiogenic cytokines HGF and VEGF 165 was determined. After the liver and pancreatic resections, circulating HGF and VEGF 165 were increased. We found significantly higher levels of HGF on POD 1-3 (p<0.01), compared to preoperative results with a peak on POD 2. After measuring the postoperative VEGF 165 levels we found significantly higher levels of circulating VEGF 165 on POD 1-5 (p<0.01) compared to the preoperative levels. On comparing liver with pancreatic resection we did not detect significantly different levels of the two growth factors in the two groups. VEGF 165 and HGF concentrations measured during the operation demonstrated no change. HGF and VEGF 165 levels detected in the wound fluid on POD 3 were ~10 times higher than the preoperative serum levels, respectively. In summary, our data show increased VEGF 165 and HGF levels after hepatopancreatic surgery. Notably, the lack of an impact of the type of organ resection on the concentration-time curve of the two growth factors suggest that high postoperative growth factor levels are part of normal wound healing and systemic inflammation. Thus, the proangiogenetic potential of growth factors may account for accelerated tumour growth when residual tumour cells are exposed to high levels of VEGF 165 and HGF.

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“…Part of the explanation is, perhaps, that a single liver lobe resection is a relatively minor procedure in the rat, although Slooter et al (1995) reported that resection of the left lateral lobe was enough to produce enhancement of tumour growth in the liver. Nevertheless, these findings indicate that the immunosuppressive effects of surgery or the release of growth factors was not the main factor for the increased extrahepatic spread after resection compared with laser thermotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…These unwanted effects of surgery may be caused, at least partly, by immunosuppression and by the release of growth factors involved in tissue healing (Eggermont et al, 1987;Loizidou et al, 1991;Panis et al, 1992;Pollock et al, 1992;Dingemans et al, 1993;Oka et al, 1994;Slooter et al, 1995). One of the advantages of local tissue destruction is that the trauma is small compared with surgery.…”

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confidence: 99%

Comparison between interstitial laser thermotherapy and excision of an adenocarcinoma transplanted into rat liver

Möller

Ivarsson²,

Stenram³

et al. 1998

Br J Cancer

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Summary The aim of this study was to compare interstitial laser thermotherapy with excision of a liver tumour. A dimethylhydrazine-induced adenocarcinoma was transplanted (implanted if not stated otherwise) into the left lateral lobe of the rat liver, and treatment was performed 8 days later. In the main experiment, rats were treated with resection of the tumour-bearing lobe or underwent interstitial laser thermotherapy, which was performed at a steady-state temperature of 460C for 30 min, 3 mm from the tumour margin. The incidence and extent of intraperitoneal spread was smaller after laser thermotherapy than after resection of the tumour-bearing lobe, with no difference in local control. Metastatic spread after resection of the median liver lobe was similar to that observed after sham procedures for thermotherapy or resection, suggesting that the advantage of thermotherapy was not due to a difference in surgical trauma. Additional studies showed that laser thermotherapy reduced intraperitoneal spread when treatment was suboptimal or in a tumour inoculation model and suggested that immunological mechanisms might be involved. It is concluded that interstitial laser thermotherapy reduces spread of liver tumour compared with resection.

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Tumour growth stimulation after partial hepatectomy can be reduced by treatment with tumour necrosis factor α

Cited by 67 publications

References 26 publications

Two-Stage Hepatectomy: A Planned Strategy to Treat Irresectable Liver Tumors

Two-Stage Hepatectomy: A Planned Strategy to Treat Irresectable Liver Tumors

Increased growth factor expression after hepatic and pancreatic resection

Comparison between interstitial laser thermotherapy and excision of an adenocarcinoma transplanted into rat liver

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