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Laparoscopy and tumour growth: a clinical and experimental study
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background and aims: Laparoscopic technique was quickly adopted in general surgery because of less pain, quicker recovery and shorter hospital stay. In the 1990´s several reports on port site metastases restrained the enthusiasm to use laparoscopic surgery in malignant diseases. The numerous reports on port site metastases initiated a debate whether laparoscopic surgery would increase the risk of tumour spread and growth. Personal experience of two patients who devloped port site metastases from an incidental gall bladder cancer (GBC) after laparoscopic cholecystectomy (LC), encouraged us to study the incidence of wound metastases from GBC after laparoscopic and open cholecystectomy (OC). Experimentally we examined whether pneumoperitoneum would increase the risk of tumour development. Several studies had demonstrated that minimally invasive procedures exert a less negative influence on the immune system and may have beneficial effects for cancer patients. We wanted to compare the long term survival after OC and LC and if the occurence of port site metastases had any impact on survival.

Material and methods: A questionnaire was sent out to all major hospitals in Sweden requesting information obout the number of port site metastases encountered 1991-94. Data on all pateints with verfied GBC were obtained from the Swedish Oncological Centres. Data on all patients with GBC registered with surgical codes for cholecystectomy were collected from the National Board of Health and Welfare (EpC). The patient files were scrutinized and long term survival data was achieved (EpC). In the first experiment on Wistar Fu rats, adenocarcinoma cells were injected intraperitoneally in animals insufflated with air, CO2 and not insufflated controls. In the following studies, rats were similarly insufflated with air,CO2 and compared to not insufflated controls. Laser Doppler blood flow in the abdominal wall was concomitantly measured. To study the effect of reduced blood flow, one rectus muscle was clamped and the other not and laser Doppler Blood flow was measured in both rectus muscles. Adenocarcinoma cells were injected into the rectus muscles in all animals at the induction of pneumoperitoneum/clamping.

Results: 14 of 55 patients developed wound metastases from GBC after LC and 12 of 187 after OC. Gallbladder perforation was overrepresented in patients with wound metastases. Improved survival was noted after LC in patients with T3 tumours. Experimentally, air and CO2 equally increased intraperitoneal tumour development, Insufflation with air,CO2 and clamping decreased blood flow in the abdominal wall and increased tumour growth at the same site.

Conclusion: Despite a high rate of wound metastases, LC does not seem to worsen the prognosis of GBC and may even have a positive effect on survival. Perforation of the malignant gallbladder seems to be associated with an increased risk of metastatic formation. In the experimental setting, pneumoperitoneum seems to increase tumour development. Other features of laparoscopic surgery such as decreased blood flow in the abdominal wall may contribute to increased risk of tumour progress.

Place, publisher, year, edition, pages
2004. , 138 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 889
Keyword [en]
Surgery, laparoscopy, tumour growth, metastases, gallbladder cancer, pneumoperitoneum, blood flow
Keyword [sv]
Kirurgi
National Category
Surgery
Research subject
Surgery
Identifiers
URN: urn:nbn:se:umu:diva-227ISBN: 91-7305-613-8 (print)OAI: oai:DiVA.org:umu-227DiVA: diva2:142744
Public defence
2004-05-14, sal B, 9 tr, Tandläkarhögskolan, Umeå Universitetssjukhus, Umeå, 13:00
Opponent
Supervisors
Available from: 2004-04-08 Created: 2004-04-08 Last updated: 2010-08-06Bibliographically approved
List of papers
1. Port site metastases from gallbladder cancer after laparoscopic cholecystectomy.: Results of a Swedish survey and review of published reports.
Open this publication in new window or tab >>Port site metastases from gallbladder cancer after laparoscopic cholecystectomy.: Results of a Swedish survey and review of published reports.
1999 (English)In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 165, no 3, 215-222 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate the incidence of port site metastases from unsuspected gallbladder cancer after laparoscopic cholecystectomy. DESIGN: Retrospective national multicentre study, 1991-94. SETTING: All 8 university and 24 central hospital, Sweden. SUBJECTS AND INTERVENTIONS: All 32 hospitals were interviewed by means of a written questionnaire. The registers of all Swedish Oncological Centres and the registers of the National Board of Health and Welfare were checked for reported cases of gallbladder cancer and surgical classification codes for cholecystectomy. To detect laparoscopic interventions incorrectly registered as open operations, all cholecystectomies registered as open were matched against the Swedish Registry of Laparoscopic Cholecystectomy for the years 1991-93 and all patients records for 1994 were scrutinised. RESULTS: Replies were obtained from 30/32 clinics (94%) and 11976 laparoscopic cholecystectomies were done. Of 447 patients with verified gallbladder carcinoma 270 had their gallbladders removed, 55 (20%) laparoscopically. 9 of these (16%) developed port site metastases and 6 died from their disease at a median of 18 months (range 5-22). Two patients are alive, 54 and 45 months after cholecystectomy. One patient has been lost to follow-up. CONCLUSIONS: Port site metastases from gallbladder cancer may be more common than previously thought. A laparoscopic procedure should not be done if cancer of the gallbladder is suspected.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-3853 (URN)10.1080/110241599750007072 (DOI)10231654 (PubMedID)
Available from: 2004-04-08 Created: 2004-04-08 Last updated: 2017-12-14Bibliographically approved
2. Wound recurrences from gallbladder cancer after open cholecystectomy
Open this publication in new window or tab >>Wound recurrences from gallbladder cancer after open cholecystectomy
2000 (English)In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 127, no 3, 296-300 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Reports of port site recurrences from gallbladder cancer after laparoscopic cholecystectomy have raised considerable concern as to whether the laparoscopic technique implies an increased risk of metastatic disease. In a previous study of gallbladder cancer and laparoscopic cholecystectomy, we reported a frequency of 16% port site metastases. The purpose of the present study was to determine the frequency of wound metastases from gallbladder cancer after open cholecystectomy. METHODS: The registers from the Swedish Oncological Centers and the National Board of Health and Welfare were checked for reported cases of gallbladder cancer and surgical classification codes for open cholecystectomy from 1991 to 1994. The study included all 8 university and 24 county hospitals in Sweden. The files from all patients with gallbladder cancer who had an open cholecystectomy were retrospectively reviewed. RESULTS: The study included 270 patients who had a cholecystectomy, of which 215 were classified as open and 55 as laparoscopic. Of the 215 patients, 11 patients were excluded because of an incorrect or deficient histopathologic or surgical classification. In 186 patients (91%), sufficient data were obtained for follow-up. Twelve patients (6.5%) had wound metastases from their gallbladder cancer. All patients with wound metastases died with a median survival of 10 months (range, 3 to 65 months). CONCLUSIONS: Wound metastases from gallbladder cancer after open cholecystectomy may be more common than previously assumed.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-3854 (URN)10.1067/msy.2000.104487 (DOI)10715985 (PubMedID)
Available from: 2004-04-08 Created: 2004-04-08 Last updated: 2017-12-14Bibliographically approved
3. Long term results after open and laparoscopic surgery for galbladder carcinoma.
Open this publication in new window or tab >>Long term results after open and laparoscopic surgery for galbladder carcinoma.
(English)Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:umu:diva-3855 (URN)
Available from: 2004-04-08 Created: 2004-04-08 Last updated: 2010-08-06Bibliographically approved
4. Effect of pneumoperitoneum induced by carbon dioxide and air on tumor load in a rat model.
Open this publication in new window or tab >>Effect of pneumoperitoneum induced by carbon dioxide and air on tumor load in a rat model.
1998 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 22, no 5, 470-472 p.Article in journal (Refereed) Published
Abstract [en]

Laparoscopic surgery for malignant disease is highly controversial mainly due to the large number of abdominal wall metastases being reported. Previous experimental studies have particularly studied CO2 pneumoperitoneum and its effect on tumor development. The purpose of this study was to compare CO2- and air-induced pneumoperitoneum with regard to intraperitoneal tumor growth. Altogether 39 rats were injected intraperitoneally with 10(5) colonic tumor cells and randomly allocated into three groups: 13 rats had a pneumoperitoneum created with CO2, 13 with air, and 13 served as controls. Tumor development was determined semiquantitatively by a peritoneal cancer index scale after 12 days. CO2 and air pneumoperitoneum equally increased intraperitoneal tumor growth compared to controls. Pneumoperitoneum induced by CO2 and air seems to increase tumor load, but the mechanisms are not established. This finding supports the hypothesis that insufflation not only by causing tumor cell movements but in fact pneumoperitoneum per se and the used gas are involved in the development of abdominal wall metastases after laparoscopic surgery.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-3856 (URN)10.1007/s002689900418 (DOI)9564290 (PubMedID)
Available from: 2004-04-08 Created: 2004-04-08 Last updated: 2017-12-14Bibliographically approved
5. Pneumoperitoneum impairs blood flow and augments tumor growth in the abdominal wall.
Open this publication in new window or tab >>Pneumoperitoneum impairs blood flow and augments tumor growth in the abdominal wall.
2004 (English)In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 18, no 2, 293-296 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Despite several clinical and experimental studies, the mechanisms behind the development of port site metastases in laparoscopic surgery have remained largely unknown. The current study was designed to investigate the effect of pneumoperitoneum on blood flow in the abdominal wall and its possible effects on tumor growth at this site. METHODS: A total of 40 Wistar Fu rats had a laser Doppler probe placed on their left rectus muscle and a suspension of 50,000 adenocarcinoma cells was injected into their right rectus muscle. The experimental group (n = 20) was insufflated with air at 10 mmHg for 45 min while abdominal blood flow was registered before and during insufflation and after exsufflation. The control group (n = 20) was not insufflated but the blood flow was recorded in the same manner. After 9 days, all animals were killed and the occurrence of tumor was observed. The tumors were analyzed with respect to weight and volume. RESULTS: The insufflation caused an 82% reduction in blood flow in the experimental group (p < 0.001). No reduction in blood flow was registered in the control group. Tumor nodules developed significantly more often in the insufflated group (20/20) compared to the controls (14/20) (p = 0.016). Tumor weight (p = 0.003) and volume (p < 0.001) were significantly increased in the insufflated group. CONCLUSIONS: Pneumoperitoneum seems to enhance tumor growth. It also causes a significant reduction in blood flow in the abdominal wall, which may contribute to the increased susceptibility of tumor take.

Keyword
Adenocarcinoma/*secondary, Air, Animals, Cell Line; Tumor, Humans, Injections; Intramuscular, Intraoperative Complications/*etiology, Ischemia/*etiology, Laser-Doppler Flowmetry, Neoplasm Seeding, Neoplasm Transplantation, Pneumoperitoneum; Artificial/*adverse effects, Rats, Rats; Inbred WF, Rectus Abdominis/*blood supply/pathology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-6004 (URN)10.1007/s00464-003-9035-7 (DOI)14691694 (PubMedID)
Available from: 2007-12-04 Created: 2007-12-04 Last updated: 2017-12-14Bibliographically approved
6. Reduction of abdominal wall blood flow by clamping or carbon dioxide insufflation increases tumor growth in the abdominal wall: an experimental study in rats.
Open this publication in new window or tab >>Reduction of abdominal wall blood flow by clamping or carbon dioxide insufflation increases tumor growth in the abdominal wall: an experimental study in rats.
2005 (English)In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 19, no 5, 720-723 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: We have previously demonstrated that there is a reduction of blood flow in the abdominal wall in rats insufflated with air concomitant with an increase in tumor growth. The present study was designed to examine whether a reduction of blood flow achieved by clamping or insufflation with carbon dioxide (CO(2)) would increase tumor growth in the abdominal wall. METHODS: In the first part of the experiments, laser Doppler blood flow of both rectus muscles was measured in 16 Wistar Fu rats. The left rectus muscle was clamped to reduce blood flow, and 5 x 10(4) adenocarcinoma cells were injected into both rectus muscles. Clamping was maintained for 45 min. In the second part, 22 rats had 5 x 10(4) adenocarcinoma cells injected into the rectus muscle and blood flow was measured. The experimental group (n = 11) was insufflated with CO(2) at 10 mmHg for 45 min; the control group (n = 11) was not insufflated. After 9 days, tumor weight and volume were analyzed. RESULTS: Clamping caused a 69% reduction of blood flow (p < 0.001), whereas no reduction was registered on the nonclamped side. Tumor weight (p = 0.028) and volume (p = 0.030) were increased on the clamped side. The insufflation of CO(2) caused a 71% reduction of blood flow, whereas no reduction was registered in the control group. Tumor weight (p = 0.006) and volume (p = 0.006) were increased in the insufflated group. CONCLUSION: Clamping, as well as CO(2) insufflation, causes a significant reduction of blood flow in the abdominal wall, which seems to increase tumor growth at the same site.

Keyword
Abdominal Neoplasms/*pathology, Abdominal Wall/*blood supply, Adenocarcinoma/*pathology, Animals, Carbon Dioxide/administration & dosage/*adverse effects, Constriction, Disease Progression, Injections; Intramuscular, Insufflation/adverse effects, Ischemia/*etiology, Laser-Doppler Flowmetry, Neoplasm Transplantation, Pneumoperitoneum; Artificial/*adverse effects, Pressure, Random Allocation, Rats, Rats; Inbred WF, Rectus Abdominis/*blood supply, Single-Blind Method, Tumor Burden
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-6039 (URN)10.1007/s00464-004-9061-0 (DOI)15798898 (PubMedID)
Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2017-12-14Bibliographically approved

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