Port-site metastasis following laparoscopic cholecystectomy:a review of the literature and a case report

European Journal of Surgical Oncology 2000; 26: 95–102

CASE REPORTS

Port-site metastasis following laparoscopic cholecystectomy: a review of the literature and a case report Yenumula P. Reddy and W. G. Sheridan Carmarthen and District N.H.S. Trust, West Wales General Hospital, Carmarthen SA31 2AF, UK

Port-site metastasis following laparoscopic cholecystectomy with unsuspected gallbladder carcinoma is a serious problem. We reviewed 45 such cases reported in the English literature to date, and add another case which occurred in a 72-year-old female 13 months after a laparoscopic cholecystectomy for gallstones, who also had an unapparent gallbladder carcinoma. Pre-operative diagnosis of gallbladder carcinoma is possible in less than 10% of cases, with a high index of suspicion. If detected during laparoscopy early conversion to open procedure is recommended. If diagnosed later, however, to contemplate further radical operation depending on histopathology would be unwise as a universal approach, because of increased associated morbidity and mortality. The prospect of cure is also very unrealistic in this condition. Key words: neoplasm metastasis; laparoscopic cholecystectomy; carcinoma; gallbladder.

Introduction Since the introduction of laparoscopic cholecystectomy by Phillipe Mouret in 1987,1 it has had explosive success worldwide and became the standard operation for gallstone disease. With more widespread adoption of the technique, the phenomenon of port-site metastasis from unsuspected gallbladder carcinoma has become evident. Gallbladder carcinoma is found in 1% of all biliary tract operations,2 in most being diagnosed only after histological examination of the gallbladder. The first case of port-site metastasis from unsuspected gallbladder carcinoma was reported by Drouard et al. in 1991.3 To date, 45 cases have been reported. We describe another case of a 72-year-old female developing metastases, in two port-sites, 13 and 14 months after laparoscopic cholecystectomy for unsuspected gallbladder carcinoma. Case report A 72-year-old female presented with symptoms of intermittent biliary colic which had persisted for 2 years. Ultrasound of the abdomen confirmed multiple gallstones in an otherwise normal gallbladder. Serum biochemistry showed slightly elevated liver enzymes with normal bilirubin. Pre-operative ERCP was normal. Laparoscopic cholecystectomy was carried out using a four-port technique and the intact gallbladder was delivered through the subumbilical port. Intraoperatively it was noticed that the gallbladder was somewhat thick-walled and adherent to the liver, resulting in a slightly difficult dissection. Although she made an uneventful recovery, histology of the gallbladder showed a welldifferentiated adenocarcinoma involving the serosa and adjacent lymph node (pT3). The patient received post-operative chemotherapy using five cycles of 5-flurouracil and folinic acid, and an abdominal computerized tomography (CT) scan 10 months

Correspondence to: Dr Y. P. Reddy, MS, F.R.C.S., 1650 Selwyn Avenue, Apartment 19H, Bronx, New York 10457, USA. E-mail: [email protected] 0748–7983/00/010095+08 $35.00/0

 2000 Harcourt Publishers Ltd

after the surgery was normal. However, 13 months post-operatively she presented with a hard nodule in one of the lateral ports, proven on FNAC to be a metastatic deposit from the gallbladder carcinoma. The nodule was widely excised but 2 months later she developed jaundice. On ultrasound examination the intrahepatic biliary radicles were dilated with coarse liver architecture. A hypoechoic nodule in the umbilical port-site was also detected, which on FNAC proved to be another metastatic deposit. ERCP showed a stricture in the common hepatic duct, which was stented. The patient died, however, 1 month later.

Review of the literature and discussion Even though the first laparoscopic cholecystectomy was carried out in 1987, the unusual complication of port-site metastasis was not reported until 1991. In a literature search using Medline we found 46 cases of port-site metastases published in the English language to date, including the present case (Table 1). It is expected that gallbladder cancer will be found in 1–2% of all biliary tract operations.24 A pre-operative diagnosis may be made in as few as 10% of cases.40 Hence, port-site metastases following laparoscopic cholecystectomy for unsuspected carcinoma is going to be a problem of some magnitude in the years to come. In the reported cases (Table 1), the age range is 40–90 years, with the highest incidence in the 7th and 8th decades and a female to male ratio of 4:1.6 These figures are consistent with the other published figures.41 In most of the cases only one port-site was involved, in six cases two and in three cases three. In 12 cases, including the present case, there were extensive intra-abdominal metastases. Johnson et al.38 reported axillary lymph-node metastasis associated with umbilical port-site metastasis. Port-site metastases were detected as early as 18 days after the surgery, on histological examination of excised port-sites during radical surgery.22 The longest interval for the development of metastases was 13 months, including the present case.33 In one case a metastasis developed with in-situ carcinoma, presumably due to spillage of bile.31 In five cases port-site metastases developed inspite of using a cellophane  2000 Harcourt Publishers Ltd

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Case reports Table 1. Port-site metastasis following laparoscopic cholecystectomy

Author

Year

Age

Sex

Interval

Number of implants

Follow-up

Gornish2 Drouard3 Barsorum4 Pazet5 Patraskeropoulos6 Fong7

1991 1991 1992 1992 1992 1993 1993 1993 1993 1993 1993 1993 1993 1993 1993 1994 1994 1994 1994 1994 1994 1994 1994 1994 1994 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1996 1996 1997 1997 1997 1997 1997 1998

53 58 73 58 — 67 60 66 40 62 49 61 71 88 73 59 65 61 64 — 69 62 41 59 65 72 69 — — 66 73 65 — 48 90 76 70 67 64 60 59 64 76 61 63 72

M M F F — F M F M F F F M F F F F F F — F F F F F F F — — F F F — F M F F M F F F F F F M F

4m 3m 3m 3m 4m 1m 24d 3m — 3w 3w — 8w 4m — 3w 3m — 10m — 6m 4w 14w 18d 3m 8m 3m — — 21/2m 2m 7m — 2m 3m 9m 6w 5m 13m 11m 3m 7m 2m 6w 12m 13

1 1 2 2 1 1+p 1+p 2 1 3 1 1+p 1+p 1 1 1 2 1 1 1+p — 3 1 1 1 1 1 1 1 2 2 1 1 1 1 1+p 1+p 1+p 1+p 3+p 1 2 1+p 1+a 1 2+p

— 4m, alive 6m, died 10m, died — 5m, died 6m, died — 8m, alive 3m, died — — died 6m, died — 17m, alive 10m, alive 6m, alive 18m, alive died 15m, died 8m, died — 11m, alive — 8m, died 11m, alive — — — — 16m, died — 1m 6m, died 10m, died — 7m, alive 13m, alive 18m, died — 18m, alive 6m, died 12m, died 22m, alive 16m, died

Clair8 Lucciriani9 O’Rourke10 Flingelstone11 Siriwaderna12 Walsh13 Landford14 Wade15 Targarona16,17 Johnson18 Nally19 Nduka20 Weiss21 Kim22 Ng23 Sandor24 Brooks25 Copher26 Jacobi27 Baer28 Norfleet29 John30 Wibbenmayer31 Sailor32 Shibata33 Cotlar34 Karayiannakis35 Lomis36 Razzetta37 Johnson38 Mori39 Reddy

m: months; w: weeks; d: days; p: intraabdominal carcinamatosis; a: axillary lymph node metastasis.

bag to retrieve the gallbladder.3233–34,37,38 In another case, a portsite metastasis developed from incidental pancreatic carcinoma following laparoscopic cholecystectomy.11 Jacobi et al.27 described port-site metastases in a case where the laparoscopic procedure had to be converted to an open procedure, due to technical reasons, although on subsequent laparotomy the previous laparotomy wound was free of metastasis. Sandor et al.24 reported a case where an umbilical port-site metastasis developed 3 months after previous laparoscopic cholecystectomy for unapparent carcinoma of the gallbladder. This metastasis was locally excised, but recurred 2 months later. Wide local excision and omentectomy was carried out, following which the patient was disease free for 11 months. The longest disease-free period following radical hepatic resection and excision of port-sites was 3 years.15 With a similar procedure another case was disease free at 11 months.22 Inspite of radical hepatic resection, one patient developed umbilical port-site metastases, as the port-sites were not resected. With chemotherapy, port-site metastasis regressed and the patient was disease free at 18 months.36 Other patients who had radiotherapy or chemotherapy,

or a combination of both, with or without excision of portsite metastases survived less than 10 months.2,3,5,8,10,21 Our patient survived for 16 months following post-operative chemotherapy. Wound metastasis following open cholecystectomy for unsuspected gallbladder carcinoma is very rare, but is more frequently encountered with the laparoscopic procedure. Moreover, the spread of cancer following laparoscopy appears aggressive and widespread, as noticed from re-operation for radical treatment.7 There is no proven explanation for this phenomenon. Various factors have been incriminated: pneumoperitoneum with carbon dioxide, high intra-abdominal pressure, laparoscopic instruments, surgical wounds from port-sites, implantation of cancer cells while extracting the gallbladder and depressed immunity. It is also possible that a lack of direct tactile sensation during the laparoscopic procedure results in the diagnosis being otherwise overlooked, until the histology is available, unlike during open cholecystectomy. Initially, it was thought that port-site metastasis may be due to extraction of the gallbladder through one of the ports, resulting in the implantation of cells locally. But this has been disproved by

Case reports the evidence of multiple port involvement and the metastases developing despite using a cellophane bag to retrieve the gallbladder.3233–34,37,38 Preferential localization of metastases to the port-sites but not to the laparotomy wound27 could be explained by implantation of tumour cells from the instruments, and turbulent gas flow, due to the gradient of pressure, mainly at the time of deflation of the pneumoperitoneum. This hypothesis has been further strengthened by laboratory research, which has shown that port-site metastases relate to the use of carbon dioxide and do not occur with gasless or open laparotomy.41 Aerosolization of tumour cells may promote diffuse peritoneal implantation, and release of pneumoperitoneum through trocar puncture sites may further inoculate tumour cells.20 Instrumentation causes exfoliation of tumour cells, which then adhere to the instruments in 40% of operative procedures, and may be the main source of dissemination of malignant cells through the peritoneal cavity.43 There is now a consensus that laparoscopic cholecystectomy is a contraindication in gallbladder carcinoma. In a large series of carcinoma of the gallbladder evaluated by laparoscopy, surgical removal was thought to be appropriate in only one of 98 cases.44 There is some evidence, from some specialized centres, that radical resection, including excision of port-sites, may prolong survival for locally advanced (pT2 or greater) lesions.15,22,24,45 To apply this approach universally is potentially dangerous, as this type of tumour has an appalling prognosis, and the prospect of all laparoscopic surgeons carrying out radial resections would be likely to result in more operative eaths than patients cured of the disease, with a great number of patients living their last few months hospitalized, with painful complications of this major surgery. In animal experiments, heparin and Gly–Arg–Asp–Ser(GRGDS) pentapeptide could inhibit peritoneal tumour-cell implantation.46 Further research using this model may reduce the problem of port-site metastasis following laparoscopic cancer surgery. Even though gasless laparoscopy has showed some promise in laboratory based studies,41 when it comes to practicality it has potentially dangerous implications. Difficult operations can be rendered more difficult by this technique as lifting the anterior abdominal causes lateral organs to be sucked inwards, reducing space and visibility, compared to insufflation which pushes all organs outwards and creates more room to see. Its universal use would probably cause more complications in the vast majority of patients, with non-malignant gallbladders, and in the 1% with malignant gallbladders it might change the site of implantation of malignant cells, possibly from the port-site to the peritoneal cavity.

3. 4. 5.

6.

7.

8.

9.

10. 11. 12.

13.

14. 15. 16.

17.

Conclusion

18.

Even though laparoscopic cholecystectomy is widely used in dealing with cholecystolithiasis, it is contraindicated in the presence of gallbladder malignancy. Evidence from the literature shows a high incidence of port-site metastases. The explanation for this phenomenon appears to be exfoliation and dissemination of tumour cells, due to instrumentation in the presence of positive intraabdominal pressure and aerosilozation of tumour cells which may promote diffuse peritoneal implantation. The release of pneumoperitoneum through trocar puncture sites may further inoculate tumour cells. Experiments using chemical agents that prevent nidation of exfoliated malignant cells may in the future provide an answer to this problem. Laparoscopic cholecystectomy should be promptly converted to an open procedure if there is suspicion of carcinoma of the gallbladder. Because of the appalling prognosis of this condition, and also the mortality and morbidity associated with the radical surgery if undertaken universally, it is unwise to contemplate radical surgery if it is later diagnosed.

19.

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Disappearing microcalcification after neoadjuvant chemotherapy—a case report A. Adwani∗, S. Lowe† and S. R. Ebbs∗ Breast Unit, Department of ∗Surgery and †Radiology, Mayday University Hospital, London Road, Croydon, Surrey CR7 7YE, UK

Key words: microcalcification; neoadjuvant chemotherapy.

Case report A 61-year-old post-menopausal female presented with a 6 cm mass in the upper outer quadrant of the left breast. She had no axillary lymphadenopathy. The contralateral breast and axilla was normal and there was no clinical evidence of distant metastases. Mammography showed a 4 cm irregular density with microcalcification in the upper outer quadrant of the left breast (Fig. 1). In addition there were small rounded axillary lymph nodes without fatty centres. Ultrasound revealed a 2 cm irregular soft tissue mass consistent with a carcinoma in the outer quadrant of

Correspondence to: Miss A. Adwani, Breast Unit, Department of Surgery, Mayday University Hospital, Croydon, Surrey CR7 7YE, UK.

 2000 Harcourt Publishers Ltd

the left breast and an 8 mm soft tissue lesion in the axilla. Fine needle aspiration cytology showed adenocarcinoma cells (C5) and core biopsy confirmed an invasive ductal carcinoma. Staging investigations showed no evidence of metastases. She underwent six courses of AC Chemotherapy (Adriamycin 60 mg/m2, Cyclophosphamide 600 mg/m2), which produced a partial response leaving vague thickening at the site of the previous lump. Mammography showed a reduction in the area of increased density with complete disappearance of the malignant microcalcification (Fig. 2). The previously noted lymph nodes were no longer visible. Ultrasound showed a 1.7 cm irregular soft tissue mass. An ultrasound guided localization biopsy was performed. Histology showed a grade 3 invasive duct carcinoma measuring 25 mm in maximum cross-sectional diameter with multiple foci of lymphatic invasion, which was completely excised. Occasional foci of high grade duct carcinoma in situ were present amidst the invasive tumour. There was no evidence of microcalcification.