Gallbladder cancer is an aggressive malignancy, with most patients presenting in stage III/IV disease. 5-year survival rate for stage 0 is 80%, stage I is 50%, stage III is 7% and stage IV is 4% or less [10]. The usual sites of metastasis are the liver followed by the peritoneum [7]. Z’graggen et al did a retrospective analysis of 10925 patients who underwent laparoscopic cholecystectomy; 37 of them had unsuspected gallbladder cancer. Out of these, 5 patients (14%) had port site metastasis of the cancer irrespective of the stage of the primary cancer [9]. Metastasis to extra abdominal distant organs is rare and lung is the most common organ [11]. Nevertheless, metastasis to the heart [12], isolated metastasis to the breast [11] and simultaneous breast and ovarian metastases [13] have been reported in literature. Laparoscopic port site recurrence of gallbladder cancer was first reported by Drouard et al [14] and Gornish et al, [15] independently, in the year 1991. A case of concurrent port site and axillary lymph node metastasis 12 weeks after laparoscopic cholecystectomy [16] and development of isolated unilateral axillary nodal metastasis 3–4 months after resection of abdominal port site metastatic recurrence have also been reported [6]. The evaluation of a patient with port site metastatic recurrence must be done meticulously. An attempt to retrieve records of the prior surgical procedure should be made. It is important to know the HPE report of the cholecystectomy specimen. Whether a protective bag or endo-bag was used during the procedure or not should be inquired for whenever possible. In the event of gallbladder rupture, the risk of seeding of the peritoneal cavity by tumour cells is increased [17]. During a laparoscopic cholecystectomy, if spillage occurs due to rupture of gallbladder when no protective bag is used, many surgeons will proceed with the resection of extraction port site/ all port sites when gallbladder carcinoma is suspected. On the contrary, this practice is not supported by literature [18, 19]. Zhu et al proposed that this procedure only provides staging information that may eventually help in prognosticating patients of the risk of recurrence and is therefore beneficial but not necessary [17].
Gallbladder carcinoma usually spreads by direct extension into the liver and porta, via locoregional lymph nodes, by peritoneal seeding and by haematogenous routes [20–25]. It has also been known that carcinoma of gallbladder can spread along nerves and via the biliary tract [24]. On very rare occasion, size of GB mass may not correlate with advanced disease, it can present as gigantic gallbladder mass with preserved planes. [26]
Possible mechanisms of spread of primary liver malignancy have been described in literature. The tumour which occupies the upper part of the right hepatic lobe may course through the lymphatic vessels to reach the lymph nodes on the upper surface of the diaphragm, mediastinal or parasternal lymph nodes [27, 28]. Malignant tumour cells may also spread from intercostal lymphatics to reach to the axillary lymph nodes. Other mechanisms of dissemination of tumour cells to the umbilicus include spread via a patent umbilical vein from portal venous channels; invasion of anterior peritoneum or by infiltration of the para-aortic glands [29]. The malignant cells may then drain from the subcutaneous lymphatic channels to the axillary lymph nodes [30].
Similar mechanisms of dissemination can be attributed for the spread of carcinoma gallbladder to the axillary nodes. The likelihood of spread of tumour from primary gallbladder cancer to the axilla by direct spread is extremely less. The more likely pathway for the spread of the tumour to the axilla is from the abdominal port site. However, it is more probable that the cause of abdominal port site metastasis is due to the systemic dissemination of the disease [9]. The axilla is a common draining site for many truncal malignancies, but gallbladder carcinoma usually spreads locally, and nodal metastasis occurs by involving the cystic, portal and peripancreatic nodes. Malignancies which may present with axillary lymph node metastasis include melanoma, carcinoma breast, malignant tumours of lung, ovary and stomach and therefore, must be excluded while evaluating the patient. Hu et al also reported 2 cases of port site and distant metastasis detected by PET scan. Both patients had undergone laparoscopic cholecystectomy for an unsuspected gallbladder carcinoma. The report highlighted the important role of FDG-PET in follow-up of patients of gallbladder cancer after surgery [31].
Available literature shows a handful of cases of axillary lymph node metastasis from a primary or recurrent gallbladder cancer. Johnson et al had reported the first case of simultaneous occurrence of axillary lymph node metastasis along with abdominal wall port site metastasis occurring 12 weeks after the laparoscopic cholecystectomy. A T1 gallbladder carcinoma had been discovered during the surgical procedure [16]. Another report cited two cases of delayed development of isolated unilateral axillary nodal metastasis 3–4 months after complete resection of an abdominal wall port site metastatic recurrence from gallbladder cancer. Both the patients were diagnosed with adenocarcinoma gallbladder postoperatively by the histopathological examination report [6].
An R0 resection of the malignancy is the only viable option for effective therapy. However, the fact is that majority of the patients are unsuspected for gallbladder cancer and are diagnosed after laparoscopic cholecystectomy [9]. Laparoscopic cholecystectomy is an acceptable treatment for T1a gallbladder carcinoma. For more advanced lesions discovered after an initial laparoscopic cholecystectomy, a more extensive surgery like partial hepatectomy in the form of wedge or anatomical segment 4b and 5 resections with supraduodenal lymphadenectomy is recommended. Many patients require biliary reconstruction as well. This procedure has improved survival of patients. The 5-year survival of patients who underwent radical resection for cancer above stage I was 51% [32, 33].
Various authors have proposed that the satisfactory treatment of port site recurrence includes resection of the port site, even if it is for palliative intentions to avoid skin ulceration. It has also been postulated that the long-term outcomes of patients who undergo re-exploration after an unsuspected laparoscopic cholecystectomy and those who are adequately surgically treated at the time of intra-operative diagnosis of gallbladder carcinoma are same [34]. Even though the outcomes are the same, a re-operation is a more extensive procedure [6].
The present case shows the rare occurrence of bilateral isolated axillary lymph node metastasis as first distant echelon site after resection of the epigastric port site metastasis and adjuvant chemoradiotherapy, 15 months after re-exploration. Such a clinical presentation has not been described earlier in literature. Based on the few available reports which have been discussed; isolated bilateral axillary lymph node metastasis without any systemic metastasis can be treated with complete surgical resection i.e., Level I, II and III axillary lymphadenectomy. However, despite aggressive surgical management in a metastatic disease, the outcome still remains poor. Finally, the practice of delivering all gallbladders using an endo-bag or a retrieval bag after laparoscopic cholecystectomy cannot be overemphasized, especially in regions with high rate of GBC.