Metastasis of Gall Bladder carcinoma - A case Report

Introduction: Metastasis of Gall Bladder Carcinoma (GBC) is very uncommon, aggressive and fatal
cancer. World wide incidence rate reported as 
in women than men, older age more affected and coexisting Gall stonesare seen in majority cases. Because
of vague symptoms at early stage tumour will not be encountered, most of the patients present in advanced
stage, soprognosis is poor, hence Metastasis of GBC forms a diagnostic and therapeutic challenge.
Case Report: A 53 years old male, known diabetic past 10 years presented with intermittent vague
symptoms of vomiting, nausea, fever, fatigue, right upper quadrant pain since 3 months. Family history
of Gallstones and cancer was present. On examination 2-3 bilateral cervical swellings present, abdominal
examination reveals liver was palpable 4 cms below the right costal margin.
Relevant investigations done. Complete blood count & Liver function tests were abnormal.
Ultrasonography (USG) of abdomen and pelvis, USG guided FNAC of liver, CT of abdomen
and pelvis, PET scan of abdomen, Histopathological and Immunohistochemistry report of left
supraclavicularlymphnode biopsy were suggestive of metastatic adenocarcinoma of GB origin. After
appropriate staging adjuvant chemotherapy started, after third chemotherapy cycle he died of due to
metastasis of GBC, two months from his initial diagnosis.
Conclusion: In the present study patient was diagnosed in advanced stage, early diagnosis could be missed
due to vague symptoms and as GBC is uncommon entity, So proper evaluation of the patient in early stage
may prolong the survival.

Keywords: Gall Bladder, Carcinoma.


Introduction
Metastasis of Gall Bladder Carcinoma (GBC) is fifth most common Gastrointestinal tumour and most common malignant tumour of biliary tract. 1 GBC is fatal cancer and carries a 5 years survival rate of < 10 %. 2 It is still remain as lethal disease, in spite of advanced diagnostic measures because majority of GBC difficult to diagnosis in early stage due to its vague symptoms and its fast distant spread due to lack of GB serosa, landing in to advanced stage. Cholelithiasis is being the most frequent etiological factor * Corresponding author. E-mail address: drshashikalagh@gmail.com (S. G Hiremani).
in majority of GBC patients. USG of abdomen and pelvis shows mass in GB with large Gallstone-likely neoplastic with likely metastatic liver. USG guided FNAC of Liver lesion shows Adenocarcinoma deposits. Contrast enhanced Computed Tomography of abdomen shows features are possibly s/o Gallbladder neoplasm extension in to Liver. PET CT scan of abdomen reveals possibilities of metastatic locally advanced GBC. Biopsy of left supraclavicular lymph node suggestive of poorly differentiated adenocarcinoma metastasis. Immunohistochemistry of left supraclavicular lymph node biopsy positive for CK 20 and villin, features favour of metastatic adenocarcinoma of GB origin.

Discussion
Occurrence of GBC vary worldwide, it is high in South American Countries and some Asian countries. GBC is more prevalent in women and female-to-male incidence ratio reported as 3. 2 The occurrences of GBC increases as age advances and reaches the peak during the seventh and eighth decades of life.
Precise aetiology of GBC is not known but some studies attributed risk factors like cholelithias is, chronic cholecystitis, choledochal cyst, free radicals, lipid peroxidation products, secondary bile acids, congenital malformations of biliary tract, heavy metals exposure, high carbohydrate diet, obesity, alcohol abuse and smoking. Cholelithias is found as coexisting risk factor in 85% of GBC patients. GBC has many different histopathological types, among them Adenocarcinoma is most (85%) prevalent type, 5 other less common types include epidermoid carcinoma, adenocanthomas, oat cell carcinoma, carcinoid tumour and anaplastic carcinomas. Papillary, medullary, colloid, scirrhous, are different forms of Adenocarcinoma of GBC. 6 Papillary adenocarcinoma most common form andhas best prognosis due its very low wall invasion. Other recent types of GBC include smetaplastic and non-metaplastic types. 7 Studies observed that there is genetic mutations of k-ras gene in 39-59%, p53 gene in 35-92% of GBC cases seen. 8 Also concluded that 83.33 % cases of metastatic GBC shows raised telomerase activity in GB tissue. 9 In activation of tumour suppressor genes and deletion of Rb gene is seen in GBC patients.
As GBC is one of aggressive tumour and going for early etastasis due to its many routes of spread. It spread by vascular, lymphatic, in traductal, in traperitoneal, neural routes, but in traductal route of GBC spread has a better prognosis. But loco regional spread more common than distant, as in our study metastases occurred in adjacent liver and lymph nodes. But distant metastases do occur, involving adrenals, kidneys, spleen, brain, bones, breast, thyroid, heart and uterus, with median survival rate 3 to 4 months in GBC with distant metastases. 10 USG of abdomen help to detect suspected GBC as in our study. USG guided FNAC of Liver help in arrival of accurate diagnosis of GBC. In our study this helped to diagnose Metastatic Liver with suspicious of GB origin. CT is a very commonly used for the diagnosis of primary tumour of GBC, metastasis especially lymphatic and peritoneal metastasis and also for tumour staging. In our study CT abdomen diagnosed metastatic GBC. PET is very good imaging modality in diagnosis of GBC, metastasis and in accurate staging. In our case PET gave more accurate diagnosis of metastatic locally advanced GBC and staging was guided to start chemotherapy.
In our case study, for more accurate confirmation of metastasis of GB origin did by IHC study, which play a significant role in the management of GBC. Subjecting biopsy of lymph node staining for tumour markers, CK 20 and Villin showed aberrant expression, features favour of metastatic adenocarcinoma GB origin.
In the management of GBC, staging is very important. According to TNM Staging,T1/T2 stage, where tumour is confined to GB wall, usually surgery is performed. In T3 tumours can be resected but with enbloc resection of adjacent organs while T4 tumours are unresectable hence adjuvant chemotherapy is mode of choice.and molecular targeted therapy are also hopeful. Unfortunately, in our study, case was diagnosed in T4 stage and adjuvant chemotherapy started. Different regimens including combination of chemotherapy drugs, Gemcitabine, Cisplatin, Oxaliplatinand 5-FU, Adriamycin, Nitrosoureas are tried, but spread of disease was progressed, involving pancrease, lungs, bones, peritoneum, unluckily patient survival rate was only two months.
Recently a study was carriedon Triptolide, to identify its anticancer effectson GBC cells and concluded that Triptolide induce apoptosis in gallbladder cells and arrest the phase, hence it can be used as a potential drug for treatment of GBC. 11 Prognosis of patients with Advanced GBC remains dismal and available surgical, adjuvant chemotherapy ,radiotherapy, molecular target therapy are hopeful and assumed powerful to some extent in prolonging survival. New effective treatment and drugs are an urgent need for GBC.

Conclusion
Early stage diagnosis of GBC can be difficult and challenging, often leading to delay in diagnose. Therefore, screening patients, who present with vague symptoms especially those who are at greater risk, essential given the possibility of coexisting GBC.

Source of funding
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