Adenocarcinoma of gall bladder in a patient with situs inversus totalis: a very rare clinical case

Abstract


Introduction
Situs inversus totalis (SIT) is a rare congenital condition with autosomal recessive inheritance and it occurs in the range of 1:8000-1:25000 of the normal population 1 .The male to female ratio is 1:1 with no racial predilection 1 .It was first reported in humans by Fabricius in 1600 2 .Most of the individuals with SIT are asymptomatic and are detected accidently at the time of clinical examination and radiological investigations for some other condition.It is not considered to predispose to cancers; however, rare cases of malignancies of lung 3 , stomach 4 , liver 4 , common bile duct 5 , colon 6 , rectum 7 , kidney 8 and gastric lymphoma 9 have been reported in the literature.
Gall bladder cancer (GBC) is a rare and usually aggressive malignancy occurring predominantly in the sixth and seventh decade of life, with a strong predilection for females (F>M = 2-3:1) 10 .It is one of the most common malignancies in North India, particularly in females 11 .It is not usually found until it has become advanced and becomes symptomatic.Risk factors for GBC are gallstones (size >3 cm), porcelain gall bladder, adenomatous gall bladder polyps (size >10 mm), Salmonella typhi infection, choledochal cysts, primary sclerosing cholangitis, anomalous pancreato-biliary junction, obesity and family history 10 .Histologically, adenocarcinoma is the most commonly isolated variety (>90% cases) followed by squamous cell cancer 12 .Management of this malignancy requires thorough preoperative assessment; knowledge of anatomical variations and their complications, a strategic management plan and vigilant perioperative care to bring out best clinical outcomes.We herein report a rare case of moderately differentiated gall bladder adenocarcinoma in 50-year-old man with SIT who presented at our institution.

Case report
A 50-year-old male, with known SIT presented at the surgical outpatient department of our institution in January 2013, with a history of intermittent dull aching pain in left upper abdomen for last six months followed by appearance of a hard lump in the left upper abdomen for the last month.No history suggestive of obstructive jaundice, altered bowel and bladder habit was present.He was a chronic smoker for the last 30 years and there was no history suggestive of diabetes mellitus, tuberculosis, any chronic illness or any previous surgery.Family history was non-contributory regarding occurrence of malignancies in the family.On general examination, he was afebrile with mild pallor and no jaundice.On examination of the cardiovascular system, apex beat was present more clearly in the right fifth intercostals space lateral to the right border of the sternum.Per abdominal examination revealed mild tenderness and a hard globular lump size of 3 × 4 cm coming out of the left subcostal margin in the midclavicular line, which was moving freely with respiration.Clinically there were no signs of free fluid, bowel sounds were normal and per rectal examination revealed no growth and any abnormality.Chest X-ray posteroanterior view showed apex and gastric fundal gas shadow towards the right side and the electrocardiography showed transposition of first and second lead and inversion of the first lead.These findings were confirmatory signs for situs inversus in our patient.Ultrasonography of the upper abdomen showed situs inversus abdominis with isoechoic, well defined mass lesion of a size of 3.6 × 2.0 cm with irregular margins in gall bladder lumen along with echogenic calculus.Contrastenhanced computed tomography image of the upper abdomen showed transposition of all major organs with liver, gallbladder and head of the pancreas on the left side and spleen, stomach and tail of pancreas on the right side.Gall bladder revealed thickened walls (3-10 mm), more marked in the fundal region with moderate enhancement and pericholecystic fat planes appeared normal (Figure 1).There was no evidence of infiltration of adjacent liver parenchymal by this mass as well as lymph node involvement in hepatoduodenal ligament.Laboratory investigations, including complete blood cell count, liver function tests, kidney function tests and biochemical tests, were within normal limits.A provisional diagnosis with the highest probability of the carcinoma gall bladder and SIT was established.As, clinically, tumour was confined to the gall bladder, but to decide the operability and confirm the absence of metastatic disease, first staging laparoscopy and intraoperative frozen section biopsy from the gall bladder mass was done.On confirmation of diagnosis of adenocarcimoma gall bladder, open radical cholecystectomy with 3 cm non-anatomical wedge resection of the gall bladder bed of liver and Roux-en-Y hepaticojejunostomy was done, via left-sided Kocher's incision.A western style portal nodal dissection which included a complete portal lymph node dissection including suprapyloric lymph nodes and skeletalisation of the portal structures along with celiac lymph nodes dissection was done.Definitive histopathological examination of the resected gall bladder showed moderately differentiated adenocarcinoma, with neoplastic cells forming papillary and acinar structure without lymphovascular or perineural invasion.Hepatic and common bile duct cut margin were not involved by the tumour.Paracholedochal and celiac lymph nodes did not show metastatic involvement.Now the patient is on his regular follow-up and doing well.Postoperative imaging studies performed six months after surgery showed no evidence of recurrence at local sites or distant metastasis.

Discussion
SIT is a rare congenital condition in which the precise aetiology is unclear; however, it is believed to be due to an autosomal recessive gene located in chromosome 14 and deletions affecting chromosomes 7 or 8 13,14 .The possible molecular pathway is the mutation affecting coiled-coil domain containing 11 (CCDC11) and axonemal heavy chain dynein type 11 genes is involved in autosomal recessive laterality defects of diverse phenotype resulting in SIT 15,16 .In addition, it has been shown that mutations in the tumour growth factor β family gene and in the trans cription factor hepatocyte nuclear factor 3β have a probable role in the process 17 .The normal development requires a 270° counter clockwise rotation that gives the normal anatomy but in SIT, the 270° rotation is in the clockwise direction 18 .It is characterised by dextrocardia and left-to-right transposition of major thoracic and abdominal organs.The liver and gall bladder are located in the left, while the stomach, spleen and pancreas are on the right; the colonic flexures are also reversed.In the majority of instances, the SIT carriers are not associated with other abnormalities and have a normal lifespan 19 .The association of SIT with various malignancies is a rarity.
Biliary tract carcinomas (BTCs) are relatively rare, representing less than 1% of all cancers, while gallbladder adenocarcinoma and cholangiocarcinoma account for 4% and 3% of all gastrointestinal cancers, respectively 20 .BTCs are invasive adenocarcinomas that arise from the epithelial lining of the gallbladder and intrahepatic and extrahepatic bile ducts.GBC represents the most common and aggressive cancer among all the BTCs and carries an extremely poor prognosis.The incidence of GBC steadily increases with age; women are affected two or three times more often than men, and more common in whites than in blacks 11 .GBC is characterised by local invasion, extensive regional lymph node metastasis, vascular encasement and distant metastases.Preoperative imaging for tumour recognition and non-invasive staging is essential to select patients for appropriate management plan and has become more reliable with advances in computed tomography, magnetic resonance imaging and positron emission tomography.Staging laproscopy should be considered if no distant metastases are found on imaging since the risk of the peritoneal metastases is high in this disease 21 .Complete surgical resection is the only potentially curative treatment available for resectable disease leading to a 5-year survival rate of 5%-10% for GBC and 10%-40% for cholangiocarcinoma 22 .Even those patients who do undergo 'curative' treatment, recurrence rates are high.Patients with unresectable or metastatic GBC, have a median survival of 13 months 10 .
In association with SIT, only four cases have been reported which were all cholangiocarcinoma 5 .We could not find any case of GBC ever reported with SIT in our literature search.Herein we are reporting a unique case of GBC in a patient of SIT.

Conclusion
Although malignancies occur rarely with SIT, a careful evaluation by advanced imaging modalities is important in order to understand anatomical abnormalities associated with SIT as well as preoperative staging of the suspected malignancy.Evidently, SIT makes the surgical procedure challenging because of difficulties in following surgical protocols due to the mirror image anatomy, cardiovascular and other anomalies.Nevertheless, the presence of anatomic variations should not alter the principles of oncologic surgery.Logically it appears that the occurrence of cancers in SIT is merely a co-incidence, with same aetiological factors responsible, as in normal individuals.Still, further studies may be required to evaluate whether the molecular and genetic changes leading to SIT may also be responsible for such a low incidence of cancers in these individuals.
Adenocarcinoma of gall bladder in a patient with situs inversus totalis: a very rare clinical caseS Sagar*, BM Singhal, V Kumar, CP Singh, D Raj Surgery Licensee OA Publishing London 2013.Creative Commons Attribution License (CC-BY) Competing interests: none declared.Conflict of interests: none declared.All authors contributed to the conception, design, and preparation of the manuscript, as well as read and approved the final manuscript.All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure.For citation purposes: Sagar S, Singhal BM, Kumar V, Singh CP, Raj D. Adenocarcinoma of gall bladder in a patient with situs inversus totalis: a very rare clinical case.OA Case Reports 2013 Sep 10;2(8):79.

Figure 1 :
Figure 1: Contrast-enhanced computed tomography image of the abdomen, showing transposition of all major organs with liver, gall bladder and head of the pancreas on the left side and spleen, stomach and tail of the pancreas on the right side.Gall bladder showing thickened walls in the fundal region (arrow) with moderate enhancement.