Hepatic Segrnentectomy on Primary Liver Cancer with Situs Inversus Totalis

We present the first case treated by hepatic segmentectomy in a 69-year-old woman with primary liver cancer and situs inversus totalis. The situs inversus did not cause any technical problems during the operation, which was conducted under guidance of intraoperative ultrasonography.


INTRODUCTION
Situs inversus totalis is a rare congenital condition, occurring with an incidence of 1:5000 to 1:10000 adults1, in which there is mirror-image transposition of both the abdominal and thoracic viscera. This condition, which has the potential to cause problems during operation, was simplified by adequate preoperative examination and intraoperative ultrasonography. We successfully performed resection of the postero-superior segment of the liver. This is the first reported case of hepatic segmentectomy performed on primary liver cancer complicated with transposition of the viscera.

CASE REPORT
A 69-year-old Japanese woman who had a history of liver cirrhosis was admitted to the National Federation of Health Insurance Osaka Central Hospital on June 21, 1991 because of a high plasma level of alphafetoprotein (AFP). At the age of 20 years, she had Correspondence to: The First Department of Surgery, Osaka University Medical School, 2-2 Yamada-oka, Suita 565, Japan. TEL; 06-879-3153, FAX; 06-879-3159 undergone laparotomy for bowel obstruction, and situs inversus totalis was detected at that time. The physical examination on admission revealed that normal heart sounds were audible in the right side of the chest. The liver and spleen were not palpable. There was no ascites. Her biochemical profile was remarkable, because plasma AFP was elevated to 291 ng/ml, serum bile acid was elevated to 51 gmol/1, and indocyanine green retention at 15 minutes was 19.3%. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum bilirubin and total protein were all within their normal limits.
Chest x-rays obtained on admission demonstrated dextrocardia. Abdominal ultrasonography revealed situs inversus totalis; that is, the liver and inferior vena cava were on the left side, and showed a hypodense mass in the postero-superior segment (Seg VII), according to Couinaud's classification of the liver segments, which was about 3 cm in diameter (Fig. 1). An abdominal computed tomographic scan showed a low-density area in the postero-superior segment of the liver. Selective celiac arteriography revealed a faint tumor stain supplied by what would have been the right hepatic artery in usual cases (Fig. 2). These findings were consistent with a diagnosis of primary liver cancer in the postero-superior segment.  The post-operative course was uneventful, and the patic artery for transcatheter arterial embolization patient is doing well 32 months after the operation.
(TAE). Fourty days after the TAE, computed tomo-The AFP concentration decreased to 46 ng/ml on the graphy showed more clearly a 20-mm tumor lesion, first postoperative day, and then gradually fell to 4 ng/ (Fig. 3). The plasma AFP level had decreased to 94 ng/ml. On August 6, 44 days after the TAE, the operation was performed. The diagnosis of situs inversus totalis was confirmed at laparotomy. The liver showed hepatic cirrhosis. Resection of the postero-superior segment was attempted. The right posterior pedicle was identified and clamped. Then minor resection of the postero-superior segment was performed using the technique of microwave coagulation (Microtaze; Nippon Shoji Kaisha, LTD.) and a Cavitron Ultrasonic Surgical Aspirator (CUSA; Valley Lab Inc.; Stanford, CT). Under guidance with intraoperative ultrasonography, the right hepatic vein in usual cases was preserved. The surgery was uncomplicated, with a blood loss of 1010 ml and an operating time of 5.5 hours. The resected tumor was well-encapsulated and 25 x 20 20 mm in size. Microscopically, the tumor was diagnosed as a combined hepatocellular and cholangio-cellular carcinoma. The liver showed inactive cirrhosis with moderate fatty change.
ml one month after the operation.

DISCUSSION
Situs inversus is a term used to describe left-to-right transposition of the normally asymmetrical organs of the body, and transposition of both the thoracic and abdominal organs is termed situs inversus totalis. This anomaly corresponds to a homologous region in humans located on the long arm of chromosome 122 Recently, Yost suggested that left-right axial information is contained in the extracellular matrix early in development and is independently transmitted to the cardiac and visceral primordia3. Although this anomaly is not considered to be a premalignant entity, 13 cases of malignancy associated with situs inversus totalis have been reported4-16. Two of those 13 cases were primary liver cancer. In 1983, Kanematsu described the first case of a primary hepatocellular carcinoma  We obtained a mirror image of the liver by using intraoperative ultrasonography to understand the anatomy of this patient. Resection of the posterosuperior segment was performed easily and without complications due to our precise understanding of the patient's anatomy.
We would like to emphasize that, when operating on a patient with primary liver cancer and situs inversus totalis, precise preoperative anatomical evaluation is important, and intraoperative ultrasonography is highly useful.

COMMENTARY
Vertebrates are unique in that they have mirror symmetry for external structures but have leftor righthanded asymmetry for internal organs1. The question of how the visceral organs, which originate in the midline, consistently migrate to the normal right or left side during development in a non-random fashion, has intrigued anatomists for ages2. Situs inversus is rare in human beings and the incidence ranges between 1:1,000 and 1:10,000 depending on the population surveyed3. In situs inversus totalis, a right/left mirror image oftransposition ofthe abdominal and thoracic viscerae occurs. In heterotaxy, the abdominal viscera may be inverted, whereas the thoracic contents may be normal, or vice versa. In isomerism, the body appears symmetric with bilateral left or right features2. The organs are often abnormal in each of these syndromes. The liver may be bilobed or symmetric, the spleen may be absent or multiple, the gut may exhibit malrotation with abnormal mesentery and the lungs may have reversed pulmonary lobulation. Cardiac defects are common and vascular abnormalities may involve the inferior vena cava, portal vein and hepatic artery2'3. The autosomal recessive Kartagener's syndrome in human beings, causing 50% situs inversus, is characterised by defective cilia4.
Although most cases of situs inversus are sporadic, inheritance patterns including X-linked, autosomal recessive and autosomal dominant have been de-scribed5. Hummel and Chapman first identified the genetic loci involved in localization control in 19596 It was designated the iv gene and has been mapped to chromosome 127 However, only 50% of mutant homozygous mice have situs inversus. This suggests that the normal allele at the iv locus specifies normal symmetry, whereas its absence allows random visceral orientations. Another new inv gene, the second gene found to control lateralization, has been described by Yokoyama and his associates8.
Patients with situs inversus may be completely asymptomatic, but more commonly, serious cardiac defects preclude long term survival. Although this anomaly is not considered to be a premalignant condition, 16 cases of cancer associated with situs inversus totalis have been reported9. It is interesting to note that two such cases were primary liver cancer and both patients underwent left hepatectomy (which is equal to right hepatectomy in the usual cases)3'1.
From the surgical point of view, recent technologic advances have enabled an accurate diagnosis of situs inversus, unless the patient requires emergency surgical treatment and no time can be spent in ultrasonic or radiologic investigations .O nce the diagnosis is made, careful preoperative anatomic assessment is needed since situs inversus is frequently accompanied by other intra-abdominal anomalies. The diagnosis of malignancy associated with situs inversus becomes straight forward once the anatomical transposition of viscerae is appreciated. The present case report is interesting. This is the third reported case ofliver cancer associated with situs inversus totalis. As the patient had liver cirrhosis, the authors decided to resect the postero-superior segment of the liver so as to leave behind as much functioning liver tissues as possible. The anatomical blood supply of the liver had been studied on three liver specimens obtained from bodies in situs inversus. The study showed that anatomical resection of the individual liver segments, like in normal patients, is possible in situs inversus11. The authors have now carried out the resection of a single liver segment and confirmed that this can really be done.