Liver and pancreas transplantation in adult donor and recipients with situs inversus totalis: a case series and review of the literature

Abstract

Background

Situs inversus totalis is a rare congenital anomaly characterized by a mirror-image orientation of abdominal, and in some cases, thoracic organs. Here, we report our situs inversus totalis transplantation experience and further review liver transplantations in adult recipients and donors with situs inversus totalis.

Case presentation

We describe three cases with situs inversus totalis. The first case was liver transplantation in a recipient (a 61-year-old Iranian man) with situs inversus totalis, the second was a liver transplantation from a donor (a 52-year-old Iranian woman) with situs inversus totalis, and finally, for the first time, a simultaneous pancreas and kidney transplantation in a recipient (a 26-year-old Iranian man) with situs inversus totalis. In patient one, hepatectomy could be performed according to the standard method and on the basis of preoperative studies. Hepatic vein and arterial anastomosis were performed as in every other patient without situs inversus totalis. To prevent biliary complications, a Roux-en-Y hepaticojejunostomy was performed. In patient two, implantation time, suprahepatic vein, portal vein, arterial, and biliary reconstruction could be done as in any other case without situs inversus totalis. Plication of the right-sided diaphragm and fixation of the falciform ligament was done for our patient. In patient three, systemic drainage was preferred to portal flow for establishing the outflow drainage of the pancreas compared with otherwise normal patients.

Conclusion

Although situs inversus totalis is a rare condition, our reported techniques are suitable, considering advantages such as easier accessibility, more acceptable placement of the implanted organs regarding vascular variations, and the appropriate location of the allograft in the proximity of other organs.

Introduction

Orthotopic liver transplantation (LTx) has become the standard and final treatment option for end-stage liver diseases. Because of the shortage of organs and the increasing number of patients who require transplantation, maximum effort is made to procure and transplant organs appropriately. Therefore, facing anatomical diversity and anomalies in the donor and recipient is inevitable [1, 2]. One of these anomalies is situs inversus totalis (SIT). It is a rare congenital abnormality characterized by a mirror-image orientation of the abdominal, and in some cases, thoracic organs relative to the midline. The incidence of SIT is about 5–25 in every 100,000 births [3]. Implanting a mirror-image organ may pose a technical challenge to a transplant surgeon because of the reversed position and orientation of the graft and vascular system. Some of the potential risks include vascular torsion and hepatic venous outflow kinking, inferior vena cava (IVC) compression, need for additional vascular reconstruction, and pressure effect on the stomach due to the placement of the greater right lobe in the recipient’s hepatic fossa [4].

In addition, SIT is often associated with other anomalies such as biliary atresia (BA), polysplenia syndrome (interrupted IVC with azygous drainage, confluent hepatic veins to the right atrium, preduodenal portal vein, hypoplastic or atretic portal vein, and aberrant hepatic arterial anatomy), congenital heart disease, Kartagener’s syndrome, and midgut malrotation that would eventually make the transplantation more complex [3, 5, 6].

The most documented association of SIT is with BA, which is a cause of end-stage liver disease among pediatrics. Approximately 28% of children with SIT have BA [7]. Accordingly, most cases of transplantation in SIT are reported in this group.

Although most people with SIT have a normal life without complications, this condition could be problematic when they require surgery, especially LTx [8]. Due to these difficulties, SIT was previously considered a contraindication for LTx. Advances in surgical technique and experience have overcome these limitations [9, 10].

However, experiences with SIT are still limited, and different techniques have been used according to each individual’s circumstances. Here, we first describe a case of LTx in a SIT recipient, then a successful LTx from a donor with SIT, and finally, for the first time, we report on a pancreas transplantation in a SIT recipient.

Case presentation

We collected medical records of patients diagnosed with SIT who underwent transplant surgery from January 2018 to September 2023, affiliated with Shiraz Organ Transplant Center, Abu-Ali-Sina Hospital, Shiraz University of Medical Sciences. The Shiraz University of Medical Sciences Ethics Committee approved this study (IR.SUMS.REC.1402.570). Three written informed consents were obtained from patients for the publication of these case reports and any accompanying images.

Case 1

A 61-year-old Iranian man with a known case of alcoholic liver cirrhosis with complete situs inversus was referred to our center with severe ascites and grade II encephalopathy. He had stopped drinking alcohol a year before. During the previous 6 months, he suffered from severe ascites and required multiple peritoneal paracentesis, resulting in three emergency department admissions. Because of the increase in creatinine level (up to 2 mg/dL) and an existing hepatorenal syndrome, the patient was on the waiting list for LTx. Computed tomography showed that the arterial blood supply to the liver originated from the celiac axis with no evidence of the replaced hepatic artery. He had no associated vascular and visceral anomalies (Fig. 1). In other words, there were no signs of intestinal malrotation or intermittent IVC. The model for end-stage liver disease (MELD) score was 24 at admission, and his height and body weight were 178 cm and 95 kg, respectively.

Fig. 1

Pre-transplant contrast-enhanced abdominal computed tomography findings showing a complete situs inversus with a mirror-image positioning of abdominal organs

In April 2022, he had LTx and received an ABO-compatible whole liver from a 75 kg, 44-year-old donor whose graft weighed 1.4 kg. Dissection of the hepatic hilum was performed without unexpected difficulty, but hepatectomy was done with standard technique (resection of recipient’s IVC with liver). The liver was directly placed into the recipient’s left upper quadrant without rotating adjustment; the right hepatic lobe was positioned on the recipient’s left side, and the left liver lobe was placed in the recipient’s previous liver fossa. The hepatic superior and inferior vena cava were directly anastomosed to the recipient’s IVC with 3–0 vascular sutures. Portal veins were anastomosed end-to-end with 6–0 polypropylene sutures. The cold ischemia time was 4 hours.

Arterial reconstruction was done using an end-to-end technique with a 7–0 continuous suture. Biliary reconstruction was performed by duct-to-duct anastomosis between the recipient’s common bile duct and the donor’s common hepatic duct with polydioxanone sutures (PDS); however, seemingly, there was some tension on the anastomosis site. Finally, to prevent the rotation of the transplanted liver, diaphragm plication and fixation of the falciform ligament to the diaphragm were carried out. The total operation time was 6.5 hours, and the patient was extubated 12 hours after the operation; no veno-venous bypass was used during the anhepatic phase. On postoperative day 12, the patient’s serum bilirubin levels increased to 5 mg/dL, and biliary fluid passed through the incision site, so exploration was done for the patient. Exploration showed that the anterior side of the previous common bile duct anastomosis was disrupted. Accordingly, we took the last biliary anastomosis and reconstituted it by a Roux-en-Y hepaticojejunostomy. The patient was discharged from the hospital on day 25 post-transplantation.

Considering the anatomical differences between the recipient with situs inversus and the recipient with normal anatomy, the transplantation technique seems modified to prevent complications following LTx. As shown in Fig. 2A, the direction of the recipient’s bile duct and portal vein had an acute angle to the donor’s liver. Due to this anatomical difference, performing Roux-en y hepaticojejunostomy would potentially result in fewer complications than duct-to-duct anastomosis. Furthermore, for portal vein anastomosis, the length of the portal vein should be as short as possible to prevent kinking and future portal vein thrombosis. Given that the left lobe of the donor’s liver is located in the space that was previously the location of the right lobe of the recipient’s liver, this mismatch can cause a possible rotation of the transplanted liver. To prevent this complication, ipsilateral diaphragm plication and fixation of the falciform ligament to the diaphragm were carried out (Fig. 2B).

Fig. 2

Completion of the suprahepatic, portal, and arterial reconstructions in the recipient with situs inversus totalis following orthotopic liver transplantation (patient 1) (A) and schematic orientation of the liver transplant inside the recipient’s body with situs inversus totalis (B)

Case 2

A 52-year-old Iranian woman was admitted due to intracerebral brain hemorrhage (ICH) and was diagnosed with brain death 2 days after admission. The patient was prepared for organ donation. Dextrocardia was discovered in chest radiography, and SIT was confirmed after abdominal ultrasonography. During the procurement procedure, we found the liver, pancreas, spleen, and stomach on the opposite side; the aorta was on the right side, and IVC was on the left side and anterior to the spine (Fig. 3A). There was no problem during the procedure; however, the operation time was longer than usual due to meticulous dissection. During bench surgery, the common bile duct was on the left side of the hilum, and the proper hepatic artery was on the right side. Still, no anatomical variation was seen in the hepatic artery, and portal vein was in the posterior position. Arterial structures were preserved with an aorta patch, and IVC was excised to the longest length possible. The donor’s liver weighed 1.2 kg.

Fig. 3

Liver anatomy in deceased donor with situs inversus totalis (patient 2) (A) and schematic orientation of the liver transplant inside the recipient’s body with normal anatomy (B)

The recipient was a 48-year-old man with a history of decompensated cirrhosis due to non-alcoholic steatohepatitis (NASH) and was a candidate for LTx. Hepatectomy was performed with the piggyback method, and the implantation was done with the liver placement in the middle part of the upper abdomen. The right lobe of the liver graft was placed toward the recipient’s left side. Outflow was established by anastomosis of the donor’s suprahepatic vena cava to the recipient’s common funnel of hepatic veins. The distal end of the donor cava was ligated. The portal vein was anastomosed using the end-to-end technique. The liver perfusion was established without any problems. Arterial reconstruction was done using the end-to-end technique by anastomosis of the donor’s hepatic artery to the recipient’s common hepatic artery. Finally, duct-to-duct anastomosis was done without tension. To prevent the rotation of the liver and to eliminate the empty space on the right side, we plicated the right diaphragm and the falciform ligament (Fig. 3B). The patient was discharged without any complications.

Case 3

A 26-year-old Iranian man with diabetic nephropathy was referred to our clinic for pancreas transplantation. He was on continuous insulin therapy without proper glycemic control from 10 years ago. He had also lost his vision due to diabetic retinopathy. During previous imaging studies, SIT was identified, and associated vascular anomalies were documented.

The donor was a 36-year-old man who developed brain death due to subdural hematoma following a traumatic brain injury. Grafts were in good condition with normal function.

During bench surgery, we made a combined patch of the celiac trunk and superior mesenteric artery (SMA) from the donor’s aorta to avoid separate anastomosis or using a Y-graft. The donor’s portal vein behind the pancreas was also prepared for venous outflow.

Laparotomy was done through a midline incision. The aorta and left-sided IVC were localized. Considering the SIT, the surgeon was on the right side of the patient. The prepared portal vein was anastomosed to the IVC as an outflow pathway, and the Carel patch was anastomosed to the recipient’s common iliac artery. The donor’s duodenum was anastomosed to the nearest loop of the jejunum from the recipient (Fig. 4).

Fig. 4

Pancreas anatomy following transplantation in recipient with situs inversus totalis (patient 3)

No unexpected event occurred following declamping, and normal blood sugar levels were achieved quickly. The kidney was transplanted on the right side to achieve better access to the iliac vessels. The hospital course was uneventful except for an episode of rejection diagnosed with elevated creatinine levels. The patient received one course of methylprednisolone and recovered completely.

Discussion

In cases of SIT, organ transplantation may be complicated. Both donors and recipients can have SIT, although matched donor-recipient combinations are unlikely to be found due to their rarity. However, there are several reports on children and adults with SIT undergoing LTx. Literature on LTx in SIT is presented in Table 1.

Table 1 Published studies on liver transplantation in adults (donors, recipients) with situs inversus

Despite SIT being a rare developmental defect during embryogenesis, it is not considered a contraindication for organ transplantation, whether as a donor or recipient. Further, we should keep in mind that the risk of surgical complications may increase because of anatomical variation in the positioning of the vasculature.

The liver is an asymmetric organ that is always affected by SIT-related anatomic abnormalities. As a result, donation from a donor with SIT and transplantation for a recipient with SIT are complicated surgical procedures. Because of the technical challenges associated with the unusual vascular architecture and concerns related to proper graft location, SIT was formerly considered a contraindication for LTx [11]. The two main problems for orthotopic LTx in SIT seem to be (i) having to place the graft’s greater right lobe over the right-sided stomach and (ii) the presence of a large empty space in the left upper quadrant, which predisposes the graft to lateral displacement and kinking of the hepatic veins [12].

Even though several successful strategies have been suggested, there has yet to be agreement on a standard technique. These techniques include (i) plication of the left diaphragm combined with graft fixation with a percutaneously inserted gastric balloon of the Sengstaken–Blakemore tube [13]; (ii) transplantation of a portion of the liver from a living donor (that is, reduced size) [8]; (iii) different degrees (15–90°) of lateral rotation of the graft (clockwise in SIT recipients and counter-clockwise in SIT donors) using standard piggyback, end-to-side, or side-to-side cavo-caval anastomosis [2, 8, 14,15,16,17]; and (iv) 180° flip of the graft (retroversus or backward facing) [18,19,20,21] (see Table 1). Regarding living donations, segmental LTx allows the transplant surgeon greater flexibility in determining the best choice. New technologies, such as three-dimensional (3D) printing, can aid surgery planning if there is enough time for preoperative planning [22].

In our case (patient 1), performing Roux-en-Y hepaticojejunostomy potentially has fewer complications compared with duct-to-duct anastomosis. In addition, for portal vein anastomosis, the length of the portal vein should be as short as possible to prevent kinking and future portal vein thrombosis. To prevent the rotation of the transplanted liver, ipsilateral diaphragm plication and fixation of the falciform ligament to the diaphragm were used.

Moreover, there were few reports on using a liver from a donor with SIT. The most challenging part of these cases is the venous outflow reconstruction. In 1995, Asfar and Ozcay [23] reported transplantation with a liver from a SIT donor. They rotated the liver 90° counter-clockwise and performed an end-to-side anastomosis between the donor’s intrahepatic vena cava and the recipient’s IVC.

In other reports, authors mentioned different methods, such as backward rotation of the liver 180° along the axis of the IVC or T-shape anastomosis between the left and middle hepatic veins and IVC. In our case (patient 2), we performed the piggyback technique for hepatectomy, IVC was preserved, and the liver was implanted with its original orientation. Anastomosis between the donor’s suprahepatic vena cava and the recipient’s common funnel of hepatic veins was performed, and there was no need for significant rotation of the liver. Another issue that should be considered is the empty space on the right side of the upper abdomen. In our case, we plicated the diaphragm, but in some case reports, the omentum has been used. Fixation of the falciform is also helpful. A smaller graft might be more logical for preventing compression on the IVC or stomach.

To the authors’ knowledge, no previous reports existed for pancreas transplantation in SIT. For this, a systemic approach must be selected due to technical difficulties that may be encountered using conventional portal-portal anastomosis. In SIT cases, the aorta is localized far from the portal system, so using iliac vessels and the superior mesenteric vein (SMV) leads to inappropriate angulation and puts the graft at risk of vascular compromise. In addition, in the method used for this case (patient 3), the graft is positioned perpendicularly, taking a better position in the abdomen with reversely placed organs. Our center's policy is to place the left kidney in the left retroperitoneum for simultaneous kidney and pancreas transplantations. In this case, we used the left kidney on the right side as it provided us with better exposure and vascular anatomy for implantation. Although we encountered complexities, our technique presented a suitable option for this anomaly due to advantages such as easier accessibility, better placement of the implanted organs regarding vascular variations, and the appropriate location of the allograft in the proximity of other organs.

Conclusion

On the basis of previous literature and our experience, we advocate applying specific techniques, which are as follows: our recommendations in organ recipients with SIT: (1) ergonomy; the transplant surgeon should be on the left side of the patient during the operation; hepatectomy can be done as a standard or piggyback method; however, we recommend using the standard technique if the patient has a good cardiopulmonary reserve that can tolerate total clamping of the IVC; (2) implantation; hepatic vein and arterial anastomosis can be performed as with normal patients, the portal vein should be shortened as much as possible, and to prevent biliary complications, we suggest Roux-en-Y hepaticojejunostomy and organ rotation are not mandatory in all cases; and (3) plication of the diaphragm and fixation of the liver are recommended in the recipient.

Our recommendations in deceased donors with SIT anatomy are as follows: (1) hepatectomy can be carried out using a standard or piggyback method based on preoperation studies; (2) suprahepatic vein, portal vein, and arterial and biliary reconstruction can be done similarly to normal patients, and implantation time can be similar; whether a liver rotation is performed depends on the surgeon’s preference; and (3) plication of the right-sided diaphragm and fixation of the falciform ligament are advised in all patients.

Our recommendations in simultaneous pancreas and kidney transplantation with SIT anomaly are as follows: (1) standing on the left side of the patient results in more comfortable access during operation; (2) for establishing outflow drainage, systemic drainage is preferred to portal drainage; (3) for anastomosis of arterial graft, if the procurement team of the liver and pancreas is the same, the patch of the celiac trunk and SMA is to be given to the pancreas, and this patch is directly anastomosed to the aorta; and (4) kidney is placed in the right side in the retroperitoneal space, and anastomosis can be done as usual.

Finally, more acceptable outcomes can be achieved with meticulous perioperative planning, a complete anatomic understanding of the liver and pancreas in the donor and recipient, and the use of novel procedures.