Classic multivisceral transplant for advanced nonresectable pseudomyxoma peritonei: a case report

Abstract

Background

Pseudomyxoma peritonei is uncommon with a poorly understood pathogenesis. The standard treatment is cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. However, radical surgical resection is not feasible for patients with extensive unresectable disease, which can lead to bowel obstruction, nutritional failure, and potentially death. In this report, we recommend classic multivisceral transplant as a potential curative treatment for advanced, unresectable pseudomyxoma peritonei, an application that, to our knowledge, has not been previously described.

Case presentation

We describe the case of a 34-year-old Iranian man with pseudomyxoma peritonei who presented with abdominal distension and weight loss. He initially underwent incomplete cytoreductive surgery due to extent of the disease. Subsequently, due to progressive disease and development of intestinal failure, he underwent a successful extraperitoneal radical exenteration and classic multivisceral transplant. No disease recurrence or significant postoperative complications were observed during 1.5 years of follow-up.

Conclusion

This case presentation demonstrates that total extraperitoneal radical exenteration followed by classic multivisceral transplant can be a viable and effective treatment option for patients with inoperable pseudomyxoma peritonei complicated by intestinal failure. It offers significant benefits to patients, improving both quality of life and life expectancy.

Introduction

Pseudomyxoma peritonei (PMP) is an extremely rare peritoneal malignancy, with an estimated incidence of one to three cases per million people per year worldwide [1, 2]. It typically originates from a perforated mucinous appendiceal neoplasm in which mucinous neoplastic cells disseminate and implant on the peritoneal surface, leading to progressive peritoneal gelatinous ascites [3] The optimal treatment is complete cytoreductive surgery (CRS) combined with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). Nonetheless, 26% of patients with appendiceal PMP will develop disease recurrence [4, 5]. Furthermore, in some patients with extensive involvement, complete tumor removal with a negative surgical margin is often unfeasible and tumor debulking is the optimal achievable practice approach. However, residual tumor inevitably leads to disease progression and necessitates repeated surgeries. This cycle often culminates in short bowel syndrome [4, 6]. Consequently, multivisceral transplantation (MVT) remains the only potential treatment option to modify the course of the disease in those who are not eligible for further conventional surgery. To date, only 15 cases of MVT for PMP have been reported in the literature [7]. Herein, we describe a case of advanced PMP that was successfully treated with total extraperitoneal exenteration and classic MVT, the first reported instance of a successful classic MVT for extensive, inoperable PMP.

Case presentation

A 34-year-old Iranian man presented to the emergency department of a general hospital in Shiraz, Iran, with an 8-month history of abdominal pain, significant weight loss (20 kg), and progressive abdominal distension. These symptoms were associated with episodes of watery nonbloody diarrhea, fever, chills, and occasional hematuria. His past medical and surgical history was unremarkable. There was no history of malignancy among his first-degree relatives. He reported occasional cigarettes smoking but denied alcohol or drug abuse.

Physical examination revealed significant abdominal distension and periumbilical protrusion without peritoneal signs and no palpable mass. Laboratory findings including complete blood count, serum creatinine and electrolytes, liver function tests, urinalysis, and C-reactive protein were within normal limits.

Abdominal ultrasonography revealed a large amount of echogenic, particulate fluid in the abdomen and pelvic cavity. Further evaluation with intravenous contrast-enhanced computed tomography (CT) of the abdomen and pelvis showed diffuse, large-volume, low-density fluid throughout the peritoneal cavity with compression of adjacent viscera and organs. The CT scan also showed diffuse nodular omental infiltration (omental cake) and multiple lobulated fluid throughout the peritoneum, omentum and mesentery with scalloping of the viscera and liver (Fig. 1).

Fig. 1.

Contrast-enhanced CT scan of the abdomen and pelvis. Diffuse large-volume low-density (gelatinous) intraperitoneal fluid is shown with red arrows. Multiple lobulated fluid throughout the peritoneum, omentum and mesentery with scalloping of the viscera and liver is shown with white arrows. A Axial image showing large-volume gelatinous fluid and lobulated mucinous collections with scalloping of the liver and adjacent viscera. B Axial image showing mucinous deposits causing lateral displacement of the stomach without mural invasion. C Sagittal image demonstrating loculated mucinous fluid with visceral scalloping. D Coronal image showing extensive peritoneal and omental implants, greatest in the right lower quadrant and pelvis. Ao aorta, K kidney, L liver, P pancreas, Sp spleen, St stomach

Esophagogastroduodenoscopy, colonoscopy, and CT scans of the head, neck, and chest revealed no pathological findings. Based on the patient’s clinical presentation, laboratory results, and imaging findings, a preliminary diagnosis of PMP was established. Due to intractable abdominal pain, on the ninth day of hospitalization, the patient underwent exploratory laparotomy. The procedure revealed a large amount (approximately 3.5 L) of yellow gelatinous mucinous ascites. As radical surgery was impossible, a sample of ascitic fluid was sent for cell count, cytology, biochemistry, and histopathological examination, and after tumor debulking, the surgery was terminated.

Histopathological examination revealed a low-grade mucinous neoplasm with low potential for recurrence (Fig. 2). Exudative ascitic fluid analysis showed a white blood cell count of 30 (lymphocyte predominant), albumin level of 0.8 g/dL, lactate dehydrogenase (LDH) of 208 units/L, total protein of 1.4 g/dL, and glucose of 16 mg/dL. Adenosine deaminase activity in the ascitic fluid was negative for tuberculosis. Cytological examination was positive for malignant cells. Fluid culture showed no bacterial growth. Therefore, after alleviating the symptoms, he was discharged with close follow-up.

Fig. 2.

The hematoxylin and eosin (H&E) section shows some atypical glandular structures (small arrow) against a background of abundant mucin material (large arrow)

Three months postoperatively, the patient was readmitted with dyspnea, severe abdominal pain, and distention. To relieve progressive symptoms, only palliative debulking operation was performed, and due to a high peritoneal cancer index (PCI), a complete CRS was not achievable. The patient was discharged on postoperative day 7 and referred to our organ transplant department at Abu-Ali-Sina Hospital in Shiraz, Iran.

After evaluation by a multidisciplinary team, classic multivisceral transplantation (MVT) was considered the best therapeutic strategy for him, and owing to bowel obstruction and oral intolerance, intestinal rehabilitation was initiated prior to transplantation. Despite receiving total parenteral nutrition (TPN) in the hospital, he developed irreversible intestinal failure and was subsequently placed at the top of the transplant waiting list.

Donor selection

The patient was listed for MVT pending the availability and selection of a suitable, hemodynamically stable, and size-matched donor. Priority was given to matching the donor’s body weight and organ size to the recipient’s remaining abdominal cavity capacity.

In December 2022, the patient underwent a classic MVT from a 28-year-old male brain-dead donor, who was hemodynamically stable, organ size-matched, blood group-identical, and HLA-typed, following a closed head injury. Serological results for cytomegalovirus (CMV) were negative.

Operative techniques

Donor

Organ procurement began with the Cattell–Braasch plus Kocher maneuver, mobilization of the right colon to the left, and isolation of the superior mesenteric artery (SMA) from the aorta. The inferior mesenteric vessels were ligated. The lesser sac was opened, the splenic flexure was mobilized, left medial visceral rotation was performed, and a total colectomy was completed using a GIA 75 linear stapler.

Subsequently, the perihepatic ligaments were released, and the diaphragmatic crura and distal esophagus were divided using a GIA 75 linear stapler. This was followed by complete mobilization of the graft from the distal esophagus to the terminal ileum with electrocautery, and finally the warm phase ended with isolation of the pancreas and the proximal part of the abdominal aorta to the celiac trunk origin. The gallbladder was irrigated.

After closure of the inferior vena cava (IVC) above the confluence of the iliac veins, cross-clamping of the subdiaphragmatic aorta and cold perfusion (with 5 L of University of Wisconsin (UW) perfusion solution), a complete multivisceral graft including the liver, stomach, duodenum, pancreas, and small intestine with an aortic patch including the origin of the SMA and the celiac trunk was procured. During the bench surgery, the lumbar and renal aortic orifices and proximal aortic stump were sutured with 5–0 polypropylene. (Fig. 3).

Fig. 3.

Multivisceral allograft with donor aortic conduit, which will provide arterial inflow to the allograft, reconstructed during cold ischemia. The lumbar and renal branches were stitch-ligated with polypropylene 5–0. SMA superior mesenteric artery

Recipient

Explant (organectomy)

Concurrently with the donor procedure, the radical extraperitoneal exenteration of the recipient was started by a separate surgical team. The procedure was performed through a midline incision extended by bilateral subcostal incisions. The entire peritoneum and abdominal organs, except for the kidneys and urinary system, were removed. The involved part of the posterior diaphragm was resected. Complete mobilization of the liver was performed using the piggyback method. The hepatic veins were clamped and divided. En bloc radical resection of the liver, stomach, duodenum, pancreas, spleen, small bowel, colon, and entire peritoneum was performed using GIA 75 linear staplers (one stapler was used to excise the distal esophagus and another to transect the rectum in its extraperitoneal part) without entering the peritoneal cavity and tumor structures to achieve complete clearance of the tumor.

Following the exenteration, the entire course of the IVC and the abdominal aorta—from the bifurcation to the origins of the SMA and celiac trunk—was exposed (Fig. 4). The mesenteric vessels were ligated and reinforced with polypropylene 5–0.

Fig. 4.

En bloc radical exenteration of the recipient’s liver, stomach, duodenum, pancreas, spleen, small bowel, and colon without opening of the peritoneum. A Explant. B Intra-abdominal cavity after resection; the entire course of the vena cava and aorta is exposed. Suprahepatic veins, SMA, and celiac trunk are closed with side-biting clamps. IVC inferior vena cava, K kidney, SMA superior mesenteric artery

Transplant

An arteriotomy was created in the recipient’s infrarenal aorta using a No. 11 blade and aortic punch. A side-to-end anastomosis was then performed between the donor aortic conduit and the recipient’s infrarenal aorta using a running 5–0 polypropylene suture. The suprahepatic IVCs of the donor and recipient were anastomosed using a 4–0 polypropylene running suture, and the infrahepatic IVC of the allograft was suture-ligated with 4–0 polypropylene. Upon completion of the vascular anastomoses, the clamps were removed, and the allograft was reperfused (Fig. 5-B). Finally, hemostasis was secured.

Fig. 5.

Recipient’s abdomen before (A) and after (B) multivisceral organ transplantation

Gastrointestinal continuity was restored with a hand-sewn esophago-esophagostomy anastomosis and an end ileostomy, respectively. Pyloroplasty was mandatory to ensure gastric emptying of the denervated stomach. Due to diffuse oozing from the operative field, the abdomen was temporarily packed with six laparotomy sponges, and after placement of a drain, the abdomen was temporarily closed and the patient was transferred to the intensive care unit (ICU) for further resuscitation and correction of coagulopathy, with a planned second-look operation within 24 hours.

The patient was returned to the operating room after 24 hours. At re-exploration, hemostasis was adequate with no active bleeding, and the allograft appeared viable with satisfactory color and peristalsis. A venting gastrostomy tube was inserted to reduce gastric distension, the abdominal fascia was left open, and the skin was closed with nylon sutures.

Prior to allograft reperfusion, the patient received a 1-g bolus of methylprednisolone (and repeated doses over the next 2 days) in addition to a single infusion dose of rabbit antithymocyte globulin (r-ATG, 6 mg/kg body weight). Tacrolimus (with a trough level of 12–15 ng/mL) was started on the first postoperative day, and mycophenolate mofetil (1 g/day) and prednisolone (25 mg/day) were initiated after discontinuation of r-ATG and methylprednisolone [8, 9].

The postoperative course was complicated by several adverse events. On postoperative day (POD) 7, the patient developed fever, tachycardia, and tachypnea indicative of overwhelming sepsis, and subsequently underwent an emergency exploratory laparotomy. Intraoperative findings were consistent with pancreatitis and saponification. In addition, intermittent bleeding was noted around the stoma, which was treated conservatively with a valid prescription of methylprednisolone pulses, regardless of any histopathological evidence of rejection. Ultimately, he made a full recovery and was discharged from the hospital after 58 days in the ICU, with continuation of the immunosuppressive regimen.

Routine follow-up CT scans were performed every 3 months after surgery as a potential early diagnostic tool and showed no signs of recurrence (Fig. 6).

Fig. 6.

The patient’s last CT scan 12 months after transplantation, showing no evidence of disease recurrence. Anastomosis of the donor aortic conduit to the recipient aorta is indicated by a red arrow

At 6 months post-transplant, the patient was readmitted for diarrhea and prerenal azotemia. After cytomegalovirus (CMV) infection and acute rejection were excluded, he was successfully treated and discharged. Throughout the first post-transplant year, he did well at his follow-up visits and reported a significant improvement in quality of life, functional status, and sleep problems compared with the pre-transplant period.

Discussion

PMP is a rare clinical entity characterized by the dissemination and implantation of mucosal cells within the peritoneal cavity. As demonstrated in our patient, the current standard of care involves CRS, which aims to achieve complete macroscopic resection of visible tumors, followed by intraoperative HIPEC to eradicate residual tumors microscopically. Despite this aggressive approach, 26% of patients with appendiceal PMP will develop disease recurrence [4, 5]. The National Comprehensive Cancer Network (NCCN) guidelines for colon cancer and PMP indicate that, while the completeness of CRS is a critical determinant of survival, the addition of HIPEC has not been consistently associated with improved overall survival [10]. For patients with unresectable PMP managed with TPN, the average survival is limited to 6–12 months [11]; palliative systemic chemotherapy offers a progression-free survival of 6–8 months [12]. Complete CRS (preferably R0 resection) is the most important factor influencing disease recurrence and patient outcome. Achieving this requires total extraperitoneal exenteration, which is not possible without hepatectomy. The absence of recurrence in our patient at 1 year may be attributed to the achievement of an R0 resection followed by classic MVT, which was also associated with a reported improvement in quality of life during the first post-transplant year.

Unlike liver or kidney transplantation, which are widely accepted treatments for end-stage organ failure, multivisceral and intestinal transplantation remains a challenging surgical procedure performed infrequently, due to the significant need for chronic use of immunosuppressants [13–15]. However, with newer immunomodulatory strategies, visceral transplantation remains the only feasible treatment option for patients with symptoms of irreversible intestinal failure [13, 16, 17]. Given the progressive nutritional failure in our patient despite TPN, MVT was indicated as the optimal strategy to restore enteral autonomy and nutritional function.

The largest reported study on radical debulking and visceral transplantation for advanced, unresectable PMP was published by Reddy et al., which included 15 patients and provided further evidence of the benefits of transplantation in these cases. In their report, eight patients received isolated small bowel transplants, and seven underwent modified MVT. The 1-year and 5-year survival rates were 79% and 55%, respectively, and two of the patients died within 90 days from surgical complications. Despite disease progression or recurrence in 91% of patients, a significant improvement in quality of life was observed. Seven patients experienced episodes of acute cellular rejection of the intestinal allografts [7].

Inclusion of liver for visceral allograft is a significant predictor for long-term patient and graft outcome and longevity [14]. Isolated intestinal transplantation is associated with poorer graft survival and higher rejection rates, attributable to the high immunogenic potential of the small bowel, which contains abundant lymphoid tissue. Interestingly, classic MVT and combined liver-intestine transplantation have shown immunologic advantages and lower graft rejection rates compared with isolated intestinal transplantation, likely due to the liver’s proven immunologic benefits and the early formation of donor-specific antibodies (DSA) in the post-transplant period [18]. The favorable outcome in our case provides additional support for this immunologic benefit.

A technical strength of our approach was the allocation of the abdominal aortic conduit to the MVT recipient for arterial inflow, which ultimately simplified vascular reconstruction by reducing the number of vascular anastomoses and possible subsequent complications.

To our knowledge, this current study is the first reported case of classic MVT in literature for a patient with unresectable PMP who had no evidence of disease recurrence or major complications after 1-year follow-up and who reported a better quality of life after transplantation. Therefore, we recommended classic MVT as a potential viable therapeutic option for patients with otherwise untreatable PMP. Our patient remains well 1 year after transplantation, with no evidence of PMP recurrence or significant complications.

This study has several limitations. Organ allocation for MVT remains challenging. Consensus is needed to establish criteria and a scoring system for organ allocation in patients requiring classic MVT. In addition, the findings are based on a single case, which significantly restricts the generalizability of our findings. Larger series and longer follow-up are needed to more definitively evaluate survival outcomes and recurrence risks following transplantation for PMP. However, we believe that our report could add to the body of evidence regarding the satisfactory treatment.

Conclusion

Total extraperitoneal radical exenteration followed by classic MVT represents a promising therapeutic option for patients with PMP for whom conventional surgery does not seem feasible. It improves both life expectancy and quality of life. Further studies are warranted to evaluate its efficacy and to establish its role in the management of patients with inoperable PMP.

Abbreviations

ATG

Antithymocyte globulin

CMV

Cytomegalovirus

CRS

Cytoreductive surgery

CT

Computed tomography

DSA

Donor-specific antibody

HIPEC

Hyperthermic intraperitoneal chemotherapy

HLA

Human leukocyte antigen

ICU

Intensive care unit

IVC

Inferior vena cava

LDH

Lactate dehydrogenase

MVT

Multivisceral transplant

NCCN

National Comprehensive Cancer Network

PCI

Peritoneal cancer index

PMP

Pseudomyxoma peritonei

POD

Postoperative day

SMA

Superior mesenteric artery

TPN

Total parenteral nutrition

UW

University of Wisconsin

Author contributions

HN and SN were the chief surgeons who performed the surgical procedures, designed the study, and revised the manuscript. SF, MML, and ME were the hepatobiliary fellow who attended the surgery and were in charge of following patients. ARS contributed to the conception and design of the study. MSR and RN performed data acquisition, interpretation, and drafting of the manuscript. All authors proofread the final version of the manuscript.

Funding

No external funding was received for this project.

Data availability

All data regarding this study has been reported in the manuscript. Please contact the corresponding author if interested in any further information.

Declarations

Ethics approval and consent to participate

All protocols were approved by the Ethics Committee of the Shiraz University of Medical Science. The study was carried out in compliance with the relevant guidelines and regulations and the Declaration of Helsinki.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.