Georgios Zavos

Impact of donor and recipient age difference on long-term allograft survival after living donor renal transplantation: analysis of 478 cases

Either deceased or living‐related renal transplantation constitutes the best therapeutic option for patients with end‐stage renal disease. In this retrospective study, an attempt to identify parameters that affect allograft survival in living donor renal transplantation was made.

A forgotten vascular technique in renal transplantation.

A 33-year-old man (end-stage renal disease due to Alport syndrome) received a right kidney from a 37-year-old dead female donor, with 3 arteries on a Carrel patch, a single vein, and a single ureter (Figure 1). The renal vein was anastomosed to the external iliac vein in the conventional end-to-side fashion. Because renal vein was short, venoplasty was previously performed to extend the renal vein that was explanted along with vena cava. Accessory superior pole renal artery had a diameter less than 1 mm and was ligated (Figure 1). The distance between the main renal artery and the inferior pole renal artery was above 2.5 cm, so we decided to shorten the patch instead of proceeding in 2 separate arterial anastomoses (Figure 2). The aortic patch was anastomosed to the external iliac artery in the conventional end-to-side fashion (Figure 3). On clamp release, there was good hemostasis and the kidney perfused well (video). The ureter was implanted to the bladder with an onlay-extravesical ureteroneocystostomy using a double-J stent for ureter. The anastomosis time was 27 minutes and the total operation time was 2 hours. The patient was

An uncommon cause of acutely altered mental status in a renal transplant recipient

Abstract Introduction. Neurological complications are quite frequent in patients after solid organ transplantation presenting with focal or generalized neurologic symptoms as well as altered mental status. Posterior reversible encephalopathy syndrome is a rare cliniconeuroradiological entity characterized by headache, altered mental status, cortical blindness, seizures, and other focal neurological signs and a diagnostic magnetic resonance imaging. Case report. We present a case of a 57-year-old woman with one episode of seizures and sudden onset of altered mental status (time and person perception) accompanied with headache at the thirtieth postoperative day after renal transplantation. Conclusion. Posterior reversible encephalopathy syndrome, although an uncommon post-renal transplantation complication, should be considered in these patients, as several factors surrounding the setting of transplantation have been implicated in its development. Thus, physicians should be aware of this condition in order to establish the diagnosis and offer appropriate treatment.

Organ Transplantation in Greece.

Organ Transplantation in Greece Greece has 5 kidney transplant programs (with 1 unit that has a broad experience of >1000 living-donor renal transplants): 1 active Liver Transplant program performing deceased-donor liver transplantations (2 additional programs that have been approved to perform liver transplants), 4 bone marrow transplant programs (nonautologous), and 1 cardiac transplant program. At this time, there is no active small bowel, pancreas, lung, or dedicated pediatric transplant program. Children older than 14 years are registered and get priority on the adult kidney list, whereas children younger than 14 years are referred to centers abroad. All transplant programs are public, and no transplantation license has been issued in private health sector. The Hellenic Transplant Organization (HTO) has been established in 1999. The HTO is administratively responsible for organ donation and transplantation processes in Greece and provides oversight for the sharing of organs between Greece and other European countries. Central coordination is available around the clock facilitated by headquarters in Athens. Hellenic Transplant Organization cooperates with intensive care unit (ICU) coordinators to screen donor eligibility and to coordinate organ evaluation and allocation based on well-established protocols.

Tuberculous enteritis: a surgical ‘Janus’ masquerading as intestinal obstruction

Dear Sirs, Tuberculosis (TB) still represents a major morbidity and mortality cause during the post-transplant (PT) period among transplant recipients. Lungs are commonly involved. In renal transplant (RT) recipients, extrapulmonary (occurring in 15%) and disseminated diseases (33–49%) are very frequent [1], while intestinal involvement is extremely rare, with a reported prevalence between 0.2% and 0.6% [2]. Atypical presentation is the rule in immunocompromised patients, while high clinical suspicion is required. In immunosuppressed patients, the ulcerative component of disease is predominant due to decreased inflammatory response, rather than bowel wall inflammation with obstruction, making gastrointestinal bleeding the most common presenting symptom [2]. Despite this fact, bowel obstruction along with perforation was the initial manifestation in our case. A 46-year-old man underwent deceased-donor RT (01/ 08) for IgA-nephropathy end-stage renal disease (DonorCMV+/Recipient-CMV+). Induction therapy (IT) included daclizumab. Panel-reactive antibodies were 0%. Because of delayed renal graft function, hemodialysis required during the early PT period. He was discharged on the 19th postoperative day with creatinine level of 1.9 mg/dl. Four months PT, creatinine levels remained stable, while 24-h urine protein levels reached 532 mg/dl. Renal graft biopsy revealed changes of acute T-cell mediated rejection (ACR) (i1t1). Treatment with a 3-day course of i.v. pulses of 500 mg methylprednisolone and appropriate tapering followed. There was no change in the immunosuppressive regimen (ISR) afterward. Six years following RT he presented with acute abdominal pain and fever, distended abdomen and diffuse abdominal tenderness. Abdominal CT scan showed thickening of the wall of the terminal ileum with obstruction and enlarged mesenteric lymph nodes (Fig. 1a). Exploratory laparotomy revealed large quantities of purulent fluid, due to distal ileal perforation. Two palpable masses, occluding the lumen partially were detected. Segmental ileal resection was performed. Pathological investigation suggested the diagnosis of TB ileitis. Tissue specimens obtained from the resected bowel segment revealed few visible bacilli on acid-fast-stain (AFB). Macroscopic study of the resected specimen revealed caseous necrotic material and multiple ileal mucosa ulcerations (Fig. 1b). Microscopic examination showed submucosal granulomas with gigantic cells and caseous necrosis (Fig. 1c and d). Thoracic CT scan revealed no other focuses. Gastric aspirate culture, AFB and PCR, as well as blood culture and PCR of the surgical wound drainage were negative for TB. Escherichia coli was detected in the peritoneal fluid and blood culture and i.v. Meropenem was initiated according to the sensitivity, parallel to the anti-TB treatment with isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol (ETH). One week later patient remained febrile despite treatment and started deteriorating rapidly with intractable fevers, profound weakness, and hemodynamic instability. Abdominal CT scan revealed a walled-off subhepatic abscess. Exploratory laparotomy was performed, where a subcapsular–subhepatic infected hematoma, requiring partial liver resection of segment-VII, was removed. During surgery patient became hemodynamically unstable and after appropriate liver packing and initial resuscitation, he was admitted to the ICU. Unpacking of the liver was performed 48 h later. Pathological study of the resected liver specimen revealed granulomas around portal triads, characteristic for TB. After his admission to the ICU, patient started to develop abnormal liver function tests (LFT’s), (AST 152 U/l and ALT 168 U/l) and high levels of total bilirubin up to 10 mg/dl. It was decided to discontinue RIF, INH, and PZA and planned to reintroduce alternate anti-TB agents sequentially, adding 1 agent per week with closely LFT’s monitoring. His condition improved progressively while LFT’s normalized within 2 weeks; he was discharged afebrile with a plan to be seen weekly. Mycobacterium Tuberculosis (MT) is a well-known opportunistic agent following RT. Risk factors for PT–TB are diabetes mellitus, previous rejection episodes, rejection treatment with antilymphocyte globulin and bolus corticosteroids, IT with anti-CD25 agents and maintenance therapy

Donor‐origin cancer in renal transplant recipients from deceased donors: worth gambling?

Dear Sirs, Transmission of donor malignancies has been reported since the early days of clinical transplantation [1]. Literature stands equivocal upon these donors with many centers suggesting using these grafts under specific indications [1–4] and others supports its full rejection [5]. We present, to our knowledge, the first and only case of donor-origin malignancy in Greek national registry. A 56-year-old male deceased donor with RCC offered two kidneys in two recipients in two renal transplant centers in Greece. The left kidney presented with a solid single yellowish subcapsular nodule of the upper pole with a maximum diameter of 2.5 cm, during the back-table procedure, which was biopsied and sent for frozen section (FS). The results were negative for RCC. Thus, the first surgical team decided to proceed to the transplantation. At the same time, the second surgical team proceeded to the implantation of the right kidney in the other recipient. Both patients were in the same immunosuppression regimen (cyclosporine – CsA, mycophenolate mofetil – MMF, and corticosteroids). Final histological report revealed a type 2 papillary RCC. The difference with FS was attributed to the difficulty in distinguishing normal corticoadrenal spongiocytes from Fuhrman-I clear-cancer cells. Due to these findings and the diameter of the tumor, the first surgical team decided not just to excise the tumor but to proceed to allograft nephrectomy. The patient who received the contralateral (right) kidney was informed about the results of the histological report and gave informed consent to keep the allograft with strict follow-up instead of its excision. Both patients have been followed up for 4 years with blood chemistries and chest X-ray. The recipient of the right kidney also underwent allograft ultrasound every 6 months and annual abdominal CT scan. Both patients have shown no evidence of metastatic disease throughout their 48-month follow-up. The latter is still on MMF, CsA, and corticosteroids with a creatinine of 1.43 mg/dl (eGRF = 53). Donor-origin cancer in transplant recipients may be transmitted with the graft (donor-transmitted cancer; DTC) or develop subsequently from the graft. The majority of recipients with DTC could undergo explant/ excision with a disease-related mortality of 20% [6]. Five-year survival was 83% for kidney recipients with DTC compared with 93% for recipients without DTC (P = 0.077) [6]. Current recommendations suggest rejecting organs from donors with a history of melanoma and lung cancer and accepting the use of donor kidneys with a history of small, incidental RCC [2]. Moreover, it has been suggested that donor kidneys with small RCC Fuhrman grade-I/II may be transplanted after appropriate surgical excision because the risk of tumor recurrence is small and the benefits of a kidney transplantation are great [1]. Additionally, these grafts should be considered for transplantation into carefully selected patients with numerous comorbidities, who might benefit from renal transplantation, but not survive the waiting period to find a graft when in hemodialysis [7]. All in all, using grafts form deceased donors with RCC is a matter of debate. To draw meaningful conclusions on this topic, we require a long-term analysis of national and international registries. The conclusions would then have to be tempered with a certain degree of philosophical considerations as to the need and the risks associated with it. Our experience consorts with emerging literature that explantation/excision is likely to benefit recipients with localized and small RCCs, but in transplants other than kidney/pancreas and malignancies other than RCC, the benefits should be balanced against the risks of disease transmission and transmission-related mortality.

Vanishing leg ulcers

CALCIFIC UREMIC ARTERIOLOPATHY, also known as calciphylaxis, is a rare, often fatal complication usually associated with end-stage renal disease (ESRD). It is characterized by skin ulceration and necrosis, leading to significant pain. The incidence of calciphylaxis has risen in the last decade, with recent estimates as high as 5% of dialysis-dependent patients, but the true prevalence is likely unknown. The relevant literature regarding its management is primarily derived from case reports and small case series that frequently describe treatment decisions based on manipulating “risk factors,” such as female sex, obesity, diabetes, use of warfarin, low albumin levels, calciumbased phosphate binders, vitamin D analogs, and long-term use of high-dose iron salts. The main focus of the current literature is on the role of parathyroidectomy as a treatment for calciphylaxis in patients with persistent ESRD, as evidenced by contemporary publications. Here, we present an impressive case of a patient with ESRD and on hemodialysis who presented with leg ulcers due to calciphylaxis that vanished after total parathyroidectomy. A 53-year-old man with ESRD who was undergoing hemodialysis presented with painful, indurated, subcutaneous plaques with overlying livedo racemose and nonhealing, stellate-shaped ulcers covered by black eschar (Fig, A). Clinical examination revealed present pulses, and lower extremity Doppler ultrasonography identified biphasic arterial blood flow bilaterally. According to his medical history, the patient was also experiencing secondary hyperparathyroidism (parathyroid hormone level, 1,456 pg/mL) and an elevated calciumphosphorus product (84 mg/d) despite

Renal Transplantation with grafts affected by tumors: learning from a ‘near miss’ case

Dear Editors, It is common sense that one of the major problems for renal transplantation – and transplantation in general – is the discrepancy between the donor and recipient numbers with far less donor than recipients. As a consequence, patients with renal failure have to wait for a long time before they can be offered an allograft. In this frame of universal shortage of organs, efforts have been made to overcome it by exploring new sources of grafts by taking various measures including the use of marginal donors to increase the donor pool along with measures to improve and prolong graft function and survival. An additional potential area, first described by Penn [1], has been to transplant kidneys after ex vivo resection of small tumors. This was a very radical idea, because firstly, there has been evidence of transmission of donor-derived malignancy into recipient [2]. Surprisingly, outcomes of the patients described in Penn’s series were not as bad as could have been anticipated. Literature stands equivocal upon these donors with many centers, suggesting using these grafts under specific indications [2–5] and others supports its full rejection [6]. We have presented our experience on the issue by the first and only case of donor-origin malignancy in Greek national registry, when incidentally, the contralateral kidney of a donor with a 1.8 cm lesion with type-2 papillary renal cell carcinoma (PRCC) was successfully implanted to a recipient [7]. The aim of this report is to further discuss the rationale behind using this kind of grafts under the angle of a novel case. A 58-year-old woman deceased donor offered two kidneys in two recipients in our renal transplant center. The patient had no personal or family medical history of malignancies. The cause of her death was subarachnoid hemorrhage. She was on antihypertensive drugs. The left kidney presented with a solid red-cortical nodule of the outer surface with a maximum diameter of 2.5 cm, during the back-table procedure, which was completely excised with wide and free margins and sent for frozen section (FS). This finding was not described in the renal ultrasound examination that was made to the donor before the harvesting of the organs. The results were positive for malignancy. Thus, the surgical team found this graft as inappropriate and decided not to proceed to its implantation. It was sent to the Pathology Laboratory for its final histological examination. The final report of the left kidney revealed clear cell renal cell carcinoma (CCRCC), Fuhrman 2 (pT1a). The right kidney graft was also procured without any obvious lesions as far as its anatomy and morphology are concerned. The patients who were candidates for renal transplantation for the contralateral (right) kidney were objectively and meticulously informed about the results of the histological report of the left kidney, and none of them gave informed consent to proceed to the transplantation. Then, the graft was offered to the other transplantation units of the country, but none of them agreed to implant it. After these procedures and as the cold-ischemia time exceeded 72 h, this graft was also thought as inappropriate and was sent to Pathology for final histological examination, which revealed a 0.8 cm lesion with type-1 PRCC, Fuhrman 2 (pT1a). To our knowledge, this is the first case of concomitant different types of RCC in kidneys offered for transplantation. Normal practice when confronted with a tumor of kidney on procurement is to have an excision biopsy and histological confirmation of clear margins before any of the organs can be transplanted [8]. The incidence of RCC in the deceased donors was estimated at 0.9% [9]. In these cases, some authors also believe that the contralateral kidney cannot be used as well because of the concerns of micro-metastasis and bilaterality of some of the RCCs [8]. If one kidney is found to have a tumor, it is important that the other kidney is closely followed up. It is easier in the live donor setting, but in deceased donation, there has to be a central database for tracking the contralateral kidney which might be transplanted into a recipient in a different unit. It is of major interest as the transplantation of contralateral healthy kidneys from deceased donors is associated with a relatively high cancer

Vascular Complications after Renal Transplantation: Another Brick in the Wall.

We read with great interest the retrospective study of Ammi et al. on their experience on vascular complications after renal transplantation (KTx) with acceptable overall incidence of renal artery (1.3%) and renal vein thrombosis (0.3%). However, we have a few queries that we would like to get clarified by the authors. First of all, around 70% of the anastomoses were performed in common iliac axis which is different than usual surgical practice. Despite the fact that no study comparing the common iliac artery (CIA) and the external iliac artery (EIA) as recipient axis is published, the results from this study did not support the superiority of CIA after multivariate analysis. Beyond surgeons’ preference and experience, are there any technical reasons for that? We agree that a prospective study evaluating the incidence of vascular complications between CIA and EIA group will be elucidative. Moreover, the distribution of the patients in each group is not equal, and it is not demonstrated whether junior surgeons prefer EIA or not. According to our experience, EIA is easier to approach that makes it ‘‘friendlier’’ to a junior surgeon. Another issue to highlight is the fact that right kidney is thought as a risk factor for postoperative vascular complications with an odds ratio 2.5e3. The authors attributed this increased risk to the vascular reconstructions needed in the right kidney to elongate vessels to perform safe anastomoses. A recent study of similar design supported although that right kidney allografts are indeed correlated with increased incidence of vascular complications (thrombosis, not hemorrhage) but in a ratio hardly reaching 1.4. This difference could be partly attributed to the number of patients included in each study and surgeons’ experience on right kidney implantation. Another query that could be discussed is the very low number of living donor-related (LD) allografts in this study. Since LD allografts demonstrate better results in terms of postoperative vascular complications, how authors think that paucity of LD KTx affect their results? In addition, since only 3.2% of total allografts were from LD origin, how can the authors explain the 22.1% of

Surgical Dead End in a Renal Transplant Recipient Associated With a Rare Thrombohemorrhagic Syndrome

BACKGROUND Primary breast angiosarcoma is an extremely rare malignancy. Association of this type of tumor with Kasabach-Merritt syndrome has only been reported in 3 cases in the past. To our knowledge, this is the first reported case of a solid-organ recipient. METHODS A 53-year-old woman who underwent a deceased-donor renal transplantation 5 years previously presented with a 12-month history of a giant ulcerated lesion on her left breast. Biopsy of the overlying skin suggested primary angiosarcoma. Concurrently, the patients bleeding from the site of the biopsy and hematology investigations indicated the presence of Kasabach-Merritt syndrome. RESULTS The case was discussed in a multidisciplinary setting. The decision was to use anthracycline-based chemotherapy as up-front treatment to assess tumor response and gain a local benefit for a subsequent resection. After the completion of 1 cycle of chemotherapy, the patient died of cardiovascular insufficiency. Primary angiosarcoma of the breast occurs in the third to fourth decade and has been reported only in women. CONCLUSIONS A high clinical suspicion and referral to a specialized center are necessary. Total mastectomy appears to be the only treatment conferring benefit; chemotherapy and radiation therapy are of little value.