Myeloproliferative disorders leading to Budd–Chiari syndrome are not contraindications for LTx according to Saigal et al. [6] and Benten et al. [7]. These can be treated while waiting on the list, or after transplant. Saigal et al. reported six cases of myeloproliferative disorder requiring liver transplant; one patient developed leukemia 6 years after transplant [6]. Benton et al. reported 11 cases of hematological malignancy including seven cases of myeloproliferative disorder with Budd–Chiari syndrome ; none had a recurrence of the disease or leukemia within a median follow-up of 66 months [7].

Post-LTx recurrence in the presence of non-resectable neuroendocrine/carcinoid metastases is very high, and LTx usually should not be considered. However, in highly selected cases, LTx may be justified. Olausson et al. suggested criteria for undertaking LTx in cases with carcinoid and pancreatic endocrine tumor : (1) hepatic tumor recurrence after surgery for cure; (2) non-resectable hepatic, metastatic disease, especially in cases of severe hormonal symptoms; and (3) disease progression after hepatic arterial embolization and medical therapy [9]. He felt that LTx may provide these patients with a favorable prognosis. No doubt, there was a risk of recurrence of tumor; however, due to the relatively indolent nature of neuroendocrine and carcinoid tumor, the LTx could potentially provide substantial years of acceptable quality life.

Serralta et al. reported three cases of LTx done for gastrointestinal stromal tumors [10]. He suggested choosing cases with GI stromal tumors sensitive to Imatinib (antineoplastic drug) that could control the potential recurrence of the tumor. Van Vilsteren et al. described 19 patients who underwent LTx for gastroenteropancreatic neuroendocrine tumors [11]. These included 11 cases of pancreatic islet cell tumor with a recurrence rate of about 23 %, whereas eight patients with carcinoid remained free of disease.

In the last 8 years, European centers have provided more details on the subject. Mazzaferro et al. summarized nine studies consisting of 203 patients, where LTx for metastatic neuroendocrine tumors was performed [12]. Recurrence-free survival up to 50 % at 3 years and 24 % at 5 years was noted. He has proposed the Milan criteria of exclusion and inclusion for LTx with neuroendocrine metastatic disease. De Herder et al. has proposed multidisciplinary surgical approach to treat the condition with hepatic resection and LTx [13]. Recently, Le Treut et al. summarized 213 cases from 35 LTx centers in 11 European countries from 1982 to 2009 with mean follow-up of 56 months [14]. Eighty-six patients (40.4 %) died from recurrence of the disease 4–165 months post-LTx, suggesting that LTx should be considered in highly selective cases with strict criteria.

Usually neuroendocrine with hepatic metastasis may not have liver failure and may not acquire adequate MELD score to get a liver for transplant purpose. United Network for Organ Sharing (UNOS) has developed strict guidelines for MELD exception points for these cases so that they may get a liver in about a year. Given these strict guidelines, live donor liver transplant in this situation could provide a suitable alternative to waiting for standard allocation.

Cutaneous epidermal malignancies (other than melanoma and Kaposi’s) prior to LTx are not considered a contraindication, since they are usually locally invasive. Recurrence of these types of skin cancers post-LTx is almost always expected. However, these are not accounted for in the tumor registry data and are not uniformly tracked or reported by transplant centers Routine follow-up with dermatologist is strongly recommended for early detection and timely excision of skin cancers. Epidermal lesions of the skin lying close to bone and cartilage or perianal region could invade and spread if left unattended for too long, and hence needs careful evaluation.

One of the most common long-term causes of death after successful LTx is related to de novo cancer, often with a functioning allograft . As alluded to before, incidence increases with the age of the recipient at the time of transplant and length of follow-up [15–19].

Increased incidence of de novo cancers after solid transplant was first predicted in 1968 by Stazal et al. [20]. This was subsequently confirmed by Penn and Starzl [21] and McKhann [22]. Since then, there have been several attempts to organize this data. Initial reports were from the Israel Penn International Transplant Tumor Registry (IPITTR ) [23]. Subsequently, the Australia and New Zealand Liver Transplant Joint Registry started reporting their data [24]. Additionally, large transplant centers in Texas, Pittsburg, Berlin, Mount Sinai, London, Baylor, Madrid, Valencia, California, Bacelona, and Korea compiled their own data (Table 15.2) [1, 5, 24–34]. There has been wide variation in the incidence of de novo cancers reported, ranging from 2.3 to 12.3 %. There are few explanations to account for these variations. For one thing, reporting in the literature has remained inconsistent; some have included lymphoid malignancies (post-transplant lymphoproliferative disorder, PTLD) while others have excluded them. Also, a majority of the reports have included locally malignant basal cell and squamous cell carcinoma of the skin along with melanoma and Kaposi’s sarcoma of the skin. Meanwhile, others have separated them in calculating the incidence. Additionally, the length of follow-up is different in all citations, and some studies have included children while others have excluded them. The mean age group of the transplant population and the distribution of age groups are different between the studies. Twelve large studies have been summarized in Table 15.2. A total of 10,235 post-LTx recipients had 877 (8.57 %) de novo malignancies. No doubt, these do provide useful information on the incidence of de novo cancer and its impact on post-transplant patients’ survival; however, it does not compare the actual standard incidence ratio (SIR), which compares the general population in the same geographical location matched for age, gender, and length of follow-up.

An attempt at such comparison was made by us in 1998, when post-transplant patients at risk (matched by age, gender, and person-years ; by adding the number years for each patient from LTx to last alive) were compared with national SEER (Surveillance Epidemiology End Results) data [35]. This compared the observed incidence of de novo cancer in the study population with expected occurrence from the SEER data, and a standardized incidence rate (SIR) was developed. The expected occurrence for the study population was calculated using a statistical method described by Marsh et al. [36]. A ratio of observed over expected was generated to arrive at SIR. The SIR of <1.0 signified a lower than expected rate, while a ratio of >1.0 signified an increased rate for given type of cancer in the study population. Since then, there have been many reports where the incidences of de novo cancers have been reported with a 95 % confidence interval (CI). A decade later, Rostgaard described another similar methodology [37]. We feel that this unified system of reporting is more informative and useful, as it eases comparison.

We found a total of 15 studies where SIR had been provided with a 95 % confidence interval for various cancer sites (Table 15.3) [35, 38–51]. Some differences are readily apparent. There is also a difference in the incidence and nature of de novo malignancies in various parts of the world. There are certain geographical, population-related risk factors and disease processes that have been identified which increase the risk for certain types of cancers. For example, the relationship between inflammatory bowel disease (IBD) and colon cancer, Barrett’s esophagus and esophageal cancer, and ethanol and/or smoking with oropharyngeal or lung cancer is well known.