Synchronous hepatocellular carcinoma and gallbladder adenocarcinoma with neuroendocrine differentiation: a case report and literature review

Background Double primary cancers have a low incidence rate, and synchronous hepatocellular carcinoma and gallbladder adenocarcinoma are rarely reported. Here, we report such a case— the 12th case of synchronous double primary cancers featuring HCC and GC, but the first case of neuroendocrine differentiation in the gallbladder. Case presentation A 77-year-old female was admitted to the hospital complaining of weakness and inappetence for six months. Contrast-enhanced computed tomography (CT) of the abdomen indicated an 11 cm space-occupying lesion in the right lobe of the liver. Later, magnetic resonance imaging showed a high possibility of a massive hepatoma, and multiple gallstones were also seen. After transhepatic arterial chemoembolization, a repeat abdominal CT showed obvious local nodular thickening in the gallbladder wall. Finally, resection of the right lobe of the liver and cholecystectomy were performed. During an approximately 2-year follow-up, the patient recovered uneventfully without recurrence or metastasis. Conclusion The disease in this case is rare and lacked typical radiological features. More precise and advanced diagnostic techniques are needed to obtain a clear diagnosis and refine treatment strategies. The management strategy should always be curative, even in the presence of multiple malignancies.

Dual EGFR and ABL Tyrosine Kinase Inhibitor Treatment in a Patient with Concomitant EGFR-Mutated Lung Adenocarcinoma and BCR-ABL1-Positive CML

Tyrosine kinase inhibitor (TKI) combination is expected to increase in the era of precision medicine. TKI combination may be required to treat double primary cancers, each having a targetable gene, or to treat a single malignancy with multiple targetable genes. Here, we demonstrate the first report of dual EGFR and ABL TKI treatment in a patient with concomitant EGFR-mutated lung adenocarcinoma and BCR-ABL1-positive chronic myeloid leukemia (CML). A 60-year-old man with an 8-year history of CML was diagnosed as advanced EGFR-mutated lung adenocarcinoma. Complete molecular response of CML had been achieved by imatinib, and ABL-TKI had been switched to nilotinib four years previously due to muscle cramps. We discontinued nilotinib and started afatinib. Although partial response of lung adenocarcinoma was achieved, cytogenetic relapse of CML was observed following nilotinib discontinuation. We applied the previously described framework of cytochrome P450 3A4-mediated oral drug-drug interactions and selected gefitinib and nilotinib to treat both malignancies. We effectively and safely administered this combination for seven months. The present report is the first to demonstrate the safety and efficacy of dual EGFR and ABL TKI treatment in a patient with concomitant EGFR-mutated lung adenocarcinoma and CML.

Genetic epidemiology of colorectal cancer and associated cancers

We review here data on familial risk in colorectal cancer (CRC) generated from the Swedish Family-Cancer Database, the largest resource of its kind in the world. Although the concordant familial risk for CRC (i.e. CRC risk in families of CRC patients) has been reasonably well established, the studies on discordant familial risks (i.e. CRC risk in families with any other cancers) are rare. Because different cancers could be caused by shared genetic susceptibility or shared environment, data of associations of discordant cancers may provide useful information for identifying common risk factors. In analyses between any of 33 discordant cancers relative risks (RRs) for discordant cancers were estimated in families with increasing numbers of probands with CRC; in the reverse analyses, RRs for CRC were estimated in families with increasing numbers of probands with discordant cancers. In separate analyses, hereditary non-polyposis colorectal cancer (HNPCC) families were excluded from the study, based on HNPCC related double primary cancers, to assess the residual familial RRs. We further reviewed familial risks of colon and rectal cancers separately in search for distinct discordant associations. The reviewed data suggested that colon cancer was associated with a higher familial risk for CRC compared to rectal cancer. The previous data had reported associations of CRC with melanoma, thyroid and eye cancers. Nervous system cancer was only associated with colon cancer, and lung cancer only associated with rectal cancer. The reviewed data on discordant association may provide guidance to gene identification and may help genetic counseling.

Simultaneous Resection for Synchronous Double Primary Cancers of the Pancreas and the Liver

Simultaneous resection of synchronous hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) is extremely rare. Case 1 is a 64-year-old woman, who had undergone anterior resection for rectal cancer 3 years earlier was pointed out to have a cystic tumor in the pancreatic tail and a solitary tumor in the liver. CT revealed a hypovascular tumor in the pancreatic tail and a liver tumor with early enhancement. With a diagnosis of simultaneous HCC and PDAC, she underwent laparotomy, in which intraoperative frozen section examination of the liver was compatible with HCC. Therefore, she underwent hepatic resection as well as distal pancreatectomy and splenectomy. The patient received adjuvant chemotherapy with S-1 and remains well with no evidence of tumor recurrence as of 28 months after resection. Case 2 is a 73-year-old man with sustained viral response to antiviral treatment for hepatitis C virus, who was pointed out to have a tumor in the pancreatic head and a solitary tumor in the liver. Gadoxetic acid-enhanced MRI exhibited enhancement compatible with HCC. With a diagnosis of concomitant HCC and PDAC, surgery was performed. Intraoperative frozen section examination was compatible with HCC, for which a pancreaticoduodenectomy was performed. The patient received adjuvant chemotherapy with S-1 and remains well with no evidence of tumor recurrence as of 16 months after resection. In conclusion, we describe 2 cases of hepato-pancreatectomy for synchronous double primary cancers of the pancreas and the liver, where exclusion of the liver tumor as a metastatic lesion from the pancreatic cancer is important.