Radiation therapy with phenotypic medicine: towards N-of-1 personalization.

In current clinical practice, radiotherapy (RT) is prescribed as a pre-determined total dose divided over daily doses (fractions) given over several weeks. The treatment response is typically assessed months after the end of RT. However, the conventional one-dose-fits-all strategy may not achieve the desired outcome, owing to patient and tumor heterogeneity. Therefore, a treatment strategy that allows for RT dose personalization based on each individual response is preferred. Multiple strategies have been adopted to address this challenge. As an alternative to current known strategies, artificial intelligence (AI)-derived mechanism-independent small data phenotypic medicine (PM) platforms may be utilized for N-of-1 RT personalization. Unlike existing big data approaches, PM does not engage in model refining, training, and validation, and guides treatment by utilizing prospectively collected patient's own small datasets. With PM, clinicians may guide patients' RT dose recommendations using their responses in real-time and potentially avoid over-treatment in good responders and under-treatment in poor responders. In this paper, we discuss the potential of engaging PM to guide clinicians on upfront dose selections and ongoing adaptations during RT, as well as considerations and limitations for implementation. For practicing oncologists, clinical trialists, and researchers, PM can either be implemented as a standalone strategy or in complement with other existing RT personalizations. In addition, PM can either be used for monotherapeutic RT personalization, or in combination with other therapeutics (e.g. chemotherapy, targeted therapy). The potential of N-of-1 RT personalization with drugs will also be presented.

A case of metastatic lymphoepithelial carcinoma of parotid gland identified on 68gallium DOTA-[Tyr3] octreotate PET CT.

The authors present the case of a 59-year-old lady diagnosed with lymphoepithelial carcinoma (LEC) of the left parotid gland. The primary tumour was identified using contrast-enhanced CT, and diagnosis was confirmed via fine needle aspiration cytology and immunohistochemistry. Staging using fluorine-18 fluorodeoxyglucose PET CT revealed regional nodal metastases, while no distant metastasis was evident. Following radical radiotherapy, a favourable locoregional response was observed on MRI, yet the patient's plasma Epstein-Barr virus load continued to rise. Given her primary tumour's somatostatin receptor type 2 (SSTR2) positivity, gallium-68 DOTA-[Tyr3] octreotate PET CT (68Ga-DOTATATE PET CT) was performed, revealing multiple distant metastases with DOTATATE avidity. Despite attempts at palliative chemotherapy and immunotherapy, disease progression led to the decision for the best supportive care. The unique presentation of metastatic LEC on 68Ga-DOTATATE PET CT suggests a potential role for SSTR2-targeted imaging in diagnosis and management.

68 Ga-DOTATATE PET/CT of Metastatic Lymphoepithelial Carcinoma of Parotid Gland.

ABSTRACT: We present a case of a 59-year-old woman with lymphoepithelial carcinoma of left parotid gland. She was treated with radical radiotherapy, but her plasma Epstein-Barr virus DNA load continued to increase despite good locoregional response. As her primary tumor was positive for somatostatin receptor type 2, we performed 68 Ga-DOTATATE PET/CT, which revealed multiple DOTATATE-avid distant metastases.

The impact of the COVID-19 pandemic on nasopharyngeal carcinoma patients - a national cancer centre experience.

Purpose or objective: The COVID-19 pandemic has resulted in significant healthcare implications, with care for cancer patients compromised due to resource diversion towards battling the pandemic. We aim to investigate the impact of the peak wave of the pandemic in 2020 on the delivery of cancer care in Singapore, specifically via our nasopharyngeal carcinoma (NPC) treatment data. This study applies real world numbers to the impact of COVID-19 on cancer care delivery in Singapore. The choice of nasopharyngeal cancer allows a good direct estimate of common treatment measures such as time to biopsy, time to staging scans, time to treatment commencement, due to its clear protocol and algorithms for staging and treatment; thus serving as an excellent surrogate for the effectiveness and timeliness of the different aspects of cancer care delivery. Materials and methods: In this retrospective study, we included all patients with newly diagnosed NPC from 1st January to 31st May from 2017 to 2020 at our centre. This time period was chosen as it coincided with the period in 2020 during the COVID-19 pandemic where there was the most strain on healthcare resources and the most restrictions on population movement within Singapore, which may impact on healthcare seeking behaviour. Narrowing down the time period to the first 5 months of the 4 respective years also allowed us to reduce the effect of annual seasonal variation in patient numbers seen as a result of holidays and festive periods such as the Lunar New Year and scheduled school holidays. Electronic medical records (EMR) were accessed. Only newly diagnosed NPC cases were included in our analysis. Patients with second synchronous primary malignancies or NPC disease recurrence were excluded. Data analysis was carried out using a combination of SPSS and Microsoft Excel. Results: Significantly, there was a reduction of 37-46.3% in newly diagnosed NPC cases during the peak of the COVID-19 pandemic from January to end May 2020 compared to the preceding three years. Despite the reduction in numbers of newly diagnosed NPC, there was no statistically significant differences in delay from biopsy to the first radiation oncology visit and from biopsy to the first day of treatment in 2020 compared to the preceding years. All the patients treated in our centre also received the standard NPC treatment for their disease stage as per international guidelines. Conclusion: We recommend a heightened awareness of the dangers of delaying cancer presentation and care in healthcare policies and resource allocation and at the same time, encourage patient's confidence in their ability to seek care. With the resurgence of new COVID-19 variants and case numbers worldwide and in Singapore, this study focuses upon the need to be aware of the exigencies of other clinical groups in resource utilization. It would be instructive to compare this study with future long term follow up to investigate the trajectory of our cancer care delivery, as well as survival outcomes.

PSMA PET Imaging and Therapy in Adenoid Cystic Carcinoma and Other Salivary Gland Cancers: A Systematic Review.

Adenoid cystic carcinoma (ACC) and other salivary gland cancers (SGCs) are rare tumors where application of prostate specific membrane antigen (PSMA) positron emission tomography (PET) and PSMA radioligand therapy have yet to be studied extensively. This review explores the role of PSMA PET imaging and therapy as a theranostic tool for ACC and other SGCs based on current literature. A comprehensive literature search on PubMed and Embase was performed. All relevant studies containing information on PSMA PET imaging in ACC and SGC were included. Ten studies (one prospective, three retrospective, five case reports and one review paper) were included. For ACC, the mean maximum standardized uptake value (SUVmax) for local recurrence and distant metastases ranged from 2.41 to 13.8 and 2.04 to 14.9, respectively. In SGC, the meanSUVmax ranged from 1.2-12.50. Most studies observed PSMA expression positivity on immunohistochemistry (IHC) when there was PSMA PET uptake. PSMA PET was able to detect lesions not detected on standard imaging. Despite the small number of studies and wide intra-patient and inter-tumor variation of PSMA uptake in ACC and SGC, 68Gallium (68Ga)-PSMA PET has promising prospects as a diagnostic and radioligand therapeutic option. Further studies to answer the various theranostics considerations are required to guide its use in the real-world setting.

FBXW24 controls female meiotic prophase progression by regulating SYCP3 ubiquitination.

BACKGROUND: An impeccable female meiotic prophase is critical for producing a high-quality oocyte and, ultimately, a healthy newborn. SYCP3 is a key component of the synaptonemal complex regulating meiotic homologous recombination. However, what regulates SYCP3 stability is unknown. METHODS: Fertility assays, follicle counting, meiotic prophase stage (leptotene, zygotene, pachytene and diplotene) analysis and live imaging were employed to examine how FBXW24 knockout (KO) affect female fertility, follicle reserve, oocyte quality, meiotic prophase progression of female germ cells, and meiosis of oocytes. Western blot and immunostaining were used to examined the levels & signals (intensity, foci) of SYCP3 and multiple key DSB indicators & repair proteins (γH2AX, RPA2, p-CHK2, RAD51, MLH1, HORMAD1, TRIP13) after FBXW24 KO. Co-IP and immuno-EM were used to examined the interaction between FBXW24 and SYCP3; Mass spec was used to characterize the ubiquitination sites in SYCP3; In vivo & in vitro ubiquitination assays were utilized to determine the key sites in SYCP3 & FBXW24 for ubiquitination. RESULTS: Fbxw24-knockout (KO) female mice were infertile due to massive oocyte death upon meiosis entry. Fbxw24-KO oocytes were defective due to elevated DNA double-strand breaks (DSBs) and inseparable homologous chromosomes. Fbxw24-KO germ cells showed increased SYCP3 levels, delayed prophase progression, increased DSBs, and decreased crossover foci. Next, we found that FBXW24 directly binds and ubiquitinates SYCP3 to regulate its stability. In addition, several key residues important for SYCP3 ubiquitination and FBXW24 ubiquitinating activity were characterized. CONCLUSIONS: We proposed that FBXW24 regulates the timely degradation of SYCP3 to ensure normal crossover and DSB repair during pachytene. FBXW24-KO delayed SYCP3 degradation and DSB repair from pachytene until metaphase II (MII), ultimately causing failure in oocyte maturation, oocyte death, and infertility.

Rare location and drainage pattern of right pulmonary veins and aberrant right upper lobe bronchial branch: A case report.

BACKGROUND: Complex aberration in lung is rare, which may increase risk of vascular injury and cause ligation of wrong pulmonary vein or bronchus by mistake during lung surgery, and result in sever complication like pulmonary congestion or atelectasis. CASE SUMMARY: A 44-year-old female was admitted for a ground glass nodule (24 mm in diameter) in her right upper lobe. Video-assisted thoracoscopic (VATS) right upper lobectomy with lymph nodes dissection was performed. During operation, we simultaneously identified extremely rare aberrations of right preeparterial bronchus, right upper lobe vein behind pulmonary artery and right middle lobe vein drained into left atrium in this patient. The patient was well recovered and discharged at the postoperative-day 4. CONCLUSION: Preoperatively, three-dimensional reconstruction can help to identify inconspicuous variation of pulmonary vessels and bronchus effectively. During lung surgery, if anatomic aberration is suspected, careful dissection of vessels and bronchus will help to confirm whether there is an aberration or not.

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma.

OBJECTIVE: Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma. METHODS: A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection. RESULTS: Both NLR (median ∆+2.8 [IQR -0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3-523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02-1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01-1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39-10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21-0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01-1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01-1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55-10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21-0.80, p = 0.009) were independent prognostic factors for PFS. CONCLUSION: Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC. ADVANCES IN KNOWLEDGE: We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.

Long non-coding RNA RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis.

A newly identified lncRNA designated as RP11-284P20.2 has been identified to be up-regulated in hepatocellular carcinoma (HCC), but its role in HCC remain poorly understood. Quantitative PCR and immunocytochemical analysis were performed using the HCC tissues to identify the potential interaction partners of RP11-284P20.2. Moreover, RP11-284P20.2 was knocked down in HCC cell lines, HepG2 and SMMC7721, to investigate the influence of this lncRNA on cell growth properties. Additionally, RNA fluorescence in situ hybridization and immunofluorescence, RNA immunoprecipitation, and RNA pull-down assays were performed to determine the interaction of RP11-284P20.2 with c-met mRNA and eukaryotic translation initiation factor 3b (EIF3b). Silencing RP11-284P20.2 inhibited cell viability, migration, invasion, and colony formation, and increased apoptosis. Overexpression of c-met abolished these effects of RP11-284P20.2 in HCC cells. Histopathological examination showed that HCC tissues with high RP11-284P20.2 expression had higher c-met protein level than that in HCC tissues with low RP11-284P20.2 expression. However, there was no positive correlation between the expression levels of RP11-284P20.2 and c-met mRNA. RP11-284P20.2 knockdown led to a decease in c-met protein expression level, but did not affect the c-met mRNA expression level. These data suggest that RP11-284P20.2 regulates c-met protein expression level, which is independent of c-Met mRNA expression level. It was also confirmed that RP11-284P20.2 has high affinity toward both c-met mRNA and EIF3b protein, and hence RP11-284P20.2 probably recruits EIF3b protein to c-met mRNA and further facilitates its translation. RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis.

Single xenotransplant of rat brown adipose tissue prolonged the ovarian lifespan of aging mice by improving follicle survival.

Prolonging the ovarian lifespan is attractive and challenging. An optimal clinical strategy must be safe, long-acting, simple, and economical. Allotransplantation of brown adipose tissue (BAT), which is most abundant and robust in infants, has been utilized to treat various mouse models of human disease. Could we use BAT to prolong the ovarian lifespan of aging mice? Could we try BAT xenotransplantation to alleviate the clinical need for allogeneic BAT due to the lack of voluntary infant donors? In the current study, we found that a single rat-to-mouse (RTM) BAT xenotransplantation did not cause systemic immune rejection but did significantly increase the fertility of mice and was effective for more than 5 months (equivalent to 10 years in humans). Next, we did a series of analysis including follicle counting; AMH level; estrous cycle; mTOR activity; GDF9, BMP15, LHR, Sirt1, and Cyp19a level; ROS and annexin V level; IL6 and adiponectin level; biochemical blood indices; body temperature; transcriptome; and DNA methylation studies. From these, we proposed that rat BAT xenotransplantation rescued multiple indices indicative of follicle and oocyte quality; rat BAT also improved the metabolism and general health of the aging mice; and transcriptional and epigenetic (DNA methylation) improvement in F0 mice could benefit F1 mice; and multiple KEGG pathways and GO classified biological processes the differentially expressed genes (DEGs) or differentially methylated regions (DMRs) involved were identical between F0 and F1. This study could be a helpful reference for clinical BAT xenotransplantation from close human relatives to the woman.

Precision De Novo Peptide Sequencing Using Mirror Proteases of Ac-LysargiNase and Trypsin for Large-scale Proteomics.

De novo peptide sequencing for large-scale proteomics remains challenging because of the lack of full coverage of ion series in tandem mass spectra. We developed a mirror protease of trypsin, acetylated LysargiNase (Ac-LysargiNase), with superior activity and stability. The mirror spectrum pairs derived from the Ac-LysargiNase and trypsin treated samples can generate full b and y ion series, which provide mutual complementarity of each other, and allow us to develop a novel algorithm, pNovoM, for de novo sequencing. Using pNovoM to sequence peptides of purified proteins, the accuracy of the sequence was close to 100%. More importantly, from a large-scale yeast proteome sample digested with trypsin and Ac-LysargiNase individually, 48% of all tandem mass spectra formed mirror spectrum pairs, 97% of which contained full coverage of ion series, resulting in precision de novo sequencing of full-length peptides by pNovoM. This enabled pNovoM to successfully sequence 21,249 peptides from 3,753 proteins and interpreted 44-152% more spectra than pNovo+ and PEAKS at a 5% FDR at the spectrum level. Moreover, the mirror protease strategy had an obvious advantage in sequencing long peptides. We believe that the combination of mirror protease strategy and pNovoM will be an effective approach for precision de novo sequencing on both single proteins and proteome samples.

The tumor suppressor DLC1 inhibits cancer progression and oncogenic autophagy in hepatocellular carcinoma.

Downregulation of deleted in liver cancer 1 (DLC1) is associated with poor prognosis of various cancers, but its functional mechanisms in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the roles of DLC1 in tumor progression and autophagy of HCC. We found that DLC1 was frequently downregulated in HCC tissues. Underexpression of DLC1 correlated with AFP level, vascular invasion, poor differentiation, and poor prognosis. In vitro assays revealed that DLC1 not only suppressed the proliferation, migration, and invasion of HCC cells, but also inhibited autophagy of HCC cells. Mechanistic investigation revealed that DLC1 decreased TCF4 expression and the interaction between ß-catenin and TCF4, then inactivated Wnt/ß-catenin signaling. Additionally, DLC1 suppressed the ROCK1 activity and the dissociation of the Beclin1-Bcl2 complex, thereby inhibiting autophagy of HCC cells. In conclusion, our findings imply that loss of DLC1 contributes to the progression and oncogenic autophagy of HCC.

Long Noncoding RNA HCAL Facilitates the Growth and Metastasis of Hepatocellular Carcinoma by Acting as a ceRNA of LAPTM4B.

Long noncoding RNAs (lncRNAs) are a new class of regulatory noncoding RNAs. Emerging evidences indicate that lncRNAs play a critical role in the development of hepatocellular carcinoma (HCC). Although several lncRNAs have been annotated, the association of most lncRNAs with HCC is unknown. In this study, we investigated lncRNA alterations in HCC by performing lncRNA microarray analysis. We identified a novel lncRNA called HCC-associated lncRNA (HCAL) that was highly expressed in HCC tissues. HCAL upregulation was clinically associated with poor differentiation, intravascular cancer embolus, and decreased survival of patients with HCC. HCAL silencing significantly inhibited the growth and metastasis of HCC cells both in vitro and in vivo. Interestingly, transcriptome-sequencing analysis of HCAL-knockdown cells showed alterations in some cancer-related pathways. Mechanistically, HCAL directly interacted with and functioned as a sponge for microRNAs such as miR-15a, miR-196a, and miR-196b to modulate LAPTM4B expression. Taken together, our findings suggest the presence of a novel lncRNA-miRNA-mRNA regulatory network, i.e., the HCAL-miR-15a/miR-196a/miR-196b-LAPTM4B network, in HCC and indicate that HCAL may be a potential target for treating HCC.

Inhibition of invasion by N-trans-feruloyloctopamine via AKT, p38MAPK and EMT related signals in hepatocellular carcinoma cells.

N-trans-feruloyloctopamine (FO) isolated from Garlic skin was identified as the primary antioxidant constituents, however, the effect of which on HCC invasion is still unclear. Herein, the FO was synthesized and its antitumor activities were evaluated in HCC cell lines. Cellular functional analyses have revealed that the reformed FO owns strong abilities of inhibiting cell proliferation and invasion in HCC cells. Molecular data have further showed that FO could significantly decrease the phosphorylation levels of Akt and p38 MAPK. In addition, the expression of Slug was inhibited and the level of E-cadherin increased. Molecular docking analysis indicates that the H-bond and hydrophobic interactions were critical for FO and E-cadherin binding, but FO did not seem to act directly on phosphorylated Akt and p38 MAPK. We have thus concluded that reformed FO inhibits cell invasion might be directly through EMT related signals (E-cadherin) and indirectly through PI3K/Akt, p38 MAPK signaling pathways. FO might be a promising drug in HCC treatment and prognosis.

Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells.

Dysregulation of inhibitor of apoptosis (IAP) proteins (IAPs) in hepatocellular carcinoma (HCC) is often associated with poor prognosis. Here we showed that AT406, an IAP antagonist, was cytotoxic and pro-apoptotic to both established (HepG2, SMMC-7721 lines) and primary HCC cells. Activation of mTOR could be a key resistance factor of AT406 in HCC cells. mTOR inhibition (by OSI-027), kinase-dead mutation or knockdown remarkably enhanced AT406-induced lethality in HCC cells. Reversely, forced-activation of mTOR by adding SC79 or exogenous expressing a constitutively active S6K1 (T389E) attenuated AT406-induced cytotoxicity against HCC cells. We showed that AT406 induced degradation of IAPs (cIAP-1 and XIAP), but didn't affect another anti-apoptosis protein Mcl-1. Co-treatment of OSI-027 caused simultaneous Mcl-1 downregulation to overcome AT406's resistance. Significantly, shRNA knockdown of Mcl-1 remarkably facilitated AT406-induced apoptosis in HCC cells. In vivo, AT406 oral administration suppressed HepG2 tumor growth in nude mice. Its activity was potentiated with co-administration of OSI-027. We conclude that mTOR could be a key resistance factor of AT406 in HCC cells.

Discovery of serum proteomic biomarkers for prediction of response to moxibustion treatment in rats with collagen-induced arthritis: an exploratory analysis.

OBJECTIVE: To examine the possible impact of moxibustion on the serum proteome of the collagen-induced arthritis (CIA) rat model. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley rats were included in this experiment. The CIA animal model was prepared by injection of type II bovine collagen in Freund's adjuvant on the first and seventh day. The 36 rats were randomly divided into two groups: the untreated CIA group (control), and the CIA plus treatment with moxibustion (CIA+moxi) group. Moxibustion was administered daily at ST36 and BL23 for 7, 14 or 21 days (n=12 rats each). Arthritis score was used to assess the severity of arthritis. At the end of each 7 day treatment, blood samples from the control group and the CIA+moxi group were collected. After removal of high abundance proteins from serum samples, two-dimensional gel combined with matrix-assisted laser desorption ionisation time-of-flight MS/MS (MALDI-TOF-MS/MS) techniques were performed to examine serum protein expression patterns of the CIA rat model with and without moxibustion treatment. In addition, the relevant proteins were further analysed with the use of bioinformatics analysis. RESULTS: Moxibustion significantly decreased arthritis severity in the rats in the CIA+moxi group, when compared with the rats in the CIA group 35 days after the first immunisation (p=0.001). Seventeen protein spots which changed >1.33 or <0.77 at p<0.05 using Bonferonni correction for multiple testing were found to be common to all three comparisons, and these proteins were used for classification of functions using the Gene Ontology method. Consequently, with the use of the Ingenuity Pathway Analysis, the top canonical pathways and a predicted proteomic network related to the moxibustion effect of CIA were established. CONCLUSIONS: Using the proteomics technique, we have identified novel candidate proteins that may be involved in the mechanisms of action underlying the beneficial effects of moxibustion in rats with CIA. Our findings suggest that immune responses and metabolic processes may be involved in mediating the effects of moxibustion. Moreover, periodxiredoxin I (PRDX1) and inositol 1,4,5-triphosphate receptor (IP3R) may be potential targets.

Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma.

Chromodomain helicase DNA binding protein 5 (CHD5) acts as a tumor suppressor in many cancers. In the present study, we demonstrated that reduced levels of CHD5 in hepatocellular carcinoma (HCC) tissues were significantly associated with metastasis and poor prognosis. Gain-of-function assays revealed that CHD5 suppressed motility and invasion of HCC cells. Subsequent investigations showed that CHD5 was epigenetically silenced by polycomb repressive complex 2 (PRC2)-mediated the trimethylation of histone H3 at lysine 27 (H3K27me3) in HCC cells. Furthermore, overexpression of CHD5 repressed enhancer of zeste homolog 2 (EZH2) and activated PRC2 target genes, such as p16 and p21. Chromatin immunoprecipitation and luciferase reporter assays also showed that CHD5 and EZH2 bind to each other's promoters and inhibit transcription. These findings uncovered, for the first time, a mutual suppression regulation between CHD5 and EZH2, which may provide new insights into their potential therapeutic significance for HCC.

Ex vivo hepatectomy and partial liver autotransplantation for hepatoid adenocarcinoma: A case report.

We previously reported the case of a 56-year-old male who underwent surgical treatment for gastric hepatoid adenocarcinoma and splenic metastasis. The present study reports the case of the same patient who underwent successful ex vivo hepatectomy and partial liver autotransplantation. Computed tomography scans demonstrated that the tumor was located in the left and caudate lobes of the liver, with hepatic vein and inferior vena cava involvement, and right portal vein compression. To clarify the association between the vessels and the tumor, a three-dimensional imaging technique was used to reconstruct the liver architecture. During the surgery, the whole liver was removed with the retrohepatic vena cava, which was replaced with a prosthetic graft without a veno-venous bypass; a portacaval shunt for the anhepatic phase was performed simultaneously. The surgery lasted 9 h, and the anhepatic phase lasted 4 h. Blood loss during the surgery was recorded at 1,500 ml. The time taken for recovery was 21 days post-surgery, and at 20 months, the patient was disease-free. To the best of our knowledge, this is the first case of ex vivo liver resection performed for hepatic metastasis of hepatoid adenocarcinoma to be reported.