Which is a more appropriate recipient for posterior circulation bypass surgery: V3 or V2? Differences in underlying disease and lesion sites between extracranial vertebral artery dissection and atherosclerotic changes. Illustrative cases.

BACKGROUND: Revascularization for extracranial vertebral artery dissection or vertebral artery atherosclerotic occlusive lesions caused by vertebrobasilar insufficiency or posterior circulation infarction is relatively rare. When bypassing the cervical external carotid artery (ECA) or common carotid artery (CCA) using a radial artery (RA) or saphenous vein (SV) graft, it is difficult to determine whether the recipient site should be the V2 or V3 portion. OBSERVATIONS: In case 1, cervical ECA-RA-V3 bypass was performed for bilateral extracranial vertebral artery dissection with the onset of ischemia, and cervical CCA-SV-V3 bypass was added 12 days later. Nine years after surgery, the bilateral vertebral artery dissection had improved, and the patient still had a patent bypass. In case 2, cervical ECA-RA-V2 bypass was performed for arteriosclerotic bilateral extracranial vertebral artery occlusion. The bypass was patent 5 years after surgery. The postoperative course was uneventful in both patients. LESSONS: The authors present cases of posterior fossa revascularization using the vertebral artery V3 and V2 portions via skull base surgery and note that it is important to consider each patient's individual characteristics when selecting the V3 or V2 portion.

Primary intraosseous cavernous hemangioma of the clivus: A case report and literature review.

Background: The radiographic presentation of the primary intraosseous cavernous hemangiomas (PICHs) is nonspecific. We report a case of clival PICH mimicking a chordoma with a literature review. Case Description: A 57-year-old woman presented with diplopia that started a few days before the presentation. She had transient diplopia at the right lateral gaze and upper gaze with normal eye movement. The symptoms disappeared spontaneously 1 week later. She had no other complaints or neurological deficits. Computed tomography revealed an intraosseous mass lesion and bone erosion of the middle and lower clivus, extending laterally to the right occipital condyle. Magnetic resonance imaging (MRI) showed hyperintense and hypointense components on T2- and T1-weighted images, respectively. The lesion was larger than on MRI performed 10 years earlier. Chordoma or chondroma was considered a possible preoperative diagnosis. An endoscopic transsphenoidal approach removed the tumor. In the operating view, the lesion appeared as "moth-eaten" bony interstices filled with vascular soft tissue. Histologically, an intraosseous cavernous hemangioma was diagnosed. Conclusion: Diagnosis before surgery is difficult without characteristic radiographic findings. When making a differential diagnosis of malignant skull lesions, PICH should be considered.

Covered self-expandable metallic stent placement for tumor bleeding from duodenal invasion in patients with unresectable pancreatic cancer.

Patients with unresectable pancreatic cancer often present with duodenal bleeding, a potentially life-threatening complication. In our case series of six unresectable pancreatic cancer patients with tumor bleeding, we explored the efficacy and safety of placement of a covered self-expandable metallic stent in the duodenum as a treatment option; we achieved a hemostasis rate of 67% (4/6), with a rebleeding rate of 50% (2/4). No complications occurred with stent placement, except for food impaction in one patient. Covered self-expandable metallic stent placement is a moderately effective treatment option for tumor bleeding in patients with unresectable pancreatic cancer. Although its hemostatic efficacy is limited, covered self-expandable metallic stent placement is safe and beneficial in some cases, warranting consideration in this disease setting with limited treatment options.

Treatment outcomes of gemcitabine plus nab-paclitaxel in pancreatic cancer patients with malignant ascites.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) therapy has been shown to improve the prognosis in patients with metastatic pancreatic cancer (PC); however, the efficacy and safety of GnP in PC patients with malignant ascites (MA) remains unknown. METHODS: We retrospectively investigated PC patients with peritoneal dissemination who had received GnP as first-line chemotherapy at our institution between March 2015 and August 2021. The following patient data were reviewed: patient characteristics, overall survival (OS), progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and relative dose intensity (RDI). The severity of MA was categorized based on the CT findings as grade 1 (small), grade 2 (moderate), or grade 3 (massive). RESULTS: A total of 189 patients were included; the study endpoints were compared between patients with each ascites grade and 41 patients without MA. The MA was classified as grade 1 in 85 patients, grade 2 in 41 patients, and grade 3 in 22 patients. In the patients with MA, the median OS, PFS and ORR were 11.2 months, 5.7 months and 24.3%, respectively. The OS and PFS decreased with increasing the severity of MA; in particular, patients with grade 2 and 3 showed a poorer prognosis. There were no differences in AEs, except for anorexia, or the RDI according to the severity of MA. CONCLUSION: GnP showed moderate efficacy with manageable safety profile in PC patients with MA. However, PC patients with moderate to massive ascites still have a dismal prognosis, and further development of effective treatments is needed.

Effectiveness and safety of MR-guided focused ultrasound thalamotomy in patients with essential tremor and low skull density ratio: a study of 101 cases.

OBJECTIVE: The objective was to investigate the effectiveness and safety of MR-guided focused ultrasound (MRgFUS) treatment in patients with essential tremor, particularly those with low skull density ratio (SDR) and including those with very low SDR, and to identify the factors influencing treatment effectiveness and to provide insights into therapeutic approaches for patients with lower SDR. METHODS: Real-world data from 101 patients who underwent MRgFUS between July 2019 and March 2022 at a single institution were analyzed. Tremor severity was assessed using the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (CRST). The patients were categorized into quartile groups based on their mean SDR, and the characteristics, treatment effectiveness, treatment parameters, and adverse events were evaluated among these subgroups. RESULTS: Patients were classified into 4 quartiles based on the mean SDR: quartile 1 (Q1) (SDR 0.26-0.37), Q2 (SDR 0.38-0.42), Q3 (SDR 0.43-0.49), and Q4 (SDR 0.50-0.75). MRgFUS significantly improved total CRST and tremor score across all SDR subgroups. Additionally, there were no significant differences in the improvement rates among the 4 subgroups. Analysis of the treatment parameters revealed that lower mean SDR was associated with lower target maximum temperature and smaller coagulation volume after focused ultrasound (FUS). Regarding adverse events, headache and nausea during FUS and facial and head edema on the day after surgery were more frequent in the Q1 subgroup (very low-SDR group). In contrast, numbness was more common in the Q4 subgroup. However, all these adverse events had resolved by the 3-month follow-up except numbness. CONCLUSIONS: This study suggested that MRgFUS is effective and safe for patients with medication-resistant essential tremor, including those with very low mean SDR. However, the very low-SDR group had insufficient temperature elevation at the target site compared with the high-SDR group, suggesting the need for a different strategy. Notably, with careful adjustments and considerations, positive outcomes can still be achieved in patients with very low SDR. Therefore, very low SDR should not be considered an absolute exclusion criterion because it is expected to increase the number of patients who benefit from MRgFUS.

Palliative radiotherapy for tumor bleeding in patients with unresectable pancreatic cancer: a single-center retrospective study.

BACKGROUND: Patients with unresectable pancreatic cancer (PC) sometimes experience gastrointestinal bleeding (GIB) due to tumor invasion of the gastrointestinal tract (tumor bleeding); no standard treatment has been established yet for this complication. Palliative radiotherapy (PRT) could be promising, however, there are few reports of PRT for tumor bleeding in patients with unresectable PC. Therefore, we evaluated the outcomes of PRT for tumor bleeding in patients with unresectable PC. METHODS: We reviewed the medical records of patients with unresectable PC diagnosed at our institution between May 2013 and January 2022, and identified patients with endoscopically confirmed tumor bleeding who had received PRT. PRT was administered at a total dose of 30 Grays (Gy) in 10 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction, and the dose selection was left to the discretion of the attending radiation oncologists. RESULTS: During the study period, 2562 patients were diagnosed as having unresectable PC at our hospital, of which 225 (8.8%) developed GIB. Among the 225 patients, 63 (2.5%) were diagnosed as having tumor bleeding and 20 (0.8%) received PRT. Hemostasis was achieved in 14 of the 20 patients (70%) who received PRT, and none of these patients developed grade 3 or more adverse events related to the PRT. The median time to hemostasis was 8.5 days (range 7-14 days). The rebleeding rate was 21.4% (3/14). The median hemoglobin level increased significantly (p < 0.001) from 5.9 to 9.1 g/dL, and the median volume of red blood cell transfusion tended (p = 0.052) to decrease, from 1120 mL (range 280-3360 mL) to 280 mL (range 0-5560 mL) following the PRT. The median overall survival (OS) was 52 days (95% confidence interval [CI] 39-317). Of the 14 patients in whom hemostasis was achieved following PRT, chemotherapy could be started/resumed in seven patients (50%), and the median OS in these patients was 260 days (95% CI 76-not evaluable [NE]). Three patients experienced rebleeding (21.4%), on days 16, 22, and 25, after the start of PRT. CONCLUSION: This study showed that PRT is an effective and safe treatment modality for tumor bleeding in patients with unresectable PC.

Case Report: Atezolizumab plus bevacizumab for combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare subtype of primary liver cancers. Therapeutic strategies for patients with cHCC-CCA are limited, and no standard systemic treatment has been established for unresectable cHCC-CCA. Here, we present six cases of cHCC-CCA treated with atezolizumab plus bevacizumab. We observed three partial responses and one stable disease as the best responses; two of these patients were still being treated with atezolizumab plus bevacizumab at the time of reporting (at least five months of treatment), whereas the remaining two patients were unable to continue treatment owing to adverse events. Atezolizumab plus bevacizumab may be an effective treatment for unresectable cHCC-CCA.

Fibroblast inhibition by tocilizumab enabled gemcitabine/nab-paclitaxel rechallenge for pancreatic cancer.

Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway inhibition may overcome chemoresistance of metastatic pancreatic cancer (MPC). We sought to determine the safety and recommended dose of tocilizumab (TCZ), an IL-6 receptor monoclonal antibody, and biological correlates of tumor shrinkage in patients with gemcitabine (GEM)/nanoparticle albumin-bound paclitaxel (nab-PTX)-refractory MPC. This phase 1 study enrolled 10 patients with MPC who had progressed after GEM/nab-PTX. Patients initially received TCZ 8 mg/kg on Day 1 and nab-PTX 100 mg/m2 + GEM 750 mg/m2 on Days 2, 9, and 16. Before and at the end of Cycle 1, biopsy of liver metastases was performed 3-5 h after levofloxacin (LVFX) administration to measure LVFX infiltration into tumor tissue. No dose-limited toxicities occurred, and the recommended dosage of TCZ was determined to be 8 mg/kg. Treatment-emergent adverse events occurred in 80% of patients, of which decreased neutrophil count was the most common. Tumor reduction during Cycle 1 was observed in four patients, who were defined as responders. In paired-biopsy samples, responder-related biological activities were an increase of cleaved PARP expression of tumor nuclei (p = 0.01), a decrease of proliferative cancer-associated fibroblasts (CAFs) (p = 0.08), and an increase of LVFX infiltration in the tumor (p = 0.04). A decrease of phosphorylated STAT3 expression (p = 0.02) favored an increase in LVFX infiltration. In conclusion, TCZ + GEM/nab-PTX-rechallenge had a manageable safety profile and showed preliminary activity via inhibition of CAF and improved intratumoral drug infiltration in MPC.

Extensive extracranial growth of spheno-orbital meningioma: illustrative case.

BACKGROUND: Spheno-orbital meningioma (SOM) typically presents with a classic triad of symptoms (i.e., proptosis, visual impairment, and ocular paresis), resulting from intraorbital tumor invasion. The authors present a very rare case of SOM in which the chief complaint was swelling of the left temporal region, which, to the best of their knowledge, has not been reported previously. OBSERVATIONS: The patient presented with marked extracranial extension to the left temporal region but unremarkable intraorbital extension, even on radiological examination. Physical examination of the patient showed almost no exophthalmos or restriction of left eye movement, consistent with the radiological findings. Four separate meningioma specimens were removed by extraction (i.e., one each from the intracranial, extracranial, and intraorbital segments of the tumor and one from the skull). The World Health Organization grade was 1 and the MIB-1 index was less than 1%, indicating a diagnosis of a benign tumor. LESSONS: SOM may be present even in patients with only temporal swelling and few ocular-related symptoms, and detailed imaging evaluations may be required to identify the tumor.

A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer.

Given the promising activity and tolerability of FOLFIRINOX as a second-line treatment for advanced biliary tract cancer (BTC), it can be an attractive first-line treatment option as well. This is a single-arm, open-label, multicenter phase II study to evaluate the safety and efficacy of FOLFIRINOX as a first-line treatment for patients with advanced BTC. Primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), tumor response and safety. This study defined primary endpoint might be met when the lower limit value of 80% confidence interval [CI] of the median PFS ≥ 6.0 months. Between June 2016 and March 2020, 35 BTC patients (21 intrahepatic, 10 extrahepatic, 2 gallbladder, 2 ampulla) including 26 unresectable and 9 recurrent disease were enrolled. After a median follow-up of 13.9 months, the median PFS and OS were 7.4 (80% CI, 5.5-7.5) and 14.7 (80% CI, 11.8-15.7) months, respectively. Complete response was achieved in 1 (2.9%) and partial response in 10 (28.6%), giving an objective response rate of 31.4% and disease control rate of 74.3%. Major grade 3-4 adverse events included neutropenia (54.3%), leukopenia (34.4%), febrile neutropenia (17.1%), thrombocytopenia (8.6%), cholangitis (8.6%), anemia, nausea, diarrhea, and peripheral sensory neuropathy (2.9% each). FOLFIRINOX was well tolerable in patients with advanced BTC, however, this study did not meet the primary endpoint to conduct a phase III trial. Thus, further explorations are required to find a subset of patients and/or certain clinical scenario which might be beneficial from FOLFIRINOX.

Retroperitoneal liposarcoma with pancreatic metastasis and gastric cancer: a case report.

On computed tomography scanning, a 63-year-old man with vomiting and anorexia was discovered to have a mass in the pancreatic body and a retroperitoneal mass extending to the right lobe of the liver. An esophagogastroduodenoscopy revealed an advanced gastric carcinoma in the middle gastric body, and a biopsy specimen revealed a poorly differentiated adenocarcinoma. The pancreatic and retroperitoneal masses were considered metastatic lesions of gastric cancer, and a biopsy was taken from the pancreatic lesion using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The histology of the EUS-FNA pancreatic specimen revealed atypical spindle-shaped cells and increased stromal collagen fibrosis, and liposarcoma was considered. Conversely, a percutaneous ultrasound-guided biopsy was taken for the retroperitoneal lesion, and the histology revealed that it was a dedifferentiated liposarcoma. On the basis of histopathological and imaging findings, the retroperitoneal liposarcoma was identified as the primary lesion, the pancreatic lesion as a metastasis of the primary liposarcoma, and the gastric carcinoma as an independent tumor. As far as we know, there have only been three reports of metastatic pancreatic liposarcoma diagnosed via EUS-FNA. In this case, the patient also had gastric cancer, and EUS-FNA was helpful in differentiating metastatic pancreatic tumors from gastric cancer.

Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis.

BACKGROUND/OBJECTIVES: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC. METHODS: We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions. RESULTS: Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38-1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively. CONCLUSIONS: This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.

Incidence of and risk factors for severe neutropenia during treatment with the modified FOLFIRINOX therapy in patients with advanced pancreatic cancer.

Although FOLFIRINOX (L-Leucovorin/5-FU/Irinotecan/Oxaliplatin) is established as one of the standard therapies for patients with metastatic pancreatic cancer, the modified FOLFIRINOX (mFOLFIRINOX) is often used in clinical practice to reduce the incidence of toxicities. Febrile neutropenia (FN) and severe neutropenia during FOLFIRINOX are especially frequently observed in Japanese patients. In this study, we evaluated the incidence of FN and severe neutropenia, and explored the risk factors for severe neutropenia in patients receiving treatment with mFOLFIRINOX. The data of patients who had received mFOLFIRINOX between December 2013 and December 2014 at the National Cancer Center Hospital East were reviewed retrospectively. We graded the neutropenia severity and defined ≥ Grade 3 neutropenia as severe neutropenia. Univariate and multivariate analysis were undertaken to evaluate the associations with risk of development of severe neutropenia. A total of 122 patients were enrolled in this study. Sixty two patients (51%) and 10 patients (8%) developed severe neutropenia and FN, respectively. Multivariate analysis identified a low baseline white blood cell count (odds ratio [OR], 14.50; 95% confidence interval (CI), 3.27-111.14; p = 0.002) and presence of heterozygosity for UGT1A1*28 or UGT1A1*6 polymorphism (OR, 2.84; 95% CI, 1.18-7.17; p = 0.023) as independent risk factors for severe neutropenia. The incidences of severe neutropenia and FN in patients receiving mFOLFIRINOX in our clinical practice were comparable to previous reports. The risk factors for severe neutropenia in patients receiving mFOLFIRINOX were a low baseline white blood cell count and presence of heterozygosity for UGT1A1*28 or UGT1A1*6 polymorphism.

Endoscopic duodenal stent placement versus gastrojejunostomy for unresectable pancreatic cancer patients with duodenal stenosis before introduction of initial chemotherapy (GASPACHO study): a multicenter retrospective study.

BACKGROUND: Endoscopic duodenal stent placement is an alternative technique to gastrojejunostomy for gastric outlet obstruction due to pancreatic cancer. We compared the efficacy of endoscopic duodenal stent placement with that of gastrojejunostomy for treating patients with pancreatic cancer who are candidates for intensive combination chemotherapies as the first line of treatment. METHODS: This retrospective observational study included 100 patients from 18 institutions in Japan. Inclusion criteria were as follows: (1) cytologically or histologically confirmed adenocarcinoma of the pancreas, (2) good performance status, (3) gastric outlet obstruction scoring system score of 0-1 and (4) no history of treatment for pancreatic cancer. RESULTS: There was no significant difference in the background characteristics of patients in the endoscopic duodenal stent placement (n = 57) and gastrojejunostomy (n = 43) groups. The median overall survival in the endoscopic duodenal stent placement and gastrojejunostomy groups was 5.9 and 6.0 months, respectively. Clinical success was achieved in 93 cases; the median time to food intake resumption was significantly shorter in the endoscopic duodenal stent placement group (median: 3 days, n = 54) than in the gastrojejunostomy group (median: 5 days, n = 43). Chemotherapy was introduced in 63% of the patients in both groups after endoscopic duodenal stent placement or gastrojejunostomy. Chemotherapy was started earlier in the endoscopic duodenal stent placement group (median: 14 days) than in the gastrojejunostomy (median: 32 days) group. CONCLUSIONS: Endoscopic duodenal stent placement showed similar or better clinical outcomes than gastrojejunostomy. Thus, it might be a promising option in patients with good performance status.

Impact of Endoscopic Ultrasound-Guided Tissue Acquisition on Decision-Making in Precision Medicine for Pancreatic Cancer: Beyond Diagnosis.

Precision medicine in cancer treatment refers to targeted therapy based on the evaluation of biomarkers. Although precision medicine for pancreatic cancer (PC) remains challenging, novel biomarker-based therapies, such as pembrolizumab, olaparib, and entrectinib, have been emerging. Most commonly, endoscopic ultrasound-guided tissue acquisition (EUS-TA) had been used for the diagnosis of PC until now. However, advances in EUS-TA devices and biomarker testing, especially next-generation sequencing, have opened up the possibility of sequencing of various genes even in limited amounts of tissue samples obtained by EUS-TA, and identifying potential genetic alterations as therapeutic targets. Precision medicine benefits only a small population of patients with PC, but biomarker-based therapy has shown promising results in patients who once had no treatment options. Now, the role of EUS-TA has extended beyond diagnosis into decision-making regarding the treatment of PC. In this review, we mainly discuss tissue sampling by EUS-TA for biomarker testing and the current status of precision medicine for PC.

Microvascular Decompression for Glossopharyngeal Neuralgia in the Semi-Sitting Position: A Report of Two Cases.

The semi-sitting position is well known to neurosurgeons. However, there are few reports of microvascular decompression surgery for glossopharyngeal neuralgia performed using the semi-sitting position. The semi-sitting position is not widely adopted in Japan, but it is considered to be a very useful neurosurgical position. Microvascular decompression surgery for glossopharyngeal neuralgia is a relatively rare procedure, and the semi-sitting position is very effective, considering the possibility of intraoperative cardiac arrest and postoperative complications of lower cranial nerve palsy. This report describes two cases of glossopharyngeal neuralgia operated in the semi-sitting position. Microvascular decompression was performed on both patients, and postoperative pain controls were good and no complications were observed. We show that the use of the semi-sitting position to perform microvascular decompression for glossopharyngeal neuralgia provides an excellent surgical view of the brainstem.

Bioprospecting of Sechium spp. varieties for the selection of characters with pharmacological activity.

Bioprospecting identifies new sources of compounds with actual or potential economic value that come from biodiversity. An analysis was performed regarding bioprospecting purposes in ten genotypes of Sechium spp., through a meta-analysis of 20 information sources considering different variables: five morphological, 19 biochemical, anti-proliferative activity of extracts on five malignant cell lines, and 188 polymorphic bands of amplified fragment length polymorphisms, were used in order to identify the most relevant variables for the design of genetic interbreeding. Significant relationships between morphological and biochemical characters and anti-proliferative activity in cell lines were obtained, with five principal components for principal component analysis (SAS/ETS); variables were identified with a statistical significance (< 0.7 and Pearson values ≥ 0.7), with 80.81% of the accumulation of genetic variation and 110 genetic bands. Thirty-nine (39) variables were recovered using NTSYSpc software where 30 showed a Pearson correlation (> 0.5) and nine variables (< 0.05), Finally, using a cladistics analysis approach highlighted 65 genetic bands, in addition to color of the fruit, presence of thorns, bitter flavor, piriform and oblong shape, and also content of chlorophylls a and b, presence of cucurbitacins, and the IC50 effect of chayote extracts on the four cell lines.

Natural Bioactive Compounds of Sechium spp. for Therapeutic and Nutraceutical Supplements.

Natural products are in great demand because certain secondary metabolites (SMs) are sources of antioxidants, flavorings, active substances, or anticancer agents with less aggressiveness and selectivity, among which triterpenes and flavonoids are of importance because they inhibit carcinogenesis. For Sechium spp. P. Br. (chayotes), there is scientific evidence of antiproliferative activity that has occurred when cancer cell lines have been treated with this fruit. In order to compare future therapeutic designs and identify new and ancestral characteristics, triterpenes and flavonoids were determined in contrasting Sechium genotypes. The obtained data were analyzed via a cladistics approach, with the aim of identifying the characteristics and state of phytochemicals and genetic variables. The concentrations of flavonoids and triterpenes were determined, and a more complex composition of secondary metabolites was found in the wild types as compared to their domesticated genotypes. Bitter fruits contained a higher number of SMs, followed by those with a neutral and sweet flavor. A cladogram showed the differentiation of the three groups based on the flavor of the fruits. The diversity of SMs decreases in evolutionary terms, in response to domestication and environmental adaptation. Therefore, genotypes can be feasibly selected based on fruit flavor for gross-breeding, and cytotoxicity can be reduced without losing possible therapeutic effects.

[A case of ferroportin disease with phenotype A gene mutation in SCL40A1 resembling phenotype B manifestation influenced by alcohol consumption].

A 57-year-old man had been detected to have an elevated transaminase level. He had a history of alcohol consumption, and abdominal ultrasonography revealed an increase in the echogenicity of the liver;hence, he was diagnosed as having alcoholic liver disease. He restricted his alcohol intake, but the elevated transaminase level did not improve. Further medical examination was performed. He was found to have hyperferritinemia (serum ferritin, 6574ng/mL) and high transferrin saturation (TSAT, 90.5%). Computed tomography (CT) revealed high CT values of the liver and spleen (94 and 84HU, respectively). These findings differed from the characteristics of a typical alcoholic liver disease. Liver biopsy revealed iron deposition within the hepatocytes and Kupffer cells and liver fibrosis (F1-2). From the gene analysis of HFE, HJV, TFR2, HAMP, and SLC40A1 genes, he was heterozygous for the G>A (G490D) mutation in the ferroportin gene (SLC40A1). He was diagnosed as having ferroportin disease. It was reported that patients with a G490D mutation exhibited ferroportin disease A, which occurs owing to a loss-of-function mutation of SLC40A1. However, he was considered to have some characteristics of ferroportin disease B, which occurs owing to a gain-of-function mutation of SLC40A1. In this case, alcohol consumption might affect the progression of iron deposition in the liver. Therapeutic venesection was performed, and his hyperferritinemia with high TSAT gradually improved. In the course of the disease, other organ damages and progression of liver fibrosis did not occur.