Low skeletal muscle mass index is independently associated with low bone mineral density in kidney transplant recipients: a retrospective observational cohort study.

BACKGROUND: Osteoporosis and osteopenia are more frequent in patients who have received kidney transplants than in healthy individuals. Although osteoporosis and sarcopenia are closely related, only few studies have considered them in the post-transplantation period. We aimed to investigate the relationship between lower bone mineral density and skeletal muscle in kidney transplant recipients. METHODS: We included 371 patients in the maintenance phase of kidney transplantation (> 6 months after transplantation) followed-up at our institution from January to December 2019. The primary endpoint was the association between bone mineral density and skeletal muscle mass index. As secondary endpoints, in addition to skeletal muscle mass index, we investigated other factors associated with low bone mineral density, including kidney function and 25-hydroxy vitamin D (25(OH)D) concentration. Considering the possibility that factors affecting bone mineral density differ between men and women, we explored these factors separately for both sexes. RESULTS: Of the 371 participants, 243 (65.4%) were men. The median age and time after transplantation were 52 and 14 years, respectively. Univariate analysis showed that age, female sex, time since transplantation, cystatin C-based estimated glomerular filtration rate (eGFRcysC), 25(OH)D, and skeletal muscle mass index were associated with bone mineral density. Multivariate analysis showed associations of bone mineral density with eGFRcysC, 25(OH)D, and skeletal muscle mass index. Multivariate analysis by sex showed significant associations with eGFRcysC, hemoglobin, and skeletal muscle mass index in men and with age, eGFRcysC, albumin, and skeletal muscle mass index in women. Bone mineral density was not associated with history of dialysis prior to transplantation or time since transplantation. CONCLUSIONS: In kidney transplant recipients, an independent association between lower bone mineral density and skeletal muscle mass index was observed in both sexes.

Effect of Abdominal Aortic Calcification on Recurrence Following Initial Hepatectomy for Colorectal Liver Metastases.

BACKGROUND/AIM: The aim of the study was to analyze the association between abdominal aortic calcification (AAC) and patient prognosis following resection of colorectal liver metastases (CRLM). AAC potentially reflects intrahepatic immunity and is involved in tumor development and progression. However, the clinical effects of AAC on colorectal cancer (CRC) prognosis after curative-intent liver resection for CRLM remain unclear. PATIENTS AND METHODS: We evaluated the effect of AAC on the clinical prognosis and metastatic patterns in 99 patients who underwent hepatectomy for CRLM between 2010 and 2019. RESULTS: The high-AAC group had significantly worse overall survival (OS) and remnant liver recurrence rate (RR) after propensity score matching to adjust for differences in baseline characteristics of patients and tumors. In multivariate Cox regression analyses, high AAC volume was an independent risk factor for poor OS and liver RR, but not poor lung RR. The expression of tumor necrosis factor-related apoptosis-inducing ligand, known as an anti-tumor marker, in liver natural killer (NK) cells was lower in the high-AAC group than in the low-AAC group. CONCLUSION: High AAC volume showed a strong relationship with remnant liver RR after curative resection of CRLM. High AAC volume may be responsible for the suppression of anti-tumor activity of liver NK cells, which results in an increased risk of liver recurrence and poor prognosis.

Impact of a new liver immune status index among patients with hepatocellular carcinoma after initial hepatectomy.

Aim: The anti-tumor effects of natural killer (NK) cells vary among individuals. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expressed on liver NK cells is a marker of anti-tumor cytotoxicity against hepatocellular carcinoma (HCC) in immune cell therapy. This study aimed to develop a liver immune status index (LISI) that predicts low TRAIL expression and validates its ability to predict recurrence after initial hepatectomy for primary HCC. Methods: A functional analysis of liver NK cells co-cultured with interleukin-2 for 3 days was performed of 40 liver transplant donors. The LISI, which predicted low TRAIL expression (25% quartile: <33%) in liver NK cells, was calculated using multiple logistic regression analysis. Next, 586 initial hepatectomy cases were analyzed based on the LISI. Results: Our model was based on the Fibrosis-4 index+0.1 (odds ratio [OR], 1.33), body mass index (OR, 0.61), and albumin levels+0.1 (OR, 0.54). The area under the receiver operating characteristic curve (AUC) of the LISI for low TRAIL expression was 0.89. Stratification of the recurrence rates (RR) revealed that LISI was an independent predictive factor of RR (moderate risk: hazard ratio, 1.44; high risk: hazard ratio, 3.02). The AUC was similar for the LISI, albumin-indocyanine green evaluation grade, albumin-bilirubin score, and geriatric nutritional risk index for predicting RR. Among the vascular invasion cases, the LISI was more useful than the other indexes. Conclusion: Our model facilitates the prediction of RR in high-risk patients by providing LISI to predict the anti-tumor effects of NK cells.

Improved detection of donor-specific HLA-class II antibody in kidney transplant recipients by modified immunocomplex capture fluorescence analysis.

Immunocomplex capture fluorescence analysis (ICFA) which basic principle is same as Luminex crossmatch (LXM), could detect donor-specific HLA antibody (DSA). The advantages of ICFA are (i) detection of DSA and (ii) no requirement of viable cells over the flow cytometry crossmatch (FCXM). However, FCXM has been widely used because of its higher sensitivity than ICFA, in particular HLA-class II antibody detection. In this study the accuracy of DSA detection against HLA-class II was investigated by modifying the original method of ICFA. Increment of the sensitivity was found when purified peripheral blood mononuclear cells (PBMCs) were used instead of whole blood. An ICFA-PBMC in addition to FCXM-T/B was conducted for 118 patients before kidney transplantation and 13 patients with de novo DSA against HLA-class II after transplantation. Significantly positive correlation was observed between the values of ICFA-PBMC and DSA mean fluorescence intensity (MFI) targeting class II (p < 0.0001). When the cutoff level of 1.4 was determined by receiver operating characteristic curve analysis, the average DSA MFI was found to be significantly higher in the ICFA-PBMC (class II) positive group comparing to that in the negative group (12,217 vs 3885, p = 0.0027). ICFA-PBMC and optimized cutoff level could provide valid information in cases of suspected DSA.

A case of intraductal tubulopapillary neoplasm of the pancreas in a branch duct: a rare case report and literature review.

BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a new disease concept defined by the World Health Organization in 2010. ITPN progresses with tubulopapillary growth in the pancreatic duct and is known to have a fair prognosis. Localization in the main pancreatic duct (MPD) is one characteristic. There are few case reports of ITPN in a branch of the pancreatic duct (BD). CASE PRESENTATION: We encountered a case of ITPN localized in BD. An 85-year-old man was followed after colonic surgery for rectal carcinoma. An abdominal computed tomography scan revealed a cystic mass in the pancreatic head and further examination was done. A T2 weighted intension picture in magnetic resonance imaging showed a 20 mm cystic lesion with an internal mass of 15 mm. Duodenal papilla were slightly open and endoscopic retrograde pancreatography revealed mild and diffuse dilatation of the main pancreatic duct and mucin in the MPD. In consideration with the image examinations, we diagnosed the tumor as an intraductal papillary mucinous neoplasm with carcinoma because of its large mural nodule (> 10 mm in size) in a cyst. Consequently, a pancreaticoduodenectomy was performed. Macroscopically, a white solid tumor sized 2.5 × 1.8 × 1.0 was identified in the head of the pancreas. The cut surface of the resected pancreas showed a side-branch type intraductal tumor with tubulopapillary architecture without mucin secretion. Immunohistochemical staining was positive for MUC1, and negative for MUC2 and MUC5AC. The final diagnosis was determined to be pancreatic ITPN from BD. At the time of this report (48 months post-surgery), the patient remains disease-free without evidence of recurrence. CONCLUSION: ITPNs localized in BD are rare and diagnosis prior to surgery is difficult. In our case, the shape was round, not papillary, and with little fluid. These characteristics are different from a branch duct type IPMN and can be a clue to suspect ITPN in BD.

A case of Turcot's syndrome type 1 with loss of immunoexpression of MSH6 in colon cancer and liver metastasis due to secondary somatic mutation in coding mononucleotide (C)8 tract: a case report.

BACKGROUND: Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding region. Immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has been recognized as an useful technique for screening of LS. Previous study has shown that the assessment of IHC, however, requires specific caution due to variable staining patterns even without germline mutations in MMR genes. CASE PRESENTATION: A 48-year-old man, who had been treated for anaplastic astrocytoma, was referred to our department for the precise examination of progressing anemia. Whole-body examination revealed two advanced carcinomas in descending colon and stomach. A hypo-vascular mass lesion was detected in liver as well. Pathological diagnosis (on surgical specimens) was poorly differentiated adenocarcinoma in descending colon, moderately differentiated tubular adenocarcinoma in stomach, and liver metastasis, which is possibly from colon. It was suspected that this case would be Turcot's syndrome-type-1 due to its specific family history having two cases of colon cancer within the second relatives. Pathogenic frameshift mutations in codon 618 of MLH1 gene was identified. Immunohistochemical analyses (IHC) demonstrated complete loss of MLH1 immuno-expression as well as of PMS2 except for those in brain tumor. Although frameshift mutation was not found in MSH6 gene, histological expression of MSH6 was patchy in primary colon carcinoma and was completely lost in the metastatic site in liver. MSH6 expression in gastric carcinoma, a coincidental cancer in this case, was intact. An abnormal (C)8 region was identified by the cloned PCR of colon and liver tumors but not from gastric cancer. Frameshift mutation in a (C)8 tract in exon 5 of the MSH6 gene was also detected in liver metastasis. CONCLUSION: This case supports a plausible mechanism, proposed by a previous literature, for the reduced expression of MSH6 in a somatic mutation manner, which might preferentially happen in colon cancer rather than in stomach carcinoma in MLH1/PMS2-deficient type of Turcot's syndrome type 1.

[A Case of Sigmoid Colon Cancer Recurrence at the Hand-Sewn Anastomosis Site Originated from Tumor Implantation].

We report a case of anastomotic recurrence following laparoscopic sigmoidectomy with hand-sewn anastomosis, which was attributable to the implantation of exfoliated cancer cells. A 78-year-old man diagnosed with early colon cancer underwent endoscopic submucosal dissection(ESD); however, ESD was suspended due to infiltrated muscle fibers. Subsequently, he underwent laparoscopic sigmoidectomy with hand-sewn anastomosis, accompanied by D3 lymph node dissection. Histopathological findings revealed a well-differentiated tubular adenocarcinoma, pT2(MP), tub1>tub2>por2, ly0, v1, PM0, DM0, RM0, N0M0, pStage Ⅰ. The follow-up CT 6 months after surgery, showed enhanced wall thickening and irregular surface of the sigmoid colon. Colonoscopy revealed a type 2 tumor located on the anastomotic line. Based on the diagnosis of anastomotic recurrence, the patient underwent partial colectomy. Histopathological findings were similar to those of the primary tumor and suggested implantation of exfoliated cancer cells as the origin of anastomotic recurrence. Cancer cells had infiltrated all layers. In conclusion, we recommend the performance of appropriate operative procedures to prevent anastomotic recurrence, such as the cleaning of the anastomosed intestinal tract. Careful follow-up in colon cancer patients is of the utmost importance and the risk of anastomotic recurrence should always be considered.

[MSI-H Small Bowel Cancer with Peritoneal Dissemination Successfully Treated with Pembrolizumab-A Case Report].

A 52-year-old man was diagnosed with small bowel adenocarcinoma(T4aN1M0, Stage ⅢA, according to the Japanese colorectal cancer classification)and treated with partial resection of the small bowel in June 2014. He also received adjuvant chemotherapy(XELOX: 8 courses)after surgery. Three and a half years after the operation, peritoneal dissemination recurred, and he received bevacizumab plus XELOX therapy. The regimen was adjusted to a total of 11 courses because of the disease progression. The primary lesion showed MSI-H. The patient was started on pembrolizumab therapy in April 2019. The tumor responded well to pembrolizumab(maximum therapeutic effect: PR, 31% reduction), but a new lesion appeared 6 months after the start of this regimen. He continued pembrolizumab therapy for 14 months without adverse events since it appeared to be clinically effective. Although MSI-H small bowel cancers are rare, accurate screening is essential to not miss the opportunity to administer pembrolizumab.

Feasibility and efficacy of repeat laparoscopic liver resection for recurrent hepatocellular carcinoma.

BACKGROUND: Repeat hepatectomy is an acceptable treatment for recurrent hepatocellular carcinoma (HCC). However, repeat laparoscopic liver resection (LLR) has not been widely adopted due to its technical difficulty. This study aimed to assess the feasibility and efficacy of repeat LLR compared with repeat open liver resection (OLR) for recurrent HCC. METHODS: We performed 42 repeat OLR and 30 repeat LLR for cases of recurrent HCC between January 2007 and March 2018. This study retrospectively compared the patients' clinicopathological characteristics and operative and short-term outcomes including surgical time, intraoperative blood loss, duration of hospital stay, and postoperative complications between the two groups. RESULTS: There were no significant differences in patient characteristics between the two groups except in terms of Child-Pugh grade. The repeat LLR group had lower median intraoperative blood loss (100 mL vs. 435 mL; P = 0.001) and shorter median postoperative hospital stay (10 days vs. 14.5 days; P = 0.002). The other results including postoperative complications were comparable between the two groups. Further, comparison of two subpopulations of the repeat LLR group stratified by previous hepatectomy type (open or laparoscopic) or tumor location (segments 7 and 8 or other) revealed no significant differences in the postoperative clinical characteristics between them, although the morbidity rate tended to be higher in patients who underwent open hepatectomy for primary HCC than in patients who underwent laparoscopic hepatectomy. CONCLUSIONS: Repeat LLR for recurrent HCC is feasible and useful with good short-term outcomes although an appropriate patient selection seems to be necessary.

A Case of Advanced Gastric Cancer with Peritoneal Metastasis Treated Successfully with Nivolumab.

Peritoneal metastasis (PM) is detected in 14% of gastric cancers at the time of initial diagnosis, with a median survival time of 4 months. A 66-year-old woman diagnosed with cT4a(SE) N2M1(LYN) cStage IV was treated with three lines of chemotherapy for a year. During the third line of chemotherapy, computed tomography (CT) scan revealed a large amount of ascites, periportal collar sign, and bilateral ureteral stenosis owing to PM. The tumor biomarkers (CEA and CA 19-9) remained elevated similar to the initial levels. The patient was administered 3 mg/kg nivolumab intravenously biweekly as the fourth line of chemotherapy. Three months after the nivolumab treatment, gastroscopy revealed an extreme reduction of the tumor size, while CT scan revealed the absence of ascites and a well-controlled tumor. There was no immune-related adverse event with nivolumab during and after the treatment, and performance status improved to 0. The patient has been alive for about 2.5 years since her first visit with her sixth line of chemotherapy (docetaxel). We report a case of advanced gastric cancer with PM that was treated successfully with nivolumab.

Simultaneous Liver-Kidney Transplantation in Patient with a History of Heparin-Induced Thrombocytopenia: A Case Report and Literature Review.

BACKGROUND Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia caused by exposure to heparin. Here, we report the case of a 58-year-old male with HIT who then underwent a successful simultaneous liver-kidney transplantation (SLKT). CASE REPORT The patient had end-stage hepatitis due to a hepatitis C virus (HCV) infection and was on hemodialysis due to nephropathy related to HCV. Furthermore, he was diagnosed with HIT caused by the administration of heparin for hemodialysis during these treatments. Fortunately, there was no evidence of thromboses and HIT antibody converted negative immediately. Four years after the occurrence of HIT, SLKT was performed for liver and kidney failure. Although the donor was heparinized, the donor grafts were flushed on a backtable by an organ preservation solution without heparin to reduce residual heparin. The subsequent transplantation was uneventful. After the operation, anticoagulation with argatroban, a direct thrombin inhibitor, was started instead of heparin. In the postoperative course, neither thrombosis nor graft dysfunction occurred. CONCLUSIONS SLKT in a patient who had a history of HIT could be performed safely.

Laproscopic treatment for small bowel bleeding after detection by double-balloon endoscopy: A case report.

INTRODUCTION: The frequency of small bowel bleeding is relatively low and the process for the diagnosis and treaVtment remains difficult. Here, we report a case of massive small bowel bleeding due to arteriovenous malformation (AVM), treated by a combination of double-balloon endoscopy and laparoscopic resection. PRESENTATION OF CASE: A 59-year-old man was admitted to our hospital due to a hemorrhagic stool. The patient presented transient hemorrhagic shock and contrast-enhanced CT revealed a hyper-vascularized tumor in the small bowel. India ink tattooing for the responsible lesion with double-balloon endoscopy was performed. The tattooed lesion was easily confirmed during the subsequent laparoscopic observation and segmental resection was done. Pathological examination showed arteriovenous malformation of the small bowel. DISCUSSION: Prior to laparoscopic resection, the localization of the responsible area might be a significant consideration when the lesion is invisible. Endoscopic marking with DBE enables intraluminal detection and laparoscopic observation from the serosal side. CONCLUSION: Preoperative marking with the use of double-balloon endoscopy followed by laparoscopic resection might be an optimal option for the treatment of massive small intestinal bleeding.

[Two Cases of Colorectal Liver Metastasis with Localized Biliary Dilatation].

We encountered 2 cases of colorectal liver metastasis with biliarydilatation mimicking cholangiocarcinoma. Case 1: A 70- year-old male patient, who was diagnosed with colorectal cancer and underwent transverse colectomy3 years prior, was preoperativelydiagnosed with cholangiocarcinoma with biliarydilatation of the medial and lateral segments. He underwent left hemi-hepatectomy. The pathological diagnosis was colorectal liver metastasis with intra-biliarytumor thrombosis. Case 2: A 67-year-old male patient was diagnosed with descending colon cancer and cholangiocarcinoma with biliarydilatation of the medial segment. He underwent left hemi-colectomyand left hemi-hepatectomy. The pathological diagnosis was descending colon cancer and colorectal liver metastasis with biliaryinfiltration. The immunopathological findings showed double positivityfor CK20 and CDX2 antibodies and negativityfor CK7 antibodyin these cancer lesions.

Cotransplantation of preactivated mesenchymal stem cells improves intraportal engraftment of islets by inhibiting liver natural killer cells in mice.

The activation of natural killer (NK) cells in the liver inhibits engraftment of intraportally transplanted islets. We attempted to modulate the activity of NK cells by cotransplanting mesenchymal stem cells (MSCs) with islets in mice. We first investigated the ability of MSCs to secrete prostaglandin E2 , a predominant inhibitor of NK cell function, in various combinations of inflammatory cytokines. Notably, we found that prostaglandin E2 production was partially delayed in MSCs activated by inflammatory cytokines in vitro, whereas liver NK cells were activated early after islet transplant in vivo. Accordingly, preactivated MSCs, but not naive MSCs, substantially suppressed the expression of activation markers in liver NK cells after cotransplant with islets. Similarly, cotransplant with preactivated MSCs, but not naive MSCs, markedly improved the survival of islet grafts. These results highlight MSC cotransplant as an effective and clinically feasible method for enhancing engraftment efficiency.

A rare case of transient left ventricular apical ballooning syndrome following living donor liver transplantation: A case report and literature review.

INTRODUCTION: Transient Left Ventricular Apical Balloon Syndrome (LV-ABS) is an unknown acute dysfunction of the left ventricle, which develops under emotional or physical stress events like the major surgical postoperative period. PRESENTATION OF CASE: A 68-year-old woman diagnosed with hepatitis C cirrhosis was admitted for living donor liver transplantation (LDLT). No evidence for underlying cardiac or pulmonary disease was found. LDLT was performed, and her intra and post-operative course was uneventful. On post-operative day 4, dyspnea and tachycardia were observed. Echocardiography showed a severe wall motion abnormality with ballooning of the apex with normal basilar wall motion and a severely impaired left ventricular function with an ejection fraction (EF) of 40%. Blood tests showed greatly increased level of N-terminal pro-brain natriuretic peptide (NT- pro BNP). Evidence of significant ischemic heart disease was not obtained and a transient LV-ABS was diagnosed. Although she required intensive care, her cardiac function became normal by conservative treatment. DISCUSSION: Transient LV-ABS has been reported to occur more frequently in post-menopausal women with reduced estrogens reported to protect myocardium from sympathetic stress after mental or physical stress events. It has been suggested that this disease arises from myocardial stunning with high levels of circulating catecholamines and stress related neuropeptides. However, even in a serious condition, cardiac function has recovered normally in all cases by appropriate care. CONCLUSION: Transient LV-ABS is one cause of cardiac dysfunction after LDLT, and it is important to strictly manage cardiac function when diagnosed as transient LV-ABS.

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis.

AIM: We investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells. METHODS: We classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences. RESULTS: There were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural-killer group 2, member D (NKG2D)- positive NK cells in PBMC and percentage of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-, NKp30-, and signal regulatory protein ß (SIRPß)-positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRPß in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)-2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups. CONCLUSION: Colorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients.

Perioperative management with phosphodiesterase type 5 inhibitor and prostaglandin E1 for moderate portopulmonary hypertension following adult-to-adult living-donor liver transplantation: a case report.

BACKGROUND: Portopulmonary hypertension (PPH) is a relatively rare but well-recognized complication of end-stage liver disease. Moderate or severe PPH (mean pulmonary artery pressure [mPAP] ≥ 35 mmHg) is usually a contraindication for liver transplantation due to high operation-related mortality. Here, we report on a patient with moderate PPH whose condition was successfully managed with a phosphodiesterase type 5 (PDE5) inhibitor (tadalafil) and prostaglandin E1, who experienced rapid improvement of PPH after living-donor liver transplantation (LDLT). CASE PRESENTATION: A 63-year-old woman with alcoholic decompensated cirrhosis was referred to our hospital for LDLT. She had mild dyspnea on exertion as well as fatigue. Echocardiography and subsequent cardiac catheterization revealed a high mPAP (35 mmHg), and she was diagnosed with moderate PPH. We commenced treatment with oral tadalafil for the PPH. A second preoperative echocardiography demonstrated improved PPH, and she underwent LDLT. An intravenous infusion of prostaglandin E1 was introduced instead of tadalafil during and after the operation. The mPAP value showed a rapid decrease in mPAP value to 22 mmHg in 2 days. After discontinuation of the prostaglandin E1, the mPAP value remained 23 mmHg. Postoperative catheterization 2 months after LDLT showed no exacerbation of PPH. She was discharged on foot 70 days after LDLT in good condition and has shown a good clinical condition more than 2 years after LDLT. CONCLUSION: LDLT could be a radical treatment for PPH with careful management and adequate patient selection. PDE5 inhibitor and PGE1 is effective and feasible for perioperative management of the patient with moderate portopulmonary hypertension in LDLT.

[A Case of Advanced Gastric Cancer with Para-Aortic Lymph Node Metastasis Treated with Conversion Surgery after S-1 plus Oxaliplatin Chemotherapy].

A 71-year-old man was diagnosed as having Type 2 gastric cancer(tub2, HER2-negative). Abdominal computed tomography( CT)revealed bulky metastatic lymph nodes around the stomach and para-aorta(No. 16a2, b1). Our clinical diagnosis was cT4a(SE)N+M1(PAN), cStage Ⅳb, and SOX therapy was immediately administered. After 3 courses of chemotherapy, the treatment effect was PR, and after 6 courses, the patient was diagnosed with ycT2(MP)N0M0, ycStageⅠB. No Grade 2 or higher adverse events were observed during chemotherapy. At this stage, we determined that radical resection was feasible; thus, distal gastrectomy and D3 dissection(para-aortic lymph node dissection)were performed. No cancer cells were found in the primary lesion on histopathology. The histological response of the primary lesion was Grade 3, and the lymph node was Grade 2b. On follow-up observation, the patient is alive without tumor recurrence at 1 year postoperatively.

[Surgical Resection of Hepatic Portal Lymph Node Metastasis after Repeated Treatment for Hepatocellular Carcinoma Recurrence].

We encountered a case of hepatic portal lymph node metastasis after repeated treatment for hepatocellular carcinoma (HCC)recurrence. A 73-year-old male patient underwent partial gastrectomy following rupture of a gastrointestinal stromal tumor 8 years ago. A 70mm tumor was simultaneously revealed in the posterior segment of the liver, and imatinib treatment was initiated based on the diagnosis of a metastatic liver tumor. Due to the absence of an increasing tendency in the tumor, extended posterior segmentectomy was performed, and the pathological diagnosis was moderately differentiated HCC. During observation, transcatheter arterial chemoembolization(TACE)plus radiofrequency ablation(RFA)therapy was performed twice, and partial resection of the liver was performed once again for HCC recurrence. Recently, PIVKA-Ⅱ showed a high value of 1,720mAU/mL, and follow-up computed tomography showed HCC recurrence in S4/8 and hepatic portal lymph node metastasis. TACE was administered for recurrent lesions in S4/8, and surgical resection of the hepatic portal lymph node was performed together. The pathological diagnosis revealed extensive liver tissue necrosis and moderately-topoorly differentiated HCC in the excised lymph nodes. Lymph node metastasis of HCC is rare, and in this case, a change in lymph flow caused by repeated treatment for HCC recurrence was considered a factor influencing the course.

Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience.

The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n = 1) in the NS3, and at L31 (n = 4), Y93 (n = 4), and L31/Y93 (n = 1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n = 12). Univariate analysis showed that a history of SMV (P < .01) and the presence of mutations in NS5A (P = .02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate.