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1.  Rerupture of nonparasitic liver cyst treated with cyst fenestration: a case report 
Surgical Case Reports  2015;1(1):71.
We herein describe a case involving spontaneous rerupture of a nonparasitic liver cyst successfully treated with cyst fenestration and an omental flap. A 59-year-old Japanese woman was transferred to our hospital for evaluation of acute abdominal pain. She had a history of conservative treatment with antibiotics for spontaneous rupture of a liver cyst 1 month previously. On arrival, she exhibited abdominal tenderness and muscular defense. Enhanced computed tomography showed ascites and a large ruptured hepatic cyst (diameter of 10 cm). We diagnosed rerupture of a liver cyst and performed laparotomy for cyst fenestration and intraperitoneal drainage. During the operation, we found the perforation site on the ventral side of the cyst and brown, muddled ascitic fluid. Cholangiography showed no bile leakage on the inner wall. Pathological investigation revealed no evidence of malignancy. The patient recovered without any adverse events and was discharged on postoperative day 8. No recurrences or complications occurred for 2 years.
PMCID: PMC4560152  PMID: 26366367
Nonparasitic liver cyst rupture; Cyst fenestration; Acute abdomen
2.  Definitive Chemoradiotherapy and Salvage Esophagectomy for Esophageal Cancer Associated With Multiple Lung Metastases: A Case Report 
International Surgery  2014;99(5):640-644.
The prognosis of esophageal cancer with distant metastasis is dismal. We report a 70-year-old man with esophageal cancer and multiple lung and lymph node metastases. Complete response was achieved following definitive chemoradiotherapy. Twenty-four months after the initial chemoradiotherapy, local recurrence was detected but there was no evidence of distant metastasis. Therefore, the patient underwent salvage esophagectomy. The surgery was well tolerated without any postoperative complications. The patient is still alive 48 months after the salvage surgery. Our experience suggests that salvage esophagectomy is an important component of multimodal therapy for the recurrence of esophageal cancer.
PMCID: PMC4253938  PMID: 25216435
Esophageal cancer; Chemoradiotherapy; Salvage surgery
3.  Speaking Tracheostomy Tube and Modified Mouthstick Stylus in a Ventilator-Dependent Patient with Spinal Cord Injury 
Communication is a serious problem for patients with ventilator-dependent tetraplegia. A 73-year-old man was presented at the emergency room in cardiopulmonary arrest after falling from a height of 2 m. After successful resuscitation, fractures of the cervical spine and cervical spinal cord injury were found. Due to paralysis of the respiratory muscles, a mechanical ventilator with a tracheostomy tube was required. First, a cuffed tracheostomy tube and a speaking tracheostomy tube were inserted, and humidified oxygen was introduced via the suction line. Using these tubes, the patient could produce speech sounds, but use was limited to 10 min due to discomfort. Second, a mouthstick stylus, fixed on a mouthpiece that fits over the maxillary teeth, was used. The patient used both a communication board and a touch screen device with this mouthstick stylus. The speaking tracheostomy tube and mouthstick stylus greatly improved his ability to communicate.
PMCID: PMC4564635  PMID: 26413357
4.  Identification of Recurrence-Related microRNAs from Bone Marrow in Hepatocellular Carcinoma Patients 
Journal of Clinical Medicine  2015;4(8):1600-1611.
Hepatocellular carcinoma (HCC) is a poor-prognosis cancer due to its high rate of recurrence. microRNAs (miRNAs) are a class of small non-coding RNA molecules that affect crucial processes in cancer development. The objective of this study is to identify the role of miRNAs in patient bone marrow (BM) and explore the function of these molecules during HCC progression. We purified miRNAs from bone marrow cells of seven HCC patients, and divided them into three fractions by cell surface markers as follows: CD14+ (macrophage), CD14−/CD45+ (lymphocyte), and CD14−/CD45−/EpCAM+ (epithelial cell). We employed microarray-based profiling to analyze miRNA expression in the bone marrow of patients with HCC. Differentially expressed miRNAs were significantly different between fractions from whole bone marrow, macrophages, and lymphocytes, and depended on stages in tumor progression. Differences in expression of miRNAs associated with cell proliferation also varied significantly between HCC patients with recurrence, multiple tumors, and advanced clinical stages. These results suggest that miRNA profiles in separated fractions of BM cells are associated with HCC progression.
PMCID: PMC4555079  PMID: 26287250
bone marrow; microRNA; hepatocellular carcinoma; recurrence
5.  Risk Factors Associated with Stenotrophomonas maltophilia Bacteremia: A Matched Case-Control Study 
PLoS ONE  2015;10(7):e0133731.
Stenotrophomonas maltophilia is an important nosocomial bacterial pathogen, as is Pseudomonas aeruginosa. Differentiation of these bacteria as bacteremic agents is critical in the clinical setting and to define a therapeutic strategy; however, the associated factors and prognosis for S. maltophilia bacteremia have not been fully evaluated to adequately characterize these factors. We first conducted a matched case-control study to clarify these questions. A total of 30 case patients with S. maltophilia bacteremia were compared with 30 control patients with P. aeruginosa bacteremia between January 2005 and August 2014, according to matching criteria based on underlying disease, age, and gender. The 30-day mortality rate for the case patients (53.3%) was significantly higher than that of the control group (30.0%) (P = 0.047, using the log-rank test). Conditional logistic regression analysis showed that the predisposing factors specific for the detection of S. maltophilia bacteremia were indwelling artificial products other than a central venous catheter, ICU stay, and previous use of anti-MRSA drugs. The high severity of illness was associated with mortality in both case and control patients. Interestingly, inappropriate antimicrobial treatment was an additional independent risk factor for mortality in only the case patients with S. maltophilia bacteremia (odds ratio = 13.64, P = 0.048). Monotherapy with fluoroquinolones inactive against the S. maltophilia isolates was mainly responsible for the inappropriate treatment. These results suggest that more precise prediction and more appropriate treatment might improve the prognosis of patients with S. maltophilia bacteremia.
PMCID: PMC4514668  PMID: 26208218
6.  Rapid intraoperative visualization of breast lesions with γ-glutamyl hydroxymethyl rhodamine green 
Scientific Reports  2015;5:12080.
We previously developed γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) as a tool to detect viable cancer cells, based on the fact that the enzyme γ-glutamyltranspeptidase (GGT) is overexpressed on membranes of various cancer cells, but is not expressed in normal tissue. Cleavage of the probe by GGT generates green fluorescence. Here, we examined the feasibility of clinical application of gGlu-HMRG during breast-conserving surgery. We found that fluorescence derived from cleavage of gGlu-HMRG allowed easy discrimination of breast tumors, even those smaller than 1 mm in size, from normal mammary gland tissues, with 92% sensitivity and 94% specificity, within only 5 min after application. We believe this rapid, low-cost method represents a breakthrough in intraoperative margin assessment during breast-conserving surgery.
PMCID: PMC4499838  PMID: 26165706
7.  A gp130-Src-YAP Module Links Inflammation to Epithelial Regeneration 
Nature  2015;519(7541):57-62.
Inflammation promotes regeneration of injured tissues through poorly understood mechanisms, some of which involve interleukin (IL)-6 family members whose expression is elevated in many diseases, including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). We show that gp130, a co-receptor for IL-6 cytokines, triggers activation of YAP and Notch, transcriptional regulators that control tissue growth and regeneration, independently of the classic gp130 effector STAT3. Through YAP and Notch, intestinal gp130 signaling stimulates epithelial cell proliferation, causes aberrant differentiation and confers resistance to mucosal erosion. gp130 associates with the related tyrosine kinases Src and Yes, which are activated upon receptor engagement to phosphorylate YAP and induce its stabilization and nuclear translocation. This signaling module is strongly activated upon mucosal injury to promote healing and maintain barrier function.
PMCID: PMC4447318  PMID: 25731159
8.  Dynamic Modulation of Thymidylate Synthase Gene Expression and Fluorouracil Sensitivity in Human Colorectal Cancer Cells 
PLoS ONE  2015;10(4):e0123076.
Biomarkers have revolutionized cancer chemotherapy. However, many biomarker candidates are still in debate. In addition to clinical studies, a priori experimental approaches are needed. Thymidylate synthase (TS) expression is a long-standing candidate as a biomarker for 5-fluorouracil (5-FU) treatment of cancer patients. Using the Tet-OFF system and a human colorectal cancer cell line, DLD-1, we first constructed an in vitro system in which TS expression is dynamically controllable. Quantitative assays have elucidated that TS expression in the transformant was widely modulated, and that the dynamic range covered 15-fold of the basal level. 5-FU sensitivity of the transformant cells significantly increased in response to downregulated TS expression, although being not examined in the full dynamic range because of the doxycycline toxicity. Intriguingly, our in vitro data suggest that there is a linear relationship between TS expression and the 5-FU sensitivity in cells. Data obtained in a mouse model using transformant xenografts were highly parallel to those obtained in vitro. Thus, our in vitro and in vivo observations suggest that TS expression is a determinant of 5-FU sensitivity in cells, at least in this specific genetic background, and, therefore, support the possibility of TS expression as a biomarker for 5-FU-based cancer chemotherapy.
PMCID: PMC4400010  PMID: 25881233
9.  Collateral Chemoresistance to Anti-Microtubule Agents in a Lung Cancer Cell Line with Acquired Resistance to Erlotinib 
PLoS ONE  2015;10(4):e0123901.
Various alterations underlying acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have been described. Although treatment strategies specific for these mechanisms are under development, cytotoxic agents are currently employed to treat many patients following failure of EGFR-TKIs. However, the effect of TKI resistance on sensitivity to these cytotoxic agents is mostly unclear. This study investigated the sensitivity of erlotinib-resistant tumor cells to five cytotoxic agents using an in vitro EGFR-TKI-resistant model. Four erlotinib-sensitive lung adenocarcinoma cell lines and their resistant derivatives were tested. Of the resistant cell lines, all but one showed a similar sensitivity to the tested drugs as their parental cells. HCC4006ER cells with epithelial mesenchymal transition features acquired resistance to the three microtubule-targeting agents, docetaxel, paclitaxel and vinorelbine, but not to cisplatin and gemcitabine. Gene expression array and immunoblotting demonstrated that ATP-binding cassette subfamily B, member 1 (ABCB1) was up-regulated in HCC4006ER cells. ABCB1 knockdown by siRNA partially restored sensitivity to the anti-microtubule agents but not to erlotinib. Moreover, the histone deacetylase inhibitor entinostat sensitized HCC4006ER cells to anti-microtubule agents through ABCB1 suppression. Our study indicates that sensitivity of tumor cells to cytotoxic agents in general does not change before and after failure of EGFR-TKIs. However, we describe that two different molecular alterations confer acquired resistance to EGFR-TKIs and cytotoxic agents, respectively. This phenomenon should be kept in mind in selection of subsequent therapy after failure of EGFR-TKIs.
PMCID: PMC4397071  PMID: 25875914
10.  A Highly Accurate Inclusive Cancer Screening Test Using Caenorhabditis elegans Scent Detection 
PLoS ONE  2015;10(3):e0118699.
Early detection and treatment are of vital importance to the successful eradication of various cancers, and development of economical and non-invasive novel cancer screening systems is critical. Previous reports using canine scent detection demonstrated the existence of cancer-specific odours. However, it is difficult to introduce canine scent recognition into clinical practice because of the need to maintain accuracy. In this study, we developed a Nematode Scent Detection Test (NSDT) using Caenorhabditis elegans to provide a novel highly accurate cancer detection system that is economical, painless, rapid and convenient. We demonstrated wild-type C. elegans displayed attractive chemotaxis towards human cancer cell secretions, cancer tissues and urine from cancer patients but avoided control urine; in parallel, the response of the olfactory neurons of C. elegans to the urine from cancer patients was significantly stronger than to control urine. In contrast, G protein α mutants and olfactory neurons-ablated animals were not attracted to cancer patient urine, suggesting that C. elegans senses odours in urine. We tested 242 samples to measure the performance of the NSDT, and found the sensitivity was 95.8%; this is markedly higher than that of other existing tumour markers. Furthermore, the specificity was 95.0%. Importantly, this test was able to diagnose various cancer types tested at the early stage (stage 0 or 1). To conclude, C. elegans scent-based analyses might provide a new strategy to detect and study disease-associated scents.
PMCID: PMC4356513  PMID: 25760772
11.  Surgical results of resectable small cell lung cancer 
Thoracic Cancer  2015;6(2):141-145.
The standard of care for patients with small cell lung cancer (SCLC) is chemotherapy and radiotherapy, even for patients with limited disease. To define the role of surgical resection in patients with limited SCLC, we investigated the outcomes of patients diagnosed with limited-stage disease (LD) SCLC.
The records of 57 LD SCLC patients who underwent surgical resection from April 1974 to March 2012 were retrospectively analyzed.
There were six women and 51 men, with a median age of 63.5 years. The overall five-year survival rate was 28.6% (median, 18.2 months). The p-stage II and III patients had a significantly worse survival than the p-stage I patients (13.4% vs. 43.4%, P = 0.0036). However, the c-stage was not found to correlate with survival. Patients who underwent pneumonectomy had a significantly worse outcome than those who underwent other surgical procedures (0.0% vs. 32.0%, P = 0.0002). In a multivariate Cox proportional hazards analysis, p-stage II or III (hazard ratio [HR] 3.040 P = 0.0017) and pneumonectomy (HR 6.177, P = 0.00159) were significant independent predictors of an adverse survival outcome.
Surgical treatment can be considered in SCLC patients with pathologically proven N0 status, although pneumonectomy should be avoided.
PMCID: PMC4448487  PMID: 26273350
Limited-stage disease; pneumonectomy; small cell lung cancer
12.  Discrimination of p53 immunohistochemistry-positive tumors by its staining pattern in gastric cancer 
Cancer Medicine  2014;4(1):75-83.
Immunohistochemistry staining of p53 is a cheap and simple method to detect aberrant function of p53. However, there are some discrepancies between the result of immunohistochemistry staining and mutation analysis. This study attempted to find a new definition of p53 staining by its staining pattern. Immunohistochemistry staining of p53 and TP53 gene mutation analysis were performed in 148 gastric cancer patients. Also SNP-CGH array analysis was conducted to four cases. Positive staining of p53 was observed in 88 (59.5%) tumors. Tumors with positive p53 staining showed malignant features compared to negative tumors. Mutation of TP53 gene was observed in 29 (19.6%) tumors with higher age and differentiated type. In positive p53 tumors, two types could be distinguished; aberrant type and scattered type. With comparison to TP53 gene mutation analysis, all the scattered type had wild-type TP53 gene (P = 0.0003). SNP-CGH array showed that scattered-type tumors had no change in the structure of chromosome 17. P53-scattered-type staining tumors may reflect a functionally active nonmutated TP53 gene. In interpretation of p53 immunohistochemistry staining, distinguishing p53-positive tumors by their staining pattern may be important in gastric cancer.
PMCID: PMC4312120  PMID: 25354498
Gastric cancer; immunohistochemistry; mutation analysis; p53; staining pattern
13.  Molecular analysis of ATP-sensitive K+ channel subunits expressed in mouse vas deferens myocytes 
British Journal of Pharmacology  2013;171(1):145-157.
ATP-sensitive K+ (KATP) channels, which are composed of KIR6.x associated with sulphonylurea receptor (SUR) subunits, have been detected in native smooth muscle cells, but it is currently not known which of these is expressed in mouse vas deferens myocytes.
Pharmacological and electrophysiological properties of KATP channels in mouse vas deferens myocytes were investigated using patch clamp techniques. Molecular biological analyses were performed to examine the properties of these KATP channels.
During conventional whole-cell recording, pinacidil elicited an inward current that was suppressed by glibenclamide, a sulfonylurea agent, and by U-37883A, a selective KIR6.1 blocker. When 0.3 mM ATP was added to the pipette solution, the peak amplitude of the pinacidil-induced current was much smaller than that recorded in its absence. When 3 mM UDP, GDP or ADP was included in the pipette solution, an inward current was elicited after establishment of the conventional whole-cell configuration, with potency order being UDP > GDP > ADP. These nucleoside diphosphate-induced inward currents were suppressed by glibenclamide. MCC-134, a SUR modulator, induced glibenclamide-sensitive KATP currents that were similar to those induced by 100 μM pinacidil. In the cell-attached configuration, pinacidil activated channels with a conductance similar to that of KIR6.1. Reverse transcription PCR analysis revealed the expression of KIR6.1 and SUR2B transcripts and immunohistochemical studies indicated the presence of KIR6.1 and SUR2B proteins in the myocytes.
Our results indicate that native KATP channels in mouse vas deferens myocytes are a heterocomplex of KIR6.1 channels and SUR2B subunits.
PMCID: PMC3874703  PMID: 24117345
KATP channels; KIR6.1; SUR2B; vas deferens myocytes
14.  Solitary pulmonary metastasis from malignant melanoma of the bulbar conjunctiva presenting as a pulmonary ground glass nodule: Report of a case 
Thoracic Cancer  2015;6(1):97-100.
We herein report a case of solitary pulmonary metastasis from malignant melanoma that presented as a pulmonary ground glass nodule. A 57-year-old man who had undergone resection of a malignant melanoma of the right bulbar conjunctiva at the age of 51 was referred to our hospital for management of ground glass opacity in his left lung. Because radiological examination suggested the nodule was an adenocarcinoma in situ, computed tomography (CT) follow-up was planned. CT examination performed nine months later showed that the nodule had grown from 6 mm to 8 mm. Moreover, CT performed one and a half years after first detection revealed that the nodule had grown up to 10 mm. The patient, therefore, underwent partial resection of the lung for diagnosis and treatment. Pathological examination of the resected specimen revealed atypical cells with melanin granules proliferating in a lepidic-like fashion. The cells were positive on S-100 staining, indicating a pulmonary metastasis from malignant melanoma. Thus, metastatic tumors from malignant melanoma can present as ground glass opacities.
PMCID: PMC4448462  PMID: 26273342
Bronchioloalveolar; differential diagnosis; melanoma; neoplasm metastasis; solitary pulmonary nodule
15.  Therapeutic strategy for postoperative recurrence in patients with non-small cell lung cancer 
World Journal of Clinical Oncology  2014;5(5):1048-1054.
Postoperative recurrence occurs in approximately half of patients with non-small cell lung cancer (NSCLC), even after complete resection. Disease recurrence after surgical resection reduces the patient’s life expectancy sharply. The prognosis after postoperative recurrence is considered to largely depend on both the mode of first recurrence (distant, locoregional or combined) and the treatment modality: (1) The majority of cases of postoperative recurrence involve distant metastasis with or without locoregional recurrence. Platinum-based systemic chemotherapy is practically accepted as the treatment for these diseases on the basis of evidence for original stage IV disease. The advent of both pemetrexed and molecular-targeted drugs has improved the survival of nonsquamous NSCLC and changed the chemotherapeutic algorithm for NSCLC; (2) Among patients with distant metastatic recurrence without locoregional recurrence at the primary tumor site, the metastasis is often limited in both organ and number. Such metastases are referred to as oligometastases. Local therapy, such as surgical resection and radiotherapy, has been suggested to be the first-line treatment of choice for oligometastatic recurrence; and (3) While locoregional recurrence is likely to cause troublesome symptoms, it is a potentially limited disease. Therefore, providing local control is important, and radiation is usually beneficial for treating local recurrence. In order to obtain better control of the disease and provide treatment with curative intent in patients with limited disease, the administration of concurrent platinum-based chemoradiotherapy is recommended according to the results of originally nonresectable stage IIIA and IIIB disease.
PMCID: PMC4259931  PMID: 25493240
Non-small cell lung cancer; Postoperative recurrence; Distant metastasis; Oligometastases; Local treatment; Locoregional recurrence
16.  Gemcitabine Induces Poly (ADP-Ribose) Polymerase-1 (PARP-1) Degradation through Autophagy in Pancreatic Cancer 
PLoS ONE  2014;9(10):e109076.
Poly (ADP-ribose) polymerase-1 (PARP-1) and autophagy play increasingly important roles in DNA damage repair and cell death. Gemcitabine (GEM) remains the first-line chemotherapeutic drug for pancreatic cancer (PC). However, little is known about the relationship between PARP-1 expression and autophagy in response to GEM. Here we demonstrate that GEM induces DNA-damage response and degradation of mono-ADP ribosylated PARP-1 through the autophagy pathway in PC cells, which is rescued by inhibiting autophagy. Hypoxia and serum starvation inhibit autophagic activity due to abrogated GEM-induced mono-ADP-ribosylated PARP-1 degradation. Activation of extracellular regulated protein kinases (ERK) induced by serum starvation shows differences in intracellular localization as well as modulation of autophagy and PARP-1 degradation in GEM-sensitive KLM1 and -resistant KLM1-R cells. Our study has revealed a novel role of autophagy in PARP-1 degradation in response to GEM, and the different impacts of MEK/ERK signaling pathway on autophagy between GEM-sensitive and -resistant PC cells.
PMCID: PMC4182782  PMID: 25271986
17.  IgG4-related disease of the ileocecal region mimicking malignancy: A case report 
•The colonic IgG4-RD is rare.•We report the case of a74-year-old female with IgG4-RD of the ileocecal region.•The patient was diagnosed asmalignant lymphoma and underwent right-hemi colectomy.•Postoperative pathologicalexamination revealed IgG4-RD of the ileocecal region.•Surgical resection for IgG4-RDis necessary for cases with concerns of malignancy.
Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease characterized by chronic fibrosing inflammation with abundant IgG4-positive plasma cells, and responds well to steroids. Previous reports of IgG4-RD have focused on pancreatic and extrapancreatic including the gastrointestinal tract, however, the colonic IgG4-RD is rare.
We herein report the case of a 74-year-old female with edematous wall thickening of the terminal ileum to the lower ascending colon confirmed by several preoperative imaging studies, who underwent right hemi-colectomy for suspected malignant lymphoma. The resected specimen showed an irregular wall thickness with subserosal sclerosis, and the lesion was 10 cm in length from the terminal ileum to the ascending colon. The patient was diagnosed with IgG4-RD by pathological examinations, which demonstrated an increased number of IgG4-positive plasma cells (150/HPF), and an elevated IgG4/IgG ratio (50%).
Gastrointestinal IgG4-RD appears to be difficult to diagnose prior to surgical resection because of its rarity, and the similarity of its features to malignancy.
The measurement of the serum IgG4 levels, immunohistochemical examination of biopsy specimens and use of several imaging modalities might help us to diagnose the disease without surgical resection, and this disease can generally be treated with steroid therapy. However, surgical resection for IgG4-RD may still be also necessary for patients with concerns regarding malignancy or with intractable gastrointestinal obstruction caused by this disease.
Gastrointestinal IgG4-RD often mimics malignancy, and we should therefore consider this disease in the differential diagnosis of colonic lesions in order to optimize the treatment.
PMCID: PMC4189076  PMID: 25194601
IgG4-related disease; Colon; Resection
18.  Spontaneous regression of breast cancer with axillary lymph node metastasis: a case report and review of literature 
Spontaneous regression (SR) of cancer is a rare but well-documented biological phenomenon. However, the mechanism remains to be elucidated. We herein report a case of the SR of breast cancer at both the primary site and metastatic axillary lymph node with spontaneously-induced T cell-mediated immunological responses. A 52-year-old female with a lump in the left axilla was diagnosed to have a small breast carcinoma with a distinct axillary lymph node metastasis. During the preoperative systemic examination, she was diagnosed to have severe type 2 diabetes mellitus, was treated with insulin, and the hyperglycemia was normalized after one month. Surgery for left breast cancer was then performed. The postoperative histopathological examination revealed the SR of breast cancer at both the primary site and metastatic axillary lymph node. Immunohistochemical studies revealed that estrogen receptor positive, AE1/AE3-positive ductal carcinoma completely underwent necrosis associated with extensive infiltration of CD3-positive T cells in the tumor nodule in the lymph node. In addition, primary ductal carcinoma cells also underwent single cell necrosis with infiltration of T cells with lymph follicle-like organization of B cells in the mammary gland. The features were suggestive that the tumor eradication in the metastatic lymph node and regression of the primary ductal carcinoma could be due to host T cell response to the ductal carcinoma. As far as we know it is the first report that shows the spontaneous regression of breast cancer, probably due to the spontaneously-induced T cell response.
PMCID: PMC4129057  PMID: 25120822
Spontaneous regression; breast cancer; cancer immunology; T cell response
19.  Cystic Liver Infection after Living Donor Liver Transplantation: A Case Report 
Case Reports in Gastroenterology  2014;8(2):169-174.
There are no reports of cystic liver infection after liver transplantation. Herein, we report a rare case of cystic liver graft infection after living donor liver transplantation (LDLT). The patient was a 24-year-old man with primary sclerosing cholangitis who underwent right lobe graft LDLT. Preoperative abdominal computed tomography (CT) revealed a liver cyst at segment 8 of the donor liver. Biliary reconstruction was performed with hepaticojejunostomy. The postoperative course was uneventful until the patient developed a high fever and abdominal pain 15 months after LDLT. Abdominal contrast CT revealed abscess formation. Percutaneous drainage of the cyst was performed and purulent liquid was drained. The fever gradually subsided after treatment. On follow-up CT, the size of the infected liver cyst was decreased. Clinicians should be aware of the potential for cystic liver infection when using grafts with liver cysts, particularly when biliary reconstruction is performed with hepaticojejunostomy.
PMCID: PMC4049011  PMID: 24932164
Cystic liver infection; Living donor liver transplantation; Percutaneous drainage; Primary sclerosing cholangitis
20.  Spontaneous Massive Necrosis of Hepatocellular Carcinoma with Narrowing and Occlusion of the Arteries and Portal Veins 
Case Reports in Gastroenterology  2014;8(1):148-155.
We herein present the case of a 77-year-old man who had fever and right hypochondriac pain. He visited his doctor and underwent contrast computed tomography (CT), and he was suspected to have a liver abscess. He received an antibiotic treatment and his symptoms soon disappeared, but the tumor did not get smaller and its density on contrast CT image got stronger. He underwent biopsy and moderately differentiated hepatocellular carcinoma (HCC) was found. Extended left hepatic and caudate lobectomy was performed. Histological examination showed moderately differentiated HCC with narrowing and occlusion both in the arteries and portal veins associated with mild chronic inflammation. The mechanisms of spontaneous regression of HCC, such as immunological reactions and tumor hypoxia, have been proposed. In our case, histological examination showed the same findings. However, the mechanism is complex, and therefore further investigations are essential to elucidate it.
PMCID: PMC4036137  PMID: 24926228
Spontaneous necrosis; Hepatocellular carcinoma; Alcoholic liver disease; Hepatectomy
21.  A case of invasive micropapillary carcinoma of the breast involving extensive lymph node metastasis 
We herein report a case of invasive micropapillary carcinoma (IMPC) involving extensive lymph node metastasis with no recurrence for over 7 years. A 41-year-old female presented with pain and a swelling mass in the left axillary region, which had been present for several months. The tumor measured 1.6 cm in diameter in the middle of upper area of the left breast. Based on the findings of a core needle biopsy the pathological diagnosis was IMPC or mucinous carcinoma. The cytology of the left axillary lymph node was positive for metastatic carcinoma. The patient underwent a left mastectomy and a left axillary dissection (level I to III). The postoperative pathological diagnosis was IMPC with mucin production, and the number of metastatic lymph nodes was 59. The patient was given adjuvant chemotherapy (four courses of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and four courses of docetaxel), radiation for the left chest wall, supraclavicular and internal thoracic area, and then received tamoxifen for 5 years. The patient has remained recurrence-free for over 7 years. IMPC is known to be an aggressive histological type associated with a high incidence of lymph node metastasis and a poor prognosis. It seems that long-term survival was obtained by performing sufficient medical treatment. Prognostic factors other than the number of lymph node metastases may also exist.
PMCID: PMC4001353  PMID: 24708742
Invasive micropapillary carcinoma; Prognostic factor
22.  Management of thrombocytopenia due to liver cirrhosis: A review 
Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis, limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding. Multiple factors, including splenic sequestration, reduced activity of the hematopoietic growth factor thrombopoietin, bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents, and antiviral treatment with interferon-based therapy, can contribute to the development of thrombocytopenia in cirrhotic patients. Of these factors, the major mechanisms for thrombocytopenia in liver cirrhosis are (1) platelet sequestration in the spleen; and (2) decreased production of thrombopoietin in the liver. Several treatment options, including platelet transfusion, interventional partial splenic embolization, and surgical splenectomy, are now available for severe thrombocytopenia in cirrhotic patients. Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis, their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials. In this review, we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume, and we describe the current management of thrombocytopenia due to liver cirrhosis.
PMCID: PMC3949268  PMID: 24627595
Liver cirrhosis; Thrombocytopenia; Thrombopoietin; Partial splenic embolization; Splenectomy
23.  Laparoscopic liver resection in the semiprone position for tumors in the anterosuperior and posterior segments, using a novel dual-handling technique and bipolar irrigation system 
Surgical Endoscopy  2014;28(8):2484-2492.
Hepatic tumors in the lower edge and lateral segments are commonly treated by laparoscopic liver resection. Tumors in the anterosuperior and posterior segments are often large and locally invasive, and resection is associated with a higher risk of insufficient surgical margins, massive intraoperative bleeding, and breaching of the tumor. Laparoscopic surgery for such tumors often involves major hepatectomy, including resection of a large volume of normal liver tissue. We developed a novel method of laparoscopic resection of tumors in these segments with the patient in the semiprone position, using a dual-handling technique with an intercostal transthoracic port. The aim of this study was to evaluate the safety and usefulness of our technique.
Of 160 patients who underwent laparoscopic liver resection at our center from June 2008 to May 2013, we retrospectively reviewed those with tumors in the anterosuperior and posterior segments. Patients were placed supine or semilateral during surgery until January 2010 and semiprone from February 2010.
Before the introduction of the semiprone position in February 2010, a total of 7 of 40 patients (17.5 %) with tumors in the anterosuperior and posterior segments underwent laparoscopic liver resection, and after introduction of the semiprone position, 69 of 120 patients (57.5 %) with tumors in the anterosuperior and posterior segments underwent laparoscopic liver resection (P < 0.001). There were no conversions to open surgery, reoperations, or deaths. The semiprone group had a significantly higher proportion of patients who underwent partial resection or segmentectomy of S7 or S8, lower intraoperative blood loss, and shorter hospital stay than the supine group (all P < 0.05). Postoperative complication rates were similar between groups.
Laparoscopic liver resection in the semiprone position is safe and increases the number of patients who can be treated by laparoscopic surgery without increasing the frequency of major hepatectomy.
Electronic supplementary material
The online version of this article (doi:10.1007/s00464-014-3469-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4077249  PMID: 24622763
Pure laparoscopic hepatectomy; Semiprone position; Anterosuperior and posterior segments; Dual-handling technique; Intercostal transthoracic port
24.  Portal vein thrombosis in liver cirrhosis 
World Journal of Hepatology  2014;6(2):64-71.
Portal vein thrombosis (PVT) is considered to be a frequent complication of liver cirrhosis. However, unlike PVT in patients without cirrhosis, very few data are available on the natural history and management of PVT in cirrhosis, despite its association with potentially life-threatening conditions, such as gastroesophageal bleeding and acute intestinal ischemia. Moreover, no consensus regarding PVT in cirrhosis exists. Suggested causes of PVT in cirrhosis include reduced portal blood flow velocity, multiple congenital or acquired thrombophilic factors, inherited or acquired conditions, and derangement of liver architecture. However, the understanding of PVT in cirrhosis is incomplete. In addition, information on the management of PVT in cirrhosis is inadequate. The aims of this review are to: (1) assemble data on the physiopathological mechanism, clinical findings, diagnosis and management of PVT in cirrhosis; (2) describe the principal factors most frequently involved in PVT development; and (3) summarize the recent knowledge concerning diagnostic and therapeutic procedures.
PMCID: PMC3934638  PMID: 24575165
Portal vein thrombosis; Liver cirrhosis; Thrombophilic factors; Anticoagulation; Splenectomy
25.  New molecular staging with G-factor supplements TNM classification in gastric cancer: a multicenter collaborative research by the Japan Society for Gastroenterological Carcinogenesis G-Project committee 
Gastric Cancer  2014;18(1):119-128.
The G-Project committee was erected by the Japan Society for Gastroenterological Carcinogenesis with an aim of establishing a new classification scheme based on molecular biological characteristics that would supplement the conventional TNM classification to better predict outcome.
In a literature search involving 822 articles on gastric cancer, eight molecules including p53, vascular endothelial growth factor (VEGF)-A, VEGF-C, matrix metalloproteinase-7 (MMP-7), human epidermal growth factor receptor 2, Regenerating islet-derived family, member 4, olfactomedin-4 and Claudin-18 were selected as candidates to be included in the new molecular classification scheme named G-factor. A total of 210 cases of gastric cancer who underwent curative R0 resection were registered from four independent facilities. Immunohistochemical staining for the aforementioned molecules was performed for the surgically resected specimens of the 210 cases to investigate the correlation between clinicopathological factors and expression of each molecule.
No significant correlation was observed between the immunostaining expression of any of the eight factors and postoperative recurrence. However, the expressions of p53 and MMP-7 were significantly correlated with overall survival (OS). When 210 gastric cancer patients were divided into three groups based on the expression of p53 and MMP-7 (G0 group: negative for both p53 and MMP-7, n = 69, G1 group: positive for either p53 or MMP-7, n = 97, G2 group: positive for both of the molecules, n = 44), G2 group demonstrated significantly higher recurrence rate (59 %) compared to 38 % in G0 (p = 0.047). The multivariate regression analysis revealed that G2 group was independently associated with a shorter disease-free survival (DFS) (hazard ratio 1.904, 95 % CI 1.098–3.303; p = 0.022), although the association with OS was not significant. Stage II patients among the G2 group had significantly inferior prognosis both in terms of OS and DFS when compared with those among the G0/G1 group, with survival curves similar to those of Stage III cases.
G-factor based on the expression of p53 and MMP-7 was found to be a promising factor to predict outcome of Stage II/III gastric cancer, and possibly to help select the treatment for Stage II cancer, thus supplementing the conventional TNM system.
PMCID: PMC4257995  PMID: 24488015
Gastric cancer; G-factor; Molecular staging; TNM classification

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