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Pyogenic liver abscesses generally occur secondary to spread from active infective lesions. We report a rare case of liver abscess in a patient without a clear source of infection. A 19-year-old man was diagnosed as having a liver abscess after investigations when he presented with chief complaints of fever and lethargy. Fusobacterium nucleatum was detected in the pus culture taken from the abscess that was drained. His condition improved with antibacterial treatment. Further examination of the gastrointestinal tract suggested that the infection had tracked through the portal vein from a scar between the rectal sigmoid and the appendix. Laparoscopic adhesiolysis and appendectomy were performed to treat the same. Fusobacterium can be identified early by Gram staining of pus from the liver abscess, which is useful for treatment. In young people with pyogenic liver abscess due to Fusobacterium nucleatum who are not immunocompromised, examination of the gastrointestinal tract should be considered to determine a cause.

Background: Despite the rapid advances that minimally invasive liver resection has gained in recent decades, open conversion is still inevitable in some circumstances. In this study, we aimed to determine the risk factors for open conversion after minimally invasive left lateral sectionectomy, and its impact on perioperative outcomes. Methods: This is a post hoc analysis of 2,445 of 2,678 patients who underwent minimally invasive left lateral sectionectomy at 45 international centers between 2004 and 2020. Factors related to open conversion were analyzed via univariate and multivariate analyses. One-to-one propensity score matching was used to analyze outcomes after open conversion versus non-converted cases. Results: The open conversion rate was 69/2,445 (2.8%). On multivariate analyses, male gender (3.6% vs 1.8%, P = .011), presence of clinically significant portal hypertension (6.1% vs 2.6%, P = .009), and larger tumor size (50 mm vs 32 mm, P < .001) were identified as independent factors associated with open conversion. The most common reason for conversion was bleeding in 27/69 (39.1%) of cases. After propensity score matching (65 open conversion vs 65 completed via minimally invasive liver resection), the open conversion group was associated with increased operation time, blood transfusion rate, blood loss, and postoperative stay compared with cases completed via the minimally invasive approach. Conclusion: Male sex, portal hypertension, and larger tumor size were predictive factors of open conversion after minimally invasive left lateral sectionectomy. Open conversion was associated with inferior perioperative outcomes compared with non-converted cases.

Background Cigarette smoking harms nearly every organ, including the heart and lungs. A comprehensive assessment of both cardiac and respiratory function is necessary for evaluating the direct effects of tobacco on the heart. However, few previous studies examining the effects of cigarette smoking on cardiac function included an assessment of lung function. This cross-sectional study investigated the influence of cigarette smoking on cardiac function, independent of respiratory function. Methods We retrospectively reviewed the medical records of 184 consecutive cases that underwent both spirometry and transthoracic echocardiography around the same time (within 1 month) in one hospital from April 2019 to March 2020. Participants were classified into three groups based on lifetime smoking exposure (pack-years): non-smoker (n = 49), low exposure (1–20 pack-years, n = 40), and high exposure (≥ 20 pack years, n = 95). Multiple linear regression analysis was used to assess the relationship among cigarette smoking, and cardiac and respiratory functions. The relationship between selected dependent variables and lifetime pack-years was assessed in two models with multiple linear regression analysis. Model 1 was adjusted for age and male sex; and Model 2 was adjusted for Model 1 plus forced expiratory volume percentage in 1 s and forced vital capacity percentage. Results Compared with the non-smokers, the participants with high smoking exposure had lower left ventricular (LV) systolic function and larger LV size. Multiple linear regression analysis revealed a negative association of cumulative lifetime pack-years with LV and right ventricular (RV) systolic functions, even after adjustment for age, sex, and spirometric parameters (forced expiratory volume percentage in 1 s and forced vital capacity percentage). Meanwhile, there was no significant association of smoking exposure with LV diastolic function (E/e′ and E/A) and RV diastolic function (e′t and e′t/a′t). Conclusions Cumulative smoking exposure was associated with a negative effect on biventricular systolic function in patients with relatively preserved cardiac function, independent of respiratory function.

Background Minimally invasive pancreaticoduodenectomy (MIPD), including laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD), is technically demanding because of pancreaticojejunostomy (PJ). Postoperative pancreatic fistula (POPF) is the most serious complication of MIPD and open pancreaticoduodenectomy (OPD). Contrary to expectations, conventional PJ in MIPD did not improve POPF rate and length of hospital stay. High POPF rates are attributed to technical issues encountered during MIPD, which include motion restriction and insufficient water tightness. Therefore, we developed wrapping double-mattress anastomosis, the Kiguchi method, which is a novel PJ technique that can improve MIPD. Herein, we describe the Kiguchi method for PJ in MIPD and compare the outcomes between this technique and conventional PJ in OPD. Methods The current retrospective study included 83 patients in whom the complete obstruction of the main pancreatic duct by pancreatic tumors was absent on preoperative imaging. This research was performed from September 2016 to August 2020 at Fujita Health University Hospital. All patients were evaluated as having a soft pancreatic texture, which is the most important factor associated with POPF development. Briefly, 50 patients underwent OPD with conventional PJ (OPD group). Meanwhile, 33 patients, including 15 and 18 who had LPD and RPD, respectively, underwent MIPD using the Kiguchi method (MIPD group). After a 1:1 propensity score matching, 30 patients in the OPD group were matched to 30 patients in the MIPD group. Results The patients’ preoperative data did not differ. The grade B/C POPF rate was significantly lower in the MIPD group than in the OPD group (6.7% vs 40.0%, p = 0.002). The MIPD group had a significantly shorter median length of hospital stay than the OPD group (24 vs 30 days, p = 0.004). Conclusion The novel Kiguchi method in MIPD significantly reduced the POPF rate in patients without complete obstruction of the main pancreatic duct.

Rhabdomyolysis is a relatively common and life-threatening disease that is sometimes complicated by acute kidney injury (AKI). Several causes have been reported, divided into traumatic and non-traumatic causes. We herein report a patient with rhabdomyolysis with AKI caused by bilateral iliopsoas hematoma. This patient had atrial fibrillation that was poorly controlled with warfarin, and bilateral iliopsoas hematoma was caused by turnover without a history of high-energy injury. Treatment with the rapid neutralization of warfarin improved his clinical condition without complications. We should pay close attention to episodes of turnover among elderly patients receiving anticoagulant therapy.

Japan is an aging society, and the incidence of diseases related to aging, such as pneumonia, heart failure, vertebral compression fracture (VCF), is increasing. Prolonged hospital stays are becoming a serious social problem, leading to elevated medical expenses. Thus, shortening the period of hospitalization is important. This study aimed to reveal determinants associated with prolonged hospital stays for patients with VCF. Our institution is the primary hospital in a rural area in the Kanto region of Japan. Altogether, 110 patients with a VCF, aged 65 years or older, including 79 women, were divided into two groups according to the average hospital stay period of 28 days: the long-stay group (mean stay 40.0 ± 11.6 days, n = 39) and the short-stay group (mean stay 20.6 ± 4.4 days, n = 71). Notably, the short-stay group included 55 women. Multivariate logistic regression analyses in male showed no variates significantly associated with prolonged hospitalization. By contrast, multivariate logistic regression analyses in female showed requiring emergency transportation to hospital was significantly associated with prolonged hospitalization [odds ratio 7.69, 95% confidence interval 1.13-52.29, P = 0.04]. In conclusion, this study implies that patients with better levels of activities of daily living are able to walk alone sooner and are easily discharged. Furthermore, the patient requiring emergency transportation might be in a poor social living environment, such as living alone. These results may give us a good opportunity to re-consider fundamental problems surrounding the elderly.

Background Distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) for borderline resectable pancreatic body cancer is increasingly being performed [ 1 , 2 ]. For survival benefits, obtaining margin-free resection (R0 resection) is crucial [ 3 ]. However, in patients with cancer abutting the root of the celiac axis and/or SMA, accurate resectability using preoperative imaging is difficult to judge [ 4 ]. Recently, we developed a novel strategy named “Retlap: Ret roperitoneal-first lap aroscopic ap proach” to achieve accurate evaluation of resectability and minimal invasiveness for difficult hepatopancreatobiliary malignancies and retroperitoneal tumors. Retlap enables direct evaluation of invasion of the roots of the celiac axis and SMA through the retroperitoneal approach. Methods This video demonstrates the case of a 50-year-old man with a 47 × 36-mm pancreatic body tumor after chemoradiotherapy. Preoperative computed tomography revealed tumor abutting on the roots of the celiac axis and SMA. Changes in the surrounding tissues due to chemoradiotherapy prevented accurate determination of the tumor invasion extent via preoperative imaging; thus, Retlap was applied. Retlap enabled us to identify and secure the roots of the celiac axis and SMA easily despite the advanced tumor. After confirming resectability, DP-CAR was performed. Results The operative time and estimated blood loss were 841 min and 572 mL. A negative surgical margin using Retlap was confirmed in frozen sections and R0 resection was achieved with uneventful postoperative course. Conclusion Retlap was technically feasible and useful for achieving accurate evaluation of resectability and minimal invasiveness for DP-CAR. Retlap can help provide optimal outcomes in locally advanced pancreatic cancer cases.

Tropomyosin-related kinase B (TrkB) plays an important role in tumor progression in various kinds of cancers; however, little is known about biological significance of TrkB in human lung cancer, especially large cell neuroendocrine carcinoma (LCNEC). We hereby investigated the expressions of TrkB and its ligand brain-derived neurotrophic factor (BDNF) in clinical specimens and their influences on phenotypes of invasiveness and tumorigenicity for LCNEC. The expressions of TrkB and BDNF analyzed by immunohistochemistry for patients samples with lung cancer (n=104) were significantly higher in neuroendocrine tumor (NET) compared with non-NET. In particular, LCNEC, a subtype of NET, exhibited significantly higher TrkB and BDNF expressions than another NET type: small cell lung cancer (SCLC), and a significant correlation between TrkB and BDNF expressions was noted in LCNEC but not in SCLC. In vitro assay, exogenous BDNF addition enhanced the invasion into matrigels of LCNEC cells, whereas inhibition of TrkB or BDNF suppressed matrix metalloproteinase-2 and -9 activities and the invasiveness. Exogenous BDNF also increased anchor-independent colony formation on soft agar gels for LCNEC, while inhibition of TrkB or BDNF suppressed the anchorage-independency. In vivo experiments, implanted LCNEC cells pretreated with TrkB-siRNA developed no subcutaneous tumor in all six nude mice, although those with control-siRNA formed tumors in four of six nude mice. In conclusion, BDNF/TrkB signal is involved in malignant progression of invasiveness and tumorigenicity for LCNEC, and may be a potential target for LCNEC without standard therapy.

Background High mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxic shock and sepsis. The purpose of the present study was to investigate the role of HMGB1 in response to ischemia-reperfusion injury. Methods Ischemia-reperfusion injury was induced in male Wistar rats by clamping the superior mesenteric artery for 60 min. Using this model, the serum concentrations and localization of HMGB1 were investigated. The histologic findings from reperfused intestines and the survival rates were compared between the anti-HMGB1 antibody treatment groups (group A treated with 6.0 mg/kg antibody and group B with 0.6 mg/kg antibody) and the control antibody treatment group (control group). Results Serum HMGB1 concentrations increased early after reperfusion and peaked at 3 h. Immunohistochemistry for HMGB1 revealed a high degree of positive staining in the epithelial cells of the damaged villi. Anti-HMGB1 antibody treatment significantly reduced this damage ( P versus 50% in the controls; P Conclusions These results suggest that HMGB1 plays a key role in small intestinal ischemia-reperfusion injury.

Retinol-binding protein 4 (RBP4) is a recently identified adipokine that was involved in insulin resistance. RBP4 is predominantly expressed from the liver in normal metabolic state to transport retinoids throughout the body, but the exact physiological function and the regulatory mechanisms of adipocyte-derived RBP4 have not been revealed. We conducted the genetic analysis about metabolic parameters in Japanese and Mongolian; the minor allele carriers of regulatory single-nucleotide polymorphism (SNP -803G>A) showed significantly higher BMI in Japanese men (P = 0.009) and women (P = 0.017), and in Mongolian women (P = 0.009). Relative quantification of RBP4 transcripts in -803GA heterozygotes showed that the minor allele-linked haplotype-derived mRNA was significantly more abundant than the transcript from major allele. RBP4 promoter assay in 3T3L1 adipocytes revealed that the minor allele increased the promoter activity double to triple and the administration of 9-cis-retinoic acid (RA) and 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP) enhanced the activity. Multiple alignment analysis of human, mouse, rat, and cattle RBP4 promoter suggested conserved seven transcription factor binding motifs. Electrophoretic mobility shift assay showed the -803G>A SNP modulate the affinity against unidentified DNA-binding factor, which was assumed to be a suppressive factor. These results collectively suggested that the minor allele of RBP4 regulatory SNP enhanced the expression in adipocytes, which may be associated with the adipogenesis.

A prospective study was conducted to ascertain the effects of preoperative enteral immunonutrition on a surgical site infection (SSI) in patients with colorectal cancer without malnutrition. Patients with colorectal cancer undergoing elective surgery without malnutrition, bowel obstruction, severe cardiopulmonary complications, diabetes, collagen disease, or renal failure were sequentially divided into an immunonutrition group (n = 33) and a control group (n = 34). In the immunonutrition group, an enteral diet supplemented with arginine, dietary nucleotides, and ω-3 fatty acids was administered for 5 days (750 ml/day) prior to surgery. The mean age was slightly higher in the immunonutrition group (69 ± 9 years) than in the control group (63 ± 11 years; P < 0.05), but no significant differences between the groups were noted for the body mass index, total protein, albumin, hemoglobin, surgical methods, operation time, or volume of intraoperative bleeding. The frequencies of superficial incisional SSI, deep incisional SSI and organ/space SSI in the immunonutrition and control groups were 0% and 11.8% (4/34; P < 0.05), 0% and 0%, and 0% and 2.9% (1/34), respectively. Preoperative enteral immunonutrition appears to be effective for preventing SSI in patients with colorectal cancer without malnutrition.

Purpose. The correlation between age and the outcome following an operation for colorectal cancer (CRC) has not yet been determined. We studied the appropriate operation for elderly CRC patients based upon the assessment of preoperative risk factors. Methods. Seventy patients with Dukes' stages B or C CRC (more than 80 years old: aged group) and 66 stage-matched patients (50–69 years old: control group) were studied. The preoperative condition, the grade of surgical intervention, the perioperative activities of daily life (ADL), and the survival rate were compared between the two groups. Results. The preoperative conditions were significantly worse and the frequencies of patients with a deterioration in ADL during the perioperative period were significantly higher in the aged group. In the aged group, the peripheral lymphocyte count was significantly lower in patients with major postoperative complications, and the 1.0% forced expiratory volume (FEV1.0%) was significantly lower in patients with a deterioration in ADL. The low grade of surgical intervention tended to be related to a poor prognosis in rectal cancer of the aged group. Conclusion. The indications for operation in elderly CRC patients should be determined based upon an appropriate assessment of preoperative conditions, such as the lymphocyte count and FEV1.0%.

BACKGROUND The Amsterdam criteria are used worldwide for the clinical diagnosis of hereditary nonpolyposis colorectal carcinoma (HNPCC). In Japan, clinical criteria (JCC) have been proposed to identify as many HNPCC cases as possible, but the suitability of the JCC remains uncertain. In this article, the authors evaluate retrospectively whether the JCC are adequate to diagnose HNPCC compared with the Bethesda guidelines (BG) and also investigated useful screening methods for HNPCC. METHODS The authors studied 452 colorectal carcinoma cases, of which 69 cases fulfilled the JCC (A, 12; B, 57) and 106 fulfilled the BG. Microsatellite instability (MSI) was examined for 452 cases. TGFβRII, immunohistochemical staining, and germline mutations of hMLH1 and hMSH2 were analyzed in high-frequency MSI cases. RESULTS High-frequency MSI was found in 21.7% (98 of 452). Germline mutations were detected in eight cases (hMLH1, three, hMSH2; five). Six cases fulfilled the JCC (A, four; B, two), and six fulfilled the BG. The germline mutation rate was significantly higher in the JCCA than in non-JCCA cases (33.3% vs. 0.91%; P < 0.001) and in cases with an age at onset younger than 50 years than older than 50 years (9.3% vs. 0.27%, P < 0.001). All germline mutation carriers had the TGFβRII mutation. Immunohistochemically, a decreased nuclear staining was found in 57.3% (47 of 82) for hMLH1 and in 18.3% (15 of 82) for hMSH2. The frequency of predicted germline mutations was higher in cases with decreased hMSH2 than hMLH1 (33.3% vs. 6.4%; P = 0.016). CONCLUSIONS The JCCA are suitable for selecting cases to analyze for gene mutations, but the JCCB are not useful for the clinical setting. The authors suggest that an age at onset younger than 50 years is also important for screening. Analyzing TGFβRII mutations and immunohistochemical staining of hMLH1 or hMSH2 for cases with MSI phenotype are useful for selecting cases who should be tested for germline mutations. Cancer 2002;94:911–20. © 2002 American Cancer Society. DOI 10.1002/cncr.10332

Background: Prostaglandin (PG) E2 has an influence on antitumor lymphocyte reactions and causes local immunosuppression at tumor sites. The contribution of cyclooxygenase (COX), a key enzyme in PGE2 synthesis, to this effect is still unclear. We examined if cyclooxygenase (COX)-2 is involved in local immunosuppression in human colon carcinoma cell lines and in clinical tumor specimens. Methods: PGE2 concentrations were measured in culture media from a highly COX-2-expressing human colon carcinoma cell line (CE-1) and other cell lines. Lymphocyte proliferation in response to a mitogen was used to evaluate immunosuppression in tumor cell-lymphocyte cocultures with and without selective COX-2 inhibitor NS-398. We also evaluated expression of COX-2 mRNA in surgical specimens of colorectal carcinoma by reverse transcription polymerase chain reaction (RT-PCR) and COX-2 protein by immunohistochemistry, correlating COX-2 expression with clinicopathologic features. Results: CE-1 cells produced large amounts of PGE2, which was significantly inhibited by NS-398. The proliferation index of lymphocytes cocultured with CE-1 cells was significantly less than that of control lymphocytes; again, this effect was inhibited by NS-398. While human colorectal carcinoma tissue expressed more COX-2 mRNA and protein than nonneoplastic tissue, no significant correlation was found between COX-2 levels and clinicopathologic features. Conclusions: Overexpression of COX-2 in colon cancer may cause local immunosuppression, and COX-2 inhibitors might be therapeutically useful against these tumors.

PURPOSE: The aim of this study was to investigate the genetic alterations of early-stage nonfamilial colorectal carcinomas regarding microsatellite instability, with special reference to the shape of the tumors and the site of the lesions. METHODS: Formalin-fixed, paraffin-embedded specimens of 44 early-stage nonfamilial colorectal carcinomas were examined for microsatellite instability with use of polymerase chain reaction. RESULTS: The 44 carcinomas consisted of 16 flat carcinomas and 28 polypoid carcinomas. Nineteen carcinomas were located in the proximal colon (9 flat type and 10 polypoid type), whereas 25 were in the distal colon and rectum (7 flat type and 18 polypoid type). Ten (22.7 percent) of the 44 carcinomas had at least one positive locus, whereas five (11.4 percent) of them had two or more positive loci. In the proximal colon the percentage of flat carcinomas with at least one positive locus was significantly greater than that of the polypoid carcinomas (4/9 (44 percent)vs. 0/10;P=0.04). Six patients had synchronous or metachronous colorectal carcinomas or both. They harbored microsatellite instability more frequently than patients with single colorectal carcinomas, and the differences were statistically significant (P

PURPOSE: The aim of this study was to elucidate pathways of carcinogenesis in the colon and rectum by investigating Ki-raspoint mutation in different types of colorectal carcinomas in the early stage. METHODS: We analyzed rates of Ki-rascodon 12 mutations in 34 small, polypoid-type carcinomas (Tis or T1), 21 superficial-type carcinomas (Tis or T1), and 42 advanced carcinomas (T2, T3, and T4). RESULTS: Frequency of Ki-rasmutations in superficial-type carcinomas was 14.3 percent (3/21), which was significantly lower than 50 percent (17/34) in small polypoid carcinomas and 40.5 percent (17/42) in advanced carcinomas. These data suggest that another pathway of colorectal carcinogenesis that does not involve Ki-raspoint mutation might exist. Among the 17 small polypoid carcinomas with Ki-raspoint mutation in which both adenomatous and carcinomatous tissue were examined, 12 showed a mutation of the same type in both carcinomatous and adenomatous tissues. In two cases, mutation was present only in carcinomatous tissue and not in adenomatous tissue; in the other three cases, Ki-raspoint mutation was present only in adenomatous tissue but not in carcinomatous tissue. CONCLUSIONS: These data suggest that carcinoma in a small polypoid lesion does not always develop from pre-existing adenoma with Ki-raspoint mutation; in a small number of the polypoid-type early carcinomas, polyclonal composition concerning the Ki-rasgene may exist.

Large cell neuroendocrine carcinoma (LCNEC) has an especially poor prognosis, and an effective therapeutic strategy has yet to be established. We have previously shown that the expressions of tropomyosin-related kinase B (TRKB) and brain-derived neurotrophic factor (BDNF) are high in LCNEC and that TRKB/BDNF signaling is involved in the proliferation, tumorigenesis, and invasive nature of LCNEC. Therefore, TRKB/BDNF signaling may offer a potential therapeutic target for LCNEC treatment. In the present study, we evaluated whether the TRKB tyrosine kinase inhibitor, k252a, has effects on tumor regression and relapse prevention on LCNEC, using a murine xenograft model. The LCNEC cell line and NCI-H810 cells were subcutaneously implanted into the flanks or intrathoracically injected into the bilateral pleural cavities of BALB/c nude mice. k252a significantly inhibited tumor volume, expression of matrix metalloproteinases and the formation of pleural dissemination by LCNEC. These results suggest that k252a has potential for tumor regression and relapse prevention in LCNEC. Since many patients with LCNEC suffer through the use of ineffective therapeutic strategies, a clinical trial using the TRKB inhibitor for LCNEC is urgently required.

Non-occlusive mesenteric ischemia (NOMI), leading to intestinal gangrene without a demonstrable occlusion in the mesenteric artery, is a rare condition with extremely high mortality. We report a case of NOMI diagnosed preoperatively by computed tomography and treated successfully with surgery, assisted by indocyanine green (ICG) fluorescence in the HyperEye Medical System (HEMS), a new device that can simultaneously detect color and near-infrared rays under room light. This allowed for precise intraoperative evaluation of the mesenteric and bowel circulation. Although the necrotic bowel wall of the distal ileum and the segmental ischemia of the jejunum were visible, the jejunum was finally preserved because perfusion of ICG fluorescence was confirmed. The patient, an 84-year-old man, had an uneventful postoperative course and is alive without critical illness 8 months after surgery. We report this case to demonstrate the potential effectiveness of HEMS during surgery for NOMI.

We investigated the pharmacokinetics of mizoribine in the acute phase after adult living donor liver transplantation (LDLT). Between February 2004 and October 2009, 16 recipients received immunosuppressive therapy that included mizoribine (100 to 200 mg/d) after undergoing LDLT. We determined the serum levels of mizoribine before (C0) and 3 (C3), 4 (C4), and 10 (C10) hours after administration on postoperative days 3, 7, and 21. We assessed area under the concentration time curve (AUC) (hour · μg/mL), normalized serum concentration (NSC) at C0 [concentration (μg/mL)/dose (mg/kg body weight)], and estimated glomerular filtration rate (eGFR). The mizoribine concentration showed increases at C3 and C4 followed by a decrease at C10 on all days. AUC was 4.3, 5.9, and 8.3 in the 200-mg/d dose group on days 3, 7, and 21, respectively. NSC at C0 increased for 3 weeks after LDLT. There was a significant correlation between the NSC at C0 and eGFR on day 21, but not on days 3 and 7. There were no correlations between the NSC at C0 and either aspartate aminotransferase, total bilirubin, albumin, trough cyclosporine, or trough tacrolimus on any day. The pharmacokinetics of mizoribine in the acute phase after LDLT seems to be affected by postoperative day and renal function.

Adipocyte lipolysis is mediated by a family of triglyceride (TG) lipases consisting of hormone-sensitive lipase (LIPE), adipose triglyceride lipase (PNPLA2) and carboxylesterase 1 (CES1); however, little is known about the relationship between the expression of each gene in different depots and TG lipase activity or obesity.We measured both mRNA expression levels of the lipolytic enzymes (LIPE, PNPLA2 and CES1) and TG lipase activities of biopsy samples obtained from subcutaneous, omental and mesenteric adipose tissues of 34 patients who underwent abdominal surgery. The results were correlated with clinical parameters: adiposity measures, parameters for insulin resistance and plasma lipid levels.PNPLA2 mRNA levels were slightly higher in omental fat than subcutaneous fat. Cytosolic TG lipase activities were positively correlated with the mRNA levels of CES1 in subcutaneous fat and mesenteric fat, while they were correlated with those of PNPLA2 in omental fat. The mRNA levels of LIPE were negatively correlated with various measures of adiposity in subcutaneous fat. The mRNA levels of CES1 were positively correlated with various measures of adiposity, particularly those estimated by CT in the three depots; they were also positively correlated with plasma LDL-cholesterol levels in omental fat. In contrast, the mRNA levels of PNPLA2 were not significantly associated with adiposity.The positive correlations of the expression of CES1 with cytosolic TG lipase activities as well as with adiposity suggest that CES1 is involved in lipolysis, thereby contributing to the development of obesity-associated phenotypes. On the other hand, the expression of LIPE is negatively correlated with adiposity. These distinct regulatory patterns of lipolytic genes may underlie the complex phenotypes associated with human obesity.

Endoscopic thymectomy is commonly used for treatment of myasthenia gravis (MG) patients due to its relatively low invasiveness. However, the long-term effects of endoscopic thymectomy have not been fully evaluated.To assess the long-term effects of extended infrasternal mediastinoscopic thymectomy (IMT) in MG patients and compare them with those of extended transsternal thymectomy (TT).Among 24 MG patients without thymoma who underwent thymectomy in our Institute between January 1997 and December 2000, 14 patients who received IMT and 10 who received TT were enrolled in the present study. Quantitative myasthenia gravis (QMG) score and anti-acetylcholine receptor antibody (anti-AChR) titers were evaluated before and at five years after surgery.After five years, QMG scores were reduced from 6.6 to 1.8 (p0.01) in the IMT group, and from 7.6 to 2.7 (p0.01) in the TT group. The anti-AChR titers were reduced from 75.2 to 40.1 (p=0.027) in the IMT group, and from 224 to 61.3 (p=0.020) in the TT group.These data suggest that the long-term therapeutic effect of IMT is equivalent to TT, and is thus suitable for the treatment of MG patients.

The thymus plays an essential role in the maturing of progenitor cells to functional T cells. Recent studies suggest that the Hedgehog (Hh) signaling pathway contributes to this differentiation process. However, there is limited information concerning the expression of Hh pathway-related proteins (Hh proteins) in the human thymus. The staining of Hh proteins in the thymic epithelium of 26 surgically resected thymoma tissues was examined by immunohistochemistry. The staining of sonic Hh (Shh) correlated relatively well with the World Health Organization histological classification of thymoma. The higher the grade, the fainter the staining. However, no significant difference in Shh staining was found between normal and neoplastic epithelia. Interestingly, Gli1 staining in thymomas was significantly greater than that in normal thymus (p0.0001). Thus, some members of the Hh signaling pathway may contribute to the development of thymoma.

Although hepatic hemangioma is common, its rupture after trauma is rare. We report a 47-year-old woman with a traumatic hepatic hemangioma rupture following a traffic accident who successfully underwent operation. Only four cases of hepatic hemangioma rupture caused by blunt trauma have been reported including this one. Each patient (two men and two women) had a giant right lobe hemangioma. The causal injury included a traffic accident in two, a fall in one, and minor trauma in another. Three patients underwent surgery, and one was conservatively managed. All the patients survived.

Nuclear factor-kB (NF-kB) is a transcription factor that participates in the induction of several genes for cytokines and enzymes that play important functional roles in various cell types. The aim of this study was to determine NF-kB activation status in human colorectal carcinoma and its correlation to the clinicopathological characteristics of patients.We examined the activation status of NF-kB in 28 resected colorectal carcinomas and in colonic mucosa from uninvolved portions of these specimens by electrophoretic mobility shift assay (EMSA) and immunohistochemical staining for the p65 subunit of NF-kB.EMSA showed much greater activation in the tumors than in normal mucosa, as did epithelial p65 immunostaining. NF-kB activation significantly increased in the more progressed cases (T3 + T4 cases or Stage IIcases). In vitro studies using lipopolysaccharide (LPS)-responsive colon carcinoma cells suggested a correlation between NF-kB activation and cell proliferation.Our findings indicated that NF-kB is constitutively activated in human colorectal carcinoma tissue and correlates with tumor progression. The regulation of this transcription factor might be therapeutically useful against these tumors.

Background: Tumor-infiltrating lymphocytes (TIL) are strictly divided into two categories: those lymphocytes in stroma and those in between cancer cells. However, there has been no fully adequate comparison of these two categories, especially analysis in relation to microsatellite instability (MSI). Methods: The materials were derived from patients with colorectal cancer who underwent surgery in Jichi Medical School and Omiya Medical Center. There were 19 hereditary non-polyposis colorectal cancer (HNPCC) patients who were compatible with Japanese criteria A and 106 patients with sporadic colorectal cancer (sCRC) in either Dukes B or C stage. As microsatellite markers, the global standard five markers were selected. Immunohistochemical analysis was performed using the anti-CD3, -CD4, -CD8 and -S-100 antibodies and the results were evaluated according to the degree of infiltration, which was classified into three grades. Results: As for stroma-infiltrating lymphocytes (SIL) in sCRCs, severe infiltration was observed in 20% of high microsatellite instability (MSI-H) patients and 12.8% of low microsatellite instability (MSI-L)/stable microsatellite (MSS) patients without a statistically significant difference. In contrast, severe infiltration of intra-tumor cell-infiltrating lymphocytes (ITCIL) was observed in 41.7% of MSI-H sCRC patients and 4.3% of MSI-UMSS patients. Thus, there was a close correlation between ITCIL severity and increased microsatellite instability (P< 0.001). In examination of ITCIL, patients with severe infiltration tended to show a better survival rate than those with moderate or mild infiltration. Conclusions: The present study suggests that different factors are involved in the infiltration of SIL and ITCIL. Although there were no statistically significant differences, the cumulative survival rates tended to be higher in severe ITCIL cases than in those with moderate and poor ITCIL (P< 0.09). We suggest that there might be a possibility of ITCIL having a role for a better prognosis after colorectal cancer surgery, which is closely related to MSI.

To compare the long-term outcome of laparoscopic-assisted colectomy (LAC) with that of open colectomy (OC) for carcinoma in patients followed up for a minimum of 4 years.We reviewed the medical records of 118 patients who underwent LAC between January 1993 and September 1999, and compared the results with those of 163 selected patients who underwent OC during the same period.Curative surgery was performed in 114 of the LAC patients. Because recurrence did not develop in any of the patients with stage I cancer, we analyzed the patterns of recurrence only in those with stage II or III disease; 58 patients were analyzed in the laparoscopic group and 130 in the open colectomy group. In the LAC group, 7 (12.1%) patients had recurrence after a median follow-up of 58 months and in the OC group, 19 (14.6%) patients had recurrence after a median follow-up of 56.5 months. The 5-year disease-free rate was similar in the LAC (87.8%) and OC (85.5%) groups (P = 0.75 by the log-rank test).Laparoscopic-assisted colectomy is effective and safe for the treatment of colorectal carcinomas under the criteria used in this study. However, further validation of these results is recommended.

Hepatocyte growth factor (HGF) is a stromal cell-derived cytokine that can stimulate matrix invasion by carcinoma cells. We analysed the concentrations of HGF and invasion-stimulatory activity in pleural fluid after lung surgery. The concentration of HGF in pleural fluids was measured by enzyme-linked immunosorbent assay in seven patients who underwent pulmonary resection for primary or metastatic lung cancer. The effect of the pleural fluid on cancer cell invasion across reconstituted basement membrane (Matrigel) was assessed with a Boyden chamber assay using a lung adenocarcinoma cell line, A549. HGF levels in the pleural fluid after lung surgery ranged from 6.0 to 23.0 ng ml−1 (average: 10.2 ± 4.3 ng ml−1). The matrix invasion of lung carcinoma cells in the presence of the pleural fluid was significantly higher than that in the presence of culture medium alone or sera from normal subjects (P < 0.01). The invasion-stimulatory activity of the pleural fluid was strongly inhibited by HGF-neutralizing antibody. Positive correlation was found between the HGF level and invasion-stimulatory activity in the pleural fluids and normal sera (P = 0.0073). This is the first report demonstrating that the lung surgery induces a considerable amount of HGF, which is closely correlated with the invasion-stimulatory activity of the pleural fluid. © 1999 Cancer Research Campaign

Background and Objectives Nitric oxide (NO), the production of which is dependent on NO synthase (NOS), has been shown to contribute to various pathogeneses in cancer. The aim of this study was to determine whether inducible NO synthase (iNOS) is overexpressed in human colon carcinoma tissue, and whether NO is produced in tumor tissue. Methods We investigated iNOS mRNA expression in 24 human colon carcinoma tissue specimens by reverse transcription–polymerase chain reaction (RT-PCR). We then examined the expression of iNOS protein and nitrotyrosine, which indicates NO production in tissue, by immunohistochemistry. The possible immunosuppressive role of NO produced by colon carcinoma cells was analyzed in vitro. Results Semiquantitative RT-PCR analysis showed that iNOS mRNA expression in carcinoma tissues is elevated significantly compared to that in noncarcinoma tissue. Immunohistochemistry revealed that iNOS and nitrotyrosine are expressed strongly in carcinoma tissues. In vitro experiments showed that the supernatant from a culture of cytokine-treated colon carcinoma cells, which contained high levels of NO, significantly reduced the phytohemagglutinin (PHA)-stimulated, human lymphocyte proliferative response (60% of the control value). Conclusions In human colon carcinoma tissue, iNOS mRNA, protein, and NO products are overexpressed and may contribute to tumor-related immunosuppression. J. Surg. Oncol. 1999;70:222–229. © 1999 Wiley-Liss, Inc.

PURPOSE: We evaluated the prevalence and features of cerebral aneurysms in the family members of people with asymptomatic aneurysms among 8680 participants undergoing magnetic resonance angiography. METHODS: Of the 8680 participants, 380 had family histories of aneurysms and 8300 did not. The prevalence and features of asymptomatic aneurysms were compared in these two subgroups. In addition, the prevalence in all living first- or second-degree relatives was evaluated in 20 families. RESULTS: The prevalence of asymptomatic aneurysms was 7.0% (606 of 8680 participants) overall and 10.5% (40 of 380 participants) and 6.8% (566 of 8300 participants) in the subgroups with and without family histories of aneurysms, respectively. The prevalence in the female participants with family histories of aneurysms (12.3%, 28 of 228 participants) was higher than that in the male participants with family histories of aneurysms (7.9%, 12 of 152 participants) (P < 0.0001). Compared with the entire group, this subgroup more commonly showed aneurysms situated at the junction of the internal carotid and posterior communicating arteries (P < 0.0005) and at the middle cerebral artery (P < 0.0001). The prevalence of aneurysms in 115 members of the 20 families was 33.9%. Although the members of 14 families with aneurysmal subarachnoid hemorrhage showed higher prevalence of ruptured and asymptomatic aneurysms (42.1%) than did the members of 6 families with only asymptomatic aneurysms (17.9%), the former had very low prevalence of asymptomatic aneurysms. CONCLUSION: The prevalence of aneurysms is significantly elevated in family members of people with asymptomatic aneurysms. It is suggested that familial asymptomatic aneurysms are more likely to rupture in families having members with aneurysmal subarachnoid hemorrhage than in those without.

We report a case of hepatic choriocarcinoma in a man diagnosed at autopsy after a rapid downhill clinical course. The patient was a 49-year-old man who presented with acute right-sided abdominal pain. There were no masses palpable on physical examination. Radiographic findings showed large multi-nodular tumors mainly in the right lobe of the liver. Fludeoxyglucose-positron emission tomography scan showed uptake only in the liver, and no uptake in the testes. We initially planned to perform a liver resection for the presumed diagnosis of intra-hepatic cholangiocarcinoma. However, the tumors grew rapidly and ruptured. Multiple lung metastases rapidly developed resulting in respiratory failure, preventing liver resection or even biopsy. He died 60 d after initial presentation with no pathological diagnosis. Postmortem studies included histopathological and immunohistological examinations which diagnosed a primary choriocarcinoma of the liver. Primary hepatic choriocarcinoma is very rare but should be considered in the differential diagnosis of a liver tumor in a middle aged man. Establishing this diagnosis may enable treatment of the choriocarcinoma. Liver biopsy and evaluation of serum human chorionic gonadotropin are recommended in these patients.

The authors report 3 cases of epidural hematoma of the posterior fossa in children. The clinical signs and symptoms are discussed. Onset of symptoms is not necessarily acute. The radiological findings are discussed. Epidural hematoms of the posterior fossa in children have a tendency to liquefy earlier than supratentorial hematomas. We emphasize the value of computed tomography for the diagonosis of epidural hematoma of the posterior fossa. One should keep in mind the possibility of the presence of an epidural hematoma of the posterior fossa in the treatement of head injury in children, even in the case of a minor head injury.