Purpose: The aim of this study was to analyze the treatment outcomes of alternating chemoradiotherapy (ACRT) for nasopharyngeal carcinoma (NPC) and to assess the safety and efficacy of this treatment. Materials and Methods: Twelve patients with stage II–IVB NPC were treated with ACRT in our hospital between 2005 and 2011. The radiotherapy period was divided into two components. In the first half, patients received 36 Gy to the whole neck field. In the second half, patients received 30~34.2Gy to the shrinking field to the primary and involved lymph nodes. A course of chemotherapy comprised of fluorouracil at a dose of 800 mg/m2/day was administered for 5 days (day 1–5), and cisplatin at 50 mg/m2/day was administered for 2 days (day 6–7). A total of three courses of chemotherapy were performed systemically before starting radiotherapy, after completing the first half of radiotherapy and after completing the second half of radiotherapy. Results: The planned radiation dose was achieved for all patients. Ten of the 12 patients completed the three courses of chemotherapy as planned. The remaining two patients completed only two courses because they refused, not due to adverse events. The five-year overall survival rate was 83%, the progression-free survival rate was 67%, the locoregional progression-free survival rate was 75%, and the distant-metastasis free survival rate was 92%. With regard to acute adverse events, the incidence of grade ≧3 hematotoxicity was 33%, and the non-hematotoxicity event was only one case of grade 3 mucositis. No late adverse events of grade ≧3 occurred. Conclusion: ACRT offered an excellent completion rate and could be safely conducted. Although a limited numbers of subjects were considered in this study, the outcomes of ACRT were favorable in terms of safety and efficacy.
Malignant melanoma (MM), an aggressive skin neoplasm, can be difficult to differentiate histologically from benign melanocytic nevi (BMN). Although immunohistochemical analysis could facilitate diagnosis of MM, markers that discriminate between benign and malignant lesions have not yet been established. However, CD10 expression is associated with MM progression. We immunostained 36 MM and 50 BMN specimens for CD10 to evaluate whether CD10 immunostaining could distinguish between BMN and MM tumors. In the 36 MM samples, we found CD10 expression in 17 (47.2%) sample tumor cells and 32 (88.9%) stromal cells, for 34 of the 36 MM specimens (94.4%) overall. In contrast, no BMN (0/50) samples had CD10+ tumor cells, although a few (8/50, 16.0%) showed stromal staining. The two specimen types thus significantly differed in CD10 expression (P<0.01), indicating that melanocytic CD10+ tumor cells are likely to be malignant. Also, melanocytic stromal cells with diffuse, strong CD10 expression are more likely to be malignant than those with light, focal CD10 expression. Although hematoxylin and eosin staining is fundamental to the diagnosis of melanocytic lesions, CD10 immunostaining may help distinguish between BMN and MM.
With widespread use of proton pump inhibitors (PPIs) has come characteristic gastric mucosal changes such as parietal cell protrusions (PCPs) and so-called fundic gland polyps (FGPs). Nevertheless, whether these lesions are actually PPI-related gastric mucosal lesions has not been fully clarified. The present study focused on this issue. We firstly examined the purported relation between the emergence of PCPs and PPI use. We also investigated the relation between PPI use and the emergence of cystically dilated glands (CDGs) that can give rise to elevated mucosal lesions such as FGPs. In addition, we performed histopathologic and immunohistochemical analyses to clarify the characteristics of PCPs and PCP-affected gastric oxyntic mucosa. A significant relation between the emergence of PCPs and PPI use was confirmed. In contrast, no significant relation was found between the emergence of CDGs and PPI use. Histologic and immunohistochemical analyses showed PCPs to be hyperplastic lesions. In the PCP-affected oxyntic mucosa, the isthmus-and-neck region of the fundic glands was elongated and the base region was shortened in relation to the total mucosal thickness. These changes were accompanied by an increase in the number of parietal cells and a decrease in the number of chief cells. Immunohistochemical analysis suggested impairment of both parietal cell differentiation and mucous neck-to-chief cell differentiation．Furthermore, our study reinforced the notion that elevated hydrostatic pressure and cytoplasmic edema due to movement of water from interstitial space toward the lumen of oxyntic glands via parietal cells give rise to the formation of PCPs, oxyntic dilatation, and CDGs. The detailed mechanism of PCP formation and its clinical implications are expected to be clarified in future studies.
Background: Exercise-induced pulmonary hypertension (EIPH) can be caused not only by pulmonary vasculopathy, but also by a significant increase in left ventricular (LV) filling pressure. This study evaluated the influence of LV diastolic function on EIPH in patients with systemic sclerosis (SSc). Methods: The study included 222 SSc patients (age 58.9 ± 13.1 years, 85% female) and 30 controls with similar age distribution. In all patients, systolic pulmonary artery pressure (SPAP) and the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e’), as an index of LV filling pressure, were measured before and after exercise Doppler echocardiography using a Master’s two-step. Results: The patients with SSc were classified into either the non-EIPH (SPAP < 50 mmHg, n = 123, 56%) or EIPH (SPAP ≥ 50 mmHg, n = 97, 44%) group. No significant change from E/e’ at rest to E/e’ post exercise was found in the controls (8.8 and 9.6), whereas significant changes were found in the non-EIPH (8.7 and 9.5 p < 0.0001) and EIPH groups (10.3 and 12.6, p < 0.0001). In addition, significant differences in E/e’ at rest and post exercise were found between the non-EIPH and EIPH groups (p <0.0001). Multivariate logistic regression analysis identified age (odds ratio, 1.036; 95% confidence interval, 1.015–1.058, p < 0.0001) and E/e’ (odds ratio, 1.154; 95% confidence interval, 1.066–1.246, p < 0.0001) as independent predictors of EIPH. Conclusions: Our results suggest that approximately one third of SSc patients have EIPH. LV diastolic function might be associated with EIPH in patients with SSc.
Chronic kidney disease (CKD) is characterized by progressive, irreversible kidney damage, and the number of patients with CKD has been increasing worldwide. Several studies suggested that hypertension, dyslipidemia, and diabetes are risk factors for CKD. In this study, we generated spontaneously hypertensive and hyperlipidemic rats (SHHRs). In SHHRs, total cholesterol and plasma glucose levels become elevated when fed a high-fat, 30% sucrose diet (HFDS). However, the molecular mechanism underlying the effect of hypertensive, dyslipidemic, and hyperglycemic conditions on the kidney remains unknown. To elucidate the mechanism, we performed proteomic analysis of the kidney in SHHRs. Four-month-old male Sprague-Dawley (SD) rats and SHHRs were fed a normal diet (ND) or HFDS ad libitum for 6 months. Proteins in the renal cytoplasm were separated by LC/MS, and proteomic analysis was performed. Differentially expressed proteins were linked using Ingenuity Pathway Analysis (IPA). We identified Rho-GDP dissociation inhibitor (Rho-GDI) signaling as a candidate pathway involved in kidney injury in SHHRs with HFDS feeding. In the kidney, the levels of Rho-GDI protein and Rho GTPase-activating protein (Rho-GAP) decreased, and that of p21-activated kinase (PAK) significantly increased. In addition, the renal expression of Arhgdia (encoding Rho-GDI), Dlc1 (encoding Rho-GAP), and Pak1 (encoding PAK) genes were, at least in part, parallel to that of proteins in SHHRs that had been fed the HFDS. Furthermore, neutrophil gelatinase-associated lipocalin (Ngal), a biomarker of kidney injury, was highly expressed in the kidney of SHHRs that had been fed the HFDS. These data suggest the possibility that the Rho-GDI signaling pathway is activated in the kidney of SHHRs that are fed the HFDS, leading to kidney injury. Taken together, our findings provide a molecular basis for the effects of hypertensive, dyslipidemic, and hyperglycemic conditions on the kidney.
Purpose: We studied the treatment outcomes of CT-guided 3-dimensional conformal radiotherapy (3DCRT) for localized prostate cancer using doses of 74–76 Gy. Materials and Methods: In total, 139 patients with T1c to T3bN0M0 prostate cancer were enrolled between October 2007 and May 2014 in this retrospective study. The median patient age was 74 years (range, 56–81 years). There were 13 low-risk, 30 intermediate-risk, and 96 high-risk patients according to National Comprehensive Cancer Network definitions. Androgen deprivation therapy (ADT) was used in 123 patients (88%), with a median treatment period of 25 months (range, 1–128 months). Biochemical relapse was evaluated according to the Phoenix definition, while adverse events were evaluated according to Common Terminology Criteria for Adverse Events (version 4.0). Median follow-up was 42 months (range, 13–94 months). Results: Three-year biochemical relapse-free survival (bRFS) rates were 100%, 100%, and 92%, respectively, for low-risk, intermediate-risk, and high-risk groups, while 3-year overall survival was 100%, 96%, and 95%, respectively. Meanwhile, 3-year distant metastasis-free survival was 100%, 100%, and 96%, and 3-year cause-specific survival was 100%, 100%, and 98%. Multivariate analysis showed that long-term ADT (24 months or longer) was a factor influencing bRFS in the high-risk group (hazard ratio 0.23, p = 0.044). Rates of grade 2 late rectal and urinary toxicities were 3.6% and 0.7% respectively, while no grade 3 or higher toxicities were observed. Conclusion: These results demonstrate the safety of high-dose CT-guided 3DCRT performed at our hospital.
Objective: Cold therapy, so-called icing, is often used immediately after muscle injuries as first aid for the suppression of inflammation and pain relief. Recent evidences show icing retards the regeneration of injured skeletal muscle. On the other hand, microcurrent electrical neuromuscular stimulation (MENS) promotes the regeneration of injured skeletal muscle. In this study, we investigated the effects of the MENS with or without icing on the regeneration of injured skeletal muscle. Methods: Eight-week-old male mice (C57BL/6J) were divided into 4 groups: control (C), cardiotoxin (CTX) injected (X), CTX injected with MENS (XM), and CTX injected with combined treatments with icing and MENS (XIM) groups. Necrosis-regeneration cycle was induced by an intramuscular injection of CTX into tibialis anterior (TA) muscles except for C group. After CTX–injection, the hindlimbs of the mice were soaked in ice-cold water (4ºC) for 20 minutes under anesthesia (XIM). After the treatments, both right and left hindlimbs of the mice in XIM and XM groups were treated with MENS (10 µA, 0.3 Hz, 250 msec) for 60 min a day and 3 days per week for 1 or 3 weeks. One and three weeks after CTX injection, TA muscles were dissected. Results: MENS with or without icing facilitated the recovery of muscle protein content and muscle fiber morphology including mean fiber cross-sectional areas of injured TA muscle, compared with non-treated condition. These facilitating effects of MENS with or without icing were accompanied with the increase in the relative number of Pax7-positive nuclei, namely satellite cells. Judging from fiber morphology, MENS with icing had enhanced stimulating effects on the regeneration of injured skeletal muscle, compared with MENS-treated condition. Conclusion: Evidence suggested that MENS with or without icing facilitated the regeneration of injured TA muscle. A combination treatment of MENS with icing might be a useful therapy for sports-related skeletal muscle injuries.
Multidetector-row computed tomography (MDCT) allows visualization and measurement of anatomical structures. Because we seek a reliable method by which we can predict displacement of the double lumen endotracheal tube (DLT) in patients when supine to lateral repositioning is required during surgery, we performed MDCT preoperatively for 84 patients scheduled for elective respiratory surgery with a left DLT. We obtained 3D MDCT reconstruction images of each patient’s bronchus and then measured the distance between the vocal cords and the bifurcation of the left upper lobe bronchus. We defined this distance as the MDCT-derived appropriate depth of placement (ADP). We used two other methods to determine ADP: the standard measurement method based on the patient’s height and the chest X-ray method based on the distance from the superior border of the sixth cervical vertebra to the tracheal bifurcation. During surgery, we evaluated the actual change in ADP when the patient was moved from the supine to the lateral position. We then compared the actual ADP with the MDCT-derived ADP to assess whether the MDCT-derived ADP predicts DLT displacement during the patient repositioning. We found that during surgery, the DLT had slipped out of position in 31 (44%) patients, had moved too deeply in 6 (7%), and had not changed in 41 (49%). Multiple logistic regression analysis showed that the MDCT-derived ADP was significantly associated with DLT displacement upon patient repositioning (odds ratio, 2.9; 95% CI, 1.5–5.6; p=0.002), whereas standard ADP and chest X-ray-derived ADP were not associated with DLT displacement. We postulate that various factors, such as extension or flexion of the neck and size of the DLT, may contribute the DLT displacement during patient repositioning. We believe, on the basis of our study data, that ADP derived from pre-operative MDCT will be useful for predicting DLT displacement when patients are moved from the supine to lateral position during surgery.
Background: Genetic polymorphisms of metabolic enzymes, as well as a patient’s sex, age, and individual susceptibility, affect the pharmacokinetics of propofol. Several reports show that polymorphisms of metabolic enzymes of propofol affect loss of consciousness during propofol anesthesia. We investigated whether genetic polymorphisms of the liver cytochrome P450 2B6 (CYP2B6), the main metabolic enzyme for propofol, and UDP-glucuronosyltransferase 1A9 (UGT1A9), as well as sex differences, affect the pharmacokinetics of propofol. Methods: Between June 2009 and May 2011, 94 patients (51 males, 43 females) who underwent respiratory surgery with total intravenous anesthesia were examined. Arterial blood samples were collected immediately or 5, 10, 20, 30 and 60 min after the termination of propofol infusion for the determination of the propofol blood concentrations and genetic polymorphisms of CYP2B6 and UGT1A9. We analyzed blood pharmacokinetics of propofol and assessed the association between genetic polymorphisms, sex differences, and blood pharmacokinetics. Stepwise multiple linear regression analysis was used to detect important factors of pharmacokinetics of propofol. Results: Although C0 (the blood concentrations of propofol immediately after the termination of propofol infusion) rose for the T/T mutation in CYP2B6, there were no significant differences in changes of blood propofol concentrations after the termination of drug infusion and in waking times for both genetic polymorphisms. C0 was significantly higher in females than in males (1.7: 1.4 μg/mL, female: male, P=0.015) and the rate of decline in the blood propofol concentration from C0 to C5 was faster in females than in males (67: 60%, P=0.015). Stepwise multiple regression analysis revealed that sex (B = 0.32, P = 0.01) was a contributor to C0 (R = 0.27, P = 0.01). Conclusions: We suggest that differences between females and males for C0 and the rate of decline in the blood propofol concentration may cause individual differences in both sensitivity and recovery of consciousness from propofol anesthesia. We conclude that polymorphisms of CYP2B6, but not UGT1A, and sex differences affect the pharmacokinetics of propofol.
Objective: An important cause of liver re-metastasis from colon cancer is remnant micrometastasis (MiM). MiM is a miniscule metastatic lesion that results from hematogenous spread of tumor cells along with or after the original metastasis from colon to liver. Thus, an adequate surgical margin is necessary to lower a patient’s risk of relapse. Questions have arisen whether the guideline 1-cm surgical margin can be reduced in cases in which neoadjuvant chemotherapy (NAC) has been performed. We conducted a histopathologic study to determine the appropriate hepatectomy margin in such cases. Methods: We studied 76 cases of colorectal liver metastasis treated between January 2005 and December 2013 at St. Marianna University School of Medicine Hospital. NAC had been performed in 35 of these cases. We evaluated patients’ sex; age; site, clinical stage, and histologic type of the primary tumor, clinical and histologic effects of the NAC, histologic characteristics and size of the hepatic macrometastasis, number of cases in which MiM was found and the number of MiMs per case, histologic characteristics and size of the MiM(s), distance from the macrometastasis to the MiM, and exact location of the MiM(s) and tested between-group differences in these variables statistically. We also tested correlation between size of the macrometastasis and both distance between the macrometastasis and MiM and the number of MiMs per case. Results: Positive, but non-significant, correlation was found between size of the macrometastasis and both distance between the macrometastasis and MiM and the number of MiMs per case. Regardless of whether NAC was performed, most MiMs we examined were within 5 mm of the macrometastasis, but some were within 9 mm. Conclusion: Our data indicate that, regardless of whether NAC is performed before hepatectomy for liver metastasis from colorectal cancer, a minimum 1-cm surgical margin is necessary to ensure inclusion of micrometastases.
Background: Biopsy of ground-glass opacity (GGO) lesions performed under endobronchial ultrasonography with a guide sheath (EBUS-GS) has produced relatively low diagnostic yields. Objectives: To clarify whether CT findings can contribute to the return of an EBUS-GS-guided diagnosis of GGO lesions. Methods: We retrospectively evaluated 58 patients with GGO lesions. Forty-four of 58 lesions were diagnosed by means of EBUS-GS-guided biopsy, and the remaining 14 undiagnosed by EBUS-GS-guided biopsy were diagnosed by CT-guided biopsy or surgery. We reviewed CT images obtained prior to EBUS-GS-guided biopsy to measure the maximum diameter of the GGO lesion, the maximum diameter of the solid component, the distance from the bifurcation of the lobe bronchus to the lesion, and the presence or absence of a “bronchus sign.” Results: The diagnostic yield for lesions with a maximum diameter of the solid component >5 mm (38/46, 82.6%) was significantly greater than that for the lesions with a maximum diameter of the solid component ≤5 mm (6/12, 50%) (p = 0.024). There was no significant difference in the diagnostic yield based on the maximum GGO diameter, the distance from the bifurcation of the lobe bronchus to the lesion, or the presence of a bronchus sign. Conclusions: Our data suggest that EBUS-GS-guided biopsy can yield a diagnosis when the maximum diameter of the solid part of the malignant GGO lesion depicted on the CT image is >5 mm.
Although the articular circumference of the radial head is known to affect lateral stability of the elbow joint, no studies have reported an association between the radial head and radial notch of the ulna, which form the joint. The objective of this study was to investigate, from an anatomical perspective, the association of contact between the radial head and radial notch of the ulna in the proximal radioulnar joint (PRUJ) with development of cartilage injury during pronation and supination of the forearm. Forty-nine elbows from 26 cadavers were included for systemic anatomical study. After the articular circumference of the radial head and the radial notch of the ulna were divided into 4 and 9 regions, respectively, the presence or absence and severity of cartilage injury were determined. The contact area between the radial head and radial notch of the ulna was 50% smaller with the forearm at the pronated position than at the supinated position. Cartilage injury was observed in the medial region of the articular circumference of the radial head and the distal regions of the radial notch of the ulna. These regions corresponded to the contact area of the PRUJ with the elbow joint extended and the forearm pronated. In this condition, the elbow joint becomes most unstable. The elbow joint lateral support complex is likely to be impinged in the humeroradial joint with the elbow joint extended and the forearm pronated, suggesting that repeated impingement might induce cartilage injury.
We have reported that mouse embryonic stem (ES) cells transfected with insulin-like growth factor (IGF) II differentiated into mature skeletal muscle cells in vitro and in vivo after transplantation. On the contrary, IGFII transfected human induced pluripotent stem (hiPS) cells did not demonstrate mature skeletal muscle differentiation. The morphogenic factor Sonic Hedgehog (SHH) was suggested to upregulate the myogenic process along with IGF through Phosphoinositide 3 kinase (PI3K)/Akt signaling pathway. We cultured hiPS cells with SHH to generate myoblasts and transplanted the cells to hind limbs of mice. SHH with IGFII supplementation rapidly enhanced myogenic gene and protein expressions (MyoD, myogenin, Mrf4, and dystrophin) of hiPS cells. After the transplantation, we observed severe inflammation in the transplanted sites with host immunocompetent cells despite systemic administration of dexamethasone and cyclosporine. Surviving transplanted myoblasts showed lower expressions of myogenic proteins (MyoD, myogenin, and dystrophin) than in vitro cultured myoblasts did. We successfully generated mature skeletal muscle cells from hiPS cells with SHH supplementation. We suggest that further studies are needed to characterize the underlying molecular mechanisms of transplanted myoblasts derived from hiPS cells for the formation of mature human skeletal muscle.
BACKGROUND The number of elderly patients with kidney disease is increasing rapidly, and we often encounter situations in which we need to weigh the benefits and risks of kidney biopsy (KBx). The decision is often difficult because reports addressing the safety and utility of KBx in the elderly are scarce. METHODS This observational study included 548 consecutive adult patients who underwent native KBx. We divided the patients into an E group, elderly patients 65 years or older, and an NE group, the remaining non-elderly patients. Baseline characteristics and complications of KBx were compared between the two groups. We also investigated the proportions of patients in whom steroid and/or immunosuppressive treatment was started after KBx. RESULTS There were 112 patients in the E group and 436 in the NE group. The baseline values differed significantly between the groups for age (71.5 ± 4.7 vs. 39.6 ± 13.9 years), estimated glomerular filtration rate (eGFR) (41.4 ± 27.1 vs. 72.0 ± 33.7 ml/min/1.73 m2), proportion of patients with diabetes (25.0% vs. 4.8%), and proportion of those who underwent surgical KBx (11.6% vs 3.0%), There was no significant difference in terms of sex. The E group experienced slightly more major complications (4.0% vs. 1.2%, p=0.05) but fewer minor complications (2.0% vs. 6.0%, p=0.10) with percutaneous KBx than the NE group did, although neither major nor minor complications occurred in patients who underwent surgical KBx. Final diagnoses after KBx, such as IgA nephropathy, IgA vasculitis, and ANCA-associated glomerulonephritis, were associated with various clinical diagnoses, indicating that the final diagnoses could not have been obtained without KBx. Treatment with steroid and/or immunosuppressant was required to a high degree in patients with ANCA-associated glomerulonephritis and minimal change disease after histologic evaluation by KBx. CONCLUSIONS The risk of KBx in the elderly patients was significantly higher than that in the non-elderly, and some diagnoses could not have been obtained without KBx. Thus, as long as nephrologists perform KBx cautiously according to strict indications, KBx can be a safe and useful option in the management of kidney disease in the elderly.
Spontaneous esophageal rupture is rare. The distal esophagus ruptures upon a sudden vomiting-induced increase in the internal esophageal pressure. We evaluated surgical management of spontaneous esophageal rupture by examining clinical details and outcomes of 10 patients treated for the disorder at our hospital between 1987 and 2014. Mean age of the patients was 58.1 years (range, 41–75 years). The sex ratio (M/F) was 9/1. Diagnosis was achieved by chest computed tomography (CT) or chest CT and esophagography. The rupture occurred in the left lower thoracic esophagus (n=8), left middle thoracic esophagus (n=1), or right lower thoracic esophagus (n=1). Mean time from symptom onset to surgery was 36.2 hours (range, 5–96 hours). Patients were divided between those treated within 24 hours of onset (early treatment group, n=5) and those treated 24 hours or more after onset (late treatment group, n=5). Treatment comprised primary repair in 7 patients and esophagectomy in 3. Postoperative complications occurred in 6 patients: surgical site infection (n=4), anastomosis leakage (n=3), intrapleural abscess (n=1), sepsis (n=1), and pneumonia (n=1). Mean postoperative hospital stay was78.5 days (range, 22–228 days). There was no in-hospital mortality. Postoperative complications were somewhat more frequent in the late treatment group (n=4, 80%) than in the early treatment group (n=3, 60%), and postoperative hospital stay was longer in this group (114.2 vs. 42.8 days). Outcomes in terms of postoperative complications and hospital stay were good in the early treatment group. In the late treatment group, severe intrathoracic contamination in 3 patients necessitated life-saving esophagectomy. When primary repair was performed, the incidence of anastomotic leakage was lowest when both layers were sutured, perforation sites were reinforced, and nutritional support was provided. Early diagnosis and treatment are essential for spontaneous esophageal rupture, and we believe that selecting the appropriate surgical technique increases survival.
Objectives: To determine whether serum levels of brain-derived neurotrophic factor (BDNF) are associated with response to electroconvulsive therapy (ECT) in treatment-resistant depressed patients with a relatively longer period of measurement. Methods: This study included 30 Japanese unipolar depressed patients with current major depressive episode. Montgomery-Äsberg Depression Rating Scale (MADRS) score was ≥21 in all subjects. ECT was performed twice a week for a total of 4–10 sessions. Serum BDNF levels were measured before ECT (T0), the day after the last ECT session (T1), and 1 month after the last ECT session (T2). Patient response to treatment was defined as a ≥50% decrease compared with the pretreatment total MADRS score. Results: Serum BDNF levels showed no significant variation among the patients during the entire study period. In responders, serum BDNF levels showed a progressive increase, and the differences between T0 and T1 and between T0 and T2 were significant (p=0.022 and p=0.007, respectively). In non-responders, serum BDNF levels showed a progressive decrease, and the difference between T0 and T2 was significant (p=0.012). No significant association was identified between change in serum BDNF level and change in total MADRS score in any of the patients following ECT. Conclusions: The present results showed that serum BDNF levels after ECT increased progressively in responders, but not in non-responders. Our results provide important information for understanding the exact role of BDNF in the antidepressive effects of ECT.
Calcitonin gene-related peptide (CGRP) is widely distributed in the central and peripheral nervous systems and regulates physiological functions. Several neuropeptides are involved in the development and progression of hepatocellular carcinoma (HCC), although the role of CGRP in HCC pathogenesis is unclear. This study attempted to clarify the effects of CGRP on tumor progression in HCC cells. CGRP and its receptors, calcitonin receptor-like receptor and receptor activity-modifying protein-1, were expressed in HCC tissues and HCC cell lines. When Huh7 cells were cultured with CGRP 10−10 and 10−9 M for 24 h, cell proliferation was significantly inhibited. In addition, the total and phosphorylated protein levels of Ras and mitogen-activated protein kinase (MAPK) family proteins, MAP kinase (MEK) 1/2 and extracellular signal-regulated kinase (ERK) 1/2, were also inhibited by CGRP 10−10M incubation. CGRP significantly increased the protein levels of cAMP response element binding protein (CREB) and its phosphorylated form in the nuclei of Huh 7 cells. Furthermore, pretreatment of CGRP receptor antagonist CGRP8–37 abolished the increases in CREB and pCREB protein levels in the nuclei of Huh7 cells. In addition, pretreatment of CGRP8–37 and cAMP inhibitor Rp-cAMP tended to reverse the ERK inhibition in Huh 7 cells cultured with CGRP. These results suggest that CGRP inhibits HCC cell proliferation via CREB activation and Ras/MEK/ERK pathway. CGRP may play an important role in the amelioration of cancer progression.
Background Although laparoscopic gastrectomy and laparoscopic colorectal surgery are being performed at increasing regularity, simultaneous laparoscopic surgery for synchronous gastric and colorectal cancer is rare, and its feasibility and safety are unknown. We addressed this question by retrospectively evaluating the short-term surgical outcomes of simultaneous laparoscopic surgery performed at our hospital for synchronous gastric and colorectal cancers. Methods The study group comprised 8 patients (5 men, 3 women, aged 51–84 years) who underwent simultaneous laparoscopic gastrectomy and colorectal surgery at St. Marianna University School of Medicine Hospital between 2011 and 2014. Patients were followed up for at least 14 months. We reviewed patient and tumor characteristics; comorbidities; specific surgical procedures performed; short-term surgical outcomes, including operation time, estimated intraoperative blood loss; postoperative morbidity; duration of postoperative hospital stay; recurrence or metastasis; and mortality. Results Median operation time for the simultaneous surgery was 674 min, and median estimated blood loss was 242 mg. There were no intraoperative complications, and no conversion to open surgery was necessary. Postoperative morbidity occurred in 2 patients—ileus in 1 and pulmonary edema in 1. Median postoperative hospital stay was 15.5 days. There were no postoperative deaths. Conclusion Short-term outcomes in our patient group suggest that simultaneous laparoscopic surgery is both feasible and safe for patients with synchronous gastric and colorectal cancer.
A 44-year-old man demonstrating cold-like symptoms from the end of August 2013 was referred to us with abnormal shadows on his chest radiograph in September 2013. Clinical examination revealed a painless red-colored mass on the sole of his left foot that had enlarged over the course of one year. The left leg showed marked non-pitting edema that had gradually progressed over a month. A chest CT revealed mediastinal lymphadenopathy and diffuse interstitial septal thickening, and lymphangitic carcinomatosis was suspected. A lung biopsy and left inguinal lymph node biopsy revealed the diagnosis of amelanotic melanoma with lung metastasis.
Cardiac metastasis from colorectal cancer is rare. Such metastasis is usually discovered during autopsy; antemortem diagnosis is rare. A 76-year-old woman in whom we had performed right hemicolectomy for ascending colon cancer was noted to have elevated tumor markers during a follow-up examination 4 months after the surgery. Chest CT indicated a cardiac tumor that was approximately 6 cm in diameter, and we suspected a metastatic cardiac tumor. Subsequently, obstructive jaundice developed as a result of lymph node metastases around an extrahepatic bile duct, and a stent was placed. The patient refused aggressive treatment and was simply followed up clinically. Within 2 months, the cardiac tumor enlarged enough to cause cardiac failure, and death ensued 7 months after the surgery. Autopsy revealed a myocardial tumor, approximately 7 x 5 cm, that extended from the right atrium to the right ventricle. The histopathologic diagnosis was cardiac metastasis from ascending colon cancer. We describe in detail this case of rapidly progressive cardiac metastasis that was discovered after surgical treatment of ascending colon cancer. In searching the medical literature, we found only 14 cases of metastasis of colorectal cancer to the heart. We describe our case in detail and review our experience in light of the available literature.
We describe 2 challenging adult cases of Bochdalek hernia. The first case is that of a 22-year-old man who presented with left upper abdominal pain. The second case is that of a 36-year-old man who reported coughing after eating. In both cases, computed tomography revealed a defect in the left posterior attachment of the diaphragm. There was no vesical hernia, but parts of the greater omentum had prolapsed into the thoracic cavity in the first case, and parts of stomach, small intestine, colon, kidney, pancreas, and spleen had prolapsed into the thoracic cavity in the second case. In the first case, we were able to close the hernia defect with sutures by means of thoracoscopic surgery, and in the other case, that of a massive hernia, closure by means of laparoscopic surgery was difficult. We converted to laparotomy to perform suture closure, and we added a mesh patch. Bochdalek hernia is a congenital diaphragmatic defect that is usually apparent in the neonatal period. Discovery of a Bochdalek hernia in an adult is rare. Surgical treatment is necessary, but there are different approaches. Selection of the appropriate procedure depends the advantage to be gained by one approach over another in each particular case. The number of reports on thoracoscopic and laparoscopic surgery for treatment of Bochdalek hernia have increased in recent years. We think that endoscopic surgery for Bochdalek hernia will increase in popularity due to improvements in techniques and devices. We describe our 2 cases in detail and review our experience in light of the available Japanese literature.
We report our experience with a case of Kabuki syndrome complicated by multiple anomalies requiring surgery. The patient was a male infant born at 41 weeks 5 days gestation, weighing 4,468 g, who presented with an imperforate anus and cleft palate. A radical operation was performed under a diagnosis of low imperforate anus without fistula. However, an anastomotic leakage occurred, requiring a colostomy. Despite the presence of an asymptomatic concomitant Morgagni hernia, the patient was placed under follow-up observation. Eight months after the infant’s birth, the stoma was closed. Eleven months after birth, Kabuki syndrome was suspected because of the characteristic facial features, and a mutation in MLL2 was diagnosed.