[Laparoscopic Abdominoperineal Resection of the Rectum in a Case with Pagetoid Spread of Anal Canal Carcinoma].

The patient, a man in his 60s, first noticed an elevated lesion around the anus 3 years ago. The lesion failed to subside with the topical drug preparations prescribed at a local clinic, and the patient was referred to the Department of Dermatology of our hospital for further workup and treatment. The findings of biopsy from the lesion suggested skin infiltration of anal canal carcinoma, and the patient was referred to the Department of Surgery. Examination here revealed only induration of the anal canal, with no abnormality of the rectal mucosa even when the endoscope was reversed to visualize the rectum. Examination by various imaging modalities failed to reveal any metastases to the lymph nodes or distant organs, and the primary lesion remained unidentified. Laparoscopic abdominoperineal excision of the rectum was performed, beginning with anal manipulation. First, a 15-mm margin was set on the skin from the tumor edge, and the skin stump was divided into 4 equal portions. After confirming by rapid intraoperative frozen-section examination that the margin was negative along the full circumference, anal manipulation was performed, leaving a distance in the vertical direction immediately below the tumor. Upon completion of the anal manipulation, intraperitoneal manipulation was performed in a routine manner. The anal skin was relaxed subcutaneously, as done during mastectomy, and the subsequent suture closure could be done smoothly. The tumor was classified as pT1bN0M0, pStage Ⅰ. The experience with this case indicates that biopsy should be proactively employed for the diagnosis in such cases, and that proactive skin biopsy is useful when dealing with intractable anal skin lesions.

[A Case of Recurrent Gastric GIST Who Survived for Long after Laparoscopic Resection and Imatinib Therapy].

A man patient in his 70s underwent left nephrectomy and laparoscopic partial gastrectomy for the treatment of a left renal cell carcinoma and gastrointestinal stromal tumor(GIST)arising from the stomach. Histopathologically, both the renal cell carcinoma and GIST were kit-positive, CD34-positive, and S-100 protein-negative, and the Ki-67 index was about 40% as determined by the hot spot method, so that it was diagnosed as an intermediate-group GIST. After surgery, the patient was followed without adjuvant therapy, as he did not wish to receive postoperative chemotherapy. A computed tomography(CT)conducted 3 years after the surgery revealed tumorous shadows in the abdominal wall, inferior periesophageal region, and dorsal aspect of the pancreas. Positron emission tomography(PET)-CT showed fluorodeoxyglucose(FDG) accumulation in these lesions. Therefore, based on a suspicion of recurrent renal cell carcinoma or GIST, we carried out abdominal wall tumor resection for both exploratory and diagnostic purposes, which yielded histopathological diagnosis of GIST, with features similar to those observed at the time of the initial operation. Because the number of tumors remained unchanged during the subsequent follow-up period, the tumorous lesions in the periesophageal region and on the dorsal aspect of the pancreas were resected laparoscopically. Each of the resected tumors showed histological features consistent with GIST. The patient was started on oral imatinib therapy after this operation. To date(5 years after the surgery for the recurrent tumors and 8 years after the initial operation), the patient has remained free of recurrence. The pattern of tumor recurrence noted in the present case(ie, metastasis/dissemination to the skeletal muscles)is relatively rare, and few reports have been published concerning long-term survivors through multidisciplinary treatment (surgical treatment and others). We report this case with a review of the literature.

[A Case of Unresectable Advanced Gastric Cancer Successfully Treated with Conversion Surgery].

A man in his 70s consulted a local clinic with a chief complaint of difficulty eating. Upper gastrointestinal endoscopy revealed a type 4 tumor spreading irregularly from immediately below the esophageal cardia to the lower gastric body. The patient was referred to our hospital with a diagnosis of advanced gastric cancer(human epidermal growth factor receptor 2 [HER2]-positive moderately-differentiated adenocarcinoma)accompanied by lymph node enlargement. We planned an open total gastrectomy after staging laparoscopy to rule out dissemination because peritoneal dissemination could not be ruled out using computed tomography(CT). To perform a total gastrectomy, a celiotomy was done after staging laparoscopy results suggested that dissemination was unlikely. However, the border between the pericardial lymph nodes and the pancreas or peritoneal artery was not visible, forcing us to terminate the staging laparotomy based on a judgment of unresectable locally advanced gastric cancer. Therefore, the patient was administered 6 cycles of combined S-1/CDDP plus trastuzumab as the primary therapy. The response to therapy was favorable, and we scheduled a surgical resection. However, the scheduled surgery was rescheduled because of COVID-19 pneumonia, and R0 resection was finally performed after the 7th cycle of S-1/CDDP plus trastuzumab therapy. Histopathologically, the regional lymph node metastasis had disappeared, the viable tumor remained within the mucosal layer, and scarring was evident from the submucosal layer to the serosa. In recent years, conversion surgery for unresectable gastric cancer has been sporadically reported. However, we are unable to definitively opine on whether this kind of surgery may contribute to improving the prognosis, resection remains indispensable for radical treatment. We report this case along with a review of the literature.

[A Case of Triple Negative Breast Cancer with Successful Control of Recurrent Disease Activity for More than Ten Years].

A woman in her 70s underwent mastectomy plus axillary lymph node excision(Bt plus Ax)in December 2011 for left breast cancer classified as pT2N1M0, pStage ⅡB. The tumor was identified as an invasive ductal carcinoma(IDC), neural/ glial antigen 2(NG2), pT2(35 mm), INF γ, ly2, v0, g+, f+, s+, extensive intraductal component(EIC)-negative, ICT- positive, NCAT-positive, n(4/18), estrogen receptor(ER)-negative, progesterone receptor(PgR)-negative, human epidermal growth factor receptor 2(HER2)-negative, Ki-67 30-40%. Postoperative adjuvant fluorouracil plus epirubicin HCl plus cyclophosphamide(FEC)plus paclitaxel(PTX)therapy was administered. The patient refused to undergo postoperative radiation therapy. Two years after the surgery, she was diagnosed as having a lung metastasis and local disease recurrence. Biopsy of the local recurrent lesion revealed the same histopathological diagnosis as before. Capecitabine was selected for treatment of the recurrent lesion. After 2 years of capecitabine treatment, the response was rated as progressive disease (PD). At this time, eribulin mesylate was selected, along with intensity-modulated radiation therapy(IMRT). This resulted in disappearance of the tumor on imaging. However, considering that the histological findings did not suggest complete response(CR)and that the tumor was triple-negative(TN), we adopted a strategy of continuing the drug therapy at reduced dose level. With this strategy, the disease activity could be successfully controlled for 6.5 years. Subsequently, liver metastasis was detected, and the drug was switched to vinorelbine ditartrate(a drug with less non-hematological toxicity). Meanwhile, a breast cancer susceptibility gene(BRCA)analysis was performed in January 2021, which was negative. Subsequently, in September 2021, we obtained a positive result for PDL1-SP142 and negative result for 22C3. About half a year later, ie, in October 2021(11 years after the surgery), we detected an increase in the size of the liver metastasis and selected atezolizumab and nab-PTX for treatment. Applicable regimens of drug therapy are still available at present and drug therapy has been continued based on a discussion and mutual understanding of the adverse reactions, etc. with the patient. Few reports have been published concerning long-term survivors among TN breast cancer cases.

Isolated IgG4-related cholecystitis with localized gallbladder wall thickening mimicking gallbladder cancer: a case report and literature review.

BACKGROUND: IgG4-related cholecystitis, which is a manifestation of IgG4-related disease in the gallbladder, is associated with autoimmune pancreatitis or IgG4-related sclerosing cholangitis in most cases; isolated gallbladder lesions without systemic manifestations are very rare. Gallbladder wall thickening is often diffuse, but sometimes localized, in which case, differentiation from gallbladder cancer becomes difficult. The characteristic features of IgG4-related cholecystitis on imaging that would enable differentiation from gallbladder cancer remain poorly described. CASE PRESENTATION: We present a rare case of isolated IgG4-related cholecystitis with localized gallbladder wall thickening that was clinically difficult to distinguish from malignancy before resection. An 82-year-old man was referred to our hospital because of gallbladder wall thickening on abdominal ultrasonography without any symptoms. Dynamic computed tomography of the abdomen showed localized wall thickening from the body to the fundus of the gallbladder that was enhanced from an early stage with a prolonged contrast effect. There were no other findings, such as pancreatic enlargement and bile duct dilatation. Magnetic resonance cholangiopancreatography revealed neither dilatation nor stenosis of the bile duct and pancreatic duct. Endoscopic ultrasonography (EUS) showed a smooth layered thickening of the gallbladder wall with a maximum thickness of 6 mm and a well-preserved outermost hyperechoic layer in the same area. Laparoscopic cholecystectomy was performed because malignancy could not be completely ruled out. Pathological examination of a resected specimen revealed IgG4-positive plasma cell infiltration, fibrosis, and phlebitis. Although the serum IgG4 level measured after resection was normal, the condition was ultimately diagnosed as probable IgG4-related cholecystitis according to the 2020 revised comprehensive diagnostic criteria for IgG4-related disease. The EUS images reflected the pathological findings, in which lymphocytic infiltration was distributed in a laminar fashion in the gallbladder wall. CONCLUSIONS: Although rare, isolated IgG4-related cholecystitis with localized wall thickening mimicking gallbladder cancer remains a clinical problem. A smooth laminar thickening of the gallbladder wall on EUS imaging could be one of the most informative characteristics for differentiating IgG4-related cholecystitis from gallbladder cancer.

[States and predictors of postpartum smoking relapse: a population based longitudinal study].

Objectives　Although more than half of women who smoke attempt to stop smoking after conception, many relapse after delivery. We conducted a population-based longitudinal study to identify the predictors of postpartum smoking relapse.Methods　Participants were expectant mothers living in Nagoya city, Japan, who notified Health Centers of their pregnancy from April 2014 to March 2015. A self-administered questionnaire was given to the expectant mothers that includes individual factors in the pregnancy: expectant mother's smoking status, age, marital status, experience of parturition, (mother's and father's) occupations, infertility treatment reception, feelings when pregnancy was confirmed, plans to return to parents' house for delivery, accessibility to help with childcare, household member(s) smoking in the same room, alcohol consumption, and depressive symptoms continuing more than 2 weeks.　We followed their smoking status at their children's "3-month-old health check-up" (3 months) and "1-year-and-6-months-old health check-up" (18 months) held in Health Centers until March 2017.　The data were analyzed using a combination of Chi-square or Fisher's exact test and logistic regression modeling. The analyses were conducted separately in primiparas and multiparas in addition to all expectant mothers.Results　Participants were 24,413 mothers; 18,041 were followed up at 3 months and 14,163 at 18 months.　Of the 18,041 mothers at 3 months, 1,031 primiparas and 695 multiparas stopped smoking when they confirmed pregnancy; 89 (8.6%) primiparas and 107 (15.4%) multiparas relapsed at 3 months. Of the 14,163 mothers at 18 months, 789 primiparas and 568 multiparas stopped smoking when they confirmed pregnancy; 155 (19.6%) primiparas and 174 (30.6%) multiparas relapsed smoking at 18 months.　As a result of logistic regression modeling, "multiparas," "younger (<25 years old)," "not married (only in multiparas)," "no plan to return to mother's parent's house for delivery," "household member(s) smoking in the same room (only in primiparas)," and "depressive symptoms (only in all mothers and primiparas)" were the predictors of postpartum smoking relapse at 3 months. "Multiparas," "not married (only in all mothers)," "no help with childcare (only in all mothers)," and "household member(s) smoking in the same room" were the predictors of postpartum smoking relapse at 18 months.Conclusion　More mothers relapsed with smoking after 3 months than before 3 months. The predictors of postpartum smoking relapse differed between 3 and 18 months. Support to continue smoking cessation was needed for each mother at an appropriate time not only in pregnancy but also after delivery.

Cancer Diaspora of Undifferentiated Cancer.

Undifferentiated cancer is a rapidly progressing cancer with poor prognosis. Sometimes, it is diagnosed at an advanced stage, and its origin is difficult to detect. A very unusual cancer was revealed by autopsy. The patient was an 83-year-old survivor of colon cancer, melanoma, and laryngeal cancer. He had been under watchful course observation after survival from laryngeal cancer but suddenly died due to aspiration pneumonia. The autopsy revealed undifferentiated cancer infiltrated the entire body, which was misdiagnosed with positron emission tomography (PET)/CT scan and MRI. The origin of this cancer was a mystery even with vigorous pathological evaluation. The patient was told that his previous cancers were all healed; however, undifferentiated cancer progressed rapidly to the entire body, just like "cancer diaspora". This report highlights the limit of diagnostic imaging tools for aggressive cancer, sounding the alarm for clinicians to look beyond old presumptions.

Comparison of Echocardiography and Myocardial Scintigraphy to Detect Cancer Therapy-Related Cardiovascular Toxicity in Breast Cancer Patients.

The mortality rate of cancer patients has been decreasing; however, patients often suffer from cardiac disorders due to chemotherapy or other cancer therapies (e.g., cancer-therapy-related cardiovascular toxicity (CVR-CVT)). Therefore, the field of cardio-oncology has drawn more attention in recent years. The first European Society of Cardiology (ESC) guidelines on cardio-oncology was established last year. Echocardiography is the gold standard for the diagnosis of CVR-CVT, but many breast cancer patients are unable to undergo echocardiography due to their surgery wounds or anatomical reasons. We performed a study to evaluate the usefulness of myocardial scintigraphy using Iodine-123 ß-methyl-P-iodophenyl-pentadecanoic acid (123I-BMIPP) in comparison with echocardiography and published the results in the Journal of Imaging last year. This is the secondary analysis following our previous study. A total of 114 breast cancer patients who received chemotherapy within 3 years underwent echocardiography, as well as Thallium (201Tl) and 123I-BMIPP myocardial perfusion and metabolism scintigraphy. The ratio of isotope uptake reduction was scored by Heart Risk View-S software (Nihon Medi-Physics). The scores were then compared with the echocardiography parameters. All the patients' charts and data from January 2022 to November 2023 were reviewed for the secondary analysis. Echocardiogram parameters were obtained from 99 patients (87% of total patients). No correlations were found between the echocardiography parameters and Heart Risk View-S scores of 201Tl myocardial perfusion scintigraphy, nor those of the BMIPP myocardial metabolism scintigraphy. In total, 8 patients out of 114 (7.0%) died within 22 months, while 3 patients out of 26 CVR-CVT patients (11.5%) died within 22 months. Evaluation by echocardiography was sometimes difficult to perform on breast cancer patients. However, other imaging modalities, including myocardial scintigraphy, cannot serve as alternatives to echocardiography. Cardiac scintigraphy detects circulation disorder or metabolism disorder in the myocardium; therefore, it should be able to reveal myocardial damage to some extent. The mortality rate of breast cancer patients was higher with CVR-CVT. A new modality to detect CVR-CVT besides echocardiography can possibly be anticipated for patients who cannot undergo echocardiography.

22q11.2 Deletion Syndrome Diagnosed 47 Years After Surgery for Tetralogy of Fallot.

A 51-year-old man presented with severe hydrocele testis, dyspnea on exertion, and systemic edema. He had a history of surgery for tetralogy of Fallot (TOF). On the second day of admission, he presented with severe nose bleeding followed by CO2 narcosis. Blood gas analysis revealed an extremely low level of Ca2+. An echocardiogram revealed an excessively enlarged right ventricle and severe pulmonary valve regurgitation (PR). Hypocalcemia, history of TOF, and characteristic facial features suggested 22q11.2 deletion syndrome, which was confirmed by fluorescence in-situ hybridization (FISH) chromosome test. Open heart redo-surgery was performed for severe PR. The surgery revealed a severely hypoplastic pulmonary valve, which is characteristic of 22q11.2 deletion syndrome. 22q11.2 syndrome thus could be overlooked until age over 50 and therefore become critical.

Pacemaker Relocation for Radiation Against Overlapping Lung Cancer.

We experienced a patient after pacemaker (PM) implantation who had lung cancer of the left upper lobe that developed just behind the PM. The patient was an 81-year-old man with many complications. Radiation was the only treatment option. The PM had to be moved to another place to avoid direct radiation exposure to it. An epicardial pacing lead was implanted on the right ventricular epicardium, and the new generator was implanted in the abdomen. The patient was treated with a total of 62 Gy of radiotherapy for lung cancer, achieving a temporary shrinkage of the tumor. During the radiotherapy period, the PM functioned well without harmful events. When radiation therapy is needed in cases where the tumor overlaps the PM, relocation surgery using an epicardial pacing lead may be a useful option.

An essential role of the cysteine-rich domain of FZD4 in Norrin/Wnt signaling and familial exudative vitreoretinopathy.

The Wnt pathway plays important yet diverse roles in health and disease. Mutations in the Wnt receptor FZD4 gene have been confirmed to cause familial exudative vitreoretinopathy (FEVR). FEVR is characterized by incomplete vascularization of the peripheral retina, which can lead to vitreous bleeding, tractional retinal detachment, and blindness. We screened for mutations in the FZD4 gene in five families with FEVR and identified five mutations (C45Y, Y58C, W226X, C204R, and W496X), including three novel mutations (C45Y, Y58C, and W226X). In the retina, Norrin serves as a ligand and binds to FZD4 to activate the Wnt signaling pathway in normal angiogenesis and vascularization. The cysteine-rich domain (CRD) of FZD4 has been shown to play a critical role in Norrin-FZD4 binding. We investigated the effect of mutations in the FZD4 CRD in Norrin binding and signaling in vitro and in vivo. Wild-type and mutant FZD4 proteins were assayed for Norrin binding and Norrin-dependent activation of the canonical Wnt pathway by cell-surface and overlay binding assays and luciferase reporter assays. In HEK293 transfection studies, C45Y, Y58C, and C204R mutants did not bind to Norrin and failed to transduce FZD4-mediated Wnt/ß-catenin signaling. In vivo studies using Xenopus embryos showed that these FZD4 mutations disrupt Norrin/ß-catenin signaling as evidenced by decreased Siamois and Xnr3 expression. This study identified a new class of FZD4 gene mutations in human disease and demonstrates a critical role of the CRD in Norrin binding and activation of the ß-catenin pathway.

Association of Dishevelled with the clathrin AP-2 adaptor is required for Frizzled endocytosis and planar cell polarity signaling.

Upon activation by Wnt, the Frizzled receptor is internalized in a process that requires the recruitment of Dishevelled. We describe a novel interaction between Dishevelled2 (Dvl2) and micro2-adaptin, a subunit of the clathrin adaptor AP-2; this interaction is required to engage activated Frizzled4 with the endocytic machinery and for its internalization. The interaction of Dvl2 with AP-2 requires simultaneous association of the DEP domain and a peptide YHEL motif within Dvl2 with the C terminus of micro2. Dvl2 mutants in the YHEL motif fail to associate with micro2 and AP-2, and prevent Frizzled4 internalization. Corresponding Xenopus Dishevelled mutants show compromised ability to interfere with gastrulation mediated by the planar cell polarity (PCP) pathway. Conversely, a Dvl2 mutant in its DEP domain impaired in PCP signaling exhibits defective AP-2 interaction and prevents the internalization of Frizzled4. We suggest that the direct interaction of Dvl2 with AP-2 is important for Frizzled internalization and Frizzled/PCP signaling.

Relationship between the trochlear groove angle and patellar cartilage morphology defined by 3D spoiled gradient-echo imaging.

OBJECTIVE: To examine whether the femoral trochlear groove angle (TGA) is a determinant of the patellar cartilage volume and patellar cartilage damage. MATERIALS AND METHODS: Patellar cartilage was evaluated by MR imaging in 66 patients (22 males and 44 females) with knee pain. Fat-suppressed 3D spoiled gradient-echo images were used to calculate the cartilage volume and to grade the cartilage damage. The proximal and distal TGAs were measured from axial PD-weighted FSE MR images with fat suppression. RESULTS: For every increase in the TGA at the distal femur, the patellar cartilage volume was significantly increased by 6.07 × 10(-3) cm(3) (95% CI: 1.27 × 10(-3), 10.9 × 10(-3)) after adjustment for age, gender, and patellar bone volume (P < 0.05). The MR grade of medial patellar cartilage damage progressed as the distal TGA became narrower, although there was no significant correlation between the distal TGA and the MR grading of patellar cartilage damage. CONCLUSION: A more flattened distal TGA was associated with increased patellar cartilage volume. However, there was no association between TGA and patellar cartilage defects.

Effectiveness of Iodine-123 ß-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) Myocardial Scintigraphy for Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD) in Breast Cancer Patients.

PURPOSE: The optimal imaging modality for evaluating Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD) other than echocardiography is currently not known. We conducted a retrospective study utilizing myocardial scintigraphy to detect early-stage CTRCD in asymptomatic breast cancer patients. PATIENTS AND METHODS: Fifty-five asymptomatic breast cancer patients who had received chemotherapy within three years were involved in this study. Echocardiography was performed for all patients before and during chemotherapy. Thallium (201Tl) and 123I-ß-methyl-P-iodophenyl-pentadecanoic acid (123I-BMIPP) myocardial perfusion and metabolism scintigraphy were performed for all patients. Scintigraphy images were reviewed by several doctors including cardiologists, radiologists, palliative care physicians, and breast surgeons. The visual image assessment was then compared with the automated analysis utilizing Heart Risk View-S software (Nihon Medi-Physics Co Ltd, Tokyo, Japan). The results of scintigraphy were then compared with previous echocardiography data. RESULTS: Measuring global longitudinal strain (GLS) was impossible in 51% of patients. Measuring left ventricular ejection fraction (LVEF) was impossible in 15% of patients. A significant reduction of 123I-BMIPP uptake was observed in 15 patients out of 55 patients (27.3%). Among the 51 patients who were not previously diagnosed with CTRCD, 11 patients (21.6%) showed a significant reduction of 123I-BMIPP uptake. CONCLUSION: Myocardial scintigraphy with 123I-BMIPP detected myocardial damage in asymptomatic patients. If echocardiography is difficult to perform, myocardial scintigraphy could provide a second option for evaluating CTRCD.

Iodine-123 ß-methyl-P-iodophenyl-pentadecanoic Acid (123I-BMIPP) Myocardial Scintigraphy for Breast Cancer Patients and Possible Early Signs of Cancer-Therapeutics-Related Cardiac Dysfunction (CTRCD).

(1) Background: The mortality of breast cancer has decreased due to the advancement of cancer therapies. However, more patients are suffering from cancer-therapeutics-related cardiac dysfunction (CTRCD). Diagnostic and treatment guidelines for CTRCD have not been fully established yet. Ultrasound cardiogram (UCG) is the gold standard for diagnosis of CTRCD, but many breast cancer patients cannot undergo UCG due to the surgery wounds or anatomical reasons. The purpose of the study is to evaluate the usefulness of myocardial scintigraphy using Iodine-123 ß-methyl-P-iodophenyl-pentadecanoic acid (123I-BMIPP) in comparison with UCG. (2) Methods: 100 breast cancer patients who received chemotherapy within 3 years underwent Thallium (201Tl) and 23I-BMIPP myocardial perfusion and metabolism scintigraphy. The images were visually evaluated by doctors and radiological technologists, and the grade of uptake reduction was scored by Heart Risk View-S software (Nihon Medi-Physics). The scores were deployed in a 17-segment model of the heart. The distribution of the scores were analyzed. (3) Results: Nine patients (9%) could not undergo UCG. No correlation was found between left ventricular ejection fraction (LVEF) and Heart Risk View-S scores of 201Tl myocardial perfusion scintigraphy nor those of BMIPP myocardial metabolism scintigraphy. In a 17-segment model of the heart, the scores of the middle rings were higher than for the basal ring. (4) Conclusions: Evaluation by UCG is not possible for some patients. Myocardial scintigraphy cannot serve as a perfect alternative to UCG. However, it will become the preferable second-choice screening test, as it could point out the early stage of CTRCD.

PLCε cooperates with the NF-κB pathway to augment TNFα-stimulated CCL2/MCP1 expression in human keratinocyte.

Phospholipase Cε (PLCε) is a unique class of PLC regulated by both Ras family small GTPases and heterotrimeric G proteins. We previously showed by using mice bearing its null or transgenic allele that PLCε plays a crucial role in various forms of skin inflammation through upregulation of proinflammatory cytokine production from keratinocytes. However, molecular mechanisms how PLCε augments cytokine production were largely unknown. We show here using cultured human keratinocyte PHK16-0b cells that induction of the expression of chemokine (C-C motif) ligand 2 (CCL2) following stimulation with tumor necrosis factor (TNF)α, which primarily depends on the activation of the NF-κB pathway, is abrogated by small interfering RNA-mediated knockdown of PLCε. Enforced expression of PLCε causes substantial CCL2 expression and cooperates with low level TNFα stimulation to induce marked overexpression of CCL2, both of which are only partially blocked by pharmacological inhibition of the NF-κB signaling. However, PLCε knockdown exhibits no effect on both the NF-κB-cis-element-mediated transcription per se and the post-translational modifications of NF-κB implicated in transcriptional regulation, suggesting that PLCε constitutes a yet unknown signaling pathway distinct from the NF-κB pathway. This pathway can cooperate with the NF-κB pathway to achieve a synergistic TNFα-stimulated CCL2 induction in keratinocytes.

Relationship between cartilage volume using MRI and Kellgren-Lawrence radiographic score in knee osteoarthritis with and without meniscal tears.

OBJECTIVE: The purpose of our study was to evaluate the correlation between the Kellgren-Lawrence (KL) radiographic score and the femoral and tibial cartilage volumes determined by MRI in patients with knee osteoarthritis. The effect of meniscal tears and extrusion on the cartilage volume was also examined. SUBJECTS AND METHODS: Knee cartilage was evaluated by MRI in 74 patients (20 men and 54 women) who were categorized according to the KL score. Sagittal fat-suppressed 3D spoiled gradient-echo images were obtained to calculate the cartilage volume. The cartilage volume was determined for the lateral femoral cartilage, medial femoral cartilage, lateral tibial cartilage, and medial tibial cartilage. The femoral condylar bone volume was measured to adjust for bone size in each cartilage volume measurement. RESULTS: After adjusting for age, sex, and femoral condylar bone volume, the cartilage volumes were significantly different between the grades in all compartments. Additionally, significant correlations were observed between the KL score and the adjusted cartilage volumes of lateral femoral cartilage and lateral tibial cartilage without a meniscal tear and between the KL score and the adjusted cartilage volume of medial femoral cartilage with and without a meniscal tear. CONCLUSION: These findings showed a significant negative association between cartilage volume and the KL score. The cartilage volume of medial femoral cartilage may be more affected by the severity of osteoarthritis grade than the presence of a meniscal tear. In contrast, the cartilage volume in the lateral tibiofemoral compartment may be easily affected by the presence of a meniscal tear.

Ivabradine for Chemotherapy-Related Cardiac Dysfunction in Breast Cancer.

A 55-year-old woman with stage IV breast cancer was diagnosed with heart failure. Her left ventricular ejection fraction (LVEF) had decreased to 37.2%. Chemotherapy-related cardiac dysfunction (CTRCD) was suspected, and standard treatment for heart failure was initiated. After five months, her LVEF remained below 50% since she could not tolerate beta-blockers. Ivabradine was introduced, which remarkably improved her LVEF to 72.6% in only three months. Her myocardium was not dilated, which may be the reason that ivabradine was effective. Ivabradine has shown to be safe and effective in the treatment of CTRCD, and improved activities of daily living of an advanced-stage cancer patient.

Giant Tumor in the Inferior Vena Cava Treated With CyberKnife.

Renal cell carcinoma (RCC) is a slow-progressing cancer that may cause tumor embolism in the inferior vena cava (IVC) and has a high mortality rate. Treatment for IVC metastasis of RCC is basically surgical resection often requiring cardiopulmonary bypass. RCC has been regarded as a radio-resistant tumor; however, stereotactic radiotherapy (SRT) has proven effective in recent years. We present a case of advanced RCC in which CyberKnife radiotherapy was successful in saving and preserving quality of life. An 81-year-old male presented with severe edema in both legs. Contrast CT scan displayed giant tumor in IVC and bilateral mediastinal lymphadenopathy. The cancer appeared to originate from the lower pole of the right kidney. The tumor protruded into the right atrium, and surgical resection with pump oxygenator was impossible due to patient's age. CyberKnife SRT was performed for tumor in the IVC. Biopsy for hilar lymph node revealed clear cell RCC, and the second CyberKnife treatment was performed. The patient is surviving over three years without any symptoms. CyberKnife was successful in preserving patient's quality of life for advanced stage IV RCC.

CyberKnife Radiotherapy for Skull Base Petroclival Metastases Including Dorello's Canal: Report of 10 Cases.

Skull base petroclival metastases cause diplopia due to abducens nerve palsy. Diplopia is visually disabling, and skull base metastasis is extremely difficult to treat even with microscopic surgery. However, stereotactic radiotherapy with CyberKnife (Accuray Incorporated, Sunnyvale, California) has been very successful in 10 cases. As the abducens nerve runs through Dorello's canal in the skull base, the radiation dose and fraction were adjusted to avoid damage to the nerve. Since these metastases are not located inside the brain but in the skull base, contrast magnetic resonance imaging (MRI) combined with fluorodeoxyglucose-positron emission tomography (FDG-PET) was essential to detect the cancers.