GnRH Agonist Therapy in a Patient with Recurrent Ovarian Granulosa Cell Tumors

A 65-yr-old woman presented 17 yr status post-hysterectomy with bilateral ovarian salpingo-oophorectomy, attributable to ovarian cancer. She was admitted to our hospital, with multiple cystic liver masses and multiple large seeded masses in her abdomen and pelvic cavity. Histological examination of the pelvic masses demonstrated granulosa cell tumors. After two courses of systemic combination chemotherapy, with paclitaxel and carboplatin, the masses in the abdomen and pelvic cavity increased, and debulking surgery also failed because of peritoneal dissemination with severe adhesion. Finally, she underwent palliative radiotherapy for only the pelvic masses obstructing the urinary and GI tracts, and monthly hormonal therapy with a gonadotrophin-releasing hormone agonist; leuprorelin 3.75 mg IM. Subsequently, multiple masses beyond the range of the radiation as well as those within the radiotherapy field partially decreased. This partial response had been maintained for more than 8 months as of the last follow-up visit. Owing to its long and indolent course and the low metabolic rate of the tumors, advanced or recurrent granulosa cell tumor (GCT) requires treatment options beyond chemotherapy, surgery, and radiotherapy. Hormonal agents may provide another treatment option for advanced or recurrent GCT in those who are not candidates for surgery, chemotherapy, or radiotherapy.     

Cell encapsulation and oxygenation in nanoporous microcontainers

With strides in stem cell biology, cell engineering and molecular therapy, the transplantation of cells to produce therapeutic molecules endogenously is an attractive and achievable alternative to the use of exogenous drugs. The encapsulation of such cell transplants in semi-permeable, nanoporous constructs is often required to protect them from immune attack and to prevent their proliferation in the host. However, effective graft immunoisolation has been mostly elusive owing to the absence of a high-throughput method to create precisely controlled, high-aspect-ratio nanopores. To address the clinical need for effective cell encapsulation and immunoisolation, we devised a biocompatible cell-encapsulating microcontainer and a method to create highly anisotropic nanopores in the microcontainer’s surface. To evaluate the efficacy of these nanopores in oxygenating the encapsulated cells, we engineered 9L rat glioma cells to bioluminesce under hypoxic conditions. The methods described above should aid in evaluating the long term survival and efficacy of cellular grafts.     

The Role of Lymph Node Metastasis in the Systemic Dissemination of Breast Cancer

Background  

Lymphatic invasion is necessary for regional lymph node (RLN) metastasis in breast cancer (BC), while systemic metastasis requires blood vessel (BV) invasion. The site of BV invasion could be at the primary BC site or through lymphovascular anastomoses. The vague pathologic term “lymphovascular invasion” (LVI) encourages the belief that peri/intratumoral BV invasion may be common. We investigated the relative contribution of RLN metastasis to systemic metastasis by studying the relationship among LVI and RLN and/or systemic metastasis in a population-based cohort of breast cancer patients.     

Reliability and validity of measures of hammer toe deformity angle and tibial torsion

BackgroundMeasures of second–fourth metatarsophalangeal joint (MTPJ) angle (indicator of hammer toe deformity) and clinical measures of tibial torsion have limited evidence for validity and reliability. The purposes of this study are to determine: (1) reliability of using a 3D digitizer (Metrecom) and computed tomography (CT) to measure MTPJ angle for toes 2–4; (2) reliability of goniometer, 3D digitizer, and CT to measure tibial torsion; (3) validity of MTPJ angle measures for toes 2–4 using goniometry and 3D digitizer compared to CT (gold standard) and (4) validity of tibial torsion measures using goniometry and 3D digitizer (Metrecom) compared to CT (gold standard).MethodsTwenty-nine subjects participated in this study. 27 feet with hammer toe deformity and 31 feet without hammer toe deformity were tested using standardized gonimetric, 3D digitizer and CT methods. ICCs (3,1), standard error of the measurement (SEM) values, and difference measures were used to characterize intrarater reliability. Pearson correlation coefficients and an analysis of variance were used to determine associations and differences between the measurement techniques.Findings3D digitizer and CT measures of MTPJ angle had high test–retest reliability (ICC = 0.95–0.96 and 0.98–0.99, respectively; SEM = 2.64–3.35° and 1.42–1.47°, respectively). Goniometry, 3D digitizer, and CT measures of tibial torsion had good test–retest reliability (ICC = 0.75, 0.85, and 0.98, respectively; SEM = 2.15°, 1.74°, and 0.72°, respectively). Both goniometric and 3D digitizer measures of MTPJ angle were highly correlated with CT measures of MTPJ angle (r = 0.84–0.90, r = 0.84–0.88, respectively) and tibial torsion (r = 0.72, r = 0.83). Goniometry, 3D digitizer, and CT measures were all different from each other for measures of hammer toe deformity (p < 0.001). Goniometry measures were different from CT measures and 3D digitizer measures of tibial torsion (p < 0.002). CT measures and 3D digitizer measures of tibial torsion were similar (p = 0.112).InterpretationsThese results suggest that 3D digitizer and CT scan measures of MTPJ angle and goniometric, 3D digitizer, and CT scan measures of tibial torsion are reliable. Goniometer and 3D digitizer measures of MTPJ angle and tibial torsion measures are highly correlated with the gold standard CT method indicating good validity of measures, but the measures are not interchangeable.     

Age and body weight adjusted warfarin initiation program for ischaemic stroke patients

Background:  Despite its proven effect, anticoagulation is not recommended to the acute ischaemic stroke due to the risk of bleeding complications. The purpose of this study is development of individualized warfarin initiation program for acute or subacute stroke patients.
Methods:  Among stroke patients who regularly visited out-patient clinics, we included patients who have continuously taken the same dose of warfarin as the prothrombin time remained at target International Nomarlized Ratio (INR). We assessed potential variables that affect the maintenance dose of warfarin. Using these variables, we developed an individualized warfarin initiation program.
Results:  The median warfarin maintenance dose (interquartile range) in the 321 included patients was 4 (3–5) mg per day. Age (adjusted R ² = 0.221, P  <   0.001) and body weight (added to age, adjusted R ² = 0.238, P  =   0.008) were significant predicting factors of the dose. We classified the maintenance doses into high (HG), standard, and low group (LG) based on the distribution of maintenance doses. Decision tree analysis categorized younger (≤55 years old) and heavier (≥55 kg) patients into HG, and very old (≥80 years old) or low body weight (<55 kg among those >56 years old) patients into LG. We recommend 7 mg of warfarin as a standard initial dose, but 10 mg was recommended for HG patients and 5 mg for LG.
Conclusion:  We expect that this individualized program may reduce the time to target INR without excessive anticoagulation. Further prospective studies are needed to reveal the efficacy and safety of applying this program for acute stroke patients.     

Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy： A pilot study

AIM： To evaluate the combination of bevacizumab with infusional 5-fluorouracil （5-FU）, leucovorin （LV） and irinotecan （FOLFIRI） in patients with advanced colorectal cancer （CRC） pretreated with combination regimens including irinotecan and oxaliplatin. METHODS： Fourteen patients （median age 56 years） with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d. RESULTS： The median number of cycles of chemotherapy was six （range 3-12）. The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo （95% CI 2.0-8.7）, and the median overall survival was 10.9 mo （95% CI 9.6-12.1）. Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles. CONCLUSION： Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.     

Distant skeletal muscle metastasis from intrahepatic cholangiocarcinoma presenting as Budd-Chiari syndrome

Intrahepatic cholangiocarcinoma is a malignant neoplasm arising from the biliary epithelium, which frequently invades adjacent organs or metastasizes to other visceral organs such as the lungs, bones, adrenals, and brain. However, distant skeletal muscle metastasis of cholangiocarcinoma has never been described before to the best of our knowledge and, furthermore, Budd-Chiari syndrome secondary to intrahepatic cholangiocarcinoma is also extremely rare. Here we present the first case overall of distant muscle metastasis from intrahepatic cholangiocarcinoma presenting as Budd-Chiari syndrome. A 44-year-old man admitted to the hospital with complaints of abdominal distension, edema of both legs, back pain and anorexia of 30 d' duration. Computed tomography and ultrasonography-guided percutaneous muscle biopsy established intrahepatic cholangiocarcinoma with disseminated thrombosis from inferior vena cava to bilateral iliac and femoral veins, and multiple skeletal muscle metastases in bilateral buttock and erector spinal muscle.     

Endoscopic transcystic stent placement for an intrahepatic abscess due to gallbladder perforation

Perforation of the gallbladder with cholecystohepatic communication is a rare cause of liver abscess. Because it is a rare entity, the treatment modality has not been fully established. We report for the first time a patient with an intrahepatic abscess due to gallbladder perforation successfully treated by endoscopic stent placement into the gallbladder who had a poor response to continuous percutaneous drainage.     

Neuropsychological symptoms of juvenile-onset batten disease: experiences from 2 studies

Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a progressive and fatal autosomal-recessive inherited lysosomal storage disorder of childhood. Core symptoms include vision loss, seizures, and mental and motor decline. This article presents data from 2 studies of neuropsychological function in juvenile neuronal ceroid lipofuscinosis. In the first cross-sectional pilot study, 15 children with genetic or clinicopathologic confirmation of juvenile neuronal ceroid lipofuscinosis completed a brief test of attention (mean age = 14.3 +/- 2.9 years, range = 8.75-18.74 years; 7 males, 8 females). Average attention performances were significantly below age-expected normative data. A second longitudinal study was then initiated to study neuropsychological function in greater depth, including change in function over time. The authors have enrolled 18 children to date (mean age = 12.88 +/- 3.59 years, range = 6.26-18.65; 11 males, 7 females). Of these, 5 children have completed a second (annual) re-evaluation. Results thus far indicate significant impairment in domains of auditory attention, memory, estimated verbal intellectual function, and verbal fluency. Neuropsychological impairment was significantly correlated with disease duration and with motor function as assessed by a disease-specific clinical neurologic rating scale. There was no significant difference between males and females in neuropsychological test performance. Neuropsychological function was worse among children with a positive seizure history. Juvenile neuronal ceroid lipofuscinosis-affected children exhibited significant and pervasive impairments on tests of auditory attention, verbal memory and repetition, verbal fluency, and an estimate of verbal intellectual ability. Preliminary follow-up data from an annual reassessment showed progressive declines in cognitive function, in particular on a task of working memory. Neuropsychological deficits are pervasive and progressive. Future research will focus on clarifying the relationship among disease duration, motor function, and neuropsychological performances, including the relative sensitivity of neuropsychological testing at different stages of motor impairment or disease duration.