Radiographic Evaluation after Arthroscopic Partial Trapeziectomy with Suture-button Suspensionplasty for Thumb Carpometacarpal Arthritis.

Arthroscopic partial trapeziectomy with suture-button suspensionplasty was developed for the surgical treatment of thumb carpometacarpal arthritis. However, the relationship between clinical results and radiographic evidence is unclear. Methods: The authors retrospectively reviewed 33 consecutive patients who underwent arthroscopic partial trapeziectomy with suture-button suspensionplasty for thumb carpometacarpal arthritis between 2016 and 2021. Clinical and radiographic outcomes were recorded, and the correlations between them were evaluated. Results: The average patient age at surgery was 69 years. Patient radiologic evidence was Eaton stage Ⅱ in three thumbs, Ⅲ in 25 thumbs, and Ⅳ in five thumbs. The average trapezial space ratio (TSR) was 0.36 immediately after the operation but declined to 0.32 after 6 months. In contrast, the average joint subluxation was reduced to 0.005 immediately after the operation compared with 0.28 before, and was maintained at 0.04 at final follow-up. A statically significant correlation was detected between grip strength and TSR (P = 0.03), and between pinch strength and TSR (P = 0.02). A significant correlation was detected between TSR and trapezium height (P = 0.0215), which remained after partial trapeziectomy. No correlation was detected between rope position and other clinical or radiographic scores. Conclusions: Suture-button can have an effect on the medialization of the first metacarpal base. Excessive trapeziectomy can result in functional deficiency of the thumb through metacarpal subsidence, which potentially causes loss of grip and pinch strength.

Clinical Results of Arthroscopic Partial Trapeziectomy With Suture-Button Suspensionplasty for Thumb Carpometacarpal Arthritis.

BACKGROUND: This study represents the clinical results, especially range of motion (ROM) improvement, of arthroscopic partial trapeziectomy with suture-button suspensionplasty for symptomatic grade II and III thumb carpometacarpal arthritis with a minimum 1-year follow-up. METHODS: Thirty-two patients (mean: 67.5 years) with grade II and III thumb carpometacarpal arthritis treated with arthroscopic partial trapeziectomy with suture-button suspensionplasty were retrospectively followed up for at least 1 year. The physical assessments included ROM, pain visual analogue scale (VAS), strength, and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. The physical variables were retrospectively compared before surgery and at the final follow-up. RESULTS: Preoperative radial abduction and palmar abduction (45.4 ± 16.4° and 54.3 ± 13.9°, respectively) were significantly increased at the final follow-up (59.7 ± 16.9° and 65.5 ± 14.2°, respectively). Preoperative VAS score, pinch strength, and DASH score (70.5 ± 14.0, 57.2 ± 24.8% and 36.8 ± 14.8, respectively) were also significantly improved at the final follow-up (7.9 ± 9.1, 91.0 ± 39.6%, and 11.7 ± 10.5, respectively). Complications involved 1 case of irritation of the superficial branch of the radial nerve and 1 case of dystonia. Two suture-buttons were removed due to patient discomfort. CONCLUSIONS: A significant increase in ROM and pain relief was obtained after suture-button suspensionplasty with arthroscopic partial trapeziectomy.

Muscle Grafts with Doxorubicin Pretreatment Produce "Empty Tubes" in the Basal Laminae, Promote Contentious Maturation of the Regenerated Axons, and Bridge 20-mm Sciatic Nerve Defects in Rats.

BACKGROUND: We newly developed a muscle graft that employs a doxorubicin pretreatment technique. The aims of this study were to reveal the biological and morphological features of the muscle tissue in the second week (Study I), to reveal the regeneration outcomes of functional and kinematic assessments of longer-term follow-up (16 weeks, Study II), and to make assessments of the muscle graft with doxorubicin pretreatment in the critical-sized nerve defect model (20 mm, Study III). METHODS: A total of 26 adult rats were used in this study. Doxorubicin treatment was accomplished by immersion in a doxorubicin solution for 10 minutes followed by a rinsing procedure. The rats were divided into three groups: the muscle graft with and without doxorubicin pretreatment (M-graft-w-Dox and M-graft-w/o-Dox) groups and the autologous nerve graft (N-graft) group. Assays of apoptosis, immunofluorescent histochemistry including CD68 (macrophage marker), scanning electron microscopy (SEM), morphometrical studies of the regenerated axons, nerve conduction studies, and kinematic studies were performed. RESULTS: The M-graft-w-Dox group contained significantly larger numbers of apoptotic cells and CD68-positive cells. SEM revealed the existence of the basal lamina, so called "empty tubes," in the M-graft-w-Dox group. Study II showed contentious maturation of the regenerated axons, especially in the compound muscle action potentials. Study III showed that even at 20 mm, the M-graft-w-Dox group promoted axonal regeneration and functional regeneration. CONCLUSION: The M-graft-w-Dox group showed superior regeneration results, and this easy and short-term procedure can expand the muscle graft clinical indication for the treatment of peripheral nerve defects.

Anterolateral thigh flap for upper extremity reconstruction in older patients.

BACKGROUND: The anterolateral thigh (ALT) flap has been used in upper extremity reconstruction. However, there is no consensus about the age at which the flap can be used safely, which is a concern when applying ALT flaps for upper extremity reconstruction in older patients. We present the results of the use of ALT flap for upper extremity reconstruction in a series of older patients. PATIENTS AND METHODS: Seventeen patients who underwent ALT flaps for soft tissue defects in the upper extremities from 2010 to 2020 were included. The patients' mean age was 63.5 (range, 26-83) years. Ten of seventeen patients were smokers. Defect locations were the dorsum of the hand in seven patients, palm in two patients, dorsum and palm in two patients, and forearm in six patients. Etiologies of the defect were traumatic in 14 patients and malignant tumor in three patients. The defect size was 8 to 25 × 5 to 11 cm. When dissecting the perforators, we preserved the surrounding small muscular and fatty tissue with the perforators and to harvest them together to prevent intima damage. Flap thinning was performed for 16 flaps to adjust the flap thickness to match defect site requirements. We used an end-to-side or interposition arterial anastomosis to regulate the blood flow. RESULTS: The flap size was 9 to 28 × 5 to 13 cm. One patient had venous congestion and vein re-anastomosis was needed. All flaps survived. One patient had a methicillin-resistant Staphylococcus aureus infection and debridement and irrigation was needed. The mean follow-up period was 20 (range, 13-37) months. Fifteen patients returned their previous activities. The mean DASH score was 30.6 (range, 3-70). CONCLUSIONS: Regardless of patient age or smoking status, the ALT flap was a safe and reliable surgical option for soft tissue defect reconstruction of the upper extremity.

Nerve regeneration using the Bio 3D nerve conduit fabricated with spheroids.

Autologous nerve grafting is the gold standard method for peripheral nerve injury with defects. Artificial nerve conduits have been developed to prevent morbidity at the harvest site. However, the artificial conduit regeneration capacity is not sufficient. A Bio 3D printer is technology that creates three-dimensional tissue using only cells. Using this technology, a three-dimensional nerve conduit (Bio 3D nerve conduit) was created from several cell spheroids. We reported the first application of the Bio 3D nerve conduit for peripheral nerve injury. A Bio 3D nerve conduit that was created from several cells promotes peripheral nerve regeneration. The Bio 3D nerve conduit may be useful clinically to treat peripheral nerve defects.

Enthesopathy of the bicipital tuberosity of the radius treated under intraoperative computed tomography.

BACKGROUND: There is no report of the application of intraoperative computed tomography to the extremities, and its usefulness is not mentioned. CASE PRESENTATION: We present a case of a patient with the elbow pain and loss of the forearm rotation due to the prominent bicipital tuberosity of the radius, which was diagnosed as enthesopathy. Surgical treatment to excise the prominent part of the bicipital tuberosity of the radius was recommended. However, it is difficult to perform the appropriate excision of the abnormal prominent part because of complications such as bicipital tendon rupture. The patient was successfully treated by surgical resection under the control of intraoperative computed tomography. CONCLUSIONS: Intraoperative computed tomography scan is a useful tool to assess the remaining volume of the abnormal bones.

The efficacy of combining a vascularized biogenic conduit and a decellularized nerve graft in the treatment of peripheral nerve defects: An experimental study using the rat sciatic nerve defect model.

BACKGROUND: Although decellularized nerve grafts are often used as a bridging material in nerve defect repair, the lack of perfusion support in this procedure limits the regeneration capacity. To address this, we applied vascularized biogenic conduits, which are fibrous membranes prefabricated around the silicone rod that contain rich vascularity and macrophages, to nerve defect repair procedures using decellularized nerve grafts. The purpose of this study is to investigate the capacity of combining a vascularized biogenic conduit and a decellularized nerve graft for peripheral nerve regeneration using a 10-mm nerve defect model in rats. MATERIALS AND METHODS: Sixteen adult male rats (F344 rats, 10-12 weeks, 200-250 g) were used in this study. For the prefabrication of vascularized biogenic conduits, a silicone rod was transplanted next to the sciatic nerve. After 8 weeks, this silicone rod was enveloped in connective tissue, called a vascularized biogenic conduit. The first rat was used to investigate the histological characteristics of vascularized biogenic conduits through immunofluorescence studies. The remaining 15 rats were divided into three groups to evaluate the efficacy of the combination of a decellularized nerve graft and a vascularized biogenic conduit: a decellularized nerve graft (DNG) group, a decellularized nerve graft with a vascularized biogenic conduit (DNG-w-VBC) group, and an autologous nerve graft (ANG) group. Eight weeks after nerve graft surgery, the assessment results of both functional recovery (electrophysical studies and target muscle atrophy) and morphological recovery (total number, diameter, and myelin thickness of the regenerated axons) of the regenerated nerves were examined. RESULTS: Immunofluorescence studies revealed that the VBC contains extracellular matrix, vascular tissue, and macrophages. The results of the DNG-w-VBC group were superior to the DNG group in electrophysiological studies (CMAP; 6.29 ± 0.80% vs. 4.02 ± 3.35%, MNCV; 50.6 ± 8.4% vs. 25.7 ± 15.6%, p < .05, respectively), regenerated axon number (11,348 ± 812 vs. 7697 ± 2197, p < .05), and mean axon diameter (2.72 ± 0.33 µm vs. 1.64 ± 0.12 µm, p < .05). CONCLUSIONS: Our study confirms that vascularized biogenic conduits supply vascularity and macrophages to nerve defect sites. Combining vascularized biogenic conduits with decellularized nerve grafts to treat nerve defects offers superior functional and morphological recovery of regenerated axons.

Long-Term Outcome of Sciatic Nerve Regeneration Using Bio3D Conduit Fabricated from Human Fibroblasts in a Rat Sciatic Nerve Model.

Previously, we developed a Bio3D conduit fabricated from human fibroblasts and reported a significantly better outcome compared with artificial nerve conduit in the treatment of rat sciatic nerve defect. The purpose of this study is to investigate the long-term safety and nerve regeneration of Bio3D conduit compared with treatments using artificial nerve conduit and autologous nerve transplantation.We used 15 immunodeficient rats and randomly divided them into three groups treated with Bio3D (n = 5) conduit, silicon tube (n = 5), and autologous nerve transplantation (n = 5). We developed Bio3D conduits composed of human fibroblasts and bridged the 5 mm nerve gap created in the rat sciatic nerve. The same procedures were performed to bridge the 5 mm gap with a silicon tube. In the autologous nerve group, we removed the 5 mm sciatic nerve segment and transplanted it. We evaluated the nerve regeneration 24 weeks after surgery.Toe dragging was significantly better in the Bio3D group (0.20 ± 0.28) than in the silicon group (0.6 ± 0.24). The wet muscle weight ratios of the tibial anterior muscle of the Bio3D group (79.85% ± 5.47%) and the autologous nerve group (81.74% ± 2.83%) were significantly higher than that of the silicon group (66.99% ± 3.51%). The number of myelinated axons and mean myelinated axon diameter was significantly higher in the Bio3D group (14708 ± 302 and 5.52 ± 0.44 µm) and the autologous nerve group (14927 ± 5089 and 6.04 ± 0.85 µm) than the silicon group (7429 ± 1465 and 4.36 ± 0.21 µm). No tumors were observed in any of the rats in the Bio3D group at 24 weeks after surgery.The Bio3D group showed significantly better nerve regeneration and there was no significant difference between the Bio3D group and the nerve autograft group in all endpoints.

Mechanism of Peripheral Nerve Regeneration Using a Bio 3D Conduit Derived from Normal Human Dermal Fibroblasts.

BACKGROUND: We previously reported the development of a scaffold-free Bio three-dimensional (3D) nerve conduit from normal human dermal fibroblasts (NHDFs). The aim of this study was to investigate the regenerative mechanism of peripheral nerve cells using a Bio 3D conduit in a rat sciatic nerve defect model. METHODS: Bio 3D conduits composed of NHDFs were developed, and cell viability was evaluated using a LIVE/DEAD cell viability assay immediately before transplantation and 1-week post-surgery. Tracking analysis using PKH26-labeled NHDFs was performed to assess the distribution of NHDFs within the regenerated nerve and the differentiation of NHDFs into functional Schwann cells (SCs). RESULTS: The assessment of the viability of cells within the Bio 3D conduit showed high cell viability both immediately before transplantation and 1-week post-surgery (88.56 ± 1.70 and 87.58 ± 9.11, respectively). A modified Masson's trichrome staining of the Bio 3D conduit revealed the formation of a prominent extracellular matrix (ECM) in between the cells. We observed, via tracking analysis, that the tube-like distribution of the NHDFs remained stable, the majority of the regenerated axons had penetrated this structure and PKH26-labeled cells were also positive for S-100. CONCLUSION: Abundant ECM formation resulted in a stable tube-like structure of the Bio 3D conduit with high cell viability. NHDFs in the Bio 3D conduit have the potential to differentiate into SCs-like cells.

Functional anatomy of the sagittal bands and mechanisms of extensor tendon dislocation: a cadaveric study.

We investigated the functional anatomy of the radial sagittal band and possible mechanisms involved in its spontaneous and traumatic rupture using seven cadaveric hands. First, the extensor tendon excursion and the change in angle between the sagittal bands and the tendon path were measured during metacarpophalangeal joint flexion. The radial bands were then divided in two different ways that mimicked spontaneous or traumatic rupture. We found no significant correlation between the extensor tendon excursion and the change in angle of the sagittal bands in the middle and ring fingers. Dislocation could occur when the radial sagittal band was only partially divided. This may explain why conservative treatment of tendon dislocation in the middle and ring fingers is feasible. Complete section of the sagittal bands in the little finger caused ulnar dislocation of the extensor tendon in only one out of seven hands.

Bio 3D Conduits Derived from Bone Marrow Stromal Cells Promote Peripheral Nerve Regeneration.

We previously reported that a nerve conduit created from fibroblasts promotes nerve regeneration in a rat sciatic nerve model. This study aims to determine whether a nerve conduit created from bone marrow stromal cells (BMSCs) can promote nerve regeneration. Primary BMSCs were isolated from femur bone marrow of two Lewis rats, and cells at passages 4-7 were used. We created seven Bio 3D nerve conduits from BMSCs using a Bio-3D Printer. The conduits were transplanted to other Lewis rats to bridge 5-mm right sciatic nerve gaps (Bio 3D group, n = 7). We created two control groups: a silicone group (S group, n = 5) in which the same nerve gap was bridged with a silicone tube, and a silicone cell group (SC group, n = 5) in which the gap was bridged with a BMSC injection. Twelve weeks after transplantation, nerve regeneration was evaluated functionally and morphologically. In addition, PKH26-labeled BMSCs were used to fabricate a Bio 3D conduit that was transplanted for cell trafficking analysis. Electrophysiological study, kinematic analysis, wet muscle weight, and morphological parameters showed significantly better nerve regeneration in the Bio 3D group than in the S group or SC group. In immunohistochemical studies, sections from the Bio 3D group contained abundant S-100-positive cells. In cell trafficking analysis, PKH26-positive cells stained positive for the Schwann cell markers S-100, p75NTR, and GFAP. Bio 3D nerve conduits created from BMSCs can promote peripheral nerve regeneration in a rat sciatic nerve model through BMSC differentiation into Schwann-like cells.

Pro-angiogenic scaffold-free Bio three-dimensional conduit developed from human induced pluripotent stem cell-derived mesenchymal stem cells promotes peripheral nerve regeneration.

Although autologous nerve grafting is widely accepted as the gold standard treatment for segmental nerve defects, harvesting autologous nerves is highly invasive and leads to functional loss of the ablated part. In response, artificial nerve conduits made of artificial materials have been reported, but the efficacy of the nerve regeneration still needs improvement. The purpose of this study is to investigate the efficacy and mechanism of the Bio three-dimensional (3D) conduit composed of xeno-free human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs). The 5-mm nerve gap of the sciatic nerve in immunodeficient rats was bridged with the Bio 3D conduit or silicone tube. Functional and histological recovery were assessed at 8 weeks after surgery. The regenerated nerve in the Bio 3D group was significantly superior to that in the silicone group based on morphology, kinematics, electrophysiology, and wet muscle weight. Gene expression analyses demonstrated neurotrophic and angiogenic factors. Macroscopic observation revealed neovascularization both inside and on the surface of the Bio 3D conduit. Upon their subcutaneous implantation, iMSCs could induce angiogenesis. The Bio 3D conduit fabricated from iMSCs are an effective strategy for nerve regeneration in animal model. This technology will be useful in future clinical situations.

Comparison of four posterior approaches of the ankle: A cadaveric study.

OBJECTIVES: The purpose of this study is to provide a detailed comparison of 4 posterior approaches of the ankle: the posteromedial, modified posteromedial (mPM), Achilles tendon-splitting (TS), and posterolateral approaches. METHODS: Cadaveric dissections were performed to assess the influence of the medial and lateral retraction forces on the neuro-vascular bundle with suspension scales and to measure the medial and lateral exposed areas of the posterior tibia and talus. Data was acquired with the ankle in neutral position and in plantar flexion. RESULTS: Both the mPM and TS approaches provided excellent visualization of the posterior tibia with the ankle in plantar flexion (16.6 cm2 and 16.2 cm2, respectively). The medial aspect of the posterior tibia, however, was significantly better exposed in the mPM approach than in the TS approach with the ankle in neutral position (8.9 cm2 vs 6.5 cm2). The lower value for medial retraction force in the mPM approach (1.9 N in neutral position and 0.9 N in plantar flexion) indicated a lower risk of injury to the neuro-vascular bundle (the tibial nerve and the posterior tibial artery). The posterior talus, however, is best visualized through the TS approach with the ankle in neutral position (4.5 cm2). CONCLUSIONS: The current study demonstrated the usefulness of the mPM approach. When internal fixation of the fibula is unnecessary, the mPM approach is preferable, considering the potential damage to the Achilles tendon associated with the TS approach.

Induced pluripotent stem cell-derived mesenchymal stem cells prolong hind limb survival in a rat vascularized composite allotransplantation model.

BACKGROUND: The reduction of systemic immunosuppressive agents is essential for the expansion of vascularized composite allotransplantation (VCA) in a clinical setting. The purpose of this study is to compare human-induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) with four other types of mesenchymal stem cells (human bone marrow-derived MSCs [BMMSCs], human adipose-derived MSCs [ADMSCs], rat BMMSCs, and rat ADMSCs) in vitro, and to investigate the in vivo immunomodulatory effect of iMSCs in a rat VCA model. MATERIALS AND METHODS: One Brown Norway (BN) rat, 2 Lewis (LEW) rats, and 1 Wistar rat were used in the mixed lymphocyte reaction (MLR), and 9 BN rats and 3 LEW rats (for donors), and 24 LEW rats (for recipients) were used in the VCA model. The abovementioned five types of MSCs were imaged to examine their morphology and were also tested for suppressor function using a MLR. The 24 recipient LEW rats were divided randomly into four groups, and subjected to orthotopic hind limb transplantation. The three control groups were the Iso group, in which transplantation was performed on from three to six LEW rats without immunosuppressive treatment (n = 6); the FK group, in which transplantation was performed from BN rats to LEW rats and recipient rats were treated with tacrolimus alone (FK 506, 0.2 mg/kg, days 0-6 postoperatively, intraperitoneally) (n = 6); and the UT group, in which transplantation was performed from BN rats to LEW rats without any immunosuppressive treatment (n = 6). The experimental group was the iMSC group, in which transplantation was performed from BN rats to LEW rats and recipient rats were treated with tacrolimus (FK 506, 0.2 mg/kg, days 0-6 postoperatively, intraperitoneally) and injected with iMSCs (2 × 106 cells, day 7, intravenously) (n = 6). Hind limb survival was assessed by daily inspection of gross appearance until 50 days postoperatively. Histology of the skin and muscle biopsy were investigated on day 14 postoperatively. A time series of the plasma cytokine level (before transplantation, and at 10, 14, and 17 days after transplantation) was also analyzed. RESULTS: The size of adherent and trypsinized iMSCs was 67.5 ± 8.7 and 9.5 ± 1.1 µm, respectively, which was the smallest among the five types of MSCs (p < .01). The absorbance in MLR was significantly smaller with rat ADMSCs (p = .0001), human iMSCs (p = .0006), rat BMMSCs (p = .0014), human ADMSCs (p = .0039), and human BMMSCs (p = .1191) compared to without MSCs. In vivo, iMSC treatment prolonged hind limb survival up to 12.7 days in macroscopic appearance, which is significantly longer than that of the FK group (p < .01). Histology of the skin and muscle biopsy revealed that mononuclear cell infiltration was significantly reduced by iMSC injection (p < .01). iMSC treatment also affected proinflammatory cytokines (interferon-gamma (IFNγ) and tumor necrosis factor α (TNFα)) and the anti-inflammatory cytokine (interleukin-10 (IL-10)) of the recipient plasma. The IFNγ levels at Δ14 and the TNFα levels at Δ14 and Δ17 of the iMSC group were significantly lower than those of the FK group (p = .0226, .0004, and .004, respectively). The IL-10 levels at Δ10 and Δ14 of the iMSC group were significantly higher than those of the FK group (p = .0013 and .0374, respectively). CONCLUSIONS: iMSCs induce T cell hyporesponsiveness to prolong hind limb survival in a rat VCA model. This immunomodulatory property against acute rejection could provide one of the promising strategies capable of enabling the toxicities of immunosuppressants to be avoided in clinical settings.

Assessment of Dorsal Subluxation in Thumb Carpometacarpal Osteoarthritis.

Background Although dorsal subluxation is a typical finding for osteoarthritis of the thumb carpometacarpal (CMC) joint, it is difficult to evaluate the subluxation after trapeziectomy and the significance of its surgical correction combined with trapeziectomy is still controversial. The purpose of this study was to develop a method to evaluate dorsal subluxation without using landmarks on the trapezium. Methods Thirty patients with thumb CMC arthritis and 13 normal patients were included in this study. Dorsal subluxation of the CMC joint was evaluated by measuring the distance between the volar tip of the thumb metacarpal base and dorsoradial border of the index metacarpal base (M1M2 overlap) on the X-ray true lateral view of the thumb as well as previously reported methods. Intraclass correlation coefficient (ICC) was used to assess inter- and intraobserver reliability for the measurement of M1M2 overlap by six examiners of different level of expertise. Dorsal subluxation was also evaluated after trapeziectomy with ligament reconstruction. Results There were almost perfect interobserver (ICC = 0.94) and intraobserver (ICC = 0.95 for an expert and 0.97 for a novice) reliabilities for the measurement of M1M2 overlap. There was a weak correlation between our method and previously reported methods. M1M2 overlap of the normal patients and the patients were 4.6 ± 1.2 mm and 2.3 ± 2.3 mm (mean ± SD), respectively. M1M2 overlap was corrected significantly after trapeziectomy with ligament reconstruction. Conclusion Dorsal subluxation of the thumb CMC joint could be evaluated by M1M2 overlap before and after trapeziectomy.

Genetic polymorphisms of the adenosine triphosphate-binding cassette transporters (ABCG2, ABCB1) and gefitinib toxicity.

The purpose of this study is to investigate associations between allelic variations of ABCG2 and ABCB1 with skin toxicity, diarrhea, liver injury and interstitial lung disease (ILD) in gefitinib-treated patients. A prospective clinical study of 83 Japanese patients with non-small-cell lung cancer was performed. Polymorphic loci in ABCG2 and ABCB1 were genotyped, and their effects on gefitinib toxicities were evaluated. ABCG2 34G>A was statistically associated with occurrence of skin rash; 13 (42%) of the 32 patients with at least one variant ABCG2 34G>A allele (G/A and A/A) developed grade 2 or worse skin rash, whereas only 10 (19%) of 51 patients homozygous for the reference allele (G/G) for the wild-type sequence for both alleles did so (P=0.046). There was no significant association between severe toxicities and polymorphisms of ABCG2 421C>A nor ABCB1 3435C>T. The results suggested that ABCG2 34G>A would be useful for predicting grade 2 or worse skin rash.

Pharmacogenetic approach for cancer treatment-tailored medicine in practice.

This article focuses on pharmacogenetic associations between genetic polymorphism of uridine diphosphate glucuronosyltransferase (UGT) 1A1 gene and irinotecan toxicity. Accumulating evidence provides support to the idea that determination of UGT1A1 polymorphisms before irinotecan treatment is clinically useful and important for predicting and avoiding related toxicities. On the basis of these backgrounds, the irinotecan label was updated in 2005 in the United States to provide pharmacogenetic information, and a dose reduction of irinotecan should be considered for patients known to be homozygous for the UGT1A1*28 allele when administered in combination with other agents or a single agent. The irinotecan/UGT1A1 issue and the development of molecular diagnostic testing are now to be translated into clinical practice.

Dynamic evolution of the spectrum of long-period fiber Bragg gratings fabricated from hydrogen-loaded optical fiber by ultraviolet laser irradiation.

Long-period fiber Bragg gratings fabricated by exposure of hydrogen-loaded fiber to UV laser light exhibit large-scale dynamic evolution for approximately two weeks at room temperature. During this time two distinct features show up in their spectrum: a large upswing in wavelength and a substantial deepening of the transmission minimum. The dynamic evolution of the transmission spectrum is explained quantitatively by use of Malo's theory of UV-induced quenching [Electron. Lett. 30, 442 (1994)] followed by refilling of hydrogen in the fiber core and the theory of hydrogen diffusion in the fiber material. The amount of hydrogen quenched by the UV irradiation is 6% of the loaded hydrogen.

Pharmacogenetics of irinotecan: a promoter polymorphism of UGT1A1 gene and severe adverse reactions to irinotecan.

This review focuses on a pharmacogenetic association between genetic polymorphism of UGT1A1 gene and severe adverse reactions to irinotecan. Although many studies used pharmacokinetic parameters as surrogate measures for predicting clinical outcomes of irinotecan chemotherapy, they have not produced consistent evidence. On the other hand, genotyping results of UGT1A1 gene appear to predict severe adverse reactions more straightforward than the pharmacokinetic parameters or the phenotypes of the enzymatic activity. A case-control study of Japanese cancer patients revealed that those with the variant UGT1A1 alleles were at significantly higher risk of severe adverse reactions to irinotecan, suggesting that the genotyping strategy would be clinically useful. Nevertheless, clinical importance of the pharmacogenetic testing should differ for different patient groups and for different clinical situations. We need to keep this issue in mind in applying the pharmacogenetic evidence in clinical practice.

Genetic polymorphism in the phenobarbital-responsive enhancer module of the UDP-glucuronosyltransferase 1A1 gene and irinotecan toxicity.

Genetic polymorphism of the UDP-glucuronosyltransferase (UGT) 1A1 gene is associated with the decreased glucuronidation activity of an active metabolite of irinotecan, SN-38, and UGT1A1*28 has been shown as a predictive factor for irinotecan toxicity. The phenobarbital-responsive enhancer module (PBREM) of the UGT1A1 promoter region has been reportedly associated with the transcriptional activity of the gene. We investigated whether the polymorphism of PBREM (T-3279G) would affect inter-patient variations in sensitivity to irinotecan toxicity. The study population comprised 119 cancer patients who had received irinotecan. We reviewed their clinical records, including patient characteristics, and observed their toxicity levels following irinotecan infusion. Genotyping was performed by sequencing analyses. Logistic regression analyses were performed to assess the relationship between genotypes and irinotecan toxicity. We identified the homozygotes of the reference allele for T-3279G in 68 patients, the heterozygotes in 37, and the homozygotes for the variant in 14. Logistic regression analysis indicated a significant association between the homozygotes for T-3279G and the severe toxicity (odds ratio 5.80; 95% confidence interval 1.67-20.1). However, multivariate analysis, including the data of UGT1A1*28 polymorphism, revealed a diminution of the association due to a highly significant linkage disequilibrium between these polymorphisms. Our results suggest that a highly significant linkage disequilibrium exists between T-3279G and UGT1A1*28 polymorphisms, and that the variants of T-3279G and UGT1A1*28 cooperatively decrease transcriptional activity of the UGT1A1 promoter. The determination of T-3279G and UGT1A1*28 genotypes might be clinically useful in predicting severe irinotecan toxicity in cancer patients.