Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has been shown to be effective in the treatmentof patients with metastatic castration-resistant prostate cancer (mCRAP) who have BRCA1/2 or ATM mutations,which are DNA repair genes. In addition to ovarian, breast, and pancreatic cancer, the indication was extended to“castration-resistant prostate cancer with BRCA mutation-positive distant metastasis” in December 2020 in Japan.Prostate cancer has also entered the era of “personalized cancer treatment based on genetic information,” or socalled “cancer genome medicine.”This article will discuss the following: 1) the relationship between DNA repair genes and prostate cancercarcinogenesis, 2) the mechanism of PARP inhibitors, 3) the results of the PROfound clinical trial of olaparib, and4) the timing of genetic testing for prostate cancer.
The outcome of patients with chronic myeloid leukemia (CML) has dramatically improved with tyrosine kinaseinhibitors (TKIs). Five TKIs, imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, are currently available inJapan. However, some patients still respond insufficiently to TKI. Additionally, adverse events that cause TKIintolerance are a critical concern. In Japan and the United States, asciminib, a CML therapeutic drug with a newmechanism of action, has become available in the daily clinic. This article outlines the unique mechanism ofaction of this new drug. Asciminib targets the allosteric regulation of the BCR-ABL1 oncoprotein, a substantialdriver of CML development. In addition, the latest clinical trials that led asciminib to its clinical application aredescribed here.
Post COVID-19 condition/long COVID, also called post-acute COVID-19 or long-haul COVID, refers to avariety of symptoms that have persisted since the acute phase of the disease or have newly emerged and persistedduring the chronic course of the disease. The most common symptoms are fatigue, shortness of breath, dysosmia,dysgeusia, etc., while psychiatric and neurological symptoms such as memory impairment, poor concentration,and headache are important issues, and brain fog is also a well-known problem. Long COVID is thought to becaused by a combination of factors, including sequelae of COVID-19-induced CNS damage, postintensive caresyndrome, chronic inflammatory reactions associated with COVID-19, and autonomic disorders; however, thepathogenesis remains unclear. Since the symptoms of long COVID are diverse, a comprehensive approach andfollow-up are necessary.
No study has investigated the minimum effective volume of 0.5% levobupivacaine for ultrasound-guided brachial plexus block via the axillary approach. To address this deficit, we sought to determine the minimum effectivevolume and evaluate the clinical efficacy of low volumes. Our study included 25 patients scheduled to undergoupper limb surgery. The minimum effective volume was determined with Dixon’s positive-negative up-and-downmethod. The study design called for a starting volume of 5 mL per nerve for the first patient, with the volume tobe decreased by 0.5 mL for the next patient if the block was successful or increased by 0.5 if the block was unsuccessful. The minimum volume was set at 1 mL. The minimum effective volume, duration of analgesia, time toonset, and use of analgesics during surgery were determined. The block success rate was 100%. The volume wasdecreased to 1 mL without block failure, and block success was achieved in the remaining 16 patients with 1 mL.The duration of analgesia was 11.2 ± 4.7 hours and was not correlated with the dose. No analgesics were usedduring surgery. These findings suggest that 1 mL of 0.5% levobupivacaine per nerve provides sufficient analgesia.
Cerebrospinal fluid leaks via petrosal bone defects are uncommon but are an important cause of intractable intracranial infection. These defects are commonly associated with temporal bone trauma and lateral skull base andmastoid surgery but may also occur with tumors, radiotherapy, otitis media, congenital malformations, or spontaneous leaks. Regardless of the cause, the defects provide a route for the spread of infection in some cases, sopatients may present with potentially recurrent episodes of meningitis and fatal intracranial infection. Definitivediagnosis of the location of the fistula and surgical repair are recommended, but available imaging methods maynot localize the source. However, such defects may lead to leakage, so determination of the location and repair arenecessary. We describe the effective surgical repair technique based on our experience, which resulted in favorableoutcomes using the transcranial surgical approach.
A 46-year-old male and a 53-year-old female each required a second surgery because of dilatation of the distalaortic arch (> 55 mm) approximately 5 years after ascending replacement for acute type A dissection. Bothpatients showed patent false lumen associated with endoleakage from the distal anastomosis. We performed distalarch to descending aorta replacement through a left thoracotomy using femorofemoral cardiopulmonary bypasswith a 50% assist rate. The dissecting flaps were excised from both the proximal and distal aortic stumps, and polyester grafts were anastomosed in a double-barrel fashion under the aortic cross-clamps. No changes in the aorticarch diameters were observed 1 year after surgery. Here, we report the efficacy of proximal double-barrel anastomosis for residual dissecting aneurysm caused by endoleakage from distal anastomosis after emergency repair fortype A dissection.
(Patient) The patient was a 74-year-old male.(History) The patient had been experiencing left papillary hematogenous secretion for approximately 3 years.He had been neglecting it for some time, but when he began to notice persistent secretion, he came to our clinic.(Present condition) On physical examination, no mass was palpable, and only bloody nipple discharge was observed. Mammary ultrasonography showed a hypoechoic mass of approximately 8 mm in size in the left nipple. Aneedle biopsy was performed, a diagnosis of invasive ductal carcinoma was made, and a thoracic muscle-sparingmastectomy and sentinel lymph node biopsy were performed. Histopathological findings showed a diagnosis ofinvasive ductal carcinoma: tubule-forming type, pT1aN0M0 stage I, ER (+), PgR (+), HER2 score 1, and ki6730%.(Discussion) Male breast cancer accounts for approximately 1% of all breast cancers. The initial presentation isoften palpable as a painless mass. Noninvasive ductal carcinoma is common, although bloody papillary dischargemay be present, and invasive ductal carcinoma may be advanced. We report this case because it was treated earlyand the patient had a good course.
An adult male patient exhibited repetitive left hemiparesis of long duration caused by infarction in the distributionof the right lenticulostriate artery (LSA). Stroke occurred ten times in total and completely recovered within ashort period. Diffusion-weighted magnetic resonance imaging at each hospitalization showed an abnormal highintensity area in the region of the posterior limb of the internal capsule and the corona radiata on the right side;sometimes, the lesion extended to the lateral part of the thalamus, which indicated an acute infarct. The time duration between each stroke ranged from short to long periods. The periods between strokes extended up to 182 daysat the longest. The clinical diagnosis corresponded to capsular warning syndrome, based on repetitive infarctionof the LSA, with complete remission; however, the clinical course included prolonged periods between strokes,with some extending to a long duration, indicating an atypical aspect.