Robot-assisted radical prostatectomy using the novel hinotoriTM surgical robot system: initial experience and operation learning curve at a single institution.

Background: The hinotoriTM surgical robot system (HSRS) is the first made-in-Japan robotic system used for radical prostatectomy. Here, we report initial results and describe our learning curve (skill development) implementing robot-assisted radical prostatectomy using HSRS (h-RARP). Methods: Between November 2021 and December 2022, 97 patients who underwent h-RARP at our institution were enrolled in this study. We retrospectively evaluated the surgical outcomes of the initial cases using h-RARP, comparing those of RARP using da Vinci surgical robot system (d-RARP) in our institution. Furthermore, the learning curves of two surgeons with the highest number of h-RARP were analyzed. Patients treated by each surgeon were categorized into two groups: 1-15 cases (earlier group) and >15 cases (later group). Preoperative patient characteristics, operation parameters, and complication rates were compared between the two groups. Results: In terms of surgical outcome, h-RARP was comparable to d-RARP. The procedures performed by the HSRS were successfully completed in all cases. There was no complication of grade 3 or higher. Comparing the two surgeons, surgeon 1, who had performed 40 d-RARP procedures, had time using robot system of the later group that was significantly shorter than that of the earlier group. However, for surgeon 2 with more than 100 d-RARP procedures, there was no statistically significant difference in time using robot system between groups. Other parameters showed no difference between earlier and later groups for the two surgeons. Conclusions: Our results show that surgical outcomes of h-RARP are comparable to those of d-RARP during the initial experience of clinical application. In addition, the surgeons' learning curves for the total RARP experience suggest that the experience of d-RARP can carry over to performance using the novel HSRS.

MGA-seq: robust identification of extrachromosomal DNA and genetic variants using multiple genetic abnormality sequencing.

Genomic abnormalities are strongly associated with cancer and infertility. In this study, we develop a simple and efficient method - multiple genetic abnormality sequencing (MGA-Seq) - to simultaneously detect structural variation, copy number variation, single-nucleotide polymorphism, homogeneously staining regions, and extrachromosomal DNA (ecDNA) from a single tube. MGA-Seq directly sequences proximity-ligated genomic fragments, yielding a dataset with concurrent genome three-dimensional and whole-genome sequencing information, enabling approximate localization of genomic structural variations and facilitating breakpoint identification. Additionally, by utilizing MGA-Seq, we map focal amplification and oncogene coamplification, thus facilitating the exploration of ecDNA's transcriptional regulatory function.

Extrachromosomal DNA in Cancer.

In cancer, complex genome rearrangements and other structural alterations, including the amplification of oncogenes on circular extrachromosomal DNA (ecDNA) elements, drive the formation and progression of tumors. ecDNA is a particularly challenging structural alteration. By untethering oncogenes from chromosomal constraints, it elevates oncogene copy number, drives intratumoral genetic heterogeneity, promotes rapid tumor evolution, and results in treatment resistance. The profound changes in DNA shape and nuclear architecture generated by ecDNA alter the transcriptional landscape of tumors by catalyzing new types of regulatory interactions that do not occur on chromosomes. The current suite of tools for interrogating cancer genomes is well suited for deciphering sequence but has limited ability to resolve the complex changes in DNA structure and dynamics that ecDNA generates. Here, we review the challenges of resolving ecDNA form and function and discuss the emerging tool kit for deciphering ecDNA architecture and spatial organization, including what has been learned to date about how this dramatic change in shape alters tumor development, progression, and drug resistance.

Efficacy of Premedication Protocol without Ranitidine for Taxane Regimen: A Multicenter Non-Randomized Historical Controlled Study.

OBJECTIVE: To study the efficacy of the prevention of immediate hypersensitivity reactions (HSRs) from omitting ranitidine in the premedication protocol in patients who had chemotherapy with taxane regimen. METHODS: This was a Multicenter, Ambispective Non-Randomized Historical Controlled Cohort Study. The incidence of HSRs in the patients who had the modified premedication without ranitidine were collected to compare with the historical group who had the standard premedication protocol with ranitidine. The relationships of each HSRs in the experimental group were compared with the historical control group using a multilevel regression analysis with the random-effects model. RESULT: A total of 441 patients were enrolled and analyzed in this study. 221 patients received the modified premedication protocol compared with 220 patients who received the standard premedication protocol in the historical group. HSRs were observed in 6 of 768 cycles of chemotherapy (0.78%) in a group of patients with the modified premedication protocol. Moreover, it was found in 4 of 761 cycles of chemotherapy (0.52%) in a group of patients with the standard premedication protocol. When comparing the relationship of the HSRs incidence between the groups using multilevel regression analysis with the random-effects model, there were no differences with a statistical significance (regression coefficients = 0.008, p-value = 0.30). CONCLUSION: The results of the study comprised evidence-based medicine supporting the safety of omitting ranitidine from the premedication protocol for the patients who had a taxane regimen and had a similar rate of HSRs to the use of ranitidine.

PEGylated liposomes: immunological responses.

A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are non-immunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system.

Hypofractionated stereotactic radiosurgery: a new treatment strategy for giant cavernous sinus hemangiomas.

OBJECTIVE Cavernous sinus hemangiomas (CSHs) are rare benign vascular tumors that arise from the dural venous sinuses lateral to the sella. Stereotactic radiosurgery (SRS) has emerged as a principal alternative to microresection for small- and medium-sized CSHs. Resection is a reasonable option for large (3-4 cm in diameter) and giant (> 4 cm in diameter) CSHs. However, management of giant CSHs remains a challenge for neurosurgeons because of the high rates of morbidity and even death that stem from uncontrollable and massive hemorrhage during surgery. The authors report here the results of their study on the use of hypofractionated SRS (H-SRS) to treat giant CSH. METHODS Between January 2008 and April 2014, 31 patients with a giant CSH (tumor volume > 40 cm3, > 4 cm in diameter) treated using CyberKnife radiosurgery were enrolled in a cohort study. Clinical status and targeted reduction of tumor volume were evaluated by means of serial MRI. The diagnosis for 27 patients was determined on the basis of typical imaging features. In 4 patients, the diagnosis of CSH was confirmed histopathologically. The median CSH volume was 64.4 cm3 (range 40.9-145.3 cm3). Three or 4 sessions of CyberKnife radiosurgery were used with a prescription dose based on the intent to cover the entire tumor with a higher dose while ensuring dose limitation to the visual pathways and brainstem. The median marginal dose to the tumor was 21 Gy (range 19.5-21 Gy) in 3 fractions for 11 patients and 22 Gy (range 18-22 Gy) in 4 fractions for 20 patients. RESULTS The median duration of follow-up was 30 months (range 6-78 months) for all patients. Follow-up MRI scans revealed a median tumor volume reduction of 88.1% (62.3%-99.4%) at last examination compared with the pretreatment volume. Ten patients developed new or aggravated temporary headache and 5 experienced vomiting during the treatment; these acute symptoms were relieved completely after steroid administration. Among the 30 patients with symptoms observed before treatment, 19 achieved complete symptomatic remission, and 11 had partial remission. One patient reported seizures, which were controlled after antiepileptic drug administration. No radiation-induced neurological deficits or delayed complications were reported during the follow-up period. CONCLUSIONS Hypofractionated SRS was an effective and safe modality for treating giant CSH. Considering the risks involved with microsurgery, it is possible that H-SRS might be able to serve as a definitive primary treatment option for giant CSH.

Identification of homogeneously staining regions in leukemia patients.

Homogeneously staining regions (HSR) or double minute chromosomes (dmin) are autonomously replicating extra-chromosomal elements that are frequently associated with gene amplification in a variety of cancers. The diagnosis of leukemia patients was based on characterization of the leukemic cells obtained from bone marrow cytogenetics. This study report two cases, one with Acute Myeloblastic Leukemia without maturation (AML-M1), aged 23-year-old female, and the other with chronic myelogenous leukemia (CML)-blast crisis, a 28-year-old female associated with double minute chromosomes. Most cases of acute myeloid leukemia with dmin in the literature (including our cases) have been diagnosed as having acute myeloid leukemia.