Outcomes in colorectal endoscopic submucosal dissection for large protruded lesions: A retrospective multicenter study.

Background and study aims Colorectal endoscopic submucosal dissection (ESD) is increasingly used for treating early-stage colorectal cancer, including large, protruded lesions (LPL). However, the challenges posed by LPLs, especially those accompanied by severe fibrosis or muscle-retracting sign (MRS), remain unclear. This study aims to investigate ESD outcomes for LPL, focusing on factors such as tumor size and, submucosal fibrosis. Patients and methods In a multicenter retrospective study (June 2012 to May 2023), data from 526 patients with 542 LPL lesions (≥ 2 cm) were analyzed. Parameters included lesion size, procedure time, dissection speed, physician experience, submucosal fibrosis, and adverse events. The tunnel method, including the double tunnel method, was used for cases with severe fibrosis or MRS. Multivariate analysis assessed factors affecting procedure difficulty, particularly LPLs ≥ 4 cm. Results The study revealed an impressive en bloc resection rate of 97.8% and a curative resection rate of 78.6% for LPLs. Notably, fibrosis and MRS were present in 25% and 18% of 4-cm LPLs, respectively, and their frequency tended to increase as the tumor diameter increased. One treatment strategy for LPLs was the tunneling method, which was used most frequently (41 cases, 7.6%). Factors affecting dissection speed included larger tumor size, submucosal fibrosis, MRS, and physician experience. Conclusions Treating LPLs through colorectal ESD presents significant challenges, especially in patients with fibrosis and MRS. This study highlights the importance of recognizing these complexities, and that more reliable resection strategy must be established for accurate pathological evaluation.

Molecular phylogeny of Hesperiidae (Lepidoptera) with an emphasis on Asian and African genera.

Despite considerable research efforts in recent years, the deeper phylogenetic relationships among skipper butterflies (Hesperiidae) remain unresolved. This is primarily because of limited sampling, especially within Asian and African lineages. In this study, we consolidated previous data and extensively sampled Asian and African taxa to elucidate the phylogenetic relationships within Hesperiidae. The molecular dataset comprised sequences from two mitochondrial and two nuclear gene regions from 563 species that represented 353 genera. Our analyses revealed seven subfamilies within Hesperiidae: Coeliadinae, Euschemoninae, Eudaminae, Pyrginae, Heteropterinae, Trapezitinae, and Hesperiinae. The systematics of most tribes and genera aligned with those of prior studies. However, notable differences were observed in several tribes and genera. Overall, the position of taxa assigned to incertae sedis in Hesperiinae is largely clarified in this study. Our results strongly support the monophyly of the tribe Tagiadini (Pyrginae), and the systematics of some genera are clarified with comprehensive discussion. We recognize 15 tribes within the subfamily Hesperiinae. Of these, nine tribes are discussed in detail: Aeromachini, Astictopterini, Erionotini, Unkanini (new status), Ancistroidini, Ismini (confirmed status), Plastingini (new status), Gretnini (confirmed status), and Eetionini (confirmed status). We propose four subtribes within Astictopterini: Hypoleucina subtrib.n., Aclerosina, Cupithina, and Astictopterina. Furthermore, we describe a new genus (Hyarotoidesgen.n.) and reinstate two genera (Zeareinst.stat. and Separeinst.stat.) as valid. Additionally, we propose several new combinations: Zea mythecacomb.n.,Sepa bononiacomb.n. & reinst.stat., and Sepa umbrosacomb.n. This study, with extensive sampling of Asian and African taxa, greatly enhances the understanding of the knowledge of the skipper tree of life.

Effectiveness of Strategy-Focused Training in Colorectal Endoscopic Submucosal Dissection: A Retrospective Observational Study.

BACKGROUND: Colorectal ESD, an advanced minimally invasive treatment, presents technical challenges, with globally varying training methods. We analyzed the learning curve of ESD training, emphasizing preoperative strategies, notably gravity traction, to guide ESD instructors and trainee programs. METHOD: This retrospective study included 881 cases guided by an experienced supervisor. Six trainees received "strategy-focused" instruction. To evaluate the number of ESD experiences in steps, the following phases were classified based on ESD experiences of each trainees: Phase 0 (0-50 ESD), Phase 1 (51-100 ESD), Phase 2 (101-150 ESD), and Phase 3 (151-200 ESD). Lesion background, outcomes, and safety were compared across phases. Factors contributing to technical difficulty in early (Phase 0 and 1) and late phases (Phase 2 and 3) were identified, along with the utility of traction ESD with device assistance. RESULT: Treatment outcomes were favorable, with 99.8% and 94.7% en bloc resection and curative resection rates, respectively. Approximately 90% self-completion rate could be achieved after experiencing about 50 cases (92.7% in Phase 1), signifying proficiency growth despite increased case difficulty. In early phases, factors such as left-sided colon, LST-NG morphology, and severe fibrosis pose challenges. In late phases, LST-NG morphology, mild and severe fibrosis remained significant. Traction-assisted ESD, utilized in 3% of cases, comprised planned (1.1%) and rescue (1.9%) methods. Planned traction aided specific lesions, while rescue traction was common in the right colon. CONCLUSION: "Strategy-focused" ESD training consistently yields successful outcomes, effectively adapting to varying difficulty factors in different proficient stages.

Clip with line-pulley securing technique with plastic detachable snare for endoscopic submucosal dissection defect closure.

Video 1Clip with line-pulley securing technique with plastic detachable snare for endoscopic submucosal dissection defect closure.

The Management of Direct Oral Anticoagulants for Colorectal Endoscopic Submucosal Dissection: A Multicenter Observational Study.

BACKGROUND: There is a lack of reports on the use of direct oral anticoagulants (DOACs) during colorectal endoscopic submucosal dissection (ESD). AIMS: We aimed to assess whether the use of DOACs is associated with a higher incidence of delayed bleeding (DB) after ESD. METHODS: A total of 4175 colorectal neoplasms in 3515 patients were dissected at our hospitals during study period. We included 3909 lesions in the final analysis. The lesions were divided into two groups: the no-AT group (3668 neoplasms) and the DOAC group (241 neoplasms). We also compared the DOAC withdrawal group (154 neoplasms) and the DOAC continuation group (87 neoplasms). RESULTS: Among the 3909 lesions, DB occurred in a total of 90 cases (2.3%). The rate of DB was 2.2% (82/3668), and 3.3% (8/241), respectively. There were no significant differences in the rate of DB between the no-AT group and the DOAC group. In the DOAC group, there were no significant differences in the rate of DB between the withdrawal group (5.2%, 8/154) and the continuation group (0%, 0/87). The multivariable analysis identified the location of the lesion in the rectum (odds ratio [OR], 4.04; 95% confidence interval [CI], 2.614-6.242; p < 0.001) and lesions ≥ 30 mm in diameter (OR, 4.14; 95% CI, 2.349-7.34; p < 0.001) as independent risk factors for DB. CONCLUSIONS: Our findings suggest that DOAC use has no significant important on the rate of DB. Prospective studies are warranted to determine whether treatment with DOACs should be interrupted prior to colorectal ESD.

Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial).

BACKGROUND: Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate. METHODS: This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study. DISCUSSION: This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.

Comparison of cold snare polypectomy for sessile serrated lesions ≥10 mm between experienced and trainee endoscopists: A propensity score matching cohort study.

Objectives: Previous studies of cold snare polypectomy (CSP) for sessile serrated lesions (SSLs) ≥10 mm were performed by experienced endoscopists, and therefore their skills might have significantly influenced results. In this study, we compared the efficacy and safety of CSP for SSLs ≥10 mm between experienced and trainee endoscopists. Methods: In a 1:1 propensity score matched retrospective cohort study, we compared the complete resection rate, en-bloc resection rate, adverse event rate, and procedure time between experienced and trainee groups. Thirteen endoscopists performed CSP, and we defined the experienced group as endoscopists with board certification from the Japan Gastroenterological Endoscopy Society. Results: We examined 616 lesions with SSLs ≥10 mm resected by CSP between February 2018 and May 2022. We excluded 61 lesions from the analysis because they had simultaneously undergone hot snare polypectomy (n = 57) or had been taken over by experienced endoscopists from trainees in the CSP procedure (n = 4). Finally, we identified 217 propensity score-matched pairs (n = 434). Between experienced and trainee groups, the results were complete resection rate (100 vs. 100%; p = 1.00), en-bloc resection rate (73.2 vs. 75.6%; p = 0.24), adverse event rate (3.2 vs. 2.8%; p = 0.77), or procedure time (6.2 vs. 5.9 min; p = 0.64). Conclusions: We have demonstrated the safety and efficacy of CSP for SSLs ≥10 mm performed by experienced and trainee endoscopists.

Cold snare defect protrusion and incomplete polyp resection after forced cold snare polypectomy: a prospective observational study.

BACKGROUND: Cold snare defect protrusions (CSDPs) that occur after cold snare polypectomy (CSP) are considered indicators of incomplete polyp resection (IPR). We have sometimes experienced difficulty resecting polyps with snaring alone; in such cases, a forcible pull on the snare by the endoscopist is necessary. We call this procedure "forced CSP (FCSP)." However, no previous studies have evaluated this procedure. METHODS: This was a prospective observational study. From November 2020 to June 2021, the frequency, safety, and validity of FCSP were evaluated at our hospital. We distinguished CSP with snaring alone performed by the assistant as conventional CSP, and CSP requiring a forcible pull on the snare by the endoscopist as FCSP. RESULTS: Of 1315 polyps removed, 105 underwent FCSP (8%). The perforation rate was 0% in both groups. The rate of CSDP after the procedure was 96.2% (101/105) with FCSP and 6.4% (77/1210) with conventional CSP (P<0.001). The rate of IPR was 12.5% (13/104) with FCSP and 6.2% (75/1208) with conventional CSP (P=0.02). Multivariable analysis identified polyps located in the cecum (risk ratio [RR], 1.13; 95%CI 1.050-1.179; P=0.003) and polyps ≥6mm in diameter (RR, 2.37; 95%CI 2.146-2.542; P<0.001) as independent risk factors for FCSP. CONCLUSIONS: FCSP was performed on 105 polyps (8%) in this study. FCSP may be associated with the occurrence of CSDP and IPR. Further studies are necessary to confirm our results.

Feasibility and Safety of Endoscopic Control for Patients with Serrated Polyposis Syndrome.

INTRODUCTION: Despite advances in endoscopic treatment, patients with serrated polyposis syndrome (SPS) occasionally require surgery due to numerous or unresectable polyps, recurrence, and treatment-related adverse events. METHODS: We retrospectively evaluated 43 patients with SPS undergoing diagnosis and treatment at Omori Red Cross Hospital from 2011 to 2022. Resection of all polyps ≥3 mm in size was planned during the clearing phase; endoscopic control was defined as complete, endoscopic polyp removal. During the surveillance phase, patients underwent annual colonoscopy and resection of newly detected polyps ≥3 mm in size. RESULTS: Thirty-eight patients (88%) achieved endoscopic control, two (5%) required surgery after endoscopic treatment because of colorectal cancer (CRC), and three (7%) have not yet achieved endoscopic control and are planning treatment. Endoscopic control was achieved with a median of four colonoscopies at 8 months. Ten polyps (median value) were resected per patient during the clearing phase. Three polyps ≥50 mm in size, six located in the appendiceal orifice, and seven with severe fibrosis could be resected by endoscopic submucosal dissection (ESD). All patients underwent treatment with a combination of cold snare polypectomy (CSP), endoscopic mucosal resection/hot polypectomy, and/or ESD. No case required surgery due to difficulty with endoscopic treatment. Delayed bleeding was observed in 2 cases (0.3%). Twenty-one patients underwent colonoscopies during the surveillance phase. Fifty-three polyps were resected using CSP; no CRC, sessile serrated lesions with dysplasia, or advanced adenoma were detected. CONCLUSION: SPS can be effectively, efficiently, and safely controlled with appropriate endoscopic management.

Efficacy and safety of cap-assisted endoscopic mucosal resection for superficial duodenal epithelial neoplasia ≤ 10 mm.

Background and study aims Endoscopic treatment strategies for small superficial duodenal epithelial neoplasia (SDET) have not been established, and the R0 resection rates of all previously reported endoscopic techniques are somewhat low. Furthermore, no reports of cap-assisted endoscopic mucosal resection (EMRC), which is reportedly associated with a relatively high R0 resection rate, have been evaluated in sufficient numbers of patients. Therefore, we assessed the efficacy and safety of EMRC for SDETs ≤ 10 mm in a retrospective cohort study. Patients and methods We examined a prospectively maintained database and identified 248 consecutive patients (248 lesions) who had undergone endoscopic resection for SDETs ≤ 10 mm between January 2017 and June 2022. Our treatment strategy was consistent, with EMRC indicated for all SDETs ≤ 10 mm without non-lifting signs. The primary endpoint was the R0 resection rate. Results Overall, 20 lesions had non-lifting signs and were selected for endoscopic submucosal dissection, while the remaining 228 lesions were treated with EMRC. As a result of EMRC, the median tumor size was 5 mm, and the mean procedure time was 5 minutes. Most of the lesions (89.2%) were located in the descending part. The R0 resection rate was 97.4% (222/228 cases), and the en bloc resection rate was 99.6%. Only seven patients(3.1%) experienced adverse events (6 patients, delayed bleeding; 1 patient, acute pancreatitis), which were successfully managed without surgical intervention. Furthermore, no recurrences were observed. Conclusions We have demonstrated that EMRC is an effective and safe treatment for SDETs ≤ 10 mm that do not have non-lifting signs.

Effectiveness of switching endoscopists for repeat surveillance colonoscopy: a retrospective study.

BACKGROUND: Surveillance colonoscopy decreases colorectal cancer mortality; however, lesions are occasionally missed. Although an appropriate surveillance interval is indicated, variations may occur in the methods used, such as scope manipulation or observation. Therefore, individual endoscopists may miss certain areas. This study aimed to verify the effectiveness of performing repeat colonoscopies with a different endoscopist from the initial procedure. METHODS: We retrospectively reviewed a database of 8093 consecutive colonoscopies performed in the Omori Red Cross Hospital from January 1st 2018 to June 30th 2021. Data from repeat total colonoscopies performed within three months were collected to assess missed lesions. The patients were divided into two groups according to whether the two examinations were performed by different endoscopists (group D) or the same endoscopist (group S). The primary outcome in both groups was the missed lesion detection rate (MLDR). RESULTS: Overall, 205 eligible patients were analyzed. In total, 102 and 103 patients were enrolled in groups D and S, respectively. The MLDR was significantly higher in group D (61.8% vs. 31.1%, P < 0.0001). Multivariate logistic regression analysis for the detection of missed lesions identified performance by the different endoscopists (odds ratio, 3.38; 95% CI, 1.81-6.30), and sufficient withdrawal time (> 6 min) (odds ratio, 3.10; 95% CI, 1.12-8.61) as significant variables. CONCLUSIONS: Overall, our study showed a significant improvement in the detection of missed lesions when performed by different endoscopists. When performing repeat colonoscopy, it is desirable that a different endoscopist perform the second colonoscopy. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of the Omori Red Cross Hospital on November 28, 2022 (approval number:22-43).

Molecular and morphological evidence reveals hidden new taxa in Ochlodesochraceus (Bremer, 1861) (Lepidoptera, Hesperiidae, Hesperiinae) from China.

Two new species of Ochlodes Scudder, 1872, Ochlodespseudochraceus Zhu, Fan & Wang, sp. nov. and Ochlodescryptochraceus Zhu, Fan & Chiba, sp. nov., are found in China and described, and Ochlodesrikuchina (Butler, 1878) stat. rev. is restored. A lectotype is designated for Pamphilaochracea Bremer, 1861, and a neotype is designated for Pamphilarikuchina Butler, 1878. Overall, the two new species are similar to Ochlodesochraceus (Bremer, 1861). They, however, can be distinguished from the latter and other species in the genus: O.pseudochraceus has long radial spots in spaces R3-5, and the lateral process of the phallus gradually widens at the distal half in male genitalia; O.cryptochraceus has the lateral process of the phallus enlarged only at the distal tip. Based on the phylogenetic analyses of the mitochondrial COI gene, members of currently defined O.ochraceus are grouped into four clades. The genetic distances between O.pseudochraceus and O.ochraceus, O.cryptochraceus and O.ochraceus, O.rikuchina and O.ochraceus, and O.pseudochraceus and O.cryptochraceus are 3.2%, 2.1%, 1.9%, and 2.7%, respectively. Based on the molecular and morphological evidence, O.pseudochraceus, O.cryptochraceus, and O.rikuchina are treated to be distinct species. The adult habitus and male and female genitalia of the new species are illustrated as well as those of O.ochraceus and O.rikuchina.

Molecular phylogeny, historical biogeography, and classification of Pseudocoladenia butterflies (Lepidoptera: Hesperiidae).

The range of the butterfly genus Pseudocoladenia includes several biodiversity hotspots, such as the Himalayas, mountains of southwestern China, and Sundaland. However, the taxonomic status of some of its species/subspecies remain controversial, and no previous phylogenetic or biogeographic analyses have been conducted. Herein, we determined the systematic relationships and biogeographic history of this genus by reconstructing its phylogeny based on six genes and 69 specimens as representatives of all known species/subspecies. Two species delimitation methods (Bayes Poisson Tree Processes and Bayesian Phylogenetics and Phylogeography) were also employed to assess the status of each taxon. Based on these results and morphological evidence, we identified 12 species and three subspecies in the genus and subsequently classified these into three species groups: P. fatih, P. dea, and P. dan. Five taxa, P. sadakoe (Sonan and Mitono, 1936) stat. nov., P. celebica (Fruhstorfer, 1909) stat. nov., P. fulvescens (Elwes and Edwarda, 1897) stat. nov., P. eacus (Latreille, 1823) stat. nov., and P. fabia (Evans, 1949) stat. nov. were all recognized as independent species. Additionally, two taxa, P. eacus sumatrana (Fruhstorfer, 1909) comb. nov. and P. eacus dhyana (Fruhstorfer, 1909) comb. nov., were placed under P. eacus (Latreille, 1823) stat. nov. as subspecies. Another new species distributed in N. Yunnan, Pseudocoladenia yunnana Fan, Cao & Hou sp. nov., was discovered and described. Divergence time and ancestral range estimation indicated that the most recent common ancestor of Pseudocoladenia was distributed in the Himalayas-Hengduan Mountain region and Indochina and diverged approximately 14.00 Ma. Continuous and episodic dispersal, vicariance, and extinction were used to determine the current geographic distribution of the genus. The P. fatih group had a prominently disjunct distribution between the Himalaya-Hengduan Mountain and Taiwan. Meanwhile, the P. dan group was first derived in Indochina and subsequently dispersed into the southeastern Asian archipelagoes. This study provides a reference for the evolutionary route of transoceanic distributed species in Asia and elaborates on the causes of biodiversity.

Mitogenomic phylogenetic analyses provide novel insights into the taxonomic problems of several hesperiid taxa (Lepidoptera: Hesperiidae).

Here, we present new molecular and morphological evidence that contributes towards clarifying the phylogenetic relations within the family Hesperiidae, and overcomes taxonomic problems regarding this family. First, nine new complete mitogenomes, comprising seven newly sequenced species and two samples of previously sequenced species collected from different localities, were obtained and assembled to analyze characteristics. The length of the mitogenomes ranges from 15,284 to 15,853 bp and encodes 13 protein-coding genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a control region. Two model-based methods (maximum likelihood and Bayesian inference) were used to infer the phylogenetic relationships. Based on the mitogenomic phylogenetic analyses and morphological evidence, we claim that the lineage that comprises two Asian genera, Apostictopterus Leech and Barca de Nicéville, should be a tribe Barcini stat. nov. of the subfamily Trapezitinae, Pseudocoladenia dea (Leech, 1894), P. festa (Evans, 1949), and Abraximorpha esta Evans, 1949 are considered distinct species. Finally, we suggest that Lotongus saralus chinensis Evans, 1932 should belong to the genus Acerbas de Nicéville, 1895, namely Acerbas saralus chinensis (Evans, 1932) comb. nov..

Safety and efficacy of a new cold snare technique with clipping for colorectal angioectasia.

Colorectal angioectasia is a major cause of lower gastrointestinal bleeding. Use of antithrombotic agents is expected to increase with aging of the population, and bleeding from angioectasia is an important issue. Although the effectiveness of endoscopic mucosal resection for colorectal angioectasia has been reported, there are no reports of cold snare technique for angioectasia (CSA). From February 2018 to February 2022, the safety of CSA was evaluated at Omori Red Cross Hospital. We investigated the incidence of bleeding (delayed post-polypectomy bleeding (DPPB) and immediate bleeding) after CSA and the incidence of rebleeding requiring repeated endoscopic treatment. During the study period, 106 angioectasias were identified during colonoscopy. We only targeted patients with bloody stools and/or anemia requiring treatment for bleeding from angioectasia. Finally, we included 11 angioectasias in this study. Rates of DPPB and rebleeding after CSA were 0 %. The rate of immediate bleeding during CSA was 27.3 % (3/11). Dilated capillaries could be observed pathologically in nine of 11 lesions (81.8 %). CSA was safe and can be a new treatment option in the future. To confirm our results and verify the long-term safety and efficacy of CSA, further studies are desirable.

Endoscopic submucosal dissection using an ultrathin endoscope for superficial pharyngeal cancer: a prospective feasibility study (with video).

Background and study aims Endoscopic submucosal dissection (ESD) of pharyngeal cancers with conventional endoscopes often is difficult, not only because of the narrow working space, but also because endoscope maneuverability in the pharynx is poor due to interference from the endotracheal tube and/or hyoid bone. However, we hypothesized that those problems could possibly be resolved by use of an ultrathin endoscope for ESD of superficial pharyngeal cancer. The aim of this prospective interventional study was to investigate the feasibility of ESD for superficial pharyngeal cancer using an ultrathin endoscope. Patients and methods This feasibility study was conducted at NTT Medical Center Tokyo between June 2020 and September 2021, and data from a total of 20 consecutively superficial pharyngeal cancers were analyzed. The primary outcome measure was the R0 resection rate. The ESD completion rate, en bloc resection rate, procedure time, and frequency of intraoperative and postoperative adverse events (AEs) were also evaluated as secondary outcome measures. Results Data from 16 patients with 20 lesions were included in the analysis. All of the lesions were successfully resected by ultrathin endoscope ESD, and the en bloc and R0 resection rates were 100 % and 85.0 % (17/20), respectively; the procedure time was 37.8 ±â€Š28.2 minutes. No intraoperative or postoperative AEs were encountered in any cases. Conclusions ESD using an ultrathin endoscope is feasible for superficial pharyngeal cancers and has potential to be a safe and effective treatment option for these cancers.