Cylindrical abdominoperineal resection for rectal cancer using the Hugo RAS system: The first ever case report for rectal cancer.

In May 2023, the Hugo RAS system obtained pharmaceutical approval for use in gastroenterological surgery in Japan. It is expected to be particularly effective in rectal cancer surgery, which require the manipulation of the deep pelvic cavity and communication with surgeons operating from the intraperitoneal and anal approaches. A 68-year-old woman presented to our hospital with bloody stools and was diagnosed with cStage I (cT2N0M0) rectal cancer and underwent abdominoperineal resection employing the Hugo RAS system. Two arm carts were placed on the left and right lateral sides with an interleg space, and trocars were placed in a straight line between the right superior iliac spine and umbilicus. Herein, we report the first abdominoperineal resection for rectal cancer using the Hugo RAS system.

Tele-proctoring for minimally invasive surgery across Japan: An initial step toward a new approach to improving the disparity of surgical care and supporting surgical education.

Aim: The aim of this study was to verify the clinical feasibility of tele-proctoring using our ultra-low latency communication system with shared internet access. Methods: Connections between two multiple remote locations at various distances were established through the TELEPRO® tele-proctoring system. The server records the latency between the two locations for tele-proctoring using the annotations. Questionnaires were administered to the surgeons, assistants, and medical staff. Respondents rated the quickness and quality of communication in terms of latency and disturbances in the audio, video, and usefulness of the live telestrations with annotation. Results: Seven hospitals tele-proctored with Sapporo Medical University between January 2021 and September 2022. The median latency of annotation between the two locations ranged from 24.5 to 48.5 ms. No major technological problems occurred, such as streaming interruption, loss of video or audio, poor resolution. The video encoding time was 10 ms, and its decoding time was 0.8 ms. The total latency positively correlated with the distance between two locations (R = 0.55, p < 0.01). The quality of communication regarding latency, disturbance, and surgical education with intraoperative annotative instructions showed similar trends, with perfectly fine being the most common response. No significant differences in surgical quality, educational effect, or social impact were observed between the latency ≥30 and <30 ms groups for whether the size of latency affects surgical education. Conclusion: The feasibility of the tele-proctoring system is expected to be a sustainable approach to help education for young surgeons and surgical supports in rural areas, thereby reducing disparities in health care.

CD8-positive T Cell Infiltration With Human Leukocyte Antigen Class 1 Expression Predicts Patients With Stage IV Colorectal Cancer Survival.

BACKGROUND/AIM: The immune microenvironment in cancer correlates with cancer progression and patient prognosis. Cancer immune microenvironment evaluation, based on CD3+ and CD8+ T cell infiltration at the center and invasive margin of the tumor, is defined as the immunoscore. An international multicenter analysis revealed that the immunoscore can accurately predict the prognosis of patients with colorectal cancer (CRC) (stage I, II, and III). However, no markers are currently available to predict the prognosis in patients with stage IV CRC. We thus aimed to analyze the immune microenvironment in patients with stage IV CRC in this study. PATIENTS AND METHODS: We analyzed the immune microenvironment of patients with stage IV CRC using immunohistochemical (IHC) staining. We evaluated the expressions of CD8 and the cases were divided into CD8 high (CD8Hi) and CD8 low (CD8Low) groups according to median CD8 expression. HLA class 1 (HLA1) expression was also evaluated using IHC staining and the cases were divided into HLA1Hi group and HLA1Low group according to 50% of HLA1 expression rate. CD8×HLA1 score was defined by the combination of CD8 and HLA1 expressions. RESULTS: CD8Hi and HLA1Hi cases were associated with better prognosis compared with CD8Low and HLA1Low cases according to a log-rank test, respectively. We defined a novel biomarker by combining CD8+ T-cell infiltration and HLA1 expression, referred to as the CD8×HLA1 score. We found that CD8×HLA1Hi cases predicted patient prognosis better than CD8×HLA1Int and CD8×HLA1Low according to a log-rank test. CONCLUSION: The combination of CD8+ T cell infiltration and HLA1 expression is crucial for cancer immune microenvironment evaluation in CRCs.

A case report of carcinoma of the papilla of Vater associated with a hyperplasia-dysplasia-carcinoma sequence by pancreaticobiliary maljunction.

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. CASE PRESENTATION: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. CONCLUSIONS: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.

Standardization of robot-assisted pelvic lymph node dissection-Development of a common understanding of regional anatomy and surgical technique based on cross-disciplinary discussion among colorectal surgery, urology, and gynecology.

BACKGROUND: Pelvic lymph node dissection is a procedure performed in gastroenterological surgery, urology, and gynecology. However, due to discrepancies in the understanding of pelvic anatomy among these departments, cross-disciplinary discussions have not been easy. Recently, with the rapid spread of robotic surgery, the importance of visual information in understanding pelvic anatomy has become even more significant. In this project, we attempted to clarify a shared understanding of pelvic anatomy through cross-disciplinary discussions. METHOD: From May 2020 to November 2021, a total of 11 discussions were held entirely online with 5 colorectal surgery specialists, 4 urologists, and 4 gynecologists. The discussions focused on evidence from each specialty and surgical videos, aiming to create a universally understandable pelvic anatomical illustration. RESULTS: The common area of dissection recognized across the three departments was identified as the obturator lymph nodes. A dynamic illustration of pelvic anatomy was created. In addition to a bird's-eye view of the pelvis, a pelvic half view was developed to enhance understanding of the deeper pelvic anatomy. The following insights were incorporated into the illustration: (1) the cardinal ligament in gynecology partly overlaps with the vesicohypogastric fascia in colorectal surgery; (2) the obturator lymph nodes continue cephalad into the fossa of Marcille in urology; and (3) the deep uterine vein in gynecology corresponds to the inferior vesical vein in colorectal surgery. CONCLUSION: Based on the dynamic illustration of pelvic anatomy from cross-disciplinary discussions, we anticipate advancements in pelvic lymph node dissection aiming for curative and safe outcomes.

Safety and short-term outcomes of robotic-assisted transabdominal preperitoneal repair for inguinal hernia in pioneering hospitals in Japan: A nationwide retrospective cohort study.

INTRODUCTION: We aimed to evaluate the safety and short-term outcomes of robotic-assisted transabdominal preperitoneal repair for inguinal hernia in 12 pioneering hospitals in Japan. METHODS: Clinical data of patients who underwent robotic-assisted transabdominal preperitoneal repair between September 1, 2016, and December 31, 2021 were collected. Primary outcome measures were intra-operative adverse events and post-operative complications, whereas secondary outcomes were surgical outcomes, including chronic pain, recurrence, and learning curve. RESULTS: In total, 307 patients were included. One case of inferior epigastric arterial injury was reported; no cases of bowel or bladder injury were reported. Thirty-five seromas were observed, including four (1.3%) cases that required aspiration. The median operative time of a unilateral case was 108 minutes (interquartile range: 89.8-125.5), and post-operative pain was rated 1 (interquartile range: 0-2) on the numerical rating scale. In complicated cases, such as recurrent inguinal hernias and robotic-assisted radical prostatectomy-associated hernias, dissection and suture were safely achieved, and no complications were observed, except for non-symptomatic seroma. All patients underwent robotic procedures, and there was no chronic post-operative inguinal pain, although one case of hernia recurrence was reported. Regarding the learning curve, plateau performance was achieved after 7-10 cases in terms of operative time (P < .001). CONCLUSION: Robotic-assisted transabdominal preperitoneal repair can be safely introduced in Japan. Regardless of the involvement of many surgeons, the mastery of robotic techniques was achieved relatively quickly. The advantage of robotic technology such as wristed instruments may expand the application of minimally invasive hernia repair for complicated cases.

Reconsidering resectable oncological conditions in pancreatic tail cancer: A multicenter retrospective study on prognostic factors in pancreatic tail cancer after resection (HOPS Pt-01).

BACKGROUND: Pancreatic tail cancer (Pt-PC) is generally considered resectable when metastasis is absent, but doubts persist in clinical practice due to the variability in local tumor extent. We conducted a multicenter retrospective study to comprehensively identify prognostic factors associated with Pt-PC after resection. METHODS: We enrolled 100 patients that underwent distal pancreatectomy. The optimal combination of factors influencing relapse-free survival (RFS) was determined using the maximum likelihood method (MLM) and corrected Akaike and Bayesian information criteria (AICc and BIC). Prognostic elements were then validated to predict oncological outcomes. RESULTS: Therapeutic interventions included neoadjuvant treatment in 16 patients and concomitant visceral resection (CVR) in 37 patients; 89 patients achieved R0. Median RFS and OS after surgery were 23.1 and 37.1 months, respectively. AICc/BIC were minimized in the model with ASA-PS (≥2), CA19-9 (≥112 U/mL at baseline, non-normalized postoperatively), need for CVR, 6 pathological items (tumor diameter ≥19.5 mm, histology G1, invasion of the anterior pancreatic border, splenic vein invasion, splenic artery invasion, lymph node metastasis), and completed adjuvant treatment (cAT) for RFS. Regarding the predictive value of these 11 factors, area under the curve was 0.842 for 5-year RFS. Multivariate analysis of these 11 factors showed that predictors of RFS include CVR (hazard ratio, 2.13; 95 % confidence interval, 1.08-4.19; p = 0.028) and cAT (0.38, 0.19-0.76; p = 0.006). CONCLUSIONS: The MLM identified certain Pt-PC cases warranting consideration beyond resectable during clinical management. Particular attention should be paid to conditions requiring CVR, even though immortal time bias remains unresolved with adjuvant treatment.

Eribulin is an immune potentiator in breast cancer that upregulates human leukocyte antigen class I expression via the induction of NOD-like receptor family CARD domain-containing 5.

Eribulin inhibits microtubule polymerization and improves the overall survival of patients with recurrent metastatic breast cancer. A subgroup analysis revealed a low neutrophil to lymphocyte ratio (NLR) (<3) to be a prognostic factor of eribulin treatment. We thus hypothesized that eribulin might be related to the immune response for breast cancer cells and we analyzed the effects of eribulin on the immune system. Immunohistochemical staining revealed that human leukocyte antigen (HLA) class I expression was increased in clinical samples after eribulin treatment. In vitro assays revealed that eribulin treatment increased HLA class I expression in breast cancer line cells. RNA-sequencing demonstrated that eribulin treatment increased the expression of the NOD-like family CARD domain-containing 5 (NLRC5), a master regulator of HLA class I expression. Eribulin treatment increased the NY-ESO-1-specific T-cell receptor (TCR) transduced T (TCR-T) cell response for New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) overexpressed breast cancer cells. The eribulin and TCR-T combined therapy model revealed that eribulin and immunotherapy using TCR-T cells has a synergistic effect. In summary, eribulin increases the expression of HLA class 1 via HLA class 1 transactivatior NLRC5 and eribulin combination with immunotherapy can be effective for the treatment of breast cancer.

Short-term outcomes of a prospective multicenter phase II trial of total neoadjuvant therapy for locally advanced rectal cancer in Japan (ENSEMBLE-1).

Aim: To evaluate the feasibility and safety of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) in Japan. Methods: This prospective, multicenter, open-label, single-arm phase II trial was conducted at five institutions. The key eligibility criteria were age ≥ 20 years, LARC within 12 cm from the anal verge, and cT3-4N0M0 or TanyN+M0 at the time of diagnosis that enabled curative resection. Preoperative short-course radiation therapy (SCRT) 5 Gy × 5 days (total 25 Gy) + CAPOX (six courses) followed by total mesorectum excision (TME) was the treatment protocol. Non-operative management (NOM) was allowed if clinical complete response (cCR) was obtained in the preoperative evaluation. The primary endpoint was the pathological complete response (pCR) rate. Results: Thirty patients (male, n = 26; female, n = 4; median age, 62.5 [44-74] years; cT [T2, n = 1; T3, n = 25; T4, n = 4]; cN [N0, n = 13; N1, n = 13; N2, n = 4]) were enrolled. The final analysis included 30 patients in total. The completion rates were 100% for SCRT and 83% for CAPOX. TME and NOM were performed in 20 and seven patients, respectively. pCR was observed in six patients (30% [95% CI 14.0%-50.8%]). The primary endpoint was met. pCR+cCR was observed in 13 (43.3%) patients. There were no treatment-related deaths. Grade ≥3 (CTCAE ver. 5.0) adverse events (≥20%), including diarrhea (23.3%) and neutropenia (23.3%). The median follow-up period was 15.6 (10.5-22.8) months, with no recurrence or regrowth in NOM. Conclusions: ENSEMBLE-1 demonstrated satisfactory pCR and cCR, and well-tolerated safety of TNT for patients with LARC in Japan.

Robotic-assisted colectomy for right-sided colon cancer: Short-term surgical outcomes of a multi-institutional prospective cohort study in Japan.

Background: In Japan, there are no substantial reports on robotic-assisted colectomy because few institutions performed the procedure, as it was not covered by national insurance until March 2022. Aim: This study aimed to evaluate the safety and feasibility of robotic-assisted colectomy for patients with curatively resectable colon cancer in Japan. Methods: This multi-institutional, prospective, single-arm, observational study enrolled patients diagnosed with curatively resectable clinical stage I-IIIC colon adenocarcinoma with D2 or D3 lymph node dissection and treated with robotic-assisted colectomy. The primary endpoint was the conversion rate to laparotomy. The non-inferiority of outcomes for robotic-assisted colectomy versus laparoscopic colectomy, which was determined from historical data, was verified. Results: One hundred patients were registered between July 2019 and March 2022 and underwent robotic-assisted colectomy performed by seven expert surgeons at six institutions. Thirteen patients were excluded because their surgeons had insufficient experience performing robotic-assisted colectomy; therefore, 87 patients were eligible for the primary endpoint analysis. There was no conversion in these 87 patients, and robotic-assisted colectomy was non-inferior to laparoscopic colectomy in terms of conversion rate (90% confidence interval 0-3.38, p = 0.0006). No intraoperative adverse events occurred, and no mortality was observed in a total of 100 patients. The rate of patients with Clavien-Dindo complications grade III or higher was 4%. Conclusion: This study showed the non-inferiority of the conversion rates between robotic-assisted colectomy and laparoscopic colectomy. Favorable perioperative outcomes also suggest the safety and feasibility of robotic-assisted colectomy.

World-first report of low anterior resection for rectal cancer with the hinotori™ Surgical Robot System: a case report.

BACKGROUND: The hinotori™ Surgical Robot System was approved for use in colorectal cancer surgery in Japan in 2022. This robot has advantages, such as an operation arm with eight axes, an adjustable arm base, and a flexible three-dimensional viewer, and is expected to be utilized in rectal cancer surgery. Herein, we report the world's first surgery for rectal cancer using the hinotori™ Surgical Robot System. CASE PRESENTATION: A 71-year-old woman presented to our hospital with bloody stools. A colonoscopy revealed type 2 advanced cancer in the rectum, and a histological examination exposed a well-differentiated adenocarcinoma. Abdominal enhanced computed tomography divulged rectal wall thickening without significant swelling of the lymph nodes or distant metastasis. Pelvic magnetic resonance imaging showed tumor invasion beyond the intrinsic rectal muscle layer. The patient was diagnosed with cStage IIa (cT3N0M0) rectal cancer and underwent low anterior resection using the hinotori™ Surgical Robot System. Based on an adequate simulation, surgery was safely performed with appropriate port placement and arm base-angle adjustment. The operating time was 262 min, with a cockpit time of 134 min. Subsequently, the patient was discharged 10 days postoperatively without complications. The pathological diagnosis was pStage IIA (cT3N0M0) and the circumferential resection margin was 6 mm. CONCLUSIONS: We report the first case of low anterior resection for rectal cancer using the hinotori™ Surgical Robot System, in which a safe and appropriate oncological surgery was performed.

Right hemicolectomy for ascending colon cancer using the hinotori surgical robot system: The first ever case report for colon cancer.

The hinotori Surgical Robot System obtained pharmaceutical approval for use in colorectal cancer surgery in October 2022 in Japan, and its advantages, including its operating arm with eight axes, adjustable arm base, and flexible 3D viewer, are expected to be utilized in colon cancer surgery. A 68-year-old woman presented to our hospital with abdominal pain and was diagnosed with cStageIIa (cT3N0M0) ascending colon cancer and underwent right hemicolectomy using the hinotori Surgical Robot System with the appropriate port placement on the arc around the hepatic flexure, which was available for both ileocecal manipulation and lymph node dissection, and adjustment of the angle of the arm base to further reduce interference. Herein we report the world's first surgery for colorectal cancer using the hinotori Surgical Robot System.

Blood Perfusion Assessment by Indocyanine Green Fluorescence Imaging for Minimally Invasive Rectal Cancer Surgery (EssentiAL trial): A Randomized Clinical Trial.

OBJECTIVE: The aim of the present randomized controlled trial was to evaluate the superiority of indocyanine green fluorescence imaging (ICG-FI) in reducing the rate of anastomotic leakage in minimally invasive rectal cancer surgery. BACKGROUND: The role of ICG-FI in anastomotic leakage in minimally invasive rectal cancer surgery is controversial according to the published literature. METHODS: This randomized, open-label, phase 3, trial was performed at 41 hospitals in Japan. Patients with clinically stage 0-III rectal carcinoma less than 12 cm from the anal verge, scheduled for minimally invasive sphincter-preserving surgery were preoperatively randomly assigned to receive a blood flow evaluation by ICG-FI (ICG+ group) or no blood flow evaluation by ICG-FI (ICG- group). The primary endpoint was the anastomotic leakage rate (grade A+B+C, expected reduction rate of 6%) analyzed in the modified intention-to-treat population. RESULTS: Between December 2018 and February 2021, a total of 850 patients were enrolled and randomized. After the exclusion of 11 patients, 839 were subject to the modified intention-to-treat population (422 in the ICG+ group and 417 in the ICG- group). The rate of anastomotic leakage (grade A+B+C) was significantly lower in the ICG+ group (7.6%) than in the ICG- group (11.8%) (relative risk, 0.645; 95% confidence interval 0.422-0.987; P =0.041). The rate of anastomotic leakage (grade B+C) was 4.7% in the ICG+ group and 8.2% in the ICG- group ( P =0.044), and the respective reoperation rates were 0.5% and 2.4% ( P =0.021). CONCLUSIONS: Although the actual reduction rate of anastomotic leakage in the ICG+ group was lower than the expected reduction rate and ICG-FI was not superior to white light, ICG-FI significantly reduced the anastomotic leakage rate by 4.2%.

Positional advantages of supine MRI for diagnosis prior to breast­conserving surgery.

The present study aimed to evaluate the rate of positive surgical margins for magnetic resonance imaging (MRI) performed in the supine position prior to breast-conserving surgery (BCS). The rate of positive surgical margins and the clinicopathological factors were examined in consecutive patients with BCS who underwent preoperative MRI performed in the supine position at Sapporo Medical University Hospital (Sapporo, Japan) and related hospitals and clinics between January 2012 and December 2013. Of 1,175 eligible patients, 1,150 were included after excluding 25 patients with either bilateral breast cancer or stage IV disease. Positive margin was defined as no cancer seen on the resected margin. The primary endpoint was the rate of positive surgical margins when preoperative MRI was performed in the supine position and the secondary endpoint was identification of the factors that predict positive margins. Of the 1,150 female patients (median age, 55 years; range, 29-97 years) who underwent BCS for breast cancer following MRI performed in the supine position, 215 (18.8%) had positive margins, which is similar to the rate with MRI in the prone position, and 930 (81.2%) had negative margins. The rate of positive surgical margins in patients of the human epidermal growth factor receptor 2 (HER2) type was significantly higher than that in the non-HER2 type group (6.5 and 2.9%; χ2 P=0.0103). There was no increase in the rate of positive margins in breast cancers with a diameter of >T2. The rate of positive surgical margins following MRI performed in the supine position was 18.8%. Supine MRI appears to be suitable for informing on the extent of resection of breast cancer.

Essential updates 2020/2021: Advancing precision medicine for comprehensive rectal cancer treatment.

In the paradigm shift related to rectal cancer treatment, we have to understand a variety of new emerging topics to provide appropriate treatment for individual patients as precision medicine. However, information on surgery, genomic medicine, and pharmacotherapy is highly specialized and subdivided, creating a barrier to achieving thorough knowledge. In this review, we summarize the perspective for rectal cancer treatment and management from the current standard-of-care to the latest findings to help optimize treatment strategy.

Gastric intramural metastasis caused by needle tract seeding after preoperative fine needle aspiration for pancreatic body cancer subsequently resected by total pancreatectomy: a case report and literature review.

BACKGROUND: Recently, there has been an increase in the number of reports of needle tract seeding (NTS) of tumor cells after a biopsy as one of the adverse events related to endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). In most of the previously reported cases of NTS in pancreatic cancer, distal pancreatectomy was performed as the initial surgery, following which metachronous metastasis was discovered in the gastric wall, whose localization matched the puncture route of the EUS-FNA. We report a case of early metastasis from pancreatic cancer in the gastric wall, which was postulated to be caused by NTS. Our patient underwent a total pancreatectomy (TP), and the NTS was resected synchronously. CASE PRESENTATION: A 70-year-old woman with a diagnosis of pancreatic head-body-tail cancer presented to our department for surgery. Transgastric EUS-FNA and biopsy established the histological diagnosis in her case. We administered neoadjuvant chemotherapy (NAC) to the patient and performed a TP. Histopathological and immunohistochemical examination subsequently confirmed the diagnosis of pT3N1aM1 pancreatic adenocarcinoma and its gastric metastasis, which was caused by NTS. It is postulated that the tumor cells of NTS had progressed to develop the metastatic lesion in the gastric wall during the NAC period. This was also resected during the initial surgery. The patient developed an early postoperative recurrence in the peritoneum 8 months after the surgery. CONCLUSION: In pancreatic head cancer cases, the puncture route is often included in the resection area of radical surgery, and NTS is seldom considered as a potential clinical problem. However, NTS can progress rapidly and may be associated with early recurrence of malignancy. Therefore, when transgastrointestinal puncture is performed for the diagnosis of pancreatic cancer, the treatment strategy should be established considering the potential development of NTS.

Synergistic antitumor effect of histone deacetylase class IIa inhibitor with lenvatinib in hepatocellular carcinoma.

BACKGROUND: Histone deacetylase (HDAC) class I and IIa are highly expressed in hepatocellular carcinoma (HCC) and associated with decreased survival. However, clinically used pan and class I inhibitors have serious adverse events. In this study, we assessed the antitumor effects and tolerability of class IIa HDAC inhibitor (HDACI) with lenvatinib, which is a standard therapy for HCC. METHODS AND RESULT: Combination therapy with class IIa HDACI and lenvatinib exerted synergistic antitumor effect in human HCC cell lines. In mouse models, this therapy showed significant antitumor effects, and few adverse events occurred. In immunoblotting, the expression of fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) was high in cell lines that showed a high antitumor effect. In addition, class IIa HDACI administration decreased the expression of FGFR4. In the small interfering RNA (siRNA) analysis, knockdown of HDAC9, which is an isoform of HDAC class IIa, reduced the expression of FGFR4 and induced apoptosis. Immunohistochemistry of human clinical specimens showed a positivity rate of 32% for FGFR4 and 84% for HDAC9 in HCC, and all FGFR4-positive patients were HDAC9 positive. CONCLUSION: Class IIa HDACI and lenvatinib combination therapy induces apoptosis by downregulating FGFR4 and blocking the FGFR signaling in FGFR4-positive HCC cell lines and has demonstrated synergistic antitumor effects and safety. This combination therapy overcomes the problems of conventional therapies and will be beneficial for FGFR4-positive HCC patients.

A phase II study of neoadjuvant capecitabine, oxaliplatin, and irinotecan (XELOXIRI) in patients with locally advanced rectal cancer.

Purpose: Addition of perioperative multi-agent chemotherapy to the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. We conducted a phase II study to evaluate the safety and efficacy of capecitabine combined with oxaliplatin and irinotecan (XELOXIRI) as triplet neoadjuvant chemotherapy in patients with LARC. Methods: Patients received neoadjuvant irinotecan and oxaliplatin and capecitabine and then underwent total mesorectal excision. The primary study endpoint was the pathological complete response (pCR) rate. Results: Between June 2013 and December 2016, 55 patients were enrolled in the study. Forty-two (77.8%) of 54 completed the study protocol. The pCR rate was 7.7% (95% CI 3.0% to 18.2%). The 3-year local recurrence rate was 3.9%, the 3-year disease-free survival (DFS) rate was 77.3, and the 3-year overall survival rate was 96.0%. Conclusion: XELOXIRI neoadjuvant chemotherapy appears to be feasible and efficacious for patients with LARC. Although neoadjuvant XELOXIRI alone did not yield our expected pCR rate, the local recurrence rate, 3-year DFS, and measures of safety met current standards.

Additional effect of anthracycline in preoperative chemotherapy with a sequential anthracycline­containing regimen preceded by pertuzumab, trastuzumab and docetaxel combination therapy.

The proper use of anthracycline-containing regimens in combination with anti-HER2-targeted therapy in a neoadjuvant setting for patients with HER2-positive breast cancer has not been resolved. Regimens preceded by anthracyclines have become the standard of care, and although the order has no significant impact on HER2-negative breast cancer, it is inconclusive as to whether a taxane-first sequence would have a similar effect on HER2-positive breast cancer. The present study aimed to investigate the benefit of a taxane-first sequence and of adriamycin and cyclophosphamide (AC) in patients with non-clinical complete response (non-cCR) to pertuzumab, trastuzumab and docetaxel (PTD). The present single-center prospective observational study was performed to investigate PTD followed by AC, and aimed to clarify the cCR rate after PTD alone and the pathological clinical response (pCR) rate after subsequent AC in patients without cCR after PTD alone. A total 24 patients were analyzed; of these, 14 achieved pCR (pCR rate, 58.3%). While four of 14 patients (28.6%) in the intention-to-treat population achieved pCR, nine of 14 patients (64.3%) achieved pCR with AC but not cCR after PTD. The median tumor reduction rate after four cycles of PTD was 58.9% (range, 20.8-100%) in all 24 patients, whereas the reduction rate after PTD-AC was 76.9% (range, 31.1-100%). Cardiac serious adverse events occurred in three patients (12.5%). In conclusion, a high pCR rate was observed for the taxane-first sequence. Patients were highly responsive to PTD, but some cases achieved additional antitumor effects after AC, which resulted in pCR without cCR after PTD alone. Since cardiotoxicity remains a significant problem, a higher risk-benefit treatment strategy is required to aim for AC omission. Trial registration number: UMIN000046338, name of registry: UMIN-CTR, date of registration: December 10, 2021.

Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer.

Despite standard-of-care treatment, more than 30% of patients with resectable colorectal cancer (CRC) relapse. Circulating tumor DNA (ctDNA) analysis may enable postsurgical risk stratification and adjuvant chemotherapy (ACT) treatment decision-making. We report results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed presurgical and postsurgical ctDNA in patients with stage II-IV resectable CRC (n = 1,039). In this cohort, with a median follow-up of 16.74 months (range 0.49-24.83 months), postsurgical ctDNA positivity (at 4 weeks after surgery) was associated with higher recurrence risk (hazard ratio (HR) 10.0, P < 0.0001) and was the most significant prognostic factor associated with recurrence risk in patients with stage II or III CRC (HR 10.82, P < 0.001). Furthermore, postsurgical ctDNA positivity identified patients with stage II or III CRC who derived benefit from ACT (HR 6.59, P < 0.0001). The results of our study, a large and comprehensive prospective analysis of ctDNA in resectable CRC, support the use of ctDNA testing to identify patients who are at increased risk of recurrence and are likely to benefit from ACT.