Modulation of allograft immune responses by Porphyromonas gingivalis lipopolysaccharide administration in a rat model of kidney transplantation.

Periodontitis is a chronic inflammatory disease that affects the periodontal tissues. Although it is associated with various systemic diseases, the impact of periodontitis on kidney transplantation (KT) outcomes, particularly allograft rejection, remains unclear. This study investigated the effect of periodontitis on transplant immunity, specifically examining Porphyromonas gingivalis-derived lipopolysaccharide (LPS-PG). In vitro experiments revealed that LPS-PG increased regulatory T cells (Tregs) in Lewis rat spleen cells. In a mixed lymphocyte reaction assay, concentrations of interferon-γ, indicative of alloreactivity, were lower than in controls when LPS-PG was added to the culture and when LPS-PG-administered Lewis rat spleen cells were used as responders. In a rat KT model, LPS-PG administration to recipients promoted mild tubulitis and low serum creatinine and blood urea nitrogen levels 5 days post-KT compared with PBS-administered controls. Furthermore, LPS-PG-administered recipients had an elevated Treg proportion in their peripheral blood and spleen cells, and increased infiltrating Tregs in kidney allografts, compared with controls. The elevated Treg proportion in peripheral blood and spleen cells had a significant negative correlation with serum creatinine, suggesting elevated Tregs modulated allograft rejection. These findings suggest that periodontitis might modulate alloimmune reactivity through LPS-PG and Tregs, offering insights to refine immunosuppressive strategies for KT recipients.

Osteosarcopenia: the coexistence of sarcopenia and osteopenia is predictive of prognosis and postoperative complications after curative resection for colorectal cancer.

PURPOSE: To establish if osteosarcopenia is related to postoperative complications, prognosis, and recurrence of colorectal cancer (CRC) after curative surgery. METHODS: The clinical data of 594 patients who underwent curative resection for CRC between January, 2013 and December, 2018 were analyzed retrospectively to examine the relationship between clinicopathological data and osteosarcopenia. The following definitions were used: sarcopenia, low skeletal muscle mass index; osteopenia, low bone mineral density on computed tomography at the level of the 11th thoracic vertebra; and osteosarcopenia, sarcopenia with osteopenia. RESULTS: Osteosarcopenia was identified in 98 patients (16.5%) and found to be a significant risk factor for postoperative complications (odds ratio 2.53; p = 0.011). The 5-year overall survival (OS) and recurrence-free survival (RFS) rates of the patients with osteosarcopenia were significantly lower than those of the patients without osteosarcopenia (OS: 72.5% and 93.9%, respectively, p < 0.0001; RFS: 70.8% and 92.4%, respectively, p < 0.0001). Multivariate analysis identified osteosarcopenia as an independent prognostic factor associated with OS (hazard ratio 3.31; p < 0.0001) and RFS (hazard ratio 3.67; p < 0.0001). CONCLUSION: Osteosarcopenia may serve as a predictor of postoperative complications and prognosis after curative surgery for CRC.

Explaining the impact of mutations on quantification of SARS-CoV-2 in wastewater.

Wastewater surveillance is an effective tool for monitoring community spread of COVID-19 and other diseases. Quantitative PCR (qPCR) analysis for wastewater surveillance is more susceptible to mutations in target genome regions than binary PCR analysis for clinical surveillance. The SARS-CoV-2 concentrations in wastewater estimated by N1 and N2 qPCR assays started to diverge around July 2022 in data from different sampling sites, analytical methods, and analytical laboratories in Japan. On the basis of clinical genomic surveillance data and experimental data, we demonstrate that the divergence is due to two mutations in the N1 probe region, which can cause underestimation of viral concentrations. We further show that this inaccuracy can be alleviated if the qPCR data are analyzed with the second derivative method or the Cy0 method instead of the crossing point method.

Conversion surgery for initially unresectable locally advanced biliary tract cancer: A multicenter collaborative study conducted in Japan and Korea.

BACKGROUND: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer. METHODS: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Korean Association of Hepato-Biliary-Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes. RESULTS: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien-Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3-year survival rate was 53.9%, and the 5-year survival rate was 39.1%. CONCLUSIONS: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required.

Blockade of histamine receptor H1 augments immune checkpoint therapy by enhancing MHC-I expression in pancreatic cancer cells.

BACKGROUND: Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective at managing certain cancers, its efficacy in treating pancreatic ductal adenocarcinoma (PDAC) has been limited. Therefore, enhancing the effect of ICB could improve the prognosis of PDAC. In this study, we focused on the histamine receptor H1 (HRH1) and investigated its impact on ICB therapy for PDAC. METHODS: We assessed HRH1 expression in pancreatic cancer cell (PCC) specimens from PDAC patients through public data analysis and immunohistochemical (IHC) staining. The impact of HRH1 in PCCs was evaluated using HRH1 antagonists and small hairpin RNA (shRNA). Techniques including Western blot, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-PCR), and microarray analyses were performed to identify the relationships between HRH1 and major histocompatibility complex class I (MHC-I) expression in cancer cells. We combined HRH1 antagonism or knockdown with anti-programmed death receptor 1 (αPD-1) therapy in orthotopic models, employing IHC, immunofluorescence, and hematoxylin and eosin staining for assessment. RESULTS: HRH1 expression in cancer cells was negatively correlated with HLA-ABC expression, CD8+ T cells, and cytotoxic CD8+ T cells. Our findings indicate that HRH1 blockade upregulates MHC-I expression in PCCs via cholesterol biosynthesis signaling. In the orthotopic model, the combined inhibition of HRH1 and αPD-1 blockade enhanced cytotoxic CD8+ T cell penetration and efficacy, overcoming resistance to ICB therapy. CONCLUSIONS: HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy.

Cumulative incidence and risk factors for recurrence of upper tract urothelial carcinoma in patients undergoing radical cystectomy.

Objectives: This study aimed to evaluate the cumulative incidence of upper tract urothelial carcinoma (UTUC) recurrence and identify its risk factors in patients who underwent radical cystectomy (RC). Patients and methods: We performed RC on 385 patients between September 2002 and February 2020. After excluding 20 patients-13 with simultaneous nephroureterectomy, 6 with distal ureteral stump positivity and 1 with urachal cancer-365 patients were included in the analysis. To predict UTUC recurrence, we examined the cancer extension pattern in cystectomy specimens and categorized them into three types: cancer located only in the bladder (bladder-only type), cancer extending to the urethra or distal ureter (one-extension type) and cancer extending to both the urethra and distal ureter (both-extension type). We determined hazard ratios for UTUC recurrence for each covariate, including this cancer extension pattern. Results: Of the 365 patients, 60% had the bladder-only type, 30% had the one-extension type and 10% had the both-extension type. During a median follow-up period of 72 months for survivors, UTUC recurred in 25 of the 365 patients, with cumulative incidences of 3.7% at 5 years and 8.3% at 10 years. The median interval from cystectomy to recurrence was 65 months (interquartile range: 36-92 months). In the multivariate analysis, the extension pattern was a significant predictor of UTUC recurrence. The hazard ratios for UTUC recurrence were 3.12 (95% confidence interval [CI] = 1.15-8.43, p = 0.025) for the one-extension type and 5.96 (95% CI = 1.98-17.91, p = 0.001) for the both-extension type compared with the bladder-only type. Conclusions: The cancer extension pattern in cystectomy specimens is predictive of UTUC recurrence. A more extensive cancer extension in cystectomy specimens elevates the risk of subsequent UTUC recurrence. Intensive long-term monitoring is essential, particularly for patients with the both-extension type.

Pathological complete response with FOLFIRINOX therapy for recurrence of pancreatic acinar cell carcinoma.

Pancreatic acinar cell carcinoma (PACC) is a very rare subtype of pancreatic cancer. Due to small number of patients, no standard chemotherapy protocol has been established. We experienced an extremely rare case of PACC with liver metastasis that showed a pathological complete response after modified FOLFIRINOX (mFFX) therapy. A 42-year-old man who underwent distal pancreatectomy for an 80 mm tumor at the pancreatic tail 3 years ago was referred to our hospital in September 2017 for the treatment of a recurrent liver tumor. Percutaneous biopsy revealed an acinar-neuroendocrine carcinoma, similar to the surgical specimen. He received eight cycles of irinotecan plus cisplatin chemotherapy. However, the tumor increased in size, and treatment was switched to mFFX therapy. The tumor in the liver shrank remarkably after nine cycles of mFFX therapy. Conversion surgery was selected, and the patient underwent hepatic left and caudate lobectomy 8 months after administration of mFFX. The resected specimen showed no viable tumor cells, indicating a pathological complete response. The histological diagnosis was reconsidered, and PACC was finally diagnosed via an additional immunohistological review. The patient has remained well with no recurrence for 6 years after surgery. This study is the first to report a case of pathological complete response with mFFX therapy for the recurrence of PACC.

Patient-derived organoids of pancreatic ductal adenocarcinoma for subtype determination and clinical outcome prediction.

BACKGROUND: Recently, two molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) have been proposed: the "Classical" and "Basal-like" subtypes, with the former showing better clinical outcomes than the latter. However, the "molecular" classification has not been applied in real-world clinical practice. This study aimed to establish patient-derived organoids (PDOs) for PDAC and evaluate their application in subtype classification and clinical outcome prediction. METHODS: We utilized tumor samples acquired through endoscopic ultrasound-guided fine-needle biopsy and established a PDO library for subsequent use in morphological assessments, RNA-seq analyses, and in vitro drug response assays. We also conducted a prospective clinical study to evaluate whether analysis using PDOs can predict treatment response and prognosis. RESULTS: PDOs of PDAC were established at a high efficiency (> 70%) with at least 100,000 live cells. Morphologically, PDOs were classified as gland-like structures (GL type) and densely proliferating inside (DP type) less than 2 weeks after tissue sampling. RNA-seq analysis revealed that the "morphological" subtype (GL vs. DP) corresponded to the "molecular" subtype ("Classical" vs. "Basal-like"). The "morphological" classification predicted the clinical treatment response and prognosis; the median overall survival of patients with GL type was significantly longer than that with DP type (P < 0.005). The GL type showed a better response to gemcitabine than the DP type in vitro, whereas the drug response of the DP type was improved by the combination of ERK inhibitor and chloroquine. CONCLUSIONS: PDAC PDOs help in subtype determination and clinical outcome prediction, thereby facilitating the bench-to-bedside precision medicine for PDAC.

Efficacy and Safety Evaluation of Energy Devices in Bench Surgery for Pancreas Transplantation.

INTRODUCTION: Bench surgery for the preparation of deceased donor pancreatic grafts is labor-intensive and time-consuming. We hypothesized that energy devices could be used during bench surgery to decrease the bench surgery time. However, because bench surgery has two unique characteristics, wet conditions and no blood flow in the vessels, it is necessary to verify the safety and efficacy under such conditions. METHODS: In an animal tissue model, we validated both ultrasonic and bipolar energy devices: Harmonic Shears and the LigaSure (LS) vessel-sealing device by evaluating heat spread and pressure resistance under bench surgery conditions. In a clinical evaluation of the LS, we compared the outcomes of 22 patients in two different bench surgery groups: with and without the use of the LS. RESULTS: Clinically, the bench surgery time was significantly shorter in the LS group than that in the conventional group (P < 0.001). In the animal tissue experiments, the highest temperature in bench surgery conditions was 60.4°C after 1 s at a 5-mm distance in the LS group. Pressure resistance of ≥ 750 mmHg was achieved in almost all trials in both veins and arteries, with no difference between Harmonic Shears and LS. There was more surgical smoke visually in bench conditions versus in dry conditions and under half bite versus full bite conditions. CONCLUSIONS: The encouraging results of our exploratory clinical and animal studies of the energy devices suggest that they may be useful in the setting of bench surgery.

Epidermoid cyst of the testis: A report of three cases.

Testicular epidermoid cysts have characteristic findings. Testicular tumor markers are negative in patients with epidermoid cysts. Clear margins and sole and small testicular tumors (20 mm or less) suggest the possibility of epidermoid cyst. Testicular-sparing surgery with intraoperative frozen section examination should be performed when suspecting epidermoid cysts. Testicular epidermoid cysts are rare tumors that account for 1% of all testicular tumors and are often clinically misdiagnosed as malignant lesions. We report three cases of epidermoid cysts. The chief manifestations were scrotal induration in two patients and pruritus scrotum in one. The median age of the patients was 23 years (18-30). All tumors were determined to be sole lesions (<20 mm in diameter). Testing for tumor markers in all patients revealed negative results. We could not rule out malignancy; hence, we performed high inguinal orchiectomy in all cases. Histologically, the inner walls of the cysts were lined with stratified squamous epithelium; their contents were keratinized. All patients were diagnosed with epidermoid cysts.

Effectiveness of adjuvant chemotherapy for patients who undergo radical cystectomy without neoadjuvant chemotherapy: A retrospective cohort study of 115 advanced bladder cancer patients with pathological lymph node classification.

OBJECTIVES: We investigated the clinical outcomes of radical cystectomy without cisplatin-based neoadjuvant chemotherapy (NAC) and identified factors affecting the effectiveness of cisplatin-based adjuvant chemotherapy (AC). METHODS: Between September 2002 and February 2020, 288 bladder cancer patients who did not receive NAC underwent radical cystectomy. We retrospectively analyzed the recurrence rates, primary recurrence sites, recurrence-free survival (RFS), and overall survival (OS) of 115 advanced bladder cancer patients (pT3-4 or pN1-3) who were divided into the AC and observation groups. Subgroup analysis was performed, focusing on pathological stage. RESULTS: In total, 51 patients received AC, and 64 patients were observed. The median follow-up duration was 95 months. The recurrence rate was lower in the AC group than in the observation group (35.3% vs. 54.7%, p = 0.041). The rate of recurrences in the lymph node area (dissection site and proximal lymph nodes) was lower in the AC group (9.8% vs. 26.6%; p = 0.031). In the subgroup analysis of patients with pN1, the probability of RFS and OS was higher in the AC group than in the observation group. The hazard ratio for RFS and OS was 0.243 (95% confidence interval [CI]: 0.077-0.768) and 0.259 (95% CI: 0.082-0.816), respectively. The 5-year RFS and OS were significantly higher in the AC group (80.0% and 79.4%) than in the observation group (35.7% and 42.9%; p < 0.008 and p < 0.012, respectively). CONCLUSIONS: AC improved RFS and OS in patients with pN1 disease who did not receive NAC and should be considered for this population.

Skeletal muscle mass during chemotherapy for haematological malignancies: a retrospective study.

OBJECTIVE: This study investigated whether baseline or alteration in muscle mass affects complications during chemotherapy or overall survival (OS) in haematological malignancies. METHODS: Skeletal Muscle Index (SMI) was evaluated by bioimpedance analysis before and after chemotherapy in patients with haematological malignancies, and the association between muscle mass and clinical data was retrospectively analysed. RESULTS: Exactly 104 patients were enrolled, with a mean age of 62.2 years. SMI was 7.85 and 6.08 in male and female patients under 65 years and 7.10 and 5.92 over 65 years, before chemotherapy, respectively. Lower baseline SMI was not correlated with worse OS in total patients (p=0.915). After a median measurement interval of 30 days after chemotherapy (n=67), body weight and SMI decreased by 2.73% and 2.87% (mean), respectively. The decrease in body weight correlated with the loss of trunk muscle mass (R2=0.2107) but was more strongly associated with the loss of lower limbs muscle mass (R2=0.3985). The muscle mass of lower limbs significantly decreased in lymphoma patients who experienced febrile neutropenia (-0.42% vs -6.04%, p=0.040). OS significantly decreased in lymphoma patients with loss of lower limbs muscle ≥2.8% (p=0.0327). CONCLUSIONS: Muscle loss occurred following anticancer treatments, significantly contributing to worse outcomes. Body composition assessment and relevant multimodal prevention of muscle loss may be vital for patients receiving chemotherapy for haematological malignancies.

Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Short-term outcomes after liver resection with vascular reconstruction: Results from a study with the National Clinical Database of Japan.

BACKGROUND: Although curative resection with vascular reconstruction improves the prognosis of blood-invading locally advanced hepatobiliary tumors, the mortality and morbidity of the procedure remains unclear. This study aimed to clarify the risk factors associated with mortality and morbidity in patients undergoing liver resection with vascular reconstruction. METHODS: This retrospective observational study included 1215 patients undergoing hepatectomy of more than one section with vascular reconstruction, except for left lateral sectionectomy registered in the National Clinical Database (NCD) between 2015 and 2019. The rates of surgical mortality and relevant clinical factors were evaluated. RESULTS: Among the four types of vascular reconstruction, portal venous reconstruction was frequently performed in 724 patients (59.6% of the enrolled patients). Surgical mortality was 8.1%. Patients with hepatic artery reconstruction had the highest surgical mortality rate of 15.8%. In other types of reconstruction, surgical mortality was 9.1% in the portal vein, 5.2% in inferior vena cava, and 4.9% in hepatic vein. Factors significantly associated with surgical mortality include age, sex (male), preoperative comorbidity (American Society of Anesthesiologists grade >3, respiratory distress, diabetes, preoperative pneumonia, weight loss, and obstructive jaundice), poorer liver functional reserve (indocyanine green retention rate at 15 min and prothrombin time/international normalized ratio >1.1) and accompanying biliary reconstruction. CONCLUSIONS: The NCD revealed the detailed status of liver resection combined with vascular reconstruction in Japan. Based on the results of this analysis, understanding the factors that influence the outcome and postoperative course of each procedure will provide patients with accurate information and opportunities to improve future outcomes.

The interplay between alterations in esophageal microbiota associated with Th17 immune response and impaired LC20 phosphorylation in achalasia.

BACKGROUND: Achalasia is an esophageal motility disorder with an unknown etiology. We aimed to determine the pathogenesis of achalasia by studying alterations in esophageal smooth muscle contraction and the associated inflammatory response, and evaluate the role of esophageal microbiota in achalasia development. METHODS: We analyzed esophageal mucosa and lower esophageal sphincter (LES) samples, obtained from patients with type II achalasia who underwent peroral endoscopic myotomy. Esophageal conditioned media obtained from patients were transferred into the mouse esophagus to determine whether the esophageal intraluminal environment is associated with achalasia. RESULTS: Approximately 30% of 20-kDa myosin light chains (LC20) was phosphorylated in LES from the control group under resting and stimulated conditions, whereas less than 10% of LC20 phosphorylation was detected in achalasia under all conditions. The hypophosphorylation of LC20 in achalasia was associated with the downregulation of the myosin phosphatase-inhibitor protein CPI-17. Th17-related cytokines, including IL-17A, IL-17F, IL-22, and IL-23A, were significantly upregulated in achalasia. α-Diversity index of esophageal microbiota and the proportion of several microbes, including Actinomyces and Dialister, increased in achalasia. Actinomyces levels positively correlated with IL-23A levels, whereas Dialister levels were positively associated with IL-17A, IL-17F, and IL-22 levels. Esophageal IL-17F levels increased in mice after oral administration of the conditioned media. CONCLUSIONS: In LES of patients with achalasia, hypophosphorylation of LC20, a possible cause of impaired contractility, was associated with CPI-17 downregulation and an increased Th17-related immune response. The esophageal intraluminal environment, represented by the esophageal microbiota, could be associated with the development and exacerbation of achalasia.

Beckwith-Wiedemann syndrome with juvenile fibrous nodules and lobular breast tumors: a case report and review of the literature.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a genomic imprinting disorder caused by diverse genetic and/or epigenetic disorders of chromosome 11p15.5. BWS presents with a variety of clinical features, including overgrowth and an increased risk of embryonal tumors. Notably however, reports of patients with BWS and breast tumors are rare, and the association between these conditions is still unclear. Insulin-like growth factor-2 (IGF2) expression is known to be associated with the development of various cancers, including breast cancer, and patients with BWS with specific subtypes of molecular defects are known to show characteristic clinical features and IGF2 overexpression. CASE PRESENTATION: A 17-year-old girl who had been diagnosed with BWS based on an umbilical hernia, hyperinsulinemia, and left hemihypertrophy at birth, visited our department with a gradually swelling left breast. Her left breast was markedly larger than her right breast on visual examination. Imaging examinations showed two tumors measuring about 10 cm each in the left breast, and she was diagnosed with juvenile fibroadenoma following core needle biopsy. The two breast tumors were removed surgically and the patient remained alive with no recurrence. The final diagnosis was juvenile fibroadenoma without malignant findings. Immunohistochemical staining using IGF2 antibody revealed overexpression of IGF2 in the cytoplasm of ductal epithelial cells. Because of her clinical features and IGF2 overexpression, molecular defects of 11p15.5 including a possible genetic background of paternal uniparental disomy of chromosome 11 or hypermethylation of imprinting center 1 was suspected. CONCLUSIONS: In this case, overexpression of IGF2 suggested a possible relationship between BWS and breast tumors. Moreover, the characteristic clinical features and IGF2 staining predicted the subtype of 11p15.5 molecular defects in this patient.

Simple pelvimetry predicts the pelvic manipulation time in robot-assisted low and ultra-low anterior resection for rectal cancer.

PURPOSE: This study explored the difficulty factors in robot-assisted low and ultra-low anterior resection, focusing on simple measurements of the pelvic anatomy. METHODS: This was a retrospective analysis of the clinical data of 61 patients who underwent robot-assisted low and ultra-low anterior resection for rectal cancer between October 2018 and April 2023. The relationship between the operative time in the pelvic phase and clinicopathological data, especially pelvic anatomical parameters measured on X-ray and computed tomography (CT), was evaluated. The operative time in the pelvic phase was defined as the time between mobilization from the sacral promontory and rectal resection. RESULTS: Robot-assisted low and ultra-low anterior resections were performed in 32 and 29 patients, respectively. The median operative time in the pelvic phase was 126 (range, 31-332) min. A multiple linear regression analysis showed that a short distance from the anal verge to the lower edge of the cancer, a narrow area comprising the iliopectineal line, short anteroposterior and transverse pelvic diameters, and a small angle of the pelvic mesorectum were associated with a prolonged operative time in the pelvic phase. CONCLUSION: Simple pelvic anatomical measurements using abdominal radiography and CT may predict the pelvic manipulation time in robot-assisted surgery for rectal cancer.

TP53 and/or BRCA1 Mutations Based on CtDNA Analysis as Prognostic Biomarkers for Primary Triple-Negative Breast Cancer.

Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations that are therapeutic targets using next-generation sequencing (NGS). In addition, circulating tumor DNA (ctDNA) is a DNA fragment released into the blood by tumor cell-derived cell death or apoptosis. Liquid biopsy with ctDNA is a novel clinical test for identifying genetic mutations in an entire population noninvasively, in real-time, and heterogeneously. Although there are several reports on ctDNA, fewer have evaluated ctDNA with NGS before an initial treatment for breast cancer patients. Therefore, we examined whether analyzing tumor-associated gene mutations in primary breast cancer based on ctDNA could serve as a biomarker for prognosis and optimal treatment selection. Ninety-five primary breast cancer patients treated at our department from January 2017 to October 2020 were included. Pretreatment plasma samples were subjected to NGS analysis of ctDNA, and correlations with patients' clinicopathological characteristics were evaluated. Fifty-nine (62.1%) patients were positive for ctDNA. ctDNA tended to be positive in hormone receptor-negative, and TP53 (34%), BRCA1 (20%), and BRCA2 (17%) gene mutations were more frequent. Regarding recurrence-free survival, the prognosis was poor in the TP53 and/or BRCA1 mutation-positive groups, especially in triple-negative breast cancer (TNBC) patients. In conclusion, the results of this study indicate that ctDNA with liquid biopsy could identify the poor prognosis group before treatment among TNBC patients and for those for whom optimal treatment selection is desirable; additionally, optimal treatment could be selected according to the ctDNA analysis results.

Complete reduction surgery of a huge recurrent adult granulosa cell tumor after neoadjuvant chemotherapy.

Adult granulosa cell tumors are rare, accounting for only 3-5% of all ovarian tumors. Adult granulosa cell tumors have late recurrences, for which complete resection is an effective option. We report a patient who underwent complete resection of a huge recurrent adult granulosa cell tumor after neoadjuvant chemotherapy. A 72-year-old woman underwent primary surgery for an adult granulosa cell tumor 19 years earlier. A huge recurrent tumor, 11 × 10 cm in size, was noted to elevate the hepatic hilum, inferior vena cava, and right renal vein. The recurrent tumor was too large to resect, thus paclitaxel and carboplatin were administered as neoadjuvant chemotherapy. The tumor shrank to 6 × 5 cm after 6 cycles of chemotherapy, then complete tumor extirpation with resection of the right kidney and temporary scission of inferior vena cava was performed. The patient was alive and well without evidence of a recurrence 1 y postoperatively. Paclitaxel and carboplatin, as neoadjuvant chemotherapy, might be an effective treatment option to achieve complete reduction surgery. This is the first report demonstrating the effectiveness of paclitaxel and carboplatin for huge recurrent adult granulosa cell tumor.