Standardized Classification of Lung Adenocarcinoma Subtypes and Improvement of Grading Assessment Through Deep Learning.

The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1 scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained convolutional neural networks improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

Efficacy and safety of add-on mirogabalin to conventional therapy for the treatment of peripheral neuropathic pain after thoracic surgery: the multicenter, randomized, open-label ADMIT-NeP study.

BACKGROUND: For chronic pain after thoracic surgery, optimal timing of its diagnosis and effective treatment remains unresolved, although several treatment options are currently available. We examined the efficacy and safety of mirogabalin, in combination with conventional pain therapy (nonsteroidal anti-inflammatory drugs and/or acetaminophen), for treating peripheral neuropathic pain (NeP) after thoracic surgery. METHODS: In this multicenter, randomized, open-label, parallel-group study, patients with peripheral NeP were randomly assigned 1:1 to mirogabalin as add-on to conventional therapy or conventional treatment alone. RESULTS: Of 131 patients of consent obtained, 128 were randomized (mirogabalin add-on group, 63 patients; conventional treatment group, 65 patients). The least squares mean changes (95% confidence interval [CI]) in Visual Analogue Scale (VAS) score for pain intensity at rest from baseline to Week 8 (primary endpoint) were - 51.3 (- 54.9, - 47.7) mm in the mirogabalin add-on group and - 47.7 (- 51.2, - 44.2) mm in the conventional group (between-group difference: - 3.6 [95% CI: - 8.7, 1.5], P = 0.161). However, in patients with Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) score (used for the screening of NeP) ≥ 12 at baseline, the greater the S-LANSS score at baseline, the greater the decrease in VAS score in the mirogabalin add-on group, while no such trend was observed in the conventional treatment group (post hoc analysis). This between-group difference in trends was statistically significant (interaction P value = 0.014). Chronic pain was recorded in 7.9% vs. 16.9% of patients (P = 0.171) at Week 12 in the mirogabalin add-on vs. conventional treatment groups, respectively. Regarding activities of daily living (ADL) and quality of life (QOL), changes in Pain Disability Assessment Scale score and the EQ-5D-5L index value from baseline to Week 8 showed significant improvement in the mirogabalin add-on group vs. conventional treatment group (P < 0.001). The most common adverse events (AEs) in the mirogabalin add-on group were dizziness (12.7%), somnolence (7.9%), and urticaria (3.2%). Most AEs were mild or moderate in severity. CONCLUSIONS: Addition of mirogabalin to conventional therapy did not result in significant improvement in pain intensity based on VAS scores, but did result in significant improvement in ADL and QOL in patients with peripheral NeP after thoracic surgery. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs071200053 (registered 17/11/2020).

Prognostic value of lymph node distribution after laparoscopic colectomy with Japanese D3 dissection.

PURPOSE: Positive pathologic lymph nodes in colorectal cancer represent an important prognostic indicator. Whether lymph node distribution or the number of metastatic nodes is more strongly associated with survival prediction remains controversial. METHODS: Among 3449 colorectal cancer surgeries performed at Nagasaki University Hospital and five affiliated institutions from April 2016 to March 2022, we investigated 604 patients who underwent laparoscopic radical resection and were diagnosed with pathological stage III cancer. Patients were divided into two groups according to whether they had central vessel metastasis (LND3 group, n=42) or not (LND1/2 group, n=562). After adjusting for background factors using propensity score matching, the LND3 group included 42 patients and the LND1/2 group included 40 patients. Patient background characteristics and prognosis were compared between these two groups. RESULTS: Before matching, frequencies of right-side colon cancer (64.3% vs 38.1%, p=0.001), multivisceral resection (11.9% vs 4.4%, p=0.039), clinical N2 status (40.5% vs 22.6%, p=0.032), and pathological N2 (73.8% vs 22.6%, p<0.001) were all greater, and the number of lymph nodes retrieved was higher (24 vs 19, p=0.042) in the LND3 group. After matching, no differences in any clinical factors were evident between groups. Five-year RFS (44.8% vs 77.1%, p=0.004) and OS (43.1% vs 83.2%, p<0.001) were worse in the LND3 group. Adjuvant chemotherapy improved RFS (adjuvant chemotherapy (+) vs adjuvant chemotherapy (-): 62.1% vs 27.7%, p=0.047) in the LND3 group. CONCLUSION: LND3-positive patients show poorer prognosis than LND1/2 patients and should be treated with an appropriate perioperative treatment strategy.

A surgical training system designed to help trainees acquire laparoscopic surgical skills at a rural Japanese institute.

PURPOSE: The Endoscopic Surgical Skill Qualification System was established in Japan to evaluate safe endoscopic surgical techniques and teaching skills. Trainee surgeons obtaining this certification in rural hospitals are disadvantaged by the limited number of surgical opportunities. To address this problem, we established a surgical training system to educate trainee surgeons. METHODS: Eighteen certified expert surgeons affiliated with our department were classified into an experienced training system group (E group, n = 9) and a non-experienced group (NE group, n = 9). Results of the training system were then compared between the groups. RESULTS: The number of years required to become board certified was shorter in the E group (14 years) than that in the NE group (18 years). Likewise, the number of surgical procedures performed before certification was lower in the E group (n = 30) than that in the NE group (n = 50). An expert surgeon was involved in the creation of the certification video of all the E group participants. A questionnaire to board-certified surgeons revealed that guidance by a board-certified surgeon and trainee education (surgical training system) was useful for obtaining certification. CONCLUSIONS: Continuous surgical training, starting with trainee surgeons, appears useful for expediting their acquisition of technical certification in rural areas.

Correlations of age with clinicopathological features, perioperative outcomes and the prognosis in patients with colorectal cancer: a Japanese multicenter study.

PURPOSE: Colorectal cancer is not common in patients under 40 years old, and its associations with clinical features and the prognosis remain uncertain. METHODS: Using a multicenter database, we retrospectively reviewed 3015 patients who underwent colorectal surgery between 2016 and 2021. Patients were divided by age into those < 40 years old (young; n = 52), 40-54 years old (middle-aged; n = 254) and > 54 years old (old; n = 2709). We then investigated age-related differences in clinicopathological features, perioperative outcomes and the prognosis. RESULTS: The proportion of young patients increased annually from 0.63% in 2016 to 2.10% in 2021. Female patients were more frequent, the performance status was better, tumors were larger, clinically node-positive and poorly differentiated adenocarcinomas were more frequent, postoperative complications were less frequent, and the hospital stay was shorter in young patients than in older patients. Young age was an independent predictor of a low risk of postoperative complications (odds ratio, 0.204; 95% confidence interval, 0.049-0.849; p = 0.028). With pathologically node-positive status, adjuvant chemotherapy was more frequent in young patients (100%) than in middle-aged (73.7%) or old (51.8%) patients (p < 0.001), and the 3-year relapse-free survival was better in the young group than in others. CONCLUSION: Despite higher rates of advanced tumors in younger patients, adequate adjuvant chemotherapy appears to improve the relapse-free survival.

Effect of revised organ transplant law in Japan on lung transplantation.

PURPOSE: To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. METHODS: Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32). CONCLUSIONS: The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period.

Short-term outcomes after laparoscopic colorectal cancer surgery in patients over 90 years old: a Japanese multicenter study.

BACKGROUND: The effect of laparoscopic surgery on short-term outcomes in colorectal cancer patients over 90 years old has remained unclear. METHODS: We reviewed 87 colorectal cancer patients aged over 90 years who underwent surgery between 2016 and 2022. Patients were divided into an open surgery group (n = 22) and a laparoscopic surgery group (n = 65). The aim of this study was to investigate the effect of laparoscopic surgery on postoperative outcome in elderly colorectal cancer patients, as compared to open surgery. RESULTS: Seventy-eight patients (89.7%) had comorbidities. Frequency of advanced T stage was lower with laparoscopic surgery (p = 0.021). Operation time was longer (open surgery 146 min vs. laparoscopic surgery 203 min; p = 0.002) and blood loss was less (105 mL vs. 20 mL, respectively; p < 0.001) with laparoscopic surgery. Length of hospitalization was longer with open surgery (22 days vs. 18 days, respectively; p = 0.007). Frequency of infectious complications was lower with laparoscopic surgery (18.5%) than with open surgery (45.5%; p = 0.021). Multivariate analysis revealed open surgery (p = 0.026; odds ratio, 3.535; 95% confidence interval, 1.159-10.781) as an independent predictor of postoperative infectious complications. CONCLUSIONS: Laparoscopic colorectal resection for patients over 90 years old is a useful procedure that reduces postoperative infectious complications.

Effect of adjuvant chemotherapy after curative resection of colorectal cancer peritoneal metastasis.

PURPOSE: Several guidelines have recommended surgical resection for localized peritoneal metastases, but the prognosis remains poor. In addition, the efficacy of adjuvant chemotherapy (AC) after curative resection is under debate. The present study compared long-term outcomes between curative and non-curative resection and evaluated the effects of AC after curative resection. METHODS: Using a multicenter database, we retrospectively reviewed 123 colorectal cancer patients with peritoneal metastases between April 2016 and December 2021. Of these patients, 49 underwent curative resection, and 74 underwent non-curative resection. RESULTS: The frequency of broad metastases was lower in the curative resection group (8.2%) than in the non-curative resection group (43.2%, p < 0.001). Among all patients, 5-year overall survival rate was higher in the curative resection group (43.0%) than in the non-curative resection group (7.3%, p = 0.004). Among patients who underwent curative resection, 5-year overall survival rate was significantly higher in the AC group (48.2%) than in the non-AC group (38.1%, p = 0.037). Multivariate analysis of all patients revealed pathological N status and non-curative resection as independent predictors of overall survival. In patients who underwent curative resection, advanced age was an independent predictor of relapse-free survival, and AC was an independent predictor of overall survival. CONCLUSION: This multicenter study of colorectal cancer patients with peritoneal metastases revealed that prognosis was more favorable for curable cases than for non-curable cases. Prognosis was more favorable in the AC group than in the non-AC group after curative resection.

Usefulness of the endoscopic surgical skill qualification system for laparoscopic colectomy for transverse colon cancer: a Japanese multicenter analysis.

PURPOSE: Laparoscopic colectomy for transverse colon cancer (TCC) can be technically demanding due to the anatomical complexity of the region. In Japan, the Endoscopic Surgical Skill Qualification System (ESSQS) was established to improve the skill of laparoscopic surgeons and further develop surgical teams. We examined the safety and feasibility of laparoscopic colectomy for TCC and evaluated the effects of the Japanese ESSQS in facilitating this approach. METHODS: We retrospectively reviewed 136 patients who underwent laparoscopic colectomy for TCC between April 2016 and December 2021. Patients were divided into an ESSQS-qualified surgeon group (surgery performed by an ESSQS-qualified surgeon, n = 52) and a non ESSQS-qualified surgeon (surgery performed by a non ESSQS-unqualified surgeon, n = 84). Clinicopathological and surgical features were compared between groups. RESULTS: Postoperative complications occurred in 37 patients (27.2%). The proportion of patients who developed postoperative complications was lower in the ESSQS-qualified surgeon group (8.0%) than that in the non ESSQS-qualified surgeon group (34.5%; p < 0.017). Multivariate analysis revealed "Operation by ESSQS-qualified surgeon surgeon" (odds ratio (OR) 0.360, 95% confidence interval (CI) 0.140-0.924; p = 0.033), blood loss (OR 4.146, 95% CI 1.688-10.184; p = 0.002), and clinical N status (OR 4.563, 95% CI 1.814-11.474; p = 0.001) as factors independently associated with postoperative complications. CONCLUSION: The present multicenter study confirmed the feasibility and safety of laparoscopic colectomy for TCC and revealed that ESSQS-qualified surgeon achieved better surgical outcomes.

Long-term outcomes and early recurrence after resection for metachronous pulmonary metastases from colorectal cancer.

PURPOSE: Properly selecting patients for aggressive curative resection for pulmonary metastases (PMs) from colorectal cancer (CRC) is desirable. We purposed to clarify prognostic factors and risk factors for early recurrence after metachronous PM resection. METHODS: Clinical data of 151 patients who underwent R0 resection for metachronous PMs from CRC at two institutions between 2008 and 2021 were reviewed. RESULTS: Seventy-six patients (50.3%) were male, and the median age was 71 (42-91) years. The numbers of colon/rectal cancers were 76/75, with pStage I/II/III/IV/unknown in 15/34/86/13/3. The duration from primary surgery to PM was 19.7 (1.0-106.4) months. The follow-up period was 41.9 (0.3-156.2) months. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 75.1%, 53.7%, and 51.1%, and the 1-, 3-, and 5-year overall survival (OS) rates were 97.7%, 87.5%, and 68.2%. On multivariate analysis, lymph node metastasis of the primary lesion (HR 1.683, 95%CI 1.003-2.824, p = 0.049) was an independent predictor of poor RFS, and history of resection for extrapulmonary metastasis (e-PM) (HR 2.328, 95%CI 1.139-4.761, p = 0.021) was an independent predictor of poor OS. Patients who experienced early recurrence (< 6 months) after PM resection showed poorer OS than others (3-year OS 50.8% vs. 90.2%, p = 0.002). On multivariate analysis, e-PM was an independent predictor of early recurrence after PM resection (OR 3.989, 95%CI 1.002-15.885, p = 0.049). CONCLUSION: Since a history of e-PM was a predictor of early recurrence and poor OS after R0 resection for PM, surgical treatment of patients with a history of e-PM should be considered carefully.

Simultaneous bilateral mastectomy and RRSO for BRCA2-positive non-invasive breast cancer in Japan: a case report and analysis of initial experience.

BACKGROUND: In Japan, genetic testing, surveillance, and risk-reducing surgery for hereditary breast and ovarian cancer (HBOC) syndrome have been covered by the Japanese national insurance system since April 2020. On the other hand, the current situation is that medical care, including surveillance of undiagnosed (cancer-free) patients, is self-funded even for individuals with HBOC. We report a case in which breast cancer was diagnosed at an early stage during surveillance for cancer-free HBOC at the patient's own expense, and risk-reducing surgery was performed at the same time as treatment for breast cancer. CASE PRESENTATION: The patient was a 63-year-old woman. Her sister had a history of breast cancer in her 30s and was found to be a BRCA2 pathogenic variant carrier by genetic testing. The patient therefore presented to the genetic department of our hospital and underwent genetic testing (out-of-pocket). A pathogenic variant was found at the same site. During annual breast and ovarian surveillance at the patient's own expense, a physician with sufficient expertise in contrast-enhanced breast magnetic resonance imaging (MRI) noticed a change in the contrast enhancement pattern on breast MRI and performed needle biopsy, revealing ductal carcinoma in situ. At the request of the patient, she underwent concurrent contralateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy in addition to breast cancer treatment. CONCLUSIONS: We encountered a case in which cancer treatment and risk-reducing surgery were performed at the same time for a pathogenic variant carrier who was very anxious about developing cancer. Surveillance of cancer-free BRCA1/2 mutation carriers and expansion of insurance coverage for surgery are important future issues.

Development and evaluation of an original phantom model of ultrasonography-guided thyroid gland biopsy for the training of surgical residents and students.

PURPOSES: Fine-needle aspiration cytology (FNAC) is a specific and important test used for the diagnosis of thyroid gland cancer. We developed a thyroid gland phantom using original manufacturing techniques and direct three-dimensional (3D) printing. The aim of this study was to confirm the effectiveness of this phantom by collecting data to evaluate puncture training. METHODS: Data from 45 ultrasonography-guided thyroid nodule FNAC procedures performed on our thyroid phantom were evaluated in our department. The first group comprised qualified physicians who specialized in thyroid gland treatment (group A; n = 10). The second and third groups comprised senior and junior residents (group B; n = 8 and group C; n = 12; respectively). The fourth group comprised students (group D; n = 15). We measured the times taken by these groups to complete each task. RESULTS: The skills of all participants in groups B, C, and D improved after using this phantom involving the major (parallel)- (0.47 ± 0.07) and short (orthogonal)-axes (0.52 ± 0.07) methods (P < 0.001). The number of erroneous punctures decreased from 53 to 3. CONCLUSIONS: Our original phantom improved the puncture skills of students and junior doctors and was suitable as a tailored training model for practicing thyroid gland transfixion.

Efficacy of left colic artery preservation with D3 lymph node dissection in laparoscopic surgery for advanced sigmoid and rectal cancer.

PURPOSE: For advanced left colon cancer, lymph node dissection at the root of the inferior mesenteric artery is recommended. Whether the left colic artery (LCA) should be preserved or resected remains contentious. METHODS: The 367 patients who underwent laparoscopic sigmoidectomy or anterior resection and who were pathologically node-positive were reviewed. Patients were divided into LCA-preserving group (LCA-P, n = 60) and LCA-non-preserving group (LCA-NP, n = 307). Propensity score matching was applied to minimize selection bias and 59 patients were matched. RESULTS: Before matching, the rates of poor performance status and cardiovascular disease were higher in the LCA-P group (p < 0.001). After matching, operation time was longer (276 vs. 240 min, p = 0.001), the frequency of splenic flexure mobilization (62.7% vs. 33.9%, p = 0.003) and lymphovascular invasion (84.7% vs. 55.9%, p = 0.001) was higher in the LCA-P group. Severe postoperative complications (CD ≥ 3) occurred only in the LCA-NP group (0% vs. 8.4%, p = 0.028). The median follow-up period was 38.5 months (range 2.0-70.0 months). The 5-year RFS rates (67.8% vs. 66.0%, p = 0.871) and OS rates (80.4% vs. 74.9%, p = 0.308) were comparable between the groups. CONCLUSIONS: Laparoscopic LCA-sparing surgery for left-sided colorectal cancer reduces the risk of severe complications and offers a favorable long-term prognosis.

Prognostic factors for lung transplant recipients focusing on age and gender: the Japanese lung transplantation report 2022.

PURPOSE: To clarify the impact of donor and recipient characteristics on the survival of recipients before and after lung transplantation in the Japanese population. METHODS: Patients' data were collected for retrospective analysis from all authorized lung transplant centers in Japan. We included 1963 patients listed for lung transplantation by the end of December 2021, comprised of 658 deceased-donor and 270 living-donor lung transplants. RESULTS: Primary disease had a significant impact on the mortality of patients waiting for transplantation. The indications for transplant significantly affected the post-transplant survival rate of deceased-donor lung transplant recipients. The recipient's age also significantly affected the post-transplant survival rate of the deceased-donor and living-donor lung transplant recipients. The recipients of grafts transplanted from donors aged 61 years or older showed a worse post-transplant survival rate (≧60 years old). The survival rate for the combination of a female donor to a male recipient among the deceased-donor lung transplant recipients was the worst among the four combinations. CONCLUSION: The donor and recipient characteristics significantly impacted the survival of recipients after lung transplantation. The underlying mechanism of the negative impact of the gender mismatch of female donor to male recipient on post-transplant survival needs to be investigated further.

A Survey of the Awareness and Educational Needs of Nurses in Nagasaki Prefecture Regarding Hereditary Breast and Ovarian Cancer.

The aim of this study was to evaluate the knowledge and educational needs with regard to hereditary breast and ovarian cancer among nurses working in breast cancer care in the Nagasaki Prefecture. In breast cancer care, the identification of patients at risk for hereditary breast and ovarian cancer is necessary for the implementation of genetic testing and counseling. Nurses should be involved in this process, since they play a crucial role in the care of patients with breast cancer. However, the knowledge regarding hereditary breast and ovarian cancer among nurses working in oncology care in Japan has not been assessed. The design of this study is cross-sectional design. We distributed 597 surveys to nurses working in breast cancer care. The surveys assessed the nurses' demographic data, their current knowledge and practices regarding cancer genetics and hereditary breast and ovarian cancer, and their attitude and preferences regarding learning about the condition. We received 317 valid replies. Nurses had limited knowledge about hereditary breast and ovarian cancer characteristics: 41.6% reported that they do not know about the condition, whereas less than 10% knew its characteristics. However, nurses were aware of hereditary breast and ovarian cancer significance and were willing to learn about it: 91% wished to learn about the condition, and 88.6% wanted to participate in study group meetings. Further, nurses' preferences regarding educational programs were clarified. Overall, our results show that educational programs should be implemented to advance nurses' knowledge of hereditary breast and ovarian cancer characteristics.

Balance of the prooxidant and antioxidant system is associated with mortality in critically ill patients.

It is well known that oxidative stress causes certain diseases and organ damage. However, roles of oxidative stress in the acute phase of critical patients remain to be elucidated. This study aimed to investigate the balance of oxidative and antioxidative system and to clarify the association between oxidative stress and mortality in critically ill patients. This cohort study enrolled 247 patients transported to our emergency department by ambulance. Blood was drawn on hospital arrival, and serum derivatives of reactive oxidant metabolites (dROMs, oxidative index) and biological antioxidant potential (BAP, antioxidative index) were measured. Modified ratio (MR) is also calculated as BAP/dROMs/7.51. There were 197 survivors and 50 non-survivors. In the non-survivors, dROMs were significantly lower (274 vs 311, p<0.01), BAP was significantly higher (2,853 vs 2,138, p<0.01), and MR was significantly higher (1.51 vs 0.92, p<0.01) compared to those in the survivors. The AUC of MR was similar to that for the APACHE II score. Contrary to our expectations, higher BAP and lower dROMs were observed on admission in non-survivors. This may suggest that the antioxidative system is more dominant in the acute phase of severe insults and that the balance toward a higher antioxidative system is associated with mortality.

EFFICACY AND SAFETY OF A DEXAMETHASONE-BASED MOUTHWASH TO PREVENT CHEMOTHERAPY-INDUCED STOMATITIS IN WOMEN WITH BREAST CANCER: A MULTICENTRE, OPEN-LABEL, RANDOMISED PHASE 2 STUDY.

PURPOSE: No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer. BASIC PROCEDURES: Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2. MAIN FINDINGS: Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed. PRINCIPAL CONCLUSIONS: The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results.

Efficacy of risk-stratified indicators for adjuvant chemotherapy with fluorouracil and oxaliplatin after hepatectomy for colorectal cancer liver metastasis.

BACKGROUND: The recurrence rate after hepatectomy for colorectal cancer liver metastasis (CRLM) is high, and there is no consensus regarding the effect of adjuvant chemotherapy (AC) using oxaliplatin (doublet AC) in these patients. METHODS: The present study included 91 patients who underwent hepatectomy for complete resection at our hospitals between 2008 and 2018. Based on whether or not they had undergone doublet AC, patients were divided into AC (n = 35) and non-AC (n = 56) groups. The recurrent risk was evaluated by the Memorial Sloan Kettering Cancer Center clinical risk score (MSKCC-CRS). RESULTS: The number of females and median age were higher in the AC group (51.4% vs 25.0%, p = 0.010 and 67 vs 61 years, p = 0.012, respectively). The median follow-up period was 45 months (range, 6-101 months). Doublet AC was an independent prognostic factor for 5-year relapse-free survival (hazard ratio, 0.225; 95%CI, 0.097-0.522; p < 0.001) and for 5-year overall survival (hazard ratio, 0.165; 95%CI, 0.057-0.476; p < 0.001) in multivariate analysis. In patients with a high risk of recurrence (MSKCC-CRS 3-5), 5-year relapse-free survival and 5-year overall survival was higher in the doublet AC group than in the non-AC group (p < 0.01). In low-risk patients (MSKCC-CRS 0-2), 5-year relapse-free survival and 5-year overall survival were similar between the groups. CONCLUSIONS: Doublet AC could have a positive effect on prognosis after curative resection of CRLM, especially in high-risk patients. The selection of patients and AC regimen should take into consideration the risk of recurrence.

Effect of oxaliplatin in elderly colon cancer patients with pathological T4 and/or N2 disease: a multicenter, propensity score-matched analysis.

PURPOSE: Although adjuvant chemotherapy (AC) using fluoro-pyrimidine and oxaliplatin (FU + oxaliplatin) is recommended after curative resection for locally advanced colon cancer patients, several randomized controlled trials have shown no additional effect of oxaliplatin in patients aged ≥ 70 years. Here, we examined the effectiveness of FU + oxaliplatin on the long-term outcome of old patients with a high risk of recurrence. METHODS: This multicenter, retrospective study included 346 colon cancer patients diagnosed with pathological T4 and/or N2 disease from 2016 to 2020. They were divided into an old group (≥ 70 years, n = 197) and a young group (< 70 years, n = 167). Propensity score matching was used to minimize selection bias, and 126 patients per group were matched. RESULTS: Before matching, the rates of poor performance status (p < 0.001) and the presence of comorbidities (76.1% vs. 47.9%, p < 0.001) were higher in the old group. Although all baseline factors were similar between groups, after matching, the AC rate was lower in the old group (45.2% vs. 65.1%, p = 0.002). In the old group, relapse-free (82.2% vs. 55.6% and 69.6%, p < 0.05) and overall survival (83.1% vs. 80.0% and 44.4%, p < 0.05) rates were significantly higher in the AC patients with FU + oxaliplatin than in the AC patients with only FU and the non-AC patients. CONCLUSION: The selected old colon cancer patients with a high risk of recurrence gained an additional benefit with respect to prognosis from FU + oxaliplatin as AC.

Effect of endoscopic surgical skill qualification system for laparoscopic multivisceral resection: Japanese multicenter analysis.

BACKGROUND: The efficacy of laparoscopic multivisceral resection (Lap-MVR) has been reported by several experienced high-volume centers. The Endoscopic Surgical Skill Qualification System (ESSQS) was established in Japan to improve the skill of laparoscopic surgeons and further develop surgical teams. We examined the safety and feasibility of Lap-MVR in general hospitals, and evaluated the effects of the Japanese ESSQS for this approach. METHODS: We retrospectively reviewed 131 patients who underwent MVR between April 2016 and December 2019. Patients were divided into the laparoscopic surgery group (LAC group, n = 98) and the open surgery group (OPEN group, n = 33). The clinicopathological and surgical features were compared between the groups. RESULTS: Compared with the OPEN group, BMI was significantly higher (21.9 vs 19.3 kg/m2, p = 0.012) and blood loss was lower (55 vs 380 ml, p < 0.001) in the LAC group. Operation time, postoperative complications, and postoperative hospital stay were similar between the groups. ESSQS-qualified surgeons tended to select the laparoscopic approach for MVR (p < 0.001). In the LAC group, ESSQS-qualified surgeons had superior results to those without ESSQS qualifications in terms of blood loss (63 vs 137 ml, p = 0.042) and higher R0 resection rate (0% vs 2.0%, p = 0.040), despite having more cases of locally advanced tumor. In addition, there were no conversions to open surgery among ESSQS-qualified surgeons, and three conversions among surgeons without ESSQS qualifications (0% vs 15.0%, p = 0.007). Multivariate analysis revealed blood loss (odds ratio 1.821; 95% CI 1.324-7.654; p = 0.010) as an independent predictor of postoperative complications. Laparoscopic approach was not a predictive factor. CONCLUSIONS: The present multicenter study confirmed the feasibility and safety of Lap-MVR even in general hospitals, and revealed superior results for ESSQS-qualified surgeons.