OBJECTIVE: To determine the predictive factors for residual disease occurring after surgical removal of congenital cholesteatomas and whether these predictive factors differ between microscopic ear surgery (MES) using data from the literature and transcanal endoscopic ear surgery (TEES) using data from our own institution.
METHODS: Twenty-three patients with a congenital cholesteatoma who underwent surgical treatment at Yamagata University Hospital between December 2011 and December 2017 were retrospectively investigated. We divide TEES into three different approaches: non-powered TEES, powered TEES and dual MES/TEES. Main outcome measures were Potsic stage, closed or open congenital cholesteatoma type, TEES surgical approach, appearance of residual disease, tympanoplasty type and hearing outcome.
RESULTS: A logistic regression analysis was conducted on the Potsic stage, closed or open type, TEES surgical approach and age to obtain the odds ratio for residual disease. The chance of residual disease significantly increased in the presence of an open-type congenital cholesteatoma (odds ratio: 30.82; 95 % confidence interval: 1.456-652.3; p = 0.0277), but not for any of the other factors including Potsic stage. The timing of the confirmation of residual disease after ossicular chain reconstruction was analyzed using a Kaplan-Meier analysis. The residual disease rate was significantly higher with an open-type congenital cholesteatoma (log-rank test, p < 0.05). In addition, all residual disease occurred within three years after surgery.
CONCLUSIONS: Our results showed that an open-type congenital cholesteatoma is the strongest predictive factor for residual disease when removing a congenital cholesteatoma by TEES.

BACKGROUND: Cervical cancer often originates from cervical cell dysplasia. Previous studies mainly focused on surgical margins and high-risk human papillomavirus persistence as factors predicting recurrence. New research highlights the significance of positive findings from endocervical curettage (ECC) during excision treatment. However, the combined influence of surgical margin and ECC status on dysplasia recurrence risk has not been investigated.
METHODS: In this retrospective study, data from 404 women with high-grade squamous intraepithelial lesions (HSIL) who underwent large loop excision of the transformation zone (LLETZ) were analyzed. Records were obtained retrospectively from the hospital\'s patient database including information about histopathological finding from ECC, endocervical margin status with orientation of residual disease after LLETZ, recurrent/persistent dysplasia after surgical treatment and need for repeated surgery (LLETZ or hysterectomy).
RESULTS: Patients with cranial (= endocervical) R1-resection together with cells of HSIL in the ECC experienced re-surgery 17 times. With statistical normal distribution, this would have been expected to happen 5 times (p < 0.001). The Fisher\'s exact test confirmed a statistically significant connection between the resection status together with the result of the ECC and the reoccurrence of dysplasia after surgery (p < 0,001). 40,6% of the patients with re-dysplasia after primary LLETZ had shown cranial R1-resection together with cells of HSIL in the ECC. Investigating the risk for a future abnormal Pap smear, patients with cranial R1-resection together with dysplastic cells in the ECC showed the greatest deviation of statistical normal distribution with SR = 2.6.
CONCLUSIONS: Our results demonstrate that the future risk of re-dysplasia, re-surgery, and abnormal Pap smear for patients after LLETZ due to HSIL is highest within patients who were diagnosed with cranial (endocervical) R1-resection and with cells of HSIL in the ECC in their primary LLETZ. Consequently, the identification of patients, who could benefit of intensified observation or required intervention could be improved.

Ovarian carcinoma remains the most lethal gynaecologic malignancy. Half of all high-grade serous ovarian cancers (HGSOCs) have a homologous recombination deficiency (HRD) with regard to the repair of double-strand DNA breaks and are candidate to receive maintenance treatment with PARP inhibitors. While a wealth of literature exists regarding the therapeutic guidance of patients from a medical standpoint, the influence of the HRD status on the surgical outlook has been comparatively limited. In this review, the clinical and biological features of advanced ovarian cancers with BRCA1/2 mutation and/or HRD status are considered with particular reference to their impact on the surgical management and on the medico-surgical sequence. The modification of the surgical indications according to the results of molecular testing in first-line and recurrent settings are discussed.

The present study aimed to clarify the prognostic role of the pre-treatment neutrophil-to-lymphocyte ratio (NLR) for the response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC). Due to conflicting results in currently available data, the specific focus of the present study was on evaluating the associations between the pre-treatment NLR and the rate of achieving a pathological complete response (pCR) and survival outcomes. For the present study, data from a cohort of 465 consecutive patients with LABC who underwent NAC at King Feisal Specialist Hospital and Research Center (Riyadh, Saudi Arabia) between 2005 and 2014 were obtained from a prospective BC database and analyzed. Patients were stratified into two groups based on an optimal NLR cut-off determined using the receiver operating characteristic curve. Logistic regression analyses were conducted to assess variables associated with pCR, and Cox regression analyses were used to assess variables associated with survival outcomes. The low pre-treatment NLR group (≤2.2) was found to exhibit a higher likelihood of achieving a pCR (odds ratio, 2.59; 95% CI, 1.52-4.38; P<0.001), along with higher 5-year disease-free survival (DFS) [75.8 vs. 64.9%; hazard ratio (HR), 0.69; 95% CI, 0.50-0.94; P=0.02] and 5-year overall survival (OS; 90.3 vs. 81.9; HR, 0.62; 95% CI, 0.39-0.98; P=0.04) rates compared with those in the high NLR group (>2.2). Sub-group analysis revealed that the observed significance in survival outcomes was driven by the triple-negative BC (TNBC) subgroup. Patients with residual TNBC disease and a high pre-treatment NLR were observed to have lower 5-year DFS (44.4 vs. 75.0%; P=0.02) and 5-year OS (55.9 vs. 84.5%; P=0.055) rates compared with those with residual TNBC disease and a low NLR. To conclude, data from the present study suggest that the pre-treatment NLR can serve as a viable independent prognostic factor for pCR following NAC in patients with LABC and for survival outcomes, particularly for patients with TNBC.

BACKGROUND: The optimal primary debulking surgery outcome of serous ovarian carcinoma (SOC) is greatly affected by primary ovarian neoplasm or metastatic lesion close to the rectum.
OBJECTIVE: To study the risk factors affecting postoperative residual primary ovarian neoplasm or metastatic lesion close to the rectum of SOC.
METHODS: The clinical and MRI data of 164 patients with SOC eligible from institution A (training and test groups) and 36 patients with SOC eligible from institution B (external validation group) were collected and retrospectively analyzed. The clinical data included age, serum carbohydrate antigen 125 (CA-125), human epididymis protein 4, and neutrophil-to-lymphocyte ratio (NLR). Magnetic resonance imaging (MRI) data included ovarian mass distribution, maximum diameter of ovarian mass, ovarian mass features, degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion, and amount of ascites. A model was established using multivariate logistic regression.
RESULTS: By univariate and multivariate logistic regressions, CA-125 (P = 0.024, odds ratio [OR] = 3.798, 95% confidence interval [CI] = 1.24-13.32), NLR (P = 0.037, OR = 3.543, 95% CI = 1.13-12.72), and degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion (P < 0.001, OR = 37.723, 95% CI = 7.46-266.88) were screened as independent predictors. The area under the curve values of the model in the training, test, and external validation groups were 0.860, 0.764, and 0.778, respectively.
CONCLUSIONS: The clinical-radiological model based on T1-weighted dual-echo MRI can be used non-invasively to predict postoperative residual ovarian neoplasm or metastasis close to SOC in the rectum.

Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic and transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that, in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-coenzyme A (CoA) synthetase 2 (ACSS2) in the nucleus to couple high glucose metabolic flux with acetyl-histone H3 modification of neural crest (NC) lineage and glucose metabolism genes. Importantly, we show that acetaldehyde is a metabolite source for acetyl-histone H3 modification in an ALDH1A3-dependent manner, providing a physiologic function for this highly volatile and toxic metabolite. In a zebrafish melanoma residual disease model, an ALDH1-high subpopulation emerges following BRAF inhibitor treatment, and targeting these with an ALDH1 suicide inhibitor, nifuroxazide, delays or prevents BRAF inhibitor drug-resistant relapse. Our work reveals that the ALDH1A3-ACSS2 couple directly coordinates nuclear acetaldehyde-acetyl-CoA metabolism with specific chromatin-based gene regulation and represents a potential therapeutic vulnerability in melanoma.

OBJECTIVE: For operable triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), clinical prognostication and postoperative decision-making relies exclusively on whether a pathologic complete response (pCR) is achieved or not. We evaluated whether extent of disease at presentation further influenced overall survival (OS) among patients with pCR or with residual disease (RD) following NAC.
METHODS: Patients with stage I-III TNBC who underwent NAC were identified from the National Cancer Database from 2010 to 2019. Overall survival was assessed by disease extent using the Kaplan-Meier method and Cox proportional hazards regression for univariate and multivariable analysis.
RESULTS: A total of 35,598 patients met inclusion criteria, and 11,967 achieved pCR. Ten-year OS was 88.5% and varied by cT and cN category at presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (90.9%) and was worst in those with cT3-4, cN2-3 disease (72.0%). A total of 23,631 patients had RD. Ten-year OS was 60.1% and varied by cT and cN category at presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (73.0%) and was worst in those with cT3-4, cN2-3 disease (36.3%). Notably, OS was significantly poorer for patients with cT3-4, cN2-3 disease at diagnosis and pCR versus those with cT1-2 cN0 and RD (aHR 1.30, 95% confidence interval 1.03-1.63, p = 0.03).
CONCLUSIONS: Among patients with TNBC, extent of disease at presentation was prognostic for OS independently of response to NAC. Patients with advanced stage at presentation had poorer OS even in the context of pCR. Further investigation is needed to evaluate whether additional adjuvant therapy strategies should be considered for these patients.

BACKGROUND: Incidental Gallbladder Cancer (IGBC) following cholecystectomy constitutes a significant portion of gallbladder cancer diagnoses. Re-exploration is advocated to optimize disease clearance and enhance survival rates. The consistent association of residual disease (RD) with inferior oncologic outcomes prompts a critical examination of re-resection\'s role as a modifying factor in the natural history of IGBC.
METHODS: All patients diagnosed with gallbladder cancer between 2012 and 2022 were included. An elastic net regularized regression model was employed to profile high-risk predictors of RD within the IGBC group. Survival outcomes were assessed based on resection margins and RD.
RESULTS: Among the 181 patients undergoing re-exploration for IGBC, 133 (73.5 %) harbored RD, while 48 (26.5 %) showed no evidence. The elastic net model, utilizing a selected λ = 0.029, identified six coefficients associated with the risk of RD: aspiration from cholecystectomy (0.141), hepatic tumor origin (1.852), time to re-exploration >8 weeks (1.879), positive margin status (2.575), higher T stage (1.473), and poorly differentiated tumors (2.241). Furthermore, the study revealed a median overall survival of 44 months (CI 38-60) for IGBC patients with no evidence of RD, compared to 31 months (23-42) for those with RD (p < 0.001).
CONCLUSIONS: Re-resection revealed a high incidence of RD (73.5 %), significantly correlating with poorer survival outcomes. The preoperative identification of high-risk features provides a reliable biological disease profile. This aids in strategic preselection of patients who may benefit from re-resection, underscoring the need to consolidate outcomes with tailored chemotherapy for those with unfavorable characteristics.

UNASSIGNED: Residual disease after neoadjuvant chemotherapy (NAC) in breast cancer patients predicts worse outcomes than pathological complete response. Differing prognostic impacts based on the anatomical site of residual tumors are not well studied.
UNASSIGNED: The study aims to assess disease-free survival (DFS) in breast cancer patients with different residual tumor sites following NAC and to develop a nomogram for predicting 1- to 3-year DFS in these patients.
UNASSIGNED: A retrospective cohort study.
UNASSIGNED: Retrospective analysis of 953 lymph node-positive breast cancer patients with residual disease post-NAC. Patients were categorized into three groups: residual disease in breast (RDB), residual disease in lymph nodes (RDN), and residual disease in both (RDBN). DFS compared among groups. Patients were divided into a training set and a validation set in a 7:3 ratio. Prognostic factors for DFS were analyzed to develop a nomogram prediction model.
UNASSIGNED: RDB patients had superior 3-year DFS of 94.6% versus 85.2% for RDN and 81.8% for RDBN (p < 0.0001). Clinical T stage, N stage, molecular subtype, and postoperative pN stage were independently associated with DFS on both univariate and multivariate analyses. Nomogram integrating clinical tumor-node-metastasis (TNM) stage, molecular subtype, pathological response demonstrated good discrimination (C-index 0.748 training, 0.796 validation cohort), and calibration.
UNASSIGNED: The location of residual disease has prognostic implications, with nodal residuals predicting poorer DFS. The validated nomogram enables personalized DFS prediction to guide treatment decisions.
Understanding the impact of residual tumor location on prognosis after breast cancer treatment After receiving neoadjuvant chemotherapy, a treatment to shrink tumors before surgery, some breast cancer patients may still have residual tumor cells. Our study focuses on how the location of these remaining tumors – whether in the breast, lymph nodes, or both – affects the likelihood of the cancer not returning within the next 1 to 3 years. This likelihood is known as ‘disease-free survival’ (DFS). We analyzed data from 953 breast cancer patients who underwent neoadjuvant chemotherapy and still had residual tumors. By comparing DFS among patients with tumors remaining in different locations, we discovered that the specific location of the residual tumor significantly impacts the patient’s long-term health and recovery. Additionally, we developed a predictive tool called a ‘nomogram’ to help doctors and patients assess the risk of cancer recurrence in the next 1 to 3 years. This tool considers various factors such as the size and type of the tumor, as well as the location and extent of the residual tumor after chemotherapy. Our research offers new insights into understanding the risk of recurrence after breast cancer treatment. This work not only enhances our comprehension of breast cancer management but also aids in devising more personalized and effective treatment strategies for patients in the future.

OBJECTIVE: Ischemic complications after nipple-sparing mastectomy (NSM) can be ameliorated by 2-stage procedures wherein devascularization of the nipple-areolar complex (NAC) and lumpectomy with or without nodal staging surgery is performed first (1S), weeks prior to a completion NSM (2S). We report the time interval between procedures in relation to the presence of residual carcinoma at 2S NSM.
METHODS: Women with breast cancer who received 2S NSM from 2015 to 2022 were identified. Both patient level and breast level analyses were conducted. Clinical staging at presentation, pathologic staging at 1S and residual disease at 2S pathology are noted. Residual disease was classified as microscopic (1-2 mm), minimal (3-10 mm), and moderate (> 10 mm).
RESULTS: 59 patients (108 breasts) underwent 2S NSM. The median time interval between 1 and 2S for all patients was 34 days: 31 days for upfront surgery invasive cancer, 41 days for upfront DCIS surgery and 31 days for those receiving neoadjuvant therapy. Completion NSM was performed within 6 weeks for 72% of the breasts analyzed. Of the 53 breasts with invasive cancer on 1S pathology, 35% (19/53) had no residual invasive disease and 24.5% (13/53) had neither residual invasive nor in situ carcinoma on final 2S. Among the 50 women who had upfront surgery, 16 (32%) had residual invasive cancer found at 2S NSM, 9 of which had less than or equal to 1 cm disease.
CONCLUSIONS: Invasive cancers were completely resected during 1S procedure in 65% of breasts. Residual disease was minimal and there was only one case of upstaging at 2S. Added time of two-stage surgery is offset by a reduction in ischemic mastectomy flap complications.