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.

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.

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.

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.

BACKGROUND: Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated with poorer survival outcomes compared with no residual disease. We performed a meta-analysis to assess the impact of varying levels of residual disease status on survival outcomes in patients with ovarian cancer who have undergone primary cytoreductive surgery or interval cytoreductive surgery in the setting of new therapies for this disease.
METHODS: Medline, Embase, and Cochrane databases (January 2011 - July 2020) and grey literature, bibliographic and key conference proceedings, were searched for eligible studies. Fixed and random-effects meta-analyses compared progression and survival by residual disease level across studies. Heterogeneity between comparisons was explored via type of surgery, disease stage, and type of adjuvant chemotherapy.
RESULTS: Of 2832 database and 16 supplementary search articles screened, 50 studies were selected; most were observational studies. The meta-analysis showed that median progression-free survival and overall survival decreased progressively with increasing residual disease (residual disease categories of 0 cm, > 0-1 cm and > 1 cm). Compared with no residual disease, hazard ratios (HR) for disease progression increased with increasing residual disease category (1.75 [95% confidence interval: 1.42, 2.16] for residual disease > 0-1 cm and 2.14 [1.34, 3.39] for residual disease > 1 cm), and also for reduced survival (HR versus no residual disease, 1.75 [ 1.62, 1.90] for residual disease > 0-1 cm and 2.32 [1.97, 2.72] for residual disease > 1 cm). All comparisons were significant (p < 0.05). Subgroup analyses showed an association between residual disease and disease progression/reduced survival irrespective of type of surgery, disease stage, or type of adjuvant chemotherapy.
CONCLUSIONS: This meta-analysis provided an update on the impact of residual disease following primary or interval cytoreductive surgery, and demonstrated that residual disease was still highly predictive of progression-free survival and overall survival in adults with ovarian cancer despite changes in ovarian cancer therapy over the last decade. Higher numerical categories of residual disease were associated with reduced survival than lower categories.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that is characterized by new bone formation in the axial musculoskeletal system, with X-ray discriminating between radiographic and non-radiographic forms. Current therapeutic options include non-steroidal anti-inflammatory drugs in addition to biological disease-modifying anti-rheumatic drugs that specifically target tumor necrosis factor-alpha (TNFα) or interleukin (IL)-17. Pain is the most critical symptom for axSpA patients, significantly contributing to the burden of disease and impacting daily life. While the inflammatory process exerts a major role in determining pain in the early phases of the disease, the symptom may also result from mechanical and neuromuscular causes that require complex, multi-faceted pharmacologic and non-pharmacologic treatment, especially in the later phases. In clinical practice, pain often persists and does not respond further despite the absence of inflammatory disease activity. Cytokines involved in axSpA pathogenesis interact directly/indirectly with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling cascade, a fundamental component in the origin and development of spondyloarthropathies. The JAK/STAT pathway also plays an important role in nociception, and new-generation JAK inhibitors have demonstrated rapid pain relief. We provide a comprehensive review of the different pain types observed in axSpA and the potential role of JAK/STAT signaling in this context, with specific focus on data from preclinical studies and data from clinical trials with JAK inhibitors.

UNASSIGNED: Some patients with breast cancer submitted to breast-conserving surgery might benefit from a postlumpectomy imaging examination previously to radiation therapy. This aims to document the complete removal of cancer and might be accomplished using mammogram with breast and axillary ultrasonography. These modalities study not only the affected side but also the contralateral side. In fact, it is well-documented that women with breast cancer have an increased risk for contralateral breast cancer. Thus, we intended to evaluate the value of postlumpectomy imaging undertaken before adjuvant radiotherapy regarding the evaluation of the contralateral breast and axilla.
UNASSIGNED: In this retrospective study, medical records for patients with breast cancer submitted to breast-conserving surgery and referred to our radiotherapy unit between 2018 and 2019 were reviewed. All patients had to be submitted to bilateral mammogram with breast and axillary ultrasonography previously to radiotherapy. Patients with bilateral disease or with a history of breast cancer were excluded.
UNASSIGNED: One thousand two hundred forty patients were analyzed. 19 (1.5%) had suspicious findings for contralateral breast disease, and 8 (0.6%) had a re-excision positive for residual malignancy. Higher age, invasive lobular carcinoma associated or not with lobular carcinoma in situ, and presence of lobular carcinoma in situ were associated with an increased risk for residual disease.
UNASSIGNED: Contralateral evaluation as part of postlumpectomy imaging revealed itself useful at detecting contralateral cancer, with some demographic and clinical features being associated with an increased risk for residual disease.

UNASSIGNED: Achieving no residual disease is essential for increasing overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients. However, the survival benefit of achieving no residual disease during both intrathoracic and abdominopelvic cytoreductive surgery is still unclear. This meta-analysis aimed to assess the survival benefit and safety of intrathoracic and abdominopelvic cytoreductive surgery in advanced ovarian cancer patients.
UNASSIGNED: We systematically searched for studies in online databases, including PubMed, Embase, and Web of Science. We used Q statistics and I-squared statistics to evaluate heterogeneity, sensitivity analysis to test the origin of heterogeneity, and Egger\'s and Begg\'s tests to evaluate publication bias.
UNASSIGNED: We included 4 retrospective cohort studies, including 490 patients, for analysis; these studies were assessed as high-quality studies. The combined hazard ratio (HR) with 95% confidence interval (CI) for OS was 1.92 (95% CI 1.38-2.68), while the combined HR for PFS was 1.91 (95% CI 1.47-2.49). Only 19 patients in the four studies reported major complications, and 4 of these complications were surgery related.
UNASSIGNED: The maximal extent of cytoreduction in the intrathoracic and abdominopelvic tract improves survival outcomes, including OS and PFS, in advanced ovarian cancer patients with acceptable complications.
UNASSIGNED: PROSPERO, identifier CRD42023468096.

BACKGROUND: Soft tissue sarcomas are a group of rare neoplasms which can be mistaken for benign masses and be excised in a non-oncologic fashion (unplanned excision). Whether unplanned excision (UE) is associated with worse outcomes is highly debated due to conflicting evidence.
METHODS: We performed a systematic review and meta-analysis following PRISMA guidelines. Main outcomes analyzed were five-year overall survival (OS), five-year local recurrence-free survival (LRFS), amputation rate and plastic reconstruction surgery rate. Risk ratios were used to compare outcomes between patients treated with planned and unplanned excision.
RESULTS: We included 16,946 patients with STS, 6017 (35.5%) with UE. UE was associated with worse five-year LRFS (RR 1.35, p = 0.019). Residual tumor on the tumor bed was associated with lower five-year LRFS (RR = 2.59, p < 0.001). Local recurrence was associated with worse five-year OS (RR = 1.82, p < 0.001). UE was not associated with a worse five-year OS (RR = 0.90, p = 0.16), higher amputation rate (RR = 0.77, p = 0.134), or a worse plastic reconstruction surgery rate (RR = 1.25, p = 0.244).
CONCLUSIONS: Unplanned excision of Soft Tissue Sarcomas and the presence of disease in tumor bed after one were associated with worse five-year LRFS. Tumor bed excision should remain the standard approach, with special consideration to the presence of residual disease.

The incidence and mortality of cervical cancer are high in Romania compared to other European countries, particularly for locally advanced cervical cancer cases, which are predominant at the time of diagnosis. Widely accepted therapeutic guidelines indicate that the treatment for locally advanced cervical cancer consists of concurrent chemoradiotherapy (total dose 85-90 Gy at point A), with surgery not being necessary as it does not lead to improved survival and results in significant additional morbidity. In Romania, the treatment for locally advanced cervical cancer differs, involving lower-dose chemoradiotherapy (total dose 60-65 Gy at point A), followed by surgery, which, under these circumstances, ensures better local control. In this regard, we attempted to evaluate the role and necessity of surgery in Romania, considering that in our study, residual lesions were found in 55.84% of cases on resected specimens, especially in cases with unfavorable histology (adenocarcinoma and adenosquamous carcinoma). This type of surgery was associated with significant morbidity (28.22%) in our study. The recurrence rate was 24.21% for operated-on patients compared to 62% for non-operated-on patients receiving suboptimal concurrent chemotherapy alone. In conclusion, in Romania, surgery will continue to play a predominant role until radiotherapy achieves the desired effectiveness for local control.