Chamberlain V, Holt LR, Shern TP
… +5 more, Gadd MA, Specht MC, Bahl M, Smith BL, Ozmen T
Ann Surg Oncol
· 2026 Jun · PMID 42371317
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BACKGROUND: Atypical ductal hyperplasia (ADH) and lobular intraepithelial neoplasia (LIN) identified on core needle biopsy have variable rates of upgrade to malignancy when surgically excised. Although excision is recomm...BACKGROUND: Atypical ductal hyperplasia (ADH) and lobular intraepithelial neoplasia (LIN) identified on core needle biopsy have variable rates of upgrade to malignancy when surgically excised. Although excision is recommended for ADH, management of LIN has shifted toward a selective approach. We evaluated upgrade rates and developed a risk stratification model to guide management. METHODS: We conducted a retrospective study of 502 women diagnosed with ADH and/or LIN on core needle biopsy from 2020 to 2023 at an academic institution. Included patients underwent surgical excision or had at least 2-year follow-up. Upgrade rates to ductal carcinoma in situ (DCIS) or invasive carcinoma were assessed. Multivariable logistic regression identified predictors of upgrade. RESULTS: Overall upgrade rates were 14.0% for ADH, 2.4% for LIN, and 18.0% for concurrent ADH+LIN (p<0.001). Among excised lesions, upgrades in ADH were predominantly DCIS (79.5%), whereas all upgrades in LIN were invasive carcinomas. All invasive cancers were low stage (stage IA). On multivariable analysis, age >70 years, prior contralateral breast cancer, dense tissue on mammography, and severe atypia were independent predictors of upgrade. Patients were stratified into low- (0 factors), moderate- (1 factor), and high-risk (≥2 factors) groups; upgrade rates were 4.2, 16.5 and 25.5%, respectively. Among patients managed nonoperatively, one ADH case was subsequently diagnosed as DCIS. CONCLUSIONS: Upgrade risk in atypical breast lesions varies by lesion type and clinical factors. A risk-based approach identifies a subset of patients-particularly those with LIN or low-risk ADH-who may be managed without excision, potentially reducing unnecessary surgery while maintaining oncologic safety.
Yu AT, Pitcher C, Khaitov S
… +5 more, Tabrizian P, Steinhagen R, Hahn SJ, Park JO, Cohen NA
Ann Surg Oncol
· 2026 Jun · PMID 42365160
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INTRODUCTION: Anastomotic leaks (AL) are a devastating complication of simultaneous resection of primary colon cancer and liver metastases. We aimed to determine the risk factors of AL using a 10-year cohort from a natio...INTRODUCTION: Anastomotic leaks (AL) are a devastating complication of simultaneous resection of primary colon cancer and liver metastases. We aimed to determine the risk factors of AL using a 10-year cohort from a nationwide database. PATIENTS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) from 2014 to 2023 was used. Patients who underwent simultaneous colectomy and liver resection were included. Multivariate analysis was performed with AL as the outcome variable. The 2:1 propensity score matching (PSM) was performed on preoperative and operative covariates. RESULTS: A total of 1517 patients were included. Median age was 60 years and 824 (54%) were male. Most liver resections were minor hepatectomies (87%). In total, 80 (5.3%) patients developed AL. On univariate analysis, higher ASA score, chronic steroid use, and intraoperative blood transfusion were statistically significant risk factors for AL. Multivariate analysis showed that higher ASA score (OR 2.55), chronic steroid use (OR 2.39), major hepatectomy (OR 1.92), and blood transfusion (OR 2.27) were independent risk factors for AL. A 2:1 PSM cohort for blood transfusions resulted in 205 patient pairs. The rate of AL in the blood transfusion cohort was higher (10.7% versus 5.0%, p < 0.01). CONCLUSIONS: In this study, we found that a higher ASA score, chronic steroid use, major hepatectomies, and blood transfusions were independent predictors of AL. In matched cohorts, there was also an increased risk for AL. Thus, for high-risk patient populations undergoing simultaneous resection of primary colon cancer and liver metastasis, consideration should be given for fecal diversion or staged procedures.
Rusidanmu A, Zhou K, Zhu X
… +19 more, Zheng D, Tu Z, Jiang H, Yang R, Liu K, Zhang H, Ye X, Yu H, Yu H, Xu P, Zhi S, Jing J, Wu X, Wu G, Peng C, Peng X, Huang B, Zheng Y, Ye P
Ann Surg Oncol
· 2026 Jun · PMID 42365159
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BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) remains the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC), although distant recurrence continues to limit long-term survival. Neoadjuvan...BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) remains the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC), although distant recurrence continues to limit long-term survival. Neoadjuvant chemoimmunotherapy (CIT) has emerged as a potential systemic-focused alternative. This prospective multicenter study explored the comparative outcomes of neoadjuvant sintilimab plus chemotherapy versus CRT in resectable, clinical node-positive ESCC. METHODS: Consecutive adults with resectable, clinical node-positive (cN+) ESCC were enrolled across four academic centers. The patients received neoadjuvant sintilimab plus platinum-based chemotherapy (CIT) or standard CRT according to predefined institutional pathways in a nonrandomized design (2:1 enrollment). The primary endpoint was pathologic complete response (pCR). The secondary endpoints included nodal downstaging, perioperative outcomes, disease-free survival (DFS), overall survival (OS), and exploratory analyses of pretreatment inflammatory biomarkers. RESULTS: The 63 patients in this study completed neoadjuvant therapy followed by esophagectomy (CIT [n = 42] or CRT [n = 21]). The pCR rate was numerically higher with CRT than with CIT (52.4 % vs 31.0 %; p = 0.110). Nodal clearance was comparable (ypN0: 85.7 % vs 78.6 %; p = 0.735) with high R0 resection rates in both groups. During a median follow-up period of approximately 22 months, DFS did not differ significantly, whereas OS showed separation on unadjusted Kaplan-Meier analysis (p = 0.04, log-rank). Exploratory analyses showed no significant associations between pretreatment inflammatory biomarkers (neutrophil-to-lymphocyte ratio [NLR], monocyte-to-lymphocyte ratio [MLR], platelet-to-lymphocyte ratio [PLR], systemic immune-inflammation index [SII]) and pathologic response. Higher baseline SII was associated with OS in unadjusted comparisons. CONCLUSIONS: In this prospective nonrandomized cohort of clinical node-positive ESCC, CIT achieved nodal downstaging and R0 resection comparable with CRT but lower pCR. The observed survival difference should be interpreted cautiously and warrants validation in randomized trials.
Tomita K, Adams AM, Takayama M
… +15 more, Pan C, Shen SE, Wang X, Wang XS, Williams LA, Arvide EM, To C, Gamboa A, Maxwell JE, Snyder RA, Kim MP, Tzeng CD, Lee JE, Katz MHG, Ikoma N
Ann Surg Oncol
· 2026 Jun · PMID 42365157
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Tsukada Y, Ikeda M, Uehara K
… +4 more, Sekimoto M, Fujita F, Suto T, Ito M
Ann Surg Oncol
· 2026 Jun · PMID 42365155
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PURPOSE: Our objective was to evaluate the utilization and clinical impact of CONNECT-LR, an asynchronous teleconsultation system for locally recurrent rectal cancer (LRRC), focusing on resectability assessment and clini...PURPOSE: Our objective was to evaluate the utilization and clinical impact of CONNECT-LR, an asynchronous teleconsultation system for locally recurrent rectal cancer (LRRC), focusing on resectability assessment and clinical trial referral. METHODS: In this multicenter, prospective observational study, we included all cases submitted to CONNECT-LR between August 2019 and March 2025, as well as referring physicians and consultants. Referring physicians securely uploaded anonymized clinical and imaging data through a dedicated platform, and consultants responded within 1 week. Data were collected in predefined categories, including consultation purposes and recommendations, physician and institutional characteristics, and user and consultant surveys assessing satisfaction and clinical course. The analysis comprised descriptive statistics. RESULTS: Overall, 77 consultations were conducted. Most referring physicians were gastrointestinal surgeons (97.4%). The primary purpose of consultation was resectability assessment in 55 cases (71.4%). Of the 34 cases initially judged as unresectable or with uncertain resectability by referring physicians, 24 (70.6%) were reclassified as resectable by consultants, and surgical resection was performed in 15 of these 34 cases (44.1%), predominantly following referral to consultants' institutions. Six patients were enrolled in a randomized controlled trial for resectable LRRC. User satisfaction was high: 93.3% of referring physicians and 76.1% of consultants reported being satisfied or somewhat satisfied. CONCLUSIONS: CONNECT-LR effectively provides expert judgment, often altering resectability assessments and increasing access to curative-intent surgery for patients with LRRC, offering a potential pathway to clinical trial participation. As a feasible, secure, and scalable model, this teleconsultation platform may help reduce regional disparities and expand access to subspecialty care for LRRC.
Afsar AP, Mullen B, Moreira AA
… +2 more, Tran BV, Vijayasekaran A
Ann Surg Oncol
· 2026 Jun · PMID 42365154
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Post-mastectomy breast reconstruction (PMBR) plays a critical role in restoring physical appearance and psychosocial well-being. However, pronounced geographic and socioeconomic disparities in PMBR access persist worldwi...Post-mastectomy breast reconstruction (PMBR) plays a critical role in restoring physical appearance and psychosocial well-being. However, pronounced geographic and socioeconomic disparities in PMBR access persist worldwide, largely driven by insurance coverage variations. We reviewed English-language literature examining regional insurance disparities in PMBR access through PubMed searches and reference screening. Access to PMBR varies dramatically across regions. Africa demonstrates the lowest utilization; fewer than 10% of eligible women undergo reconstruction, primarily through out-of-pocket payments. In Asia, South Korea's national insurance coverage achieves 77% PMBR rates, whereas limited coverage in China and India restricts access to affluent urban populations. Europe, Australia, New Zealand, and Brazil provide universal coverage with variable utilization. North America demonstrates legislative mandates in the United States, yet socioeconomic disparities persist, while Canada offers universal coverage with underutilization. Policy interventions requiring legislative mandates, guideline-based surgical counseling, and rural outreach are essential to address these equity gaps.
Ann Surg Oncol
· 2026 Jun · PMID 42365150
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BACKGROUND: Emerging evidence implicates sialic acid-binding immunoglobulin-like lectin (SIGLEC) family members as emerging immune checkpoints and as having a role in cancer progression. However, as a relatively unique S...BACKGROUND: Emerging evidence implicates sialic acid-binding immunoglobulin-like lectin (SIGLEC) family members as emerging immune checkpoints and as having a role in cancer progression. However, as a relatively unique SIGLEC member, SIGLEC12 has rarely been studied in cancer, and its clinical significance in pancreatic ductal adenocarcinoma (PDAC) remains largely unknown. This study aimed to investigate the expression pattern and prognostic value of SIGLEC12 in PDAC. METHODS: A retrospective cohort of 145 patients with PDAC was enrolled. SIGLEC12 expression was assessed by immunohistochemistry on tumor microarrays. The association between SIGLEC12 and overall survival (OS) and recurrence-free survival (RFS) was evaluated using the Kaplan-Meier method and Cox regression analysis. The potential effect modification of SIGLEC12 was assessed by interaction analyses. RESULTS: SIGLEC12 expression was significantly upregulated in PDAC tissues at both protein and messenger RNA levels (P < 0.001). High SIGLEC12 expression was associated with poorer OS and RFS and was an independent prognostic factor (OS: hazard ratio [HR] 1.928, P = 0.0004; RFS: HR 1.569, P = 0.022). Interaction analyses revealed that the prognostic effects of carbohydrate antigen 19-9 (CA19‑9) and adjuvant chemotherapy (ACT) were significantly modified by SIGLEC12. Notably, elevated CA19-9 predicted poorer survival, and ACT improved survival only in patients with low SIGLEC12 expression and not in those with high SIGLEC12 expression. CONCLUSIONS: SIGLEC12 is frequently upregulated in PDAC and predicts poor prognosis. Notably, our exploratory findings suggest that SIGLEC12 may modify the prognostic effect of CA19‑9 and the therapeutic benefit of ACT. These findings position SIGLEC12 as a promising prognostic biomarker and novel therapeutic target in PDAC, with potential for further roles in refining risk stratification and guiding personalized treatment decisions.
Ueki Y, Horimoto Y, Yuan M
… +9 more, Wu R, Ushiyama Y, Ishizuka Y, Onagi H, Hayashi T, Kawate T, Ishikawa T, Watanabe J, Kutomi G
Ann Surg Oncol
· 2026 Jun · PMID 42362880
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BACKGROUND: Among HER2-positive breast cancer patients, those who do not achieve pathological complete response (non-pCR) after neoadjuvant chemotherapy (NAC) generally have poorer outcomes. Although additional postopera...BACKGROUND: Among HER2-positive breast cancer patients, those who do not achieve pathological complete response (non-pCR) after neoadjuvant chemotherapy (NAC) generally have poorer outcomes. Although additional postoperative therapies have been developed, it remains unclear which patients truly require treatment intensification. This study aimed to identify prognostic factors in non-pCR patients. METHODS: Of 283 patients with HER2-positive invasive breast cancer treated with NAC, including anti-HER2 therapy between 2006 and 2023, 174 were classified as non-pCR. Of these, 37 patients developed distant metastases (Met group) and 137 remained metastasis-free (non-Met group). Gene expression profiling was performed by using pretreatment biopsies from six Met and six non-Met cases. Immunohistochemical validation was conducted in an independent cohort of 101 patients who did not achieve pCR. RESULTS: Gene expression analysis identified multiple genes with differential expression between the Met and non-Met groups; MYCN, CCNE1, and IL6 were upregulated in the Met group, whereas KIT and ERBB4 were downregulated. Among these, MYCN and cyclin E1 showed concordant results at the protein level. Immune-related gene set analysis further suggested increased regulatory T-cell infiltration in the Met group. In the validation cohort, cyclin E1 positivity was significantly higher in the Met group (50% vs. 20%, P = 0.005), and cyclin E1-positive patients had significantly shorter disease recurrence-free survival (P = 0.005). Cyclin E1 expression was thus associated with poorer outcomes in HER2-positive breast cancer patients with non-pCR. CONCLUSIONS: These findings support cyclin E1 as a prognostic biomarker that may contribute to risk stratification and individualized postoperative treatment strategies.
Wu Y, Zhang X, Du W
… +3 more, Yuan J, Li W, Fang Q
Ann Surg Oncol
· 2026 Jun · PMID 42362878
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BACKGROUND: Neoadjuvant immunochemotherapy (NICT) has transformed the treatment of locally advanced oral squamous cell carcinoma (OSCC), yet the prognostic reliability of the eighth-edition American Joint Committee on Ca...BACKGROUND: Neoadjuvant immunochemotherapy (NICT) has transformed the treatment of locally advanced oral squamous cell carcinoma (OSCC), yet the prognostic reliability of the eighth-edition American Joint Committee on Cancer (AJCC) pathologic nodal staging in this context remains unclear. This study sought to develop a ypN staging system for post-NICT OSCC. METHODS: This retrospective study analyzed 559 patients with locally advanced OSCC who received NICT followed by radical surgery across two centers (training cohort, n = 226; external validation cohort, n = 333). A proposed ypN staging system integrating viable node burden and macro- extranodal extension (ENE) status was developed and externally validated. Model performance was compared with the eighth-edition AJCC staging using Harrell's C-index, the Akaike Information Criterion, and decision curve analysis. RESULTS: Three prognostic groups emerged (0, 1-2, and ≥3 viable metastatic lymph nodes). Multivariate analysis showed that micro-ENE did not add significant risk (hazard ratio, 1.12; P = 0.79), whereas macro-ENE independently predicted recurrence. The proposed staging framework, which categorizes patients into ypN0 (0 viable nodes), ypN1 (1 to 2 viable nodes without macroscopic ENE), ypN2 (≥3 viable nodes without macroscopic ENE), and ypN3 (≥1 viable nodes with macroscopic ENE), produced a clearly distinct prognostic gradient, with 3-year disease-free survival rates of 84.1, 61.2, 31.8, and 9.1%, respectively. This system outperformed the eighth-edition AJCC staging in both cohorts, demonstrating higher C-indices (0.78 vs 0.70; 0.76 vs 0.69), lower AICs, and superior net clinical benefit. CONCLUSIONS: The proposed ypN staging system, grounded in viable metastatic lymph node burden and macro-ENE, offers improved prognostic discrimination for post-NICT OSCC.
Dong Y, Pereyra D, Podrascanin V
… +10 more, Li Z, Santol J, Ammann M, Fonkoua LAK, Graham RP, Conboy CB, Tran NH, Warner SG, Smoot RL, Starlinger P
Ann Surg Oncol
· 2026 Jun · PMID 42362876
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BACKGROUND: Despite the theoretical advantages of neoadjuvant therapy (NAT) in intrahepatic cholangiocarcinoma (iCCA), its impact on post-recurrence overall survival (PROS) remains poorly defined. This study investigated...BACKGROUND: Despite the theoretical advantages of neoadjuvant therapy (NAT) in intrahepatic cholangiocarcinoma (iCCA), its impact on post-recurrence overall survival (PROS) remains poorly defined. This study investigated the association between NAT and post-recurrence outcomes. METHODS: This single-center retrospective study included consecutive patients with histologically confirmed iCCA who underwent curative-intent liver resection at Mayo Clinic Rochester (2000-2024). Neoadjuvant therapy was administered to selected patients with high-risk features. The association between NAT and PROS was evaluated using Kaplan-Meier analysis and multivariable Cox regression adjusted for relevant covariates. RESULTS: Among 343 patients with iCCA, NAT recipients were younger, more often treated in the contemporary era, and included a higher proportion of major resections. Targetable molecular alterations (IDH1, FGFR2) were markedly enriched in the NAT group (48.2% vs 13.9%). Neoadjuvant therapy was associated with significantly improved PROS (median, 31.9 vs 16.4 months; p = 0.006) and remained an independent predictor of survival on multivariable Cox regression (hazard ratio, 0.506; p = 0.008), even after the study accounted for era-dependent molecular-profiling. In contrast, older age and early recurrence were independently associated with worse PROS. Recurrence patterns, including location, timing, and median time to recurrence, remained comparable over time. After recurrence, NAT recipients more frequently underwent curative-intent local therapies and advanced systemic treatments. CONCLUSIONS: Neoadjuvant therapy was associated with improved PROS for resected iCCA patients, consistent with a potential role in biologic selection. Recipients of NAT showed enriched targetable molecular alterations and better PROS despite stable recurrence patterns. These findings position PROS as a relevant endpoint in NAT-treated iCCA, complementing conventional survival metrics.