Surgical management remains the cornerstone in the management of gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs), yet surgical indications and procedures are often inconsistent. To inform the development of a research agenda to strengthen the evidence in NETs surgical care, we conducted a scoping review to map the existing literature on surgery for gastro-entero-pancreatic (GEP) NETs. The scoping review was conducted following the expanded framework of Arksey and O'Malley. A literature search was run on MEDLINE, Embase, and Scopus in October 2024 for studies published since 2000 reporting on any surgical intervention, performed under general or loco-regional anesthesia on adults with GEP-NETs at any stage. Among the 10,000 studies screened, 260 were included. Publications included were mostly reviews covering a broad range of topics. Of the 120 original investigations, 96.7% were retrospective cohort studies and 43% were single center. There were only four prospective cohort studies. Of all publications included, the most common topics were observation of small pancreatic NETs, treatment of liver metastases, safety of minimally invasive surgery, and prognostication. Of original investigations, the majority compared surgical approaches, followed by examination of lymph node harvest and defining size cutoff for observation of pancreatic NETs. This scoping review highlights limitations and gaps in the evidence supporting surgical care for GEP-NETs. Very few original investigations report prospective or multi-institutional data, and examination of pancreatic NETs dominate the literature. Future research should prioritize prospective, multi-institutional studies, stage- and primary-site-specific analyses, and interventional trials evaluating surgery relative to other therapies.
In contrast to rectal cancer, the influence of postoperative complications on locoregional recurrence (LRR) in colon cancer is understudied, with conflicting reports. This study aimed to determine the impact of postoperative complications on LRR and overall survival (OS) in colon cancer. This population-based cross-sectional cohort study was carried out in 50 Dutch hospitals. Patients who underwent resection for stage I-III colon cancer between January 2014 and December 2015 were eligible. LRR comprised any intraabdominal recurrence, including peritoneal metastases. A total of 7983 patients were included with a median follow-up of 62.5 months (interquartile range 58.1-80.3). Postoperative complications occurred in 2239 (28.0%) patients and included anastomotic leakage requiring re-intervention in 394 (4.9%), any other surgical complication in 944 (11.8%), and only non-surgical complications in 901 patients (11.3%). The 5-year LRR rate was 13.5%, 8.8% and 8.8%, respectively, as compared with 6.8% in patients without complications (Fine-Gray p<0.001). Only anastomotic leakage was an independent risk factor for LRR (cause-specific hazard ratio [HR] 1.45 [95% confidence interval (CI) 1.07-1.96]). Five-year OS probability was 78.9% for patients without complications versus 71.1%, 68.5%, and 62.7% for patients with anastomotic leakage, any other surgical complication, and non-surgical complications only, respectively (log-rank p<0.001). Both surgical and non-surgical complications were an independent risk factor for worse OS (HR 1.12 [95% CI 1.00-1.26); HR 1.21 [95% CI 1.08-1.36], respectively). This study demonstrates an increased risk of LRR after all types of postoperative complications in patients with stage I-III colon cancer, but only anastomotic leakage remained independently associated with LRR. Both surgical and non-surgical complications were associated with worse OS.
Up to 40% of patients undergoing pancreatoduodenectomy (PD) for resectable pancreatic ductal adenocarcinoma do not receive adjuvant chemotherapy (aCT). This study aimed to evaluate the impact of postoperative pancreatic fistula (POPF) on aCT delivery and timing and to explore how preoperative variables influence these outcomes according to the occurrence of a POPF. This multicenter retrospective study included patients from 25 pancreatic centers. Propensity score matching was performed based on anatomical, biological, and conditional variables. Multivariable regression analyses were used to identify independent predictors of aCT omission and delay. Among 1590 patients, 267 (16.8%) developed a POPF. Overall, aCT was administrated in 1,146 patients (72.1%) with a median time to first dose delivery of 56 days (26). After matching, POPF was associated with a significantly lower likelihood of aCT delivery (p < 0.001) and a significant delay in its initiation (p < 0.001). Independent predictors of aCT omission were age ≥ 70 (odds ratio [OR] 2.480, 95% confidence interval [CI] 1.439-4.274; p < 0.001), chronic renal failure (OR 4.554, 95% CI 1.320-15.708; p = 0.016), and chronic obstructive pulmonary disease (OR 2.775, 95% CI 1.021-7.546; p = 0.045) when POPF occurred. In the absence of POPF, apart from age ≥ 70, venous contact (OR 1.574, 95% CI 1.114-2.224; p = 0.010) and tumor size > 20 mm (OR 0.713, 95% CI 0.523-0.972; p = 0.032) were predictors of aCT delivery. Postoperative pancreatic fistula is a key driver of aCT delivery after pancreatoduodenectomy. Its interaction with patient frailty highlights the need for preoperative risk assessment to better select candidates for upfront surgery in resectable pancreatic ductal adenocarcinoma.
Socioeconomic status (SES) has been associated with survival in breast cancer; yet its role in sarcomas of the breast remains poorly studied. We aimed to investigate whether individual-level SES, approximated by educational attainment and household income, is associated with overall survival in a nationwide cohort of women with sarcomas of the breast within a universal healthcare system. We conducted a nationwide cohort study by using linked Swedish population registers. Women diagnosed with an incident borderline or malignant phyllodes tumor (PT), angiosarcoma, or soft-tissue sarcoma of the breast from 1993 to 2018 were included and followed through 2019. Socioeconomic status was defined by highest attained education and household disposable income. The primary outcome was all-cause death. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by using multivariable Cox proportional hazards regression. A total of 473 women were included (median age, 51 years). The cohort comprised 198 borderline PT, 179 malignant PT, 25 angiosarcomas, and 71 soft-tissue sarcomas. Median follow-up was 13.1 years. In multivariable analyses, educational level was not associated with overall survival (OS) (≤9 vs. >13 years, HR 1.29, 95% confidence interval [CI] 0.76-a2.22; 10-13 vs. >13 years, HR 1.16, 95% CI, 0.71-1.89]). Lower household income was associated with worse OS (Q1 vs. Q5, HR 2.35, 95% CI 1.22-4.52; Q2 vs. Q5, HR 1.98, 95% CI 1.06-3.7). Lower income, but not education level, was associated with worse OS in patients with sarcomas of the breast. These results underscore the presence of survival disparities among patients with rare breast tumors, even within a universal healthcare system.
Nipple-sparing mastectomy (NSM) confers similarly excellent patient-reported outcomes (PROs) as skin-sparing mastectomy; however, the relative weight of individual patient- and treatment-related factors on satisfaction with breasts and psychosocial well-being following NSM is unclear. We assessed predictors of PROs following NSM. Patients undergoing NSM between April 2018 and July 2021 at a single institution were included in a prospective examination. Routinely collected preoperative and postoperative BREAST-Q responses were recorded. Univariable and multivariable linear regression identified predictors of satisfaction with breasts and psychosocial well-being. 333 patients underwent NSM; median age was 43 years (interquartile range [IQR] 37-49 years). Of patients, 86% received two-stage reconstruction with tissue expander (TE) followed by an implant; 12% received postmastectomy radiation (PMRT). At 1 year, receipt of PMRT predicted lower satisfaction (b = - 32 [95% confidence interval (CI) - 42- - 22], p < 0.001) and psychosocial well-being (b = - 43 [- 56- - 30], p < 0.001), as did TEs, compared with autologous tissue reconstruction for both satisfaction (b = -15 [- 27- - 3.4], p = 0.012) and well-being (b = -31 [- 52- - 11], p =0.004). At 2 years, PMRT remained a significant negative predictor of satisfaction (b = -14 [95% CI -24- - 3.5], p = 0.009) and well-being (b = -16 [95% CI -31- - 0.97], p = 0.04) but reconstruction type was not (p = ns). Full-thickness skin-flap necrosis predicted poorer satisfaction at 1 year (b = -19 [95% CI - 34- - 4.6], p = 0.01) but not at 2 years (p = ns). Higher preoperative psychosocial well-being was positively associated with postoperative scores at 1 and 2 years. Receipt of PMRT is persistently and negatively associated with PROs at up to 2 years after NSM. Longer follow-up is needed to assess the impact of reconstruction type on these outcomes.
Colorectal liver metastases (CRLM) are the main determinant of survival in colorectal cancer, and radical resection offers the best oncological outcomes. However, heterogeneous clinicopathological features make appropriate patient selection essential. Numerous clinical risk scores (CRS) have been proposed to predict outcomes after liver resection for CRLM. This study evaluated the prognostic performance of 11 established CRS regarding survival after curative-intent resection of CRLM. This retrospective study included patients who underwent curative-intent liver resection for CRLM at University Hospital RWTH Aachen, Germany, between 2010 and 2021. The following CRS were analyzed: Fong, Nordlinger, Nagashima, Konopke, Basingstoke Predictive Index, Tumor Burden Score, Resection Severity Index, Kulik, RAS-mutation CRS, Comprehensive Evaluation of Relapse Risk (CERR) score, and the Genetic and Morphological Evaluation score. Overall survival (OS) was compared using Kaplan-Meier analysis and log-rank testing. Predictive accuracy was assessed using the Akaike information criterion, Harrell's C-index for OS, and area under the curve (AUC) analyses for 1- and 5-year survival. A total of 528 patients were included, with a median OS of 26 months (95% confidence interval [CI] 23-28). All CRS except the Resection Severity Index significantly stratified patients according to OS. CERR consistently ranked among the top three scores for both the Akaike information criterion (1725) and the C-index (0.61) and had the highest accuracy for predicting 1-year survival (AUC 0.654, p = 0.001) and 5-year survival (AUC 0.62, p < 0.001). Although the CERR demonstrated the most consistent predictive performance, 10 of 11 evaluated CRS effectively stratified patients according to long-term survival after CRLM resection.
Recurrence impacts outcome after resection for pancreatic ductal adenocarcinoma (PDAC). However, isolated pulmonary metastases exhibit favorable overall survival (OS). Outcomes for patients with pulmonary metastases and concurrent recurrence at other sites are not well studied. This study aimed to assess OS for patients with differing pulmonary recurrence patterns after surgery for PDAC. The study included adult patients with PDAC resected between 2009 and 2018 at Karolinska University Hospital. The following three recurrence patterns occurring within 3 years after surgery were compared: metastases involving the liver (liver), pulmonary metastases not involving the liver (lung), and metastases involving neither lung nor the liver (other). Survival analyses with flexible parametric regressions and the Kaplan-Meier method were undertaken. Of 343 patients included in the study, 293 (85%) experienced recurrence within 3 years. The recurrences included 145 (49%) to the liver, 61 (21%) to the lung, and 87 (30%) to other sites. The median OS values for the mentioned groups were 13 months (95% confidence interval [CI], 12-16 months), 30 months (95% CI, 27-35 months), and 20 months (95% CI, 19-26 months) respectively (p ≤ 0.001 for all). Flexible parametric survival regressions showed distinct recurrence-specific mortality risks. Compared with no recurrence, the mortality conferred by the lung was 7-fold higher, by other was 12-fold higher, and by the liver was 23-fold higher (p ≤ 0.001 for all), demonstrating a clear prognostic hierarchy. Pulmonary metastases, a frequent recurrence pattern after PDAC surgery, exhibit superior OS compared with other sites, even if combined with peritoneal or other distant spread. This finding supports further consideration of targeted treatment strategies for this subgroup.
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
Complications after pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) are associated with delays or omission of adjuvant chemotherapy (AC). Similar data for patients who undergo distal pancreatectomy (DP) are lacking. A retrospective cohort study was conducted using the SEER-Medicare database to identify patients who underwent upfront DP for PDAC (2010-2019). Multilevel logistic regression and Cox proportional hazards models were used to evaluate the association of postoperative complications with AC omission and delay as well as survival endpoints based on receipt of AC. Of 1029 patients identified, 613 (59.6 %) received AC. Patients with complications had lower rates of AC (50.0 % vs 61.1 %; p = 0.013) and multi-agent AC (25.0 % vs 28.2 %; p = 0.039) and higher rates of delays in AC (42.9 % vs 21.4 %; p < 0.001) than those without complications. In multivariable analysis, complications were associated with a lower rate of AC (hazard ratio [HR], 0.67; 95 % confidence interval [CI], 0.54-0.84; p < 0.001) and a higher rate of delayed AC (odds ratio [OR], 3.36; 95 % CI 1.92-5.91; p < 0.001). For survival, receipt of AC overall (HR, 0.56; 95 % CI 0.47-0.67; p < 0.001), even when delayed (HR, 0.72; 95 % CI 0.57-0.90; p = 0.005), was associated with better overall survival (OS) than no AC. However, delayed AC was associated with worse OS than timely AC (HR, 1.27; 95 % CI 1.01-1.62; p = 0.04). Patients who experienced a postoperative complication after DP for left-side PDAC had lower rates of AC overall and higher rates of delayed AC, both associated with worse OS.
Enucleating multiple insulinomas adjacent to the main pancreatic duct poses significant risks of parenchymal injury and postoperative complications. While indocyanine green (ICG) fluorescence aids in tumor localization, excessive background fluorescence and diminished intensity during prolonged procedures can obscure tumor margins. A 38-year-old male presented with multiple insulinomas located in the pancreatic head, tail, and uncinate process. The head and tail lesions were within 1 mm of the main pancreatic duct. Laparoscopic enucleation was planned using combined ICG fluorescence and intraoperative ultrasound (IOUS). The patient received 25 mg of intravenous ICG 24 hours preoperatively. Intraoperative probing revealed no fluorescence from the preoperative ICG dose. Subsequently, a 12.5 mg intravenous ICG bolus was administered. Tumor enhancement was achieved in 15 seconds, and distinct tumor demarcation appeared at 30 minutes as background fluorescence dissipated. Guided by real-time ICG and IOUS, the tumors were safely enucleated using cold sharp dissection near the duct. Intraoperative portal vein blood sampling confirmed a significant decline in insulin and C-peptide levels. Blood loss was 50 mL, and operative time was 200 minutes. The patient was discharged on postoperative day 4 without pancreatic fistula. Integrating an intraoperative 12.5 mg ICG bolus with IOUS provides precise localization and enables safe, parenchyma-sparing enucleation of multiple insulinomas near the main pancreatic duct. Preoperative ICG administration 24 hours prior is not recommended.
Mucinous gastric adenocarcinoma (MGC) is a rare, aggressive malignancy. This study aimed to explore whether MGC is associated with poorer survival compared with nonmucinous gastric adenocarcinoma (NMGC) and to further investigate the potential impact of neoadjuvant chemotherapy (NAC) on MGC by assessing overall survival (OS), tumor regression grade (TRG), and histological subtypes. A retrospective analysis was conducted on 492 patients with MGC and 7945 patients with NMGC undergoing resection at Zhejiang Cancer Hospital (2014-2023). Patients were categorized into neoadjuvant and surgery groups. MGC was further classified as pure (≥ 80%) or mixed (< 80%). OS was analyzed using Kaplan-Meier and Cox regression, with propensity score matching (PSM) for adjustment. After PSM, OS did not differ between MGC and NMGC. Patients with MGC receiving NAC had significantly worse OS than those undergoing surgery, with NAC as an independent risk factor. TRG analysis showed a markedly lower proportion of responders (TRG 0-1) in MGC than NMGC, indicating reduced chemosensitivity. Among subtypes, NAC remained an adverse factor in pure MGC, while mixed MGC showed no significant difference after PSM. MGC exhibits poor pathological response and no survival benefit from NAC, supporting upfront surgery as the preferred approach. TRG findings highlight intrinsic chemoresistance, particularly in pure MGC, underscoring the need for histology-based individualized strategies.
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 13%. Surgical resection followed by adjuvant chemotherapy remains the only curative approach. However, complications such as postoperative pancreatic fistula (POPF) and postpancreatectomy hemorrhage (PPH) often delay or prevent further treatment. Reliable preoperative biomarkers for predicting these complications are lacking. This study investigated soluble CD40 (sCD40) as a potential predictive marker for pancreas-specific complications after pancreatoduodenectomy (PD) in patients with PDAC. Preoperative serum samples from 185 patients with PDAC undergoing pylorus-preserving pancreatoduodenectomy or a Whipple procedure were analyzed using enzyme-linked immunosorbent assay to quantify sCD40 levels. Clinical and postoperative data were systematically collected and classified. Of the 185 patients, 151 underwent pylorus-preserving PD and 34 a Whipple procedure. Clinically relevant POPF occurred in 9.7% and PPH in 7.6% of patients. Preoperative sCD40 levels were significantly lower in patients who developed POPF or PPH (P = 0.025 and P = 0.008). The association remained significant in multivariable analysis. Receiver operating characteristic analysis demonstrated an area under the curve of 0.660 for sCD40. Adding leukocytes and body mass index improved predictive performance (area under the curve 0.705 for POPF and 0.752 for PPH). Reduced preoperative sCD40 serum levels are associated with a higher risk of POPF and PPH after PD. Combining sCD40 with leukocytes and BMI may enhance preoperative risk assessment in patients with PDAC.
The peripheral nervous system can contribute to tumor development, progression, and metastasis; however, the clinical relevance of neuronal features within the tumor microenvironment in patients with gastric cancer (GC) remains to be fully elucidated. Bulk transcriptomic and clinical data from publicly available databases were used to evaluate an xCell score that quantified the relative enrichment of neuron-associated gene expression programs in GC tumors. This allowed stratification into neuron score-high and neuron score-low groups within each cohort, with the upper two-thirds defined as high. Associations between neuronal enrichment and tumor biology were evaluated through analyses of neurotransmitter receptor expression, gene set enrichment, tumor microenvironment composition, genomic features, and patient survival. Neuron score-high GC exhibited characteristic enrichment of β-adrenergic, dopamine, and muscarinic acetylcholine receptor gene expression, consistent with enhanced neurochemical signaling potential. At the tumor cell level, the neuron score-high group was associated with activation of epithelial-mesenchymal transition (EMT) programs, whereas cell proliferation-related pathways were preferentially enriched in neuron score-low tumors. Neuron score-high tumors further displayed attenuated antitumor immune infiltration, increased stromal components, and elevated intratumor heterogeneity despite a lower mutation burden. Across both cohorts, neuron score-high tumors were associated with worse overall survival and remained independently associated with prognosis in multivariate analyses. Neuron score-high GC tumors were consistently associated with distinct patterns of neurotransmitter receptor gene expression, enhanced EMT programs with reduced cell proliferation, attenuated antitumor immune infiltration, increased intratumor heterogeneity, and worse prognosis. These observations identify the neuron score in bulk tumors as a potential indicator of GC biology.
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
Neoadjuvant therapy followed by esophagectomy has become the standard of care in locally advanced esophageal cancer. However, the adequacy of lymph node dissection (LND) for patients with a pathologic complete response (pCR) during esophagectomy after neoadjuvant therapy remains undetermined. Our meta-analysis aimed to investigate whether adequate LND was associated with survival benefits in complete responders to neoadjuvant therapy. A systematic online search was conducted to investigate the relationship between the extent of LND and survival in patients with pCR, with overall survival (OS) as the primary endpoint and disease-free survival as the secondary endpoint. Subgroup analyses were performed per LND thresholds, pathology, and geographic regions. Our study included eight studies involving a total of 2578 patients with pCR. The pooled data demonstrated a significant association between adequacy of LND and improved OS (hazard ratio 0.70; 95% confidence interval 0.58-0.84, p < 0.001). However, no significant survival advantage on disease-free survival was observed (hazard ratio 0.72; 95% confidence interval 0.24-2.20, p = 0.568). Moreover, extensive LND did not bring additional survival benefits to OS when the harvested lymph nodes exceeded 40. Subgroup analyses revealed that adequate LND was significantly associated with superior OS in the Western and adenocarcinoma-predominant populations but not in the Eastern population or in those with squamous cell carcinoma. Adequate lymphadenectomy might correlate with better OS in patients with pCR, specifically in those with adenocarcinoma. Our findings suggested that the extent of LND should be tailored to histology and populations, which should be interpreted with caution.
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）