Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

Non-viral precision T cell receptor replacement for personalized cell therapy.

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRß). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial ( NCT03970382 ). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

Simultaneous Hepatic and Visceral Resection: Preoperative Risk Stratification and Implications on Return to Intended Oncologic Therapy.

PURPOSE: Sequence of therapies for synchronous liver metastasis (LM) is complex, with data supporting individualized approaches, although no guiding tools are currently available. We assessed the impact of simultaneous hepatic and visceral resections (SHVR) on textbook outcome (TO) and return to intended oncologic therapy (RIOT), and provide risk-stratification tools to guide individualized decision making and counseling. METHODS: Patients with synchronous LM undergoing hepatectomy ± SHVR were included (2015-2021). Primary and secondary outcomes were TO and RIOT (days), respectively. Using multivariable modeling, a risk score for TO was developed. Decision tree analysis using recursive partitioning was performed for hierarchical risk stratification. The associations between SHVR, TO, and RIOT were examined. RESULTS: Among 533 patients identified, 124 underwent SHVR. TO overall was 71.7%; 79.2% in the non-SHVR group and 46.8% in the SHVR group (p < 0.001). SHVR was the strongest predictor of non-TO (right colon/small bowel: odds ratio [OR] 4.63, 95% confidence interval [CI] 2.65-8.08; left colon/rectum: OR 6.09, 95% CI 2.59-14.3; stomach/pancreas: OR 6.69, 95% CI 1.46-30.7; multivisceral: OR 10.9, 95% CI 3.03-39.5). A composite score was developed yielding three risk strata for TO (score 0-2: 89% vs. score 3-5: 67% vs. score ≥ 6: 37%; p < 0.001). Decision tree analysis was congruent, identifying SHVR as the most important determinant of TO. In patients with colorectal LM, SHVR was associated with delayed time to RIOT (p = 0.004); the risk-stratification tool for TO was equally predictive of RIOT (p < 0.01). CONCLUSIONS: SHVR is associated with reduced likelihood of TO and in turn delayed RIOT. As SHVR is increasingly performed in order to consolidate cancer care, patient selection considering these different outcomes is critical.

Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

BRAF Mutations Are Associated with Poor Survival Outcomes in Advanced-stage Mismatch Repair-deficient/Microsatellite High Colorectal Cancer.

BACKGROUND: Mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) is a unique disease entity with growing interest given the rise of young-onset CRC. Given its heterogeneous behavior and potential for highly effective treatment outcomes, we sought to identify the clinical and molecular features that offer prognostic value for MMR-D CRC. MATERIALS/METHODS: This was a retrospective cohort study of patients with metastatic CRC with MMR-D or microsatellite instability in a real-world database. Overall survival (OS) was determined by the date of metastatic disease to date of death with stratification made based on factors including BRAF and RAS mutation status, age, and MMR protein loss type. RESULTS: There were 1101 patients in the study. Patients with BRAF mutations had worse OS compared with patients with wild-type BRAF with a median survival of 18.9 months versus 33.2 months (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.25-1.86, P < .001). Patients with age >50 were found to have decreased OS versus age ≤50 with a median survival of 21.4 months versus 38.7 months (HR 1.66, 95% CI: 1.33-2.07, P < .001). BRAF mutations and age >50 remained significant predictors of OS in multivariate analysis. CONCLUSION: BRAF mutations and age >50 are associated with worse survival outcomes for patients with MMR-D mCRC. RAS mutations and specific MMR alterations are not associated with survival outcomes.

Integrating a Disease-Focused Tumor Board as a Delivery-of-Care Model to Expedite Treatment Initiation for Patients With Liver Malignancies.

BACKGROUND: Patients with hepatobiliary malignancies are especially vulnerable to treatment delays. This study sought to evaluate the impact of implementing a new delivery-of-care model centered around a hepatobiliary multidisciplinary tumor board (HB-MTB) and integrated with an optimized patient workflow process to expedite treatment initiation. METHODS: A hybrid type 2 study (effectiveness-implementation) was performed. Implementation measures were examined prospectively using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) approach during 5 years after the HB-MTB program deployment (2015-2020). The primary outcome was effectiveness, measured as time to treatment initiation (TTI) using a before and after design (1 year each). The patients were grouped into before (BP) and after (AP) categories based on date of HB-MTB program implementation. Multivariable Cox and linear regression analyses were performed to examine and compare time to treatment initiation between groups. RESULTS: The HB-MTB program enrolled 2457 patients (reach). The RE-AIM measures were favorable and improved over time (P < 0.01 for all). The median TTI was lower for the AP group than for the BP group (17 vs 24 days; P < 0.01). In the multivariable Cox and linear regressions, treatment in the AP group was associated with a faster TTI (hazard ratio, 1.75; 95 % confidence interval, 1.31-2.35; p < 0.01), and a mean of 13 days faster treatment initiation than the BP group (P < 0.01). CONCLUSIONS: Implementation of an HB-MTB program integrated with an optimized patient workflow was successful and led to faster treatment initiation. This delivery-of-care model can serve as a blueprint to expedite treatment of patients with cancer.

High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia.

The P2RY8-CRLF2 and IGH-CRLF2 rearrangements induce the overexpression of cytokine receptor-like factor 2 (CRLF2) and have been associated with relapse and poor prognosis in B-cell acute lymphoblastic leukemia (B-ALL). Additionally, they are frequently documented in high-risk Hispanic populations. To better understand the potential causes of the adverse prognosis of childhood B-ALL in Mexico, we analyzed these rearrangements and the CRLF2 mRNA and protein levels in 133 Mexican children with B-ALL. We collected bone marrow samples at diagnosis and evaluated the CRLF2 gene expression by qRT-PCR and the total CRLF2 protein by flow cytometry. P2RY8-CRLF2 and IGH-CRLF2 were detected by RT-PCR and FISH, respectively. The median time of follow-up to determine the prognostic significance of the CRLF2 abnormalities was three years. In 82% of the participants, the mRNA levels correlated with the cell-surface and intracellular CRLF2 protein levels. The P2RY8-CRLF2 rearrangement was present in 31.5% (42/133) of the patients, while the IGH-CRLF2 rearrangement was detected in 13.5% (9/67) of patients with high expression of CRLF2 (6.8% of the total sample). CRLF2 copy number variations (gain) were also detected in 7.5% (5/67) of patients with high protein levels. The overall survival (OS) presented significantly lower rates in patients with high white blood cell count (≥50x109/L) regardless of CRLF2 expression, but high levels of CRLF2 gene expression appears to contribute to the reduction of OS within this group of patients. In conclusion, in our cohort, a high occurrence of CRLF2 abnormalities was documented, particularly the P2RY8-CRLF2 rearrangement, which might represent a characteristic of the Mexican population. Targeted therapy to treat this group of patients could improve OS.

Prophylactic Perioperative Antibiotics in Open Pancreaticoduodenectomy: When Less Is More and When It Is Not. A National Surgical Quality Improvement Program Propensity-Matched Analysis.

INTRODUCTION: We hypothesized that first-generation cephalosporins (G1CEP) provide adequate antimicrobial coverage for pancreaticoduodenectomy (PD) when no biliary stent is present but might be inferior to second-generation cephalosporins or broad-spectrum antibiotics (G2CEP/BS) in decreasing surgical-site infection (SSI) rates when a biliary stent is present. METHODS: The National Surgical Quality Improvement Program 2014-2019 was used to select patients who underwent elective open PD. We divided the population into no-stent versus stent groups based on the status of biliary drainage and then divided each group into G1CEP versus G2CEP/BS subgroups based on the choice of perioperative antibiotics. We matched the subgroups per a propensity score match and analyzed postoperative outcomes. RESULTS: Six thousand two hundred forty five cases of 39,779 were selected; 2821 in the no-stent (45.2%) versus 3424 (54.8%) in the stent group. G1CEP were the antibiotics of choice in 2653 (42.5%) versus G2CEP/BS in 3592 (57.5%) cases. In the no-stent group, we matched 1129 patients between G1CEP and G2CEP/BS. There was no difference in SSI-specific complications (20.3% versus 21.0%; P = 0.677), general infectious complications (25.7% versus 26.9%; P = 0.503), PD-specific complications, overall morbidity, length of stay, or mortality. In the stent group, we matched 1244 pairs. G2CEP/BS had fewer SSI-specific complications (19.9% versus 26.6%; P < 0.001), collections requiring drainage (9.6% versus 12.9%; P = 0.011), and general infectious complications (28.5% versus 34.1%; P = 0.002) but no difference in overall morbidity, mortality, length of stay, and readmission rates. CONCLUSIONS: G2CEP/BS are associated with reduced rates of SSI-specific and infectious complications in stented patients undergoing open elective PD. In patients without prior biliary drainage, G1CEP seems to provide adequate antimicrobial coverage.

Surgical approach to pancreaticoduodenectomy for pancreatic adenocarcinoma: uncomplicated ends justify the means.

BACKGROUND: Pancreaticoduodenectomy (PD) remains the cornerstone of managing pancreatic ductal adenocarcinoma (PDAC) of the pancreas head/neck, but it is associated with high morbidity. We hypothesize that, in absence of pancreatectomy-specific morbidity (PSM), minimally invasive PD (MIPD) provides improved short-term outcomes compared to open PD (OPD). METHODS: NSQIP pancreatectomy-targeted database 2014-2019 was utilized. PSM was defined as the occurrence of delayed gastric emptying (DGE) and/or post-operative pancreatic fistula (POPF). The cohort was divided into No-PSM and PSM groups. Propensity score match was applied in each group to compare outcomes of MIPD vs. OPD. RESULTS: 8,121 patients were selected. Patients were divided into No-PSM (N = 6267) and PSM (N = 1854) groups. In No-PSM group, we matched 1656 OPD to 552 MIPD patients. MIPD had longer operations (423 vs. 359 min; p < 0.001) but less overall morbidity (22.1% vs. 29.1%; p = 0.001) mostly attributed to less bleeding and sepsis. MIPD patients also had a one-day shorter median LOS (6 vs. 7 days; p = 0.005) and higher rates of home discharge (92.8% vs. 89.6%; p = 0.027). No difference was noted in mortality and 30-day readmission. In PSM group, 441 OPD were matched to 147 MIPD peers. MIPD had longer operations but without short-term benefits. General morbidity (61.2% vs. 61.9%), median LOS (12 vs. 12 days), mortality (2.7% vs. 1.8%), and readmission rates (32.7% vs. 26.5%) were similar. Same conclusions were drawn in the per-protocol analysis. CONCLUSION: PSM is common following PD for PDAC. In the absence of PSM, MIPD is associated with less postoperative morbidity and shorter LOS.

Characterization of Philadelphia-like Pre-B Acute Lymphoblastic Leukemia: Experiences in Mexican Pediatric Patients.

Ph-like subtypes with CRLF2 abnormalities are frequent among Hispano-Latino children with pre-B ALL. Therefore, there is solid ground to suggest that this subtype is frequent in Mexican patients. The genomic complexity of Ph-like subtype constitutes a challenge for diagnosis, as it requires diverse genomic methodologies that are not widely available in diagnostic centers in Mexico. Here, we propose a diagnostic strategy for Ph-like ALL in accordance with our local capacity. Pre-B ALL patients without recurrent gene fusions (104) were classified using a gene-expression profile based on Ph-like signature genes analyzed by qRT-PCR. The expressions of the CRLF2 transcript and protein were determined by qRT-PCR and flow cytometry. The P2RY8::CRLF2, IGH::CRLF2, ABL1/2 rearrangements, and Ik6 isoform were screened using RT-PCR and FISH. Surrogate markers of Jak2-Stat5/Abl/Ras pathways were analyzed by phosphoflow. Mutations in relevant kinases/transcription factors genes in Ph-like were assessed by target-specific NGS. A total of 40 patients (38.5%) were classified as Ph-like; of these, 36 had abnormalities associated with Jak2-Stat5 and 4 had Abl. The rearrangements IGH::CRLF2,P2RY8::CRLF2, and iAMP21 were particularly frequent. We propose a strategy for the detection of Ph-like patients, by analyzing the overexpression/genetic lesions of CRLF2, the Abl phosphorylation of surrogate markers confirmed by gene rearrangements, and Sanger sequencing.

The Impact of Socioeconomic Deprivation on Clinical Outcomes for Pancreatic Adenocarcinoma at a High-volume Cancer Center: A Retrospective Cohort Analysis.

OBJECTIVE: To assess the impact of a granular measure of SED on pancreatic surgical and cancer-related outcomes at a high-volume cancer center that employs a standardized clinic pathway. SUMMARY OF BACKGROUND DATA: Prior research has shown that low socioeconomic status leads to less treatment and worse outcomes for PDAC. However, these studies employed inconsistent definitions and categorizations of socioeconomic status, aggregated individual socioeconomic data using large geographic areas, and lacked detailed clinicopathologic variables. METHODS: We conducted a retrospective cohort study of 1552 PDAC patients between 2008 and 2015. Patients were stratified using the area deprivation index, a validated dataset that ranks census block groups based on SED. Multivariable models were used in the curative surgery cohort to predict the impact of SED on (1) grade 3/4 Clavien-Dindo complications, (2) initiation of adjuvant therapy, (3) completion of adjuvant therapy, and (4) overall survival. RESULTS: Patients from high SED neighborhoods constituted 29.9% of the cohort. Median overall survival was 28 months. The rate of Clavien-Dindo grade 3/4 complications was 14.2% and completion of adjuvant therapy was 65.6%. There was no evidence that SED impacted surgical evaluation, receipt of curative-intent surgery, postoperative complications, receipt of adjuvant therapy or overall survival. CONCLUSIONS: Although nearly one-quarter of curative-intent surgery patients were from high SED neighborhoods, this factor was not associated with measures of treatment quality or survival. These observations suggest that treatment at a high-volume cancer center employing a standardized clinical pathway may in part address socioeconomic disparities in pancreatic cancer.

Neoadjuvant Chemotherapy for Intrahepatic Cholangiocarcinoma: A Propensity Score Survival Analysis Supporting Use in Patients with High-Risk Disease.

BACKGROUND: Upfront surgery is the current standard for resectable intrahepatic cholangiocarcinoma (ICC) despite high treatment failure with this approach. We sought to examine the use of neoadjuvant chemotherapy (NAC) as an alternative strategy for this population. METHODS: The National Cancer Database was used to identify patients with resectable ICC undergoing curative-intent surgery (2006-2014). Utilization trends were examined and survival estimates between NAC and upfront surgery were compared; propensity score-matched models were used to examine the association of NAC with overall survival (OS) for all patients and risk-stratified cohorts. Models accounted for clustering within hospitals, and results represent findings from a complete-case analysis. RESULTS: Among 881 patients with ICC, 8.3% received NAC, with no changes over time (Cochran-Armitage p = 0.7). Median follow-up was 50.9 months, with no difference in unadjusted survival with NAC versus upfront surgery (median OS 51.8 vs. 35.6 months, and 5-year OS rates of 38.2% vs. 36.6%; log rank p = 0.51), and no survival benefit in the propensity score-matched analysis (hazard ratio [HR] 0.78, 95% CI 0.54-1.11; p = 0.16). However, for patients with stage II-III disease, NAC was associated with a trend towards improved survival (median OS of 47.6 months vs. 25.9 months, and 5-year OS rates of 34% vs. 25.7%; log-rank p = 0.10) and a statistically significant survival benefit in the propensity score-matched analysis. (HR 0.58, 95% CI 0.37-0.91; p = 0.02). CONCLUSION: NAC is associated with improved OS over upfront surgery in patients with resectable ICC and high-risk of treatment failure. These data support the need for prospective studies to examine NAC as an alternative strategy to improve OS in this population.

Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

Epidural analgesia for hepatopancreatobiliary operations and postoperative urinary tract infections: an unrecognized association of "best-practices" and adverse outcomes.

BACKGROUND: Thoracic epidural analgesia (TEA) is considered "best-practices" for pain-control following HPB operations. It is unknown if TEA increases the risk of UTI. We sought to examine the association of TEA and UTI following HPB operations. METHODS: A retrospective cohort study of patients undergoing elective HPB operations was performed (ACS-NSQIP [2014-2016]). Patients were categorized by TEA utilization. The primary outcome was UTI. Multivariable logistic regression models were created to examine the association of TEA with UTI; including sensitivity and interaction analyses for age and gender. RESULTS: Among 28,571 patients included, 5764 (20.2%) had TEA. UTI occurred more frequently with TEA (3.5% vs. 2.2%, p < 0.01). After multivariable analysis, TEA was associated with increased risk of UTI (1.59 [1.34-1.89]); when stratified by age and gender, the association persisted with an incremental increased risk observed in males over 70 years (1.91 [1.41-2.59]). UTI was associated with increased risk of sepsis (16.8% vs. 5.6%, P < 0.001), LOS (9 versus 6 days, P < 0.001) and readmission rates (21.4% vs. 12.3%, P < 0.001). CONCLUSION: Despite TEA recommended as a best-practice standard for HPB operations, the increased risk of UTI calls for evaluation of current practices and consideration of alternative strategies for high-risk vulnerable populations - elderly males.

Nonmosaic Trisomy 19p13.3p13.2 Resulting from a Rare Unbalanced t(Y;19)(q12;p13.2) Translocation in a Patient with Pachygyria and Polymicrogyria.

Nonmosaic trisomy involving 19p13.3p13.2 is a very uncommon abnormality. At present, only 12 cases with this genetic condition have been reported in the literature. However, the size of the trisomic fragment is heterogeneous and thus, the clinical spectrum is variable. Herein, we report the clinical and cytogenetic characterization of a 5-year-old boy with nonmosaic trisomy 19p13.3p13.2 (7.38 Mb), generated by a derivative Y chromosome resulting from a de novo unbalanced translocation t(Y;19)(q12;p13.2). We demonstrated the integrity of the euchromatic regions in the abnormal Y chromosome to confirm the pure trisomy 19p. Our patient shares some clinical features described in other reported patients with pure trisomy 19p, such as craniofacial anomalies, developmental delay, and heart defects. Different to previous reports, our case exhibits frontal pachygyria and polymicrogyria. These additional features contribute to further delineate the clinical spectrum of trisomy 19p13.3p13.2.

Surgical Principles in the Management of Small Bowel Neuroendocrine Tumors.

OPINION STATEMENT: Small bowel neuroendocrine tumors (SB NETs) are increasing in frequency and becoming more common in surgical practice. It is often difficult to make the diagnosis of a SB NET at an early stage, as the primary tumor tends to be small and patients are asymptomatic until there is regional or distant metastasis, when they develop abdominal pain, partial obstruction, or bleeding and/or develop carcinoid syndrome. Despite this advanced presentation at the time of diagnosis, patients with metastatic SB NETs, as compared to other gastrointestinal malignancies, have favorable survival, which can be improved by appropriate surgical interventions. With the lack of randomized studies, there is reasonable controversy surrounding the optimal management of patients with SB NETs. As such, treatment of these patients is driven primarily by physician experience and available data based predominantly on retrospective studies. Based on this, current recommendations advocate for patients with SB NETs (localized or metastatic) to be managed at experienced centers by a multidisciplinary team. Eligible patients should undergo surgical resection of primary and regional disease as outlined in this article. Additionally, patients with metastatic disease should be evaluated on a case by case basis to evaluate surgical options that may mitigate bowel symptoms (i.e., pain, intestinal angina, obstruction) and carcinoid symptoms (flushing, diarrhea, hemodynamic instability) and prolong survival. Unlike other gastrointestinal malignancies, aggressive surgical management of these patients, even in the context of unresectable metastatic disease, can improve patients' symptoms and long-term survival. The principles outlined in this article are geared to guide appropriate management of SB NET patients with improvement in quality of life and overall survival outcomes.

Tumor grade may be used to select patients with multifocal hepatocellular carcinoma for resection.

BACKGROUND: While resection is a recommended treatment for patients with stage 1 hepatocellular carcinoma (HCC), it remains controversial for multifocal disease. We sought to identify patients with multifocal HCC with survival after resection similar to patients with clinical stage 1 HCC. METHODS: The National Cancer Database was queried to identify patients that underwent resection for HCC. RESULTS: In this study, 2990 patients with a single tumor, and 1087 patients with multifocal disease confined to one lobe underwent resection. In the multifocal cohort, patients with clinical stage 3 (HR 1.54, CI 1.31-1.81, p < 0.0001) or 4 (HR 2.27, CI 1.57-3.29, p < 0.0001) disease, and those with moderately-differentiated (HR 1.32, CI 1.06-1.64, p = 0.012) or poorly differentiated/undifferentiated tumors (HR 1.53, CI 1.20-1.95, p = 0.0006) were associated with worse overall survival (OS). There was no difference in OS between patients with well-differentiated clinical stage 2 multifocal HCC and those with all grades of clinical stage 1 HCC (median of 84.8 (CI 66.3-107.2) vs 76.2 months (CI 71.2-81.3), respectively, p = 0.356). CONCLUSIONS: Patients with well-differentiated, clinical stage 2 multifocal HCC confined to one lobe experience similar OS following hepatic resection to patients with clinical stage 1 disease. These findings may impact the management of select patients with multifocal HCC.

Guidelines Insights: Hepatobiliary Cancers, Version 2.2019.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.