Retrospective case-control study examining the relationship between recurrence-free survival and changes in pre- and post-radioiodine therapy serum thyroglobulin levels in patients with differentiated thyroid cancer.

PURPOSE: Thyroglobulin assay is important to assess the residual or recurrence of differentiated thyroid cancer (DTC). Patients with positive serum thyroglobulin levels after radioactive iodine (RAI) adjuvant therapy could achieve long-term recurrence-free survival (RFS). The patient's prognosis could not be confidently estimated based solely on the evaluation of thyroglobulin levels. We investigated the recurrence rate and RFS of patients who received adjuvant RAI therapy after surgery for DTC to clarify the relationship between changes in pre- and post-therapy serum thyroglobulin levels and RFS. MATERIALS AND METHODS: Patients who underwent adjuvant RAI therapy between May 2007 and March 2021 were included in this study, whereas those with positive anti-thyroglobulin antibodies, distant metastases, or gross residual tumors were excluded. The change in pre- and post-treatment serum thyroglobulin levels under thyroid-stimulating hormone stimulation was calculated and classified as follows: group A, thyroglobulin levels decreased by ˃10%; group B, thyroglobulin levels within a range of 10% or less; and group C, thyroglobulin levels increased by ˃10%. RFS outcomes were analyzed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, and multivariate analysis was performed using the Cox proportional hazard model. RESULTS: A total of 74 patients were included. Relapse was seen in 13 of 46 patients in group A, 9 of 15 in group B, and 10 of 13 in group C. Median RFS was 129.00 (95% confidence interval CI 77.79-180.21), 113.00 (95% CI 86.83-139.17), and 33 months (95% CI 6.026-59.974) in groups A, B, and C, respectively. Patients in group C exhibited significantly shorter RFS than those in groups A and B (P = 0.001). CONCLUSIONS: Changes in thyroglobulin levels pre- and post-therapy were associated with RFS. Patients with decreased post-therapy thyroglobulin levels had a favorable prognosis, even if their thyroglobulin levels were positive after RAI therapy.

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial.

BACKGROUND: In patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma. METHODS: NORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing. FINDINGS: Between Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49-71) in the neoadjuvant FOLFIRINOX group versus 73% (62-84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2-34·9) versus 38·5 months (27·6-not reached; hazard ratio [HR] 1·52 [95% CI 1·00-2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46-67) in the neoadjuvant FOLFIRINOX group versus 70% (55-83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2-34·9) versus 34·4 months (19·4-not reached; HR 1·46 [95% CI 0·99-2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event. INTERPRETATION: This phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven. FUNDING: Norwegian Cancer Society, South Eastern Norwegian Health Authority, The Sjöberg Foundation, and Helsinki University Hospital Research Grants.

Surveillance With Serial Imaging and CA 19-9 Tumor Marker Testing After Resection of Pancreatic Cancer: A Single-Center Retrospective Study.

OBJECTIVES: Most patients receiving curative-intent surgery for pancreatic cancer will experience cancer recurrence. However, evidence that postoperative surveillance testing improves survival or quality of life is lacking. We evaluated the use and characteristics of surveillance with serial imaging and CA 19-9 tumor marker testing at an NCI-designated comprehensive cancer center. METHODS: We conducted a retrospective cohort study of patients who entered surveillance after curative-intent resection of pancreatic adenocarcinoma. We abstracted information from the electronic medical record about oncology office visits, surveillance testing (cross-sectional imaging and CA 19-9 tumor marker testing), and pancreatic cancer recurrence, with follow-up through 2 years after pancreatectomy. We conducted analyses to describe the use of surveillance testing and to characterize the sensitivity and specificity of CA 19-9 tumor marker testing for the identification of cancer recurrence. RESULTS: We identified 90 patients entering surveillance after pancreatectomy. CA 19-9 was the most frequently used surveillance test, followed by CT imaging. Forty-seven patients (52.2%) experienced recurrence within two years of pancreatectomy. Recurrence risk was 58.8% versus 31.8% in patients with elevated versus normal CA 19-9 at diagnosis ( P =0.03). Elevated CA 19-9 at any point during surveillance was significantly associated with 2-year recurrence risk ( P <0.001). Elevated CA 19-9 had a sensitivity of 83% (95% CI 0.72-0.95) and specificity of 87% (0.76-0.98) for identification of recurrence within 2 years of pancreatectomy. CONCLUSIONS: CA 19-9 demonstrates clinical validity for identifying recurrence of pancreatic cancer during surveillance. Surveillance approaches with reduced reliance on imaging should be prospectively evaluated.

Tumor Marker Trajectories and Survival Analysis in Patients With Normal Carcinoembryonic Antigen Ranges After Colorectal Cancer Resection.

BACKGROUND: Evidence regarding postoperative CEA for predicting long-term outcomes of colorectal cancer remains controversial, especially in patients with normal postoperative CEA. OBJECTIVE: To investigate the risk difference among different postoperative CEA trajectories in patients with normal postoperative CEA after curative colorectal cancer resection. DESIGN: This cohort study was conducted at a comprehensive cancer center and included data retrieved from a prospectively collected database between January 2006 and December 2018. SETTINGS: Retrospective cohort study. PATIENTS: Patients with colorectal cancer who underwent surgery for primary stage I to III colorectal adenocarcinoma were included and those with postoperative CEA >5 ng/mL were excluded. INTERVENTIONS: Standard curative radical resection was performed. MAIN OUTCOME MEASURES: Ten-year overall survival and disease-free survival were analyzed. RESULTS: The study population (n = 8156) was categorized into 6 trajectories: persistent-ultralow (n = 2351), persistent-low (n = 2474), gradually decrease (n = 401), persistent-medium (n = 1727), slightly increase (n = 909), and around-upper-limit (n = 394). The median follow-up time was 7.8 years, and the median time frame in which CEA was measured to determine trajectory was 2.6 years. The persistent-ultralow group had the highest 10-year overall survival (85.1%) and disease-free survival (82.7%). The around-upper-limit group had the lowest 10-year overall survival (55.5%) and disease-free survival (53.4%). The adjusted HR trend was comparable to the crude HR of the persistent-ultralow group. Consequently, the higher initial serum CEA groups had higher HRs of overall survival and disease-free survival. The adjusted HR of overall survival was 2.96 (95% CI, 2.39-3.66) and of disease-free survival was 2.66 (95% CI, 2.18-3.69) for the around-upper-limit groups. LIMITATIONS: Retrospective design. CONCLUSIONS: The postoperative serum CEA trajectory is an independent factor associated with long-term outcomes. Although CEA levels were all within normal range, higher levels of postoperative serum CEA trajectory correlated with worse long-term oncological outcomes. See Video Abstract. TRAYECTORIAS DE MARCADORES TUMORALES Y ANLISIS DE SUPERVIVENCIA EN PACIENTES CON RANGOS NORMALES DE ANTGENO CARCINOEMBRIONARIO POSTERIOR A RESECCIN DE CNCER COLORRECTAL: ANTECEDENTES:La evidencia sobre el CEA post operatorio para la predicción de los resultados a largo plazo del cáncer colorrectal sigue siendo controversial, especialmente en pacientes con CEA post quirúrgico normal.OBJETIVO:Investigar la diferencia de riesgo entre diferentes trayectorias postoperatorias del CEA en pacientes con CEA post quirúrgico normal tras la resección curativa del cáncer colorrectal.DISEÑO:Este estudio de cohorte se realizó en un centro oncológico integral e incluyó datos recuperados de una base de datos recopilada prospectivamente entre enero de 2006 y diciembre de 2018.AJUSTES:Estudio de cohorte retrospectivo.PACIENTES:Se incluyeron pacientes con el diagnostico de CCR que fueron sometidos a cirugía por adenocarcinoma colorrectal primario en estadio I-III. Se excluyeron pacientes con CEA postoperatorio >5 ng/mL.INTERVENCIONES:Se realizó una resección radical curativa estandarizada.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron la supervivencia general a diez años y la supervivencia libre de enfermedad.RESULTADOS:La población de estudio (n = 8156) fue clasificada en seis trayectorias, que incluyeron ultrabajo persistente (n = 2351), bajo persistente (n = 2474), disminución gradual (n = 401), medio persistente (n = 1727), aumento leve (n = 909) y alrededor del límite superior (n = 394). La mediana del tiempo de seguimiento fue de 7,8 años y la mediana del período de tiempo en el que el CEA fue medido para determinar la trayectoria fue de 2,6 años. El grupo ultrabajo persistente tuvo la mayor supervivencia general a 10 años (85,1 %) y supervivencia libre de enfermedad (82,7 %). El grupo alrededor del límite superior tuvo la supervivencia general a 10 años más baja (55,5 %) y la supervivencia libre de enfermedad (53,4 %). La tendencia del índice de riesgo ajustado fue comparable al índice de riesgo bruto del grupo ultrabajo persistente. En consecuencia, los grupos con CEA sérico iniciales más altos tenían índices de riesgos más altos de supervivencia general y supervivencia libre de enfermedad. Los índices de riesgos ajustados de supervivencia general/supervivencia libre de enfermedad fueron 2,96/2,66 (intervalo de confianza del 95 %: 2,39-3,66/2,18-3,69) para los grupos cercanos al límite superior.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:La trayectoria del CEA sérico postoperatorio es un factor independiente asociado con resultados a largo plazo. Aunque los niveles de CEA se encontraban todos dentro del rango normal, los niveles más altos de trayectoria del CEA en suero posoperatorio se correlacionaron con peores resultados oncológicos a largo plazo. (Traducción-Dr Osvaldo Gauto ).

Transanal minimally invasive surgery for benign and malignant rectal lesions: midterm outcomes from a tertiary center.

BACKGROUND: Although transanal minimally invasive surgery (TAMIS) for rectal neoplasia has gained wide acceptance, the mid-term and long-term outcomes are not widely reported in the literature. OBJECTIVE: Describe the mid-term outcomes of patients who underwent TAMIS for benign and malignant rectal lesions in a single center. DESIGN: Retrospective cohort study. SETTINGS: Tertiary referral center. PATIENTS AND METHODS: Demographic, clinical, and oncological outcomes of patients who underwent TAMIS between January 2015 and December 2022 were prospectively collected. The indication for TAMIS was based on the National Comprehensive Cancer Network guidelines. The follow up for the cancer patients included clinical examination, tumor markers every 6 months and MRI rectum at the end of one year. In addition, colonoscopy and CT scan at years one and three and a final CT scan and colonoscopy at year five. MAIN OUTCOME MEASURES: Mid-term oncological and clinical outcome. RESULTS: Thirty elective TAMIS procedures included adenocarcinoma for 33.3% (n=10) of the patients, 20% (n=6) neuroendocrine tumor and the 40% (n=12) were adenomatous lesions. Negative resection margins were achieved in all malignant lesions. Perioperative complications occurred in 2 patients (6.6%), one patient had breaching into the peritoneal cavity, and postoperative hypotension occurred in another patient. The median follow-up time was 23 months (range: 5-72 months). Two patients with adenoma and positive margins developed recurrent adenoma (6.6%) and one patient with initial polypectomy biopsy of adenocarcinoma, had TAMIS with histopathology of adenoma and distant metastasis had developed. CONCLUSIONS: TAMIS for local excision of rectal neoplasia is a valid option with favorable mid-term outcomes provided there is adherence to careful selection criteria. LIMITATIONS: Retrospective nature and small number of the patients.

[Perioperative management and operative treatment of malignant tumor of anal canal merging severe abdominal protuberance].

Objective: To report the perioperative management and robot-assisted minimally invasive surgery results of one case with malignant tumor of anal canal combined with severe abdominal distention. Methods: A 66-year-old male suffer from adenocarcinoma of anal canal (T3N0M0) with megacolon, megabladder and scoliosis. The extreme distention of the colon and bladder result in severe abdominal distention. The left diaphragm moved up markedly and the heart was moved to the right side of the thoracic cavity. Moreover, there was also anal stenosis with incomplete intestinal obstruction. Preoperative preparation: fluid diet, intravenous nutrition and repeated enema to void feces and gas in the large intestine 1 week before operation. Foley catheter was placed three days before surgery and irrigated with saline. After relief of abdominal distention, robotic-assisted abdominoperineal resection+ subtotal colectomy+colostomy was performed. Results: Water intake within 6 hours post-operatively; ambulance on Day 1; anal passage of gas on Day 2; semi-fluid diet on Day 3; safely discharged on Day 6. Conclusion: Robotic-assisted minimally invasive surgery is safe and feasible for patients with malignant tumor of anal canal combined with severe abdominal distention after appropriate and effective preoperative preparation to relieve abdominal distention.

Neoplasms of the Appendix.

BACKGROUND: Neoplasms of the vermiform appendix are rare. They comprise a heterogeneous group of entities requiring differentkinds of treatment. METHODS: This review is based on publications retrieved by a selective literature search in the PubMed, Embase, and Cochranedatabases. RESULTS: 0.5% of all tumors of the gastrointestinal tract arise in the appendix. Their treatment depends on their histopathologicalclassification and tumor stage. The mucosal epithelium gives rise to adenomas, sessile serrated lesions, adenocarcinomas,goblet-cell adenocarcinomas, and mucinous neoplasms. Neuroendocrine neoplasms originate in neuroectodermal tissue. Adenomasof the appendix can usually be definitively treated by appendectomy. Mucinous neoplasms, depending on their tumorstage, may require additional cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC). Adeno -carcinomas and goblet-cell adenocarcinomas can metastasize via the lymphatic vessels and the bloodstream and should thereforebe treated by oncological right hemicolectomy. Approximately 80% of neuroendocrine tumors are less than 1 cm in diameterwhen diagnosed and can therefore be adequately treated by appendectomy; right hemicolectomy is recommended if the patienthas risk factors for metastasis via the lymphatic vessels. Systemic chemotherapy has not been shown to be beneficial forappendiceal neoplasms in prospective, randomized trials; it is recommended for adenocarcinomas and goblet-cell adenocarcinomasof stage III or higher, in analogy to the treatment of colorectal carcinoma.

Efficacy of Systemic Chemotherapy in Patients With Low-grade Mucinous Appendiceal Adenocarcinoma: A Randomized Crossover Trial.

Importance: Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease. Objective: To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma. Design, Setting, and Participants: This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was planned. Eligible patients had histological evidence of a metastatic low-grade mucinous appendiceal adenocarcinoma, with radiographic imaging demonstrating the presence of mucinous peritoneal carcinomatosis and were not considered candidates for complete cytoreductive surgery. Key exclusion criteria were concurrent or recent investigational therapy, evidence of bowel obstruction, and use of total parenteral nutrition. Data were analyzed from November 2021 to May 2022. Interventions: Patients were randomized to either 6 months observation followed by 6 months of chemotherapy, or initial chemotherapy followed by observation. Main Outcomes and Measures: The primary end point was the percentage difference in tumor growth in treatment and observation groups. Key secondary end points included patient-reported outcomes in the chemotherapy and observation periods, objective response rate, rate of bowel complications, and differences in overall survival (OS). Results: A total of 24 patients were enrolled, with median (range) age of 63 (38 to 82) years, and equal proportion of men and women (eg, 12 men [50%]); all patients had ECOG performance status of 0 or 1. A total of 11 patients were randomized to receive chemotherapy first, and 13 patients were randomized to receive observation first. Most patients (15 patients [63%]) were treated with either fluorouracil or capecitabine as single agent; 3 patients (13%) received doublet chemotherapy (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin or folinic acid, fluorouracil, and irinotecan hydrochloride), and bevacizumab was added to cytotoxic chemotherapy for 5 patients (21%). Fifteen patients were available to evaluate the primary end point of difference in tumor growth during treatment and observation periods. Tumor growth while receiving chemotherapy increased 8.4% (95% CI, 1.5% to 15.3%) from baseline but was not significantly different than tumor growth during observation (4.0%; 95% CI, -0.1% to 8.0%; P = .26). Of 18 patients who received any chemotherapy, none had an objective response (14 patients [77.8%] had stable disease; 4 patients [22.2%] had progressive disease). Median (range) OS was 53.2 (8.1 to 95.5) months, and there was no significant difference in OS between the observation-first group (76.0 [8.6 to 95.5] months) and the treatment-first group (53.2 [8.1 to 64.1] months; hazard ratio, 0.64; 95% CI, 0.16-2.55; P = .48). Patient-reported quality-of-life metrics identified that during treatment, patients experienced significantly worse fatigue (mean [SD] score, 18.5 [18.6] vs 28.9 [21.3]; P = .02), peripheral neuropathy (mean [SD] score, 6.67 [12.28] vs 38.89 [34.88]; P = .01), and financial difficulty (mean [SD] score, 8.9 [15.2] vs 28.9 [33.0]; P = .001) compared with during observation. Conclusions and Relevance: In this prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma, patients did not derive clinical benefit from fluorouracil-based chemotherapy, given there were no objective responses, no difference in OS when treatment was delayed 6 months, and no difference in the rate of tumor growth while receiving chemotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01946854.

Impact of Adherence to Operative Standards and Stage-Specific Guideline-Recommended Therapy in Nonmetastatic Pancreatic Adenocarcinoma.

BACKGROUND: Achieving optimal surgical outcomes in pancreatic adenocarcinoma requires a combination of both curative-intent resection to oncologic standards and stage-specific neoadjuvant or adjuvant therapy. This investigation sought to examine factors associated with receipt of standard-adherent surgery (SAS) and guideline-recommended therapy (GRT) and determine the impact of compliance on patient survival. PATIENTS AND METHODS: From the 2006-2016 National Cancer Database, 21,304 patients underwent resection for nonmetastatic pancreatic adenocarcinoma. SAS was defined as pancreatic resection with negative margins and ≥ 15 lymph nodes examined. Stage-specific GRT was defined by current National Comprehensive Cancer Network guidelines. Multivariable models were used to determine predictors of adherence to SAS and GRT and prognostic impact on overall survival. RESULTS: Overall, SAS was achieved in 39% and GRT in 65% of patients, but only 30% received both SAS and GRT. Increasing age, minority race, uninsured status, and greater comorbidities were associated with a decreased odds of receiving both SAS and GRT (all p < 0.05). SAS (HR 0.79; CI 0.76-0.81; p < 0.001) and GRT (HR 0.67; CI 0.65-0.69; p < 0.001) were each independently associated with a survival advantage. Receipt of both SAS and GRT was associated with significant improvement in median OS compared with receiving neither (2.2 years vs 1.1 years; p < 0.001) which was independently associated with a 78% increased risk of death (HR 1.78; CI 1.70-1.86; p < 0.001). CONCLUSIONS: Despite survival benefits associated with adherence to operative standards and receipt of guideline-recommended therapy, compliance remains poor. Future efforts must be directed toward improved education and implementation efforts around both operative standards and therapy guidelines.

Gastric Cancer Surgery in the US: a Contemporary Trend Analysis of Lymphadenectomy and the Impact of Minimally Invasive Approaches.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend harvesting 16 or more lymph nodes for the adequate staging of gastric adenocarcinoma. This study examines the rate of adequate lymphadenectomy over recent years, its predictors, and its impact on overall survival(OS). STUDY DESIGN: The National Cancer Database was utilized to identify patients who underwent surgical treatment for gastric adenocarcinoma between 2006-2019. Trend analysis was performed for lymphadenectomy rates during the study period. Logistic regression, Kaplan-Meier survival plots, and Cox proportional hazard regression were utilized. RESULTS: A total of 57,039 patients who underwent surgical treatment for gastric adenocarcinoma were identified. Only 50.5% of the patients underwent a lymphadenectomy of ≥ 16 nodes. Trend analysis showed that this rate significantly improved over the years, from 35.1% in 2006 to 63.3% in 2019 (p < .0001). The main independent predictors of adequate lymphadenectomy included high-volume facility with ≥ 31 gastrectomies/year (OR: 2.71; 95%CI:2.46-2.99), surgery between 2015-2019 (OR: 1.68; 95%CI: 1.60-1.75), and preoperative chemotherapy (OR:1.49; 95%CI:1.41-1.58). Patients with adequate lymphadenectomy had better OS than patients who did not: median survival: 59 versus 43 months (Log-Rank: p < .0001). Adequate lymphadenectomy was independently associated with improved OS (HR:0.79; 95%CI:0.77-0.81). Laparoscopic and robotic gastrectomies were independently associated with adequate lymphadenectomy compared to open, OR: 1.11, 95%CI:1.05-1.18 and OR: 1.24, 95%CI:1.13-1.35, respectively. CONCLUSION: Although the rate of adequate lymphadenectomy improved over the study period, a large number of patients still lacked adequate lymph node dissection, negatively impacting their OS despite multimodality therapy. Laparoscopic and robotic surgeries were associated with a significantly higher rate of lymphadenectomy ≥ 16 nodes.

Predictive value of computed tomography on surgical resectability in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: Results from a prospective, multicentre phase 2 trial (NEOLAP-AIO-PAK-0113).

PURPOSE: To assess the role of current imaging-based resectability criteria and the degree of radiological downsizing in locally advanced pancreatic adenocarcinoma (LAPC) after multiagent induction chemotherapy (ICT) in multicentre, open-label, randomized phase 2 trial. METHOD: LAPC patients were prospectively treated with multiagent ICT followed by surgical exploration within the NEOLAP trial. All patients underwent CT scan at baseline and after ICT to assess resectability status according to national comprehensive cancer network guidelines (NCCN) criteria and response evaluation criteria in solid tumors (RECIST) at the local study center and retrospectively in a central review. Imaging results were compared in terms of local and central staging, downsizing and pathological resection status. RESULTS: 83 patients were evaluable for central review of baseline and restaging imaging results. Downstaging by central review was rarely seen after multiagent ICT (7.7%), whereas tumor downsizing was documented frequently (any downsizing 90.4%, downsizing to partial response (PR) according to RECIST: 26.5%). Patients with any downsizing showed no significant different R0 resection rate (37.3%) as patients that fulfilled the criteria of PR (40.9%). The sensitivity of any downsizing for predicting R0 resection was 97% with a negative predictive value (NPV) of 0.88. ROC-analysis revealed that tumor downsizing was a predictor of R0 resection (AUC 0.647, p = 0.028) with a best cut-off value of 22.5% downsizing yielding a sensitivity of 65% and a specificity of 61%. CONCLUSIONS: Imaging-based tumor downsizing and not downstaging can guide the selection of patients with a realistic chance of R0-resection in LAPC after multi-agent ICT.

[Pathology and Pathophysiology of BPH and Relevant Incidental Findings in TUR-P]. / Pathologie und Pathophysiologie der BPH und relevante Zufallsbefunde in der TUR-P.

Pathology and Pathophysiology of BPH and Relevant Incidental Findings in TUR-P Abstract: Benign prostatic hyperplasia (BPH) is defined as nodular prostate enlargement due to cellular proliferation of prostate glands and stroma. Beside adenocarcinoma, BPH is one of the most common diseases in the prostate. Transurethral resection of the prostate (TURP) is surgical treatment of choice for BPH. Resected tissue fragments are examined in the pathology and belong to the most commonly submitted urologic specimens. Up to date, pathophysiology of BPH is not yet completely understood. Different hormones such as androgens, dihydrotestosterone, estrogens as well as growth factors, inflammation, and environmental influences are important in the process. The diagnosis of BPH is usually straightforward. In this context, it is important to mention incidental findings, which may come along as "bad surprises" while examining TURP tissue fragments. Prostatic intraepithelial neoplasia (PIN) or incidental acinar adenocarcinoma of the prostate as well as the potential preneoplastic atypical adenomatoid hyperplasia (AAH) represent a few examples. According to literature, the histologic examination of TURP tissue reveals a high-grade PIN in up to 5%. Incidental adenocarcinoma is encountered in 5-13%. These frequencies justify a relatively laborious examination of the entire or majority resected TURP tissue.

Cholecystoappendiceal Fistula From Appendiceal Adenocarcinoma Requiring a Right Hemicolectomy With Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.

Bilioenteric fistulae are rare and difficult to manage complications of chronic cholecystitis. While cholecystoduodenal and cholecystocolic fistulae are more common, a cholecystoappendiceal fistula is an extremely rare finding. We report the presentation and operative management of a 59-year-old male with cholecystoappendiceal fistula and associated abscess in the gallbladder fossa. The patient was appropriately resuscitated, the abscess drained by interventional radiology, and after a complete workup, underwent a laparoscopic appendectomy and cholecystectomy. Pathology revealed moderately differentiated appendiceal adenocarcinoma requiring a right hemicolectomy with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). He has recovered well postoperatively with no complications. This case highlights the importance of having a very high index of suspicion for underlying malignancy when managing a fistula of any kind. To the best of our understanding, this is only the second reported case of a cholecystoappendiceal fistula.

Disparities in NCCN Guideline-Compliant Care for Patients with Early-Stage Pancreatic Adenocarcinoma at Minority-Serving versus Non-Minority-Serving Hospitals.

BACKGROUND: Racial/ethnic disparities in pancreatic adenocarcinoma (PDAC) outcomes may relate to receipt of National Comprehensive Cancer Network (NCCN) guideline-compliant care. We assessed the association between treatment at minority-serving hospitals (MSH) and receipt of NCCN-compliant care. PATIENTS AND METHODS: Patients who underwent resection of early-stage PDAC between 2006 and 2019 were identified from the National Cancer Database (NCDB). MSH was defined as the top decile of facilities treating minority ethnicities (Black and/or Hispanic). Factors associated with receipt of NCCN-compliant care and its impact on overall survival (OS) were assessed. RESULTS: Among 44,873 patients who underwent resection of PDAC, most were treated at non-MSH (n = 42,571, 94.9%), while a smaller subset were treated at MSH (n = 2302, 5.1%). Patients treated at MSH were more likely to be at a younger median age (MSH 66 years versus non-MSH 67 years), Black or Hispanic (MSH 58.4% versus non-MSH 12.0%), and not insured (MSH 7.8% versus non-MSH 1.6%). While 71.7% (n = 31,182) of patients were compliant with NCCN care, guideline-compliant care was lower at MSH (MSH 62.5% versus non-MSH 72.2%). On multivariable analysis, receiving care at MSH was associated with not receiving guideline-compliant care [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.74]. At non-MSH, non-white patients had lower odds of receiving guideline-compliant PDCA care (OR 0.85, 95% CI 0.78-0.91). Failure to comply was associated with worse overall survival (OS) [hazard ratio (HR) 1.50, 95% CI 1.46-1.54, all p < 0.001]. CONCLUSIONS: Patients with PDAC treated at MSH and minorities treated at non-MSH were less likely to receive NCCN-compliant care. Failure to comply with guideline-based PDAC treatment was associated with worse OS.

The efficacy of adjuvant radioactive iodine after reoperation in patients with persistent or recurrent differentiated thyroid cancer: a systematic review.

OBJECTIVE: The effectiveness of adjuvant radioiodine (RAI) after reoperation in patients with persistent or recurrent differentiated thyroid cancer (DTC) is controversial. Although various organizations recognize that strong evidence for the use of RAI is lacking, they continue to recommend the use of adjuvant RAI therapy for select groups of patients. This is concerning as RAI therapy has potential side effects such as gastrointestinal symptoms, bone marrow suppression, and gonadal damage. METHODS: Four electronic databases were systematically searched for randomized trials or observational studies that examined the outcomes of adjuvant RAI after reoperation for recurrent DTC, among patients of any age. The baseline characteristics, treatment response, disease progression, and overall survival of these studies were synthesized and reported. A meta-analysis of the use of RAI on progression-free survival was also performed. RESULTS: Six observational studies, comprising a combined cohort of 437 patients who underwent reoperation, were included from 1212 records. Adjuvant RAI after reoperation in recurrent DTC was not associated with longer progression-free or overall survival. There was also no association of RAI with excellent structural or biochemical treatment response, lower thyroglobulin levels, nor a lower rate of second recurrence or distant metastases. CONCLUSIONS: Adjuvant RAI after reoperation in recurrent DTC was not associated with improved cancer or treatment-related outcomes. However, as the included studies were of inadequate quality, there is an urgent need for randomized trials and well-analyzed cohort studies. Physicians should exercise clinical judgment to prescribe adjuvant RAI for only selected, high-risk patients.

A comparative analysis of treatment efficacy in intermediate-risk thyroid cancer.

PURPOSE: This study aimed to evaluate the efficacy of different treatment combinations on patient survival in intermediate-risk differentiated thyroid cancer (DTC). METHODS: The 2004-2017 National Cancer Database was queried for intermediate-risk papillary (PTC), follicular (FTC), or Hurthle cell (HTC) thyroid cancer patients. Four treatments were analyzed using Kaplan Meier and multivariable Cox regression: surgery, surgery with adjuvant radioiodine ablation (S + RAI), surgery with adjuvant thyroid-stimulating hormone suppression therapy (S + THST), and S + RAI + THST. Kaplan-Meier and multivariable Cox proportional-hazards analyses evaluated treatment-associated overall survival (OS). RESULTS: Of 65,736 patients, 72.2% were female and the average age was 45.4 ± 15.4 years. The 10-year OS rates for PTC, FTC, and HTC were 93.2%, 85.2%, and 78.5%, respectively. S + RAI + THST exhibited higher OS than surgery alone and S + RAI (all p < 0.05). Compared to surgery alone, S + RAI + THST demonstrated reduced mortality in PTC (Hazard Ratio [HR]: 0.628, p < 0.001), FTC (HR: 0.490, p < 0.001), and HTC (HR: 0.520, p = 0.006). Similarly, adjuvant RAI + THST reduced mortality regardless of lymphovascular invasion (HR: 0.490, p < 0.001), N1a (HR: 0.570, p < 0.001) or N1b metastasis (HR: 0.621, p < 0.001), or positive margin status (HR: 0.572, p < 0.001). CONCLUSIONS: Treatment combinations demonstrated varying efficacies in intermediate-risk DTC depending on histology and tumor characteristics, with S + RAI + THST exhibiting the greatest treatment response.

Perioperative Modified FLOT Versus EOX in Locally Advanced Resectable Gastric and Gastro-Oesophageal Junction Adenocarcinoma: Results of a Matched-Pair Analysis.

BACKGROUND AND OBJECTIVES: There is limited real-world data on the efficacy of 2-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT) compared to epirubicin, oxaliplatin, and capecitabine (EOX) as perioperative therapy in esophagogastric adenocarcinomas (EGAC). METHODS: The data of 611 patients with EGAC treated with perioperative chemotherapy and planned for curative resection between January 2013 and December 2019 were retrieved. Patients receiving EOX and a dose-modified version of FLOT (mFLOT) were evaluated. A 1:1 matching, using age, tumour location, signet ring histology, and Eastern Cooperative Oncology Group performance status, without replacement was performed by using nearest neighbour matching method. The primary endpoint of the study was 3-year event-free survival (EFS). RESULTS: A total of 593 patients (261 with EOX and 332 with mFLOT) were matched. One hundred and nighty-eight patients (76%) and 285 patients (86%) in the EOX and mFLOT cohorts underwent curative resection, respectively (p = 0.002). With a median follow-up of 35 and 53 months, respectively, the primary outcome of 3-year EFS was statistically superior in patients receiving mFLOT as compared to the EOX regimen (60% vs. 39%; p < 0.001). There was a greater incidence of grade 3 and grade 4 neutropenia (neoadjuvant: 18% vs. 2%; p < 0.001, adjuvant: 18% vs. 1%; p = 0.001) and febrile neutropenia (neoadjuvant: 8% vs. 1.1%; p < 0.001, adjuvant: 6% vs. 0; p = 0.001) with mFLOT. INTERPRETATION AND CONCLUSION: mFLOT is associated with improved resection rates and survival in comparison to EOX as perioperative therapy in gastric adenocarcinomas in this large real-world cohort, with manageable increase in clinically relevant toxicities such as grade 3 and grade 4 febrile neutropenia and neutropenia.

Artifactual Cystic Spaces in Prostatic Transurethral Resections and Related Specimens: A Potential Diagnostic Confounder.

Aims. Histopathologic benign mimickers of prostate cancer have mostly focused on glandular mimics, with non-glandular mimics mainly limited to inflammatory conditions. While there is a paucity of literature recognizing small cystic (presumably artifactual) spaces in transurethral resection specimens, in some instances they can become florid enough to mimic vascular or epithelial neoplasms. Herein, we detailed histologic, immunophenotypic, and clinicopathologic findings in a large series of specimens showing prominent diagnostically confounding cystic spaces. Methods and Results. Sixty specimens were obtained (50 transurethral resections, 7 aquablations, 3 laser enucleations), from 17 different surgeons. Seven specimens had concurrent genitourinary pathology (4 prostatic adenocarcinoma, 1 solitary fibrous tumor, 1 prostatic atypia, 1 urothelial carcinoma in situ). The extent of cystic change among overall tissue examined ranged from 1 mm-8 mm (mean 3.4 mm), with luminal content of cystic spaces characterized as empty (72%), both empty and fluid-like (17%), and both empty and mucin-like (11%; mucin histochemical stain was negative on all specimens). Notable differences in degree of tissue cautery artifact or inflammation was not found. Immunohistochemistry performed on 30 specimens showed cystic spaces negative for S100, ERG, pankeratin, and CD45. Conclusion. Although artifactual in nature, in some instances small cystic spaces encountered in prostatic transurethral resections and more novel related procedures can become florid enough to warrant recognition as a potential diagnostic confounder of vascular or epithelial neoplasms.

[What to do in front of the association between colonic adenocarcinoma and lymphoma ?] / Que faire devant l'association d'un adenocarcinome et d'un lymphome coliques ?

Synchronous presentation of a colonic adenocarcinoma and lymphoma is extremely rare. We describe here, the sixth observation of a marginal zone B-cell lymphoma, which was incidentally diagnosed in a 77-year-old patient, who was operated for adenocarcinoma of hepatic flexure. This case shows the importance to be aware of this rare association and highlights the dilemma of its management.

Preliminary tolerance analysis of adjuvant chemotherapy in older patients after resection of stage III colon cancer from the PRODIGE 34-FFCD randomized trial.

BACKGROUND: Colon adenocarcinoma mainly occurs in older patients. Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients. METHODS: The purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma. We report a preliminary tolerance analysis on 50% of the first patients enrolled. RESULTS: The analysis was conducted on 491 patients (378 in Group 1 and 113 in Group 2). Patients in Group 2 were older and showed more frailty criteria than those in Group 1. Cumulative grade 3-5 toxicities were more frequent in patients treated with oxaliplatin in Group 1 or with fluoropyrimidine in Group 2 than in patients treated with fluoropyrimidine in Group 1. At least one course was deferred in more than half of the patients in all groups. Early treatment cessation was more frequent in Group 2. CONCLUSION: No safety concerns were raised for the continuation of accrual. The frailty criteria distribution suggests that the investigator's evaluation for group allocation was accurate.