Morbidity and Outcomes of Primary Tumor Management in Patients with Widely Metastatic Well-Differentiated Small Bowel Neuroendocrine Tumors.

BACKGROUND: The benefit of primary tumor resection in distant metastatic small bowel neuroendocrine tumors (SBNETs) is controversial, with treatment-based morbidity not well-defined. We aimed to determine the impact of primary tumor resection on development of disease-specific complications in patients with metastatic well-differentiated SBNETs. PATIENTS AND METHODS: A retrospective analysis was performed of patients diagnosed with metastatic well-differentiated jejunal/ileal SBNETs at a single tertiary care cancer center from 1980 to 2016. Outcomes were compared on the basis of treatment selected at diagnosis between patients who underwent initial medical treatment or primary tumor resection. RESULTS: Among 180 patients, 71 underwent medical management and 109 primary tumor resection. Median follow-up was 116 months. Median event-free survival did not differ between treatment approaches (log-rank p = 0.2). In patients medically managed first, 16/71 (23%) required surgery due to obstruction, perforation, or bleeding. These same complications led to resection at presentation in 31/109 (28%) surgically treated patients. Development of an obstruction from the primary tumor was not associated with disease progression/recurrence (HR 1.14, 95% CI 0.75-1.75) with all patients recovering postoperatively. Ongoing tumor progression requiring secondary laparotomy was associated with worse mortality (HR 7.51, 95% CI 3.3-16.9; p < 0.001) and occurred in 20/109 (18%) primary tumor resection and 7/16 (44%) initially medically treated patients. CONCLUSIONS: Rates of event-free survival among patients with metastatic SBNETs do not differ on the basis of primary tumor management. The development of an obstruction from the primary tumor was not associated with worse outcomes with all patients salvaged. Regardless of initial treatment selected, patients with metastatic SBNET should be closely followed for early signs of primary tumor complications.

A Growing Divide? Social Determinants of the Use of Nonoperative Management of Rectal Cancer and Its Impact on Survival.

INTRODUCTION: Nonoperative management (NOM) of locally advanced rectal cancer was described as early as 2004. Initial national data demonstrated increase in utilization of NOM from 1998 to 2010, but newer national utilization data are not available. METHODS: We performed a retrospective cohort study using the National Cancer Database to assess utilization and 5-y overall survival (OS) of NOM of locally advanced rectal cancer. All patients had American Joint Committee on Cancer stage 2 or 3 rectal cancer, were over 40 y old, received both chemotherapy and radiation therapy, and were not being treated with palliative intent. RESULTS: 74,780 patients were analyzed. 64,540 (86.2%) underwent a definitive resection, 10,330 (13.8%) had NOM. Utilization of NOM steadily increased from 11.3% in 2010 to 18.6% in 2018. Multivariate regression identified the highest predictors of utilization of NOM to be uninsured status, government insurance, Black race, and treatment at a community cancer center. Multivariate regression identified NOM as the highest hazard for mortality (hazard ratio = 2.286, confidence interval 2.209-2.366). After propensity score matching, the mean estimated 5-y OS was 52.0% for those managed operatively compared to 39.8% for those managed nonoperatively. CONCLUSIONS: From 2004 to 2018, the utilization of NOM of locally advanced rectal cancer significantly increased. However, there was a significant discrepancy in OS in comparison to surgical resection for these patients. Further study is needed to determine the long-term oncologic safety of NOM.

Incomplete cytoreductive surgery for appendiceal and colorectal peritoneal carcinomatosis: Characteristics and outcomes of an overlooked group.

BACKGROUND OND OBJECTIVES: Complete cytoreductive surgery (CRS) may prolong survival for selected patients with peritoneal carcinomatosis from colorectal cancer (CRC). However, there is a paucity of data on outcomes following incomplete procedures. METHODS: Patients with incomplete CRS for well-differentiated (WD) and moderate/poorly-differentiated (M/PD) appendiceal cancer, right and left CRC were identified at a single tertiary center (2008-2021). RESULTS: Of 109 patients, 10% were WD and 51% M/PD appendiceal cancers, and 16% right and 23% left CRC. There were no differences in gender, BMI (mean = 27), ASA score, previous abdominal surgery (72%), and extent of CRS. The PC Index differed between appendiceal and colorectal cancers (mean = 27 vs. 17, p < 0.01). Overall, the perioperative outcomes were similar among the groups, with 15% experiencing complications. Postoperatively, 61% received chemotherapy, and 51% required ≥1 subsequent procedure. The 1 and 3-year survival for the WD, M/PD, right and left CRC subgroups were 100%, 67%, 44%, 51%, and 88%, 17%, 12%, and 23%, respectively (p = 0.02). CONCLUSIONS: Incomplete CRS was associated with significant morbidity and number of subsequent palliative procedures. Prognosis correlated with histologic subtype; WD appendiceal cancer patients having superior outcomes, while those with right sided CRC the worst survival. These data may help guiding expectations in the setting of incomplete procedures.

What Can an Aging Pouch Tell Us? Outcomes of Ileoanal Pouches Over 20 Years Old.

BACKGROUND: Little is known about the long-term functional outcomes of restorative proctocolectomy. OBJECTIVE: The aim of this study was to examine ileoanal pouch outcomes 20 and 30 years postoperatively. DESIGN: This is a retrospective case series. SETTING: This study was conducted at a tertiary care referral center. PATIENTS: Patients who underwent restorative proctocolectomy between 1980 and 1994 were identified. Those with ≥20 years of in-person follow-up were included. MAIN OUTCOMES MEASURES: Pouch function, pouchitis, anal stricture, and pouch failure rates were analyzed. RESULTS: A total of 203 patients had ≥20 years of follow-up. Of those, 71 had ≥30 years of follow-up. Initial diagnoses included ulcerative colitis (83%), indeterminate colitis (9%), familial adenomatous polyposis (4%), and Crohn's disease (3%). Twenty-one percent of those with ulcerative or indeterminate colitis later transitioned to Crohn's disease. Mean daily stool frequency was 7 (IQR 6-8), 38% experienced seepage, 31% had anal stenosis, 47% experienced pouchitis, and 18% had pouch failure. Over time, stool frequency increased in 41% of patients, stayed the same in 43%, and decreased in 16%. Patients older than 50 years at the time of construction had more daily bowel movements (median 8 vs 6; p = 0.02) and more seepage (77% vs 35%; p = 0.005) than those younger than 50 years. Patients with Crohn's disease had higher stool frequency (median 8 vs 6; p < 0.001) and higher rates of anal stenosis (44% vs 26%; p = 0.02), pouchitis (70% vs 40%; p < 0.001), and pouch failure (38% vs 12%; p < 0.001) compared to non-Crohn's patients. Patients with ≥30 years of follow-up had similar function as those with 20-30 years of follow-up. LIMITATIONS: This was a retrospective, single-institution study. Only 35% of pouches created during the study period had >20 years of follow-up. CONCLUSIONS: Most patients maintain reasonably good function and retain their pouches after 20 years. Over time, stool frequency and seepage increase. Older age and Crohn's disease are associated with worse outcomes. See Video Abstract at http://links.lww.com/DCR/B801. QU NOS DICE UN RESERVORIO A LARGO PLAZO RESULTADOS DE LOS RESERVORIOS ILEOANALES MAYORES DE AOS: ANTECEDENTES:se sabe poco sobre los resultados funcionales a largo plazo de la proctocolectomía restauradora.OBJETIVO:El objetivo de este estudio fue examinar los resultados del reservorio ileoanal 20 y 30 años después de la operación.DISEÑO:Serie de casos retrospectiva.ENTORNO CLÍNICO:Centro de referencia de atención terciariaPACIENTES:Se identificaron pacientes que se sometieron a proctocolectomía restauradora entre 1980 y 1994. Se incluyeron aquellos con ≥20 años de seguimiento en persona.PRINCIPALES MEDIDAS DE VALORACIÓN:Se analizaron la función, inflamación, tasas de falla del reservorio y estenosis anal.RESULTADOS:Un total de 203 pacientes tuvieron ≥20 años de seguimiento. De ellos, 71 tenían ≥30 años de seguimiento. Los diagnósticos iniciales incluyeron colitis ulcerosa (83%), colitis indeterminada (9%), poliposis adenomatosa familiar (4%) y enfermedad de Crohn (3%). El 21% de las personas con colitis ulcerosa o indeterminada pasaron posteriormente a la enfermedad de Crohn. La frecuencia promedio de las deposiciones diarias fue de 7 (rango intercuartil 6-8), el 38% experimentó filtración, el 31% tuvo estenosis anal, el 47% experimentó pouchitis y el 18% tuvo falla del reservorio. Con el tiempo, la frecuencia de las deposiciones aumentó en el 41% de los pacientes, se mantuvo igual en el 43% y disminuyó en el 16%. Los pacientes mayores de 50 años en el momento de la construcción tenían más evacuaciones intestinales diarias (media 8 vs 6, p = 0,02) y más filtraciones (77% vs 35%, p = 0,005) que los menores de 50 años. Los pacientes con enfermedad de Crohn tenían mayor frecuencia de deposiciones (media 8 vs 6, p < 0,001) y tasas más altas de estenosis anal (44% vs 26%, p = 0,02), inflamacion (70% vs 40%, p <0,001) y falla del reservorio (38% frente a 12%, p <0,001) en comparación con pacientes que tenian enfermedad de Crohn. Los pacientes con ≥30 años de seguimiento tuvieron una función similar a aquellos con 20-30 años de seguimiento.LIMITACIONES:Este fue un estudio retrospectivo de una sola institución. Solo el 35% de los reservorios creados durante el período de estudio tuvieron más de 20 años de seguimiento.CONCLUSIONES:La mayoría de los pacientes mantienen una función razonablemente buena y conservan el reservorio después de 20 años. Con el tiempo, la frecuencia de las deposiciones y la filtración aumentan. La vejez y la enfermedad de Crohn se asocian con peores resultados. Consulte Video Resumen en http://links.lww.com/DCR/B801. (Traducción - Dr. Ingrid Melo).

Has National Colorectal Cancer Awareness Month increased endoscopy screening rates and public interest in colorectal cancer?

BACKGROUND: National Colorectal Cancer Awareness Month occurs each March to promote awareness and screening for colorectal cancer. The effectiveness of this public health campaign is unknown. The aim of this study was to determine the impact of National Colorectal Cancer Awareness Month on rates of screening endoscopies and on public interest in colorectal cancer. METHODS: To examine the impact of National Colon Cancer Awareness Month on screening endoscopy rates, the National Endoscopy Database was retrospectively reviewed from 2002 through 2014. A time series of monthly number of colorectal cancer screening endoscopies per endoscopist in the data set was evaluated. To examine public interest in colorectal cancer, Google Trends data were collected on the monthly rates of terms related to colorectal cancer from January 2004 to July 2019. Impact of the month on screening endoscopies and public interest was assessed through an analysis of variance. Seasonality was tested for by how well a sinusoidal model fit the time series as opposed to a linear model utilizing a sum-of-squares F test. RESULTS: Review of National Endoscopy Database yielded 1,398,996 endoscopies, 94% were colonoscopies and 6% sigmoidoscopies, with 47% for colorectal cancer screening. Colorectal cancer screening endoscopy rates were not impacted by the month of the year, and these rates had no seasonality. However, Google searches related to colorectal cancer were significantly impacted by month of the year, specifically March, with significant seasonality observed in the data. CONCLUSIONS: National Colorectal Cancer Awareness Month is associated with an increased public interest in colorectal cancer based on user Google search trends. Yet, this has not translated into a demonstrable increase in the rates of screening. This presents an opportunity to capitalize on this increased public interest and harness this enthusiasm into increased screening.

Endoscopic Step Up: A Colon-Sparing Alternative to Colectomy to Improve Outcomes and Reduce Costs for Patients With Advanced Neoplastic Polyps.

BACKGROUND: The optimal strategy for colonic polyps not amenable to traditional endoscopic polypectomy is unknown. Endoscopic step up is a promising strategy for definitive treatment. OBJECTIVE: The purpose of this study was to determine whether endoscopic step up leads to improved outcomes and decreased costs compared with planned colectomy for endoscopically unresectable colon polyps. DESIGN: This was a retrospective review of a prospective database. SETTING: The study was conducted at a tertiary referral center. PATIENTS: Consecutive patients referred for endoscopically unresectable colon polyps 15 to 50 mm in size were included. INTERVENTIONS: Patients underwent planned colectomy or endoscopic step up at the surgeon's discretion. Endoscopic step up began with diagnostic colonoscopy in the operating room. If the polyp was amenable to endoscopic removal, endoscopic mucosal resection or endoscopic submucosal dissection was performed with progression to combined endoscopic-laparoscopic surgery or laparoscopic colectomy, as indicated. MAIN OUTCOME MEASURES: The primary outcome was 30-day adverse events. We also examined length of stay, hospital charges, insurer payments, and polyp recurrence. RESULTS: A total of 52 patients underwent planned colectomy (48 laparoscopic), and 38 underwent endoscopic step up (28 endoscopic mucosal resection, 2 endoscopic submucosal dissection, 6 combined endoscopic-laparoscopic surgery, and 2 colectomy). Compared with planned colectomy, endoscopic step-up patients had fewer complications (13% vs 33%; p = 0.03) and shorter length of stay (median, 0 vs 4 d; p < 0.001). There was 1 readmission in the endoscopic step-up group and 5 in the planned colectomy group. Endoscopic step-up patients had lower hospital costs ($4790 vs $13,004; p < 0.001) and insurer payments ($2431 vs $19,951; p < 0.001). One-year polyp recurrence-free survival was 84% (95% CI, 67%-93%) in endoscopic step-up patients. All of the recurrences were benign, <1 cm, and managed endoscopically. LIMITATIONS: The study was limited by its nonrandomized design and short follow-up. CONCLUSIONS: An endoscopic step-up approach to colon polyps is associated with less morbidity, decreased healthcare costs, and colon preservation in 95% of patients. Additional studies are needed to evaluate long-term quality of life and polyp recurrence in this group. See Video Abstract at http://links.lww.com/DCR/B188. ENDOSCOPIC STEP UP: UNA ALTERNATIVA A COLECTOMíA PARA PRESERVACIóN DE COLON CON LOS PROPóSITOS DE MEJORAR RESULTADOS Y REDUCIR COSTOS EN PACIENTES CON PóLIPOS NEOPLáSICOS AVANZADOS: Se desconoce la estrategia óptima para los pólipos de colon no susceptibles a la polipectomia endoscópica tradicional. Endoscopic Step Up es una estrategia prometedora para el tratamiento definitivo.Determinar si Endoscopic Step Up produce mejores resultados y menores costos en comparación con la colectomía programada para pólipos de colon endoscópicamente no resecables.Revisión retrospectiva de una base de datos prospectiva.Centro de referencia de tercer nivel.Pacientes consecutivos remitidos para pólipos de colon endoscópicamente irresecables de tamaño 15-50 mm.Los pacientes se sometieron a colectomía programada o Endoscópico Step Up a discreción del cirujano. Endoscopic Step Up comenzó con una colonoscopia diagnóstica en el quirófano. Si el pólipo era susceptible de extirpación endoscópica, la resección endoscópica de la mucosa o la disección submucosa endoscópica se realizaba con progresión a cirugía endoscópica-laparoscópica combinada o colectomía laparoscópica, según a cosnideraciones clínicas en el transoperatorio.El resultado primario fue los eventos adversos a 30 días. Duración de la estadía hospitalaria, los cargos hospitalarios, los pagos de las aseguradoras y la recurrencia de pólipos también fueron examinados.Un total de 52 pacientes se sometieron a colectomía programada (48 laparoscópicas) y 38 se sometieron a Endoscopic Step Up (28 resección endoscópica de la mucosa, 2 disección submucosa endoscópica, 6 cirugía endoscópica-laparoscópica combinada y 2 colectomía). En comparación con la colectomía programada los pacientes endoscópicos Step Up tuvieron menos complicaciones (13% versus 33%, p = 0.03) y una estadía hospitalaria más corta (mediana 0 versus 4 días, p <0.001). Hubo 1 reingreso hospitalario en el grupo Endoscopic Step Up y 5 en el grupo de colectomía programada. Los pacientes endoscópicos Step Up tuvieron costos hospitalarios más bajos ($ 4,790 versus $ 13,004, p <0,001) y pagos de la aseguradora ($ 2,431 versus $ 19,951, p <0,001). La supervivencia libre de recurrencia de pólipos a un año fue del 84% (IC 95% 67-93) en pacientes endoscópicos Step Up. Todas las recurrencias fueron benignas, <1 cm, y manejadas endoscópicamente.Diseño no aleatorizado y seguimiento corto.El abordaje endoscópico Step Up para pólipos de colon se asocia con menos morbilidad, disminución de los costos de atención médica y preservación del colon en el 95% de los pacientes. Se ocupan más estudios para evaluar la calidad de vida a largo plazo y la recurrencia de pólipos en este grupo. Consulte Video Resumen en http://links.lww.com/DCR/B188. (Traducción-Dr Adrián Ortega Robles).

Navigating the management of follicular variant papillary thyroid carcinoma subtypes: a classic PTC comparison.

BACKGROUND: There are three subtypes of follicular variant papillary thyroid carcinoma (fvPTC): completely encapsulated, well circumscribed, and infiltrative. While infiltrative tumors are more aggressive than completely encapsulated, controversy exists regarding management of fvPTC subtypes. We compared the clinicopathologic features of fvPTC subtypes to those of classic PTC (cPTC) to help guide fvPTC management, using cPTC as a reference. METHODS: A retrospective review was performed on 316 patients with PTC treated at a single institution from 2004 to 2011. There were 197 cPTC and 119 fvPTC tumors, including completely encapsulated (n = 46), well circumscribed (n = 46), and infiltrative (n = 27). Clinicopathologic data were compared between groups. RESULTS: fvPTC patients had larger tumors than cPTC patients (1.6 cm vs. 1.2 cm, p = 0.001), but age, sex, and family history did not differ. Thirty-one percent of cPTC tumors had extrathyroidal extension compared to 0 % of completely encapsulated, 0 % of well-circumscribed, and 52 % of infiltrative fvPTC tumors (p < 0.05). Central lymph node metastasis occurred in 50 % of cPTC compared to 0 % in completely encapsulated, 20 % in well-circumscribed, and 72 % in infiltrative fvPTC tumors (p < 0.05). Notably, lymph node metastasis was significantly lower in completely encapsulated than in well-circumscribed tumors, without a difference in the median number of nodes sampled. There were no differences in lymphovascular invasion or extranodal extension. CONCLUSIONS: Like cPTC tumors, infiltrative fvPTC tumors have aggressive clinicopathologic features and thus should be treated similarly. Conversely, completely encapsulated and well-circumscribed tumors have less aggressive features compared to cPTC and are more self-limiting; however, well-circumscribed tumors still have a notable incidence of lymph node metastasis. Clinicians should consider this variability in their management algorithm for fvPTC.

Features Associated With Metastases Among Well-Differentiated Neuroendocrine (Carcinoid) Tumors of the Appendix: The Significance of Small Vessel Invasion in Addition to Size.

BACKGROUND: The risk of metastatic disease among carcinoid tumors of the appendix increases with tumor size. However, it is unclear if any features other than size are also associated with an increased risk of metastatic disease. OBJECTIVE: The aim of this study was to review the characteristics of appendiceal carcinoid tumors and determine if other histologic features besides size should guide surgical decision making. DESIGN: This study involved a retrospective case series. SETTINGS: This study was conducted at a single tertiary acute care hospital. PATIENTS: Patients diagnosed with an appendiceal carcinoid tumor between 2000 and 2014 were identified. Goblet cell carcinoids, adenocarcinomas with neuroendocrine features, and tumors from other primary locations were excluded. INTERVENTIONS: Simple appendectomy or segmental/total colectomy with lymphadenectomy was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were metastases, recurrence, and overall survival. RESULTS: Seventy-nine patients were included. The overall incidence of metastatic disease was 10%. Patients with metastatic disease were more likely to be male (75% vs 28%, p = 0.008), have small-vessel invasion (43% vs 5%, p = 0.001), and have larger tumors (median 2.0 cm vs 0.5 cm, p < 0.001). Among tumors <2 cm, the incidence of metastases among tumors with small-vessel invasion was 60% compared with 0% among those without small-vessel invasion (p < 0.001). Among tumors ≥2 cm, the incidence of metastases was 50% irrespective of small-vessel invasion. If small-vessel invasion was used as a second indication for performing a right hemicolectomy along with size ≥2 cm, both the sensitivity and negative predictive value would have been 100% compared with 63% and 96% if size was used alone. Patients with metastatic disease had a higher incidence of recurrence (13% vs 0%, p = 0.003), but overall survival was 100% in both groups. LIMITATIONS: Small sample size, retrospective design, and limited long-term follow-up were the limitations of this study. CONCLUSIONS: Carcinoid tumors of the appendix <2 cm with small-vessel invasion have similar metastatic potential as tumors ≥2 cm. Therefore, a recommendation for a right hemicolectomy should be considered for tumors <2 cm with small-vessel invasion. Additional prospective multicenter studies are warranted.

Silencing of UCHL1 by CpG promoter hyper-methylation is associated with metastatic gastroenteropancreatic well-differentiated neuroendocrine (carcinoid) tumors.

BACKGROUND: Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors with varying metastatic potential. The underlying molecular basis for metastasis by GEP-NETs remains undefined. METHODS: Quantitative PCR and immunohistochemistry (IHC) staining for ubiquitin carboxyl-terminal esterase L1 (UCHL1) gene and protein expression was performed on a group of localized and metastatic well-differentiated GEP-NET samples acquired from a prospectively maintained tissue bank. The ability of extent of UCHL1 IHC staining to differentiate localized and metastatic tumors was compared with Ki-67 index. RESULTS: Among 46 total samples, UCHL1 expression at both the gene and protein level was significantly greater among localized GEP-NETs compared with metastatic tumors and metastases (p < 0.001). Hypermethylation of the UCHL1 promoter was commonly observed among metastatic primary tumors and metastases (those with the lowest UCHL1 expression) but not among localized tumors (p < 0.001). Poor staining (<50 %) for UCHL1 was observed in 27 % of localized tumors compared with 87 % of metastatic tumors (p = 0.001). The presence of <50 % staining for UCHL1 was 88 % sensitive and 73 % specific for identifying metastatic disease. In contrast, there was no association between Ki-67 index and metastatic disease. In multivariable analysis, only UCHL1 staining <50 % [odds ratio (OR) 24.5, p = 0.035] and vascular invasion (OR 38.4, p = 0.03) were independent risk factors for metastatic disease at the time of initial surgery. CONCLUSIONS: Loss of UCHL1 expression by CpG promoter hypermethylation is associated with metastatic GEP-NETs. Extent of UCHL1 staining should be explored as a potentially clinically useful adjunct to Ki-67 index in evaluating GEP-NETs for aggressive features.

Preoperative BRAF(V600E) mutation screening is unlikely to alter initial surgical treatment of patients with indeterminate thyroid nodules: a prospective case series of 960 patients.

BACKGROUND: Preoperative B-type Raf kinase Val600Glu mutation, or BRAF(V600E), analysis has been proposed as a tool to guide initial surgery for indeterminate thyroid nodules. This study sought to determine if cytologic markers of malignancy are associated with the BRAF(V600E) mutation and if preoperative BRAF(V600E) testing would alter the initial management of patients with indeterminate nodules. METHODS: Patients who underwent surgery for a thyroid nodule between 2003 and 2012 at a tertiary care center were prospectively enrolled. Stored nodule samples were retrospectively genotyped for the BRAF(V600E) mutation. BRAF(V600E) status, demographics, cytologic and histopathologic findings, and choice of initial surgery were examined. RESULTS: A total of 960 patients were enrolled, of which 310 (32%) had an indeterminate nodule. The BRAF(V600E) mutation was identified in 13 patients (4%), 12 of whom had either cytologic atypia or were Bethesda category V. Three percent of Bethesda category III or IV nodules that were malignant harbored the mutation compared with 42% of Bethesda category V malignancies. Nuclear grooves (P = .030), pseudoinclusions (P < .001), and oval nuclei (P = .022) were all more common among BRAF(V600E) mutants. The sensitivities of using BRAF testing alone, cytologic atypia/Bethesda category V classification, or both, were 15%, 73%, and 76%, respectively. Twelve of the 13 BRAF(V600E) mutants had total thyroidectomies initially due to worrisome cytologic features, and therefore the initial management of only one patient would have been altered if BRAF(V600E) testing had been performed preoperatively. CONCLUSIONS: Preoperative mutation screening for BRAF(V600E) does not meaningfully improve risk stratification and is unlikely to alter the initial management of patients with indeterminate nodules.

Does bethesda category predict aggressive features in malignant thyroid nodules?

BACKGROUND: It has been speculated that the Bethesda Classification System for thyroid fine-needle aspirate (FNA) may be used to predict aggressive features among histologically proven malignancies. We sought to evaluate whether malignancies that were characterized as Bethesda category V or VI have more aggressive features than malignancies that were category III or IV. METHODS: A prospectively maintained database was reviewed to identify thyroid malignancies treated at a single center from 2004 to 2009. Only cancers that could be definitively matched to a preoperative FNA were included. Associations between Bethesda category, patient demographics, histopathologic findings, and outcomes were examined. RESULTS: A total of 360 cancers were analyzed: 73 (20 %) were Bethesda category III or IV and 287 (80 %) were category V or VI. The majority of Bethesda III and IV cancers were follicular variants of papillary thyroid carcinoma (fvPTC), whereas the majority of Bethesda V and VI cancers were classic PTC (52 and 67 %, respectively, p < 0.01). Extrathyroidal extension (30 vs. 16 %, p = 0.02), lymph node metastases (50 vs. 31 %, p = 0.05), and multifocality (51 vs. 37 %, p = 0.03) were more common among Bethesda V and VI nodules. However, when Bethesda III or IV classic PTC and fvPTC were compared to Bethesda V or VI cancers of the same histologic subtype, there were no differences in any features. Recurrence and overall survival were the same in all groups. CONCLUSIONS: Bethesda category may help to predict the most likely histologic subtype of thyroid cancer, but it does not have any prognostic significance once the histologic diagnosis is known.

Thyroid stimulating hormone increases iodine uptake by thyroid cancer cells during BRAF silencing.

BACKGROUND: The BRAF(V600E) mutation is present in 62% of radioactive iodine-resistant thyroid tumors and is associated with downregulation of the sodium-iodide symporter (NIS) and thyroid stimulating hormone receptor (TSHr). We sought to evaluate the combined effect of BRAF inhibition and TSH supplementation on (131)I uptake of BRAF(V600E)-mutant human thyroid cancer cells. MATERIALS AND METHODS: WRO cells (a BRAF(V600E)-mutant follicular-derived papillary thyroid carcinoma cell line) were transfected with small interfering RNA targeting BRAF for 72 h in a physiological TSH environment. NIS and TSHr expression were then evaluated at three levels: gene expression, protein levels, and (131)I uptake. These three main outcomes were then reassessed in TSH-depleted media and media supplemented with supratherapeutic concentrations of TSH. RESULTS: NIS gene expression increased 5.5-fold 36 h after transfection (P = 0.01), and TSHr gene expression increased 2.8-fold at 24 h (P = 0.02). NIS and TSHr protein levels were similarly increased 48 and 24 h after transfection, respectively. Seventy-two hours after BRAF inhibition, (131)I uptake was unchanged in TSH-depleted media, increased by 7.5-fold (P < 0.01) in physiological TSH media, and increased by 9.1-fold (P < 0.01) in supratherapeutic TSH media. CONCLUSIONS: The combined strategy of BRAF inhibition and TSH supplementation results in greater (131)I uptake than when either technique is used alone. This represents a simple and feasible approach that may improve outcomes in patients with radioactive iodine-resistant thyroid carcinomas for which current treatment algorithms are ineffective.

Early referral for 24-h esophageal pH monitoring may prevent unnecessary treatment with acid-reducing medications.

BACKGROUND: Gastroesophageal reflux disease (GERD) affects nearly 25 % of adults; however, an objective diagnosis is rarely established. We hypothesized that patients' symptoms and response to acid-reducing therapy are poor predictors of the outcome of 24-h esophageal pH monitoring. METHODS: A review of 24-h esophageal pH monitoring studies performed at an ambulatory tertiary care center between 2004 and 2011 was performed. Demographics, type of GERD symptoms, and duration and response to acid-reducing medications before referral for pH monitoring were collected. DeMeester score, symptom sensitivity index (SSI), and symptom index (SI) were tabulated and compared with the patients' symptoms and response to medical therapy. RESULTS: One hundred patients were included. Of all reported symptoms, only heartburn was more common in patients with positive DeMeester scores, but there were no correlations between any symptoms and SSI or SI scores. Sixty-nine percent of patients with esophageal symptoms had a positive DeMeester score compared with only 29 % of patients with extraesophageal symptoms (P < 0.01). Esophageal symptoms and endoscopic evidence of GERD significantly increased the likelihood of having a positive DeMeester score, but they had no influence on SSI or SI scores. There was no correlation between response to acid-reducing medications and DeMeester, SSI, or SI scores. A total of 536 person-years of acid-reducing medications were prescribed to the study population, of which 151 (28 %) were prescribed to patients who had a negative pH study. CONCLUSIONS: Extraesophageal symptoms and response to empiric trials of acid-reducing medications are poor predictors of the presence of GERD and the DeMeester score is more likely to identify GERD in patients who met other empiric diagnostic criteria than SSI or SI. Early referral for 24-h esophageal pH monitoring may avoid lengthy periods of unnecessary medical therapy.

Horseshoe Fistulae in the Age of LIFT.

BACKGROUND: Horseshoe fistula is a challenging benign anorectal condition to treat. The aim of this study was to assess the utilization and success of different definitive fistula repair techniques in the treatment of horseshoe fistula. METHODS: This was a retrospective case series which included all patients who were treated for horseshoe fistula from 2006 to 2019 at a single, tertiary care center and whom had at least one follow-up visit. Patients were excluded if < 18 years of age or carried a diagnosis of Crohn's disease. Patients were assessed for fistula recurrence and incontinence. RESULTS: Sixty-eight patients were identified. On average, they were 47 years old, 63% male, and 18% current smokers. Seventy-nine percent required seton during their treatment course. Of the 8 first attempts at fistula repair, the types of repair included flap (15%), LIFT (35%), fistulotomy (31%), plug (12%), and fistulotomy and immediate reconstruction (1%). Recurrence for these procedures was as follows: flap 30%, LIFT 21%, fistulotomy 14%, plug 88%, and fistulotomy and immediate reconstruction 0%. Twelve patients who recurred underwent 17 additional procedures to attempt to cure their fistula. Overall, of those who underwent any attempt at definitive repair, 82% of patients were cured of their fistula, 12% had a chronic seton, and 6% had a chronic fistula. Thirteen percent of those who were cured had incontinence. The mean follow-up time was 1.1 years. Patients required a median of 3 procedures (range 1-11). CONCLUSION: Horseshoe fistula remains a complex anorectal condition. Successful repair can be performed in > 80% of patients. However, repair can often require multiple surgical procedures.

Impact of the first COVID-19 surge on the outcomes of diverticulitis.

Introduction: During the first surge of the COVID-19 pandemic, healthcare utilization changed. We sought to examine the impact of the first COVID-19 surge on the outcomes of patients whose elective surgeries for diverticulitis were postponed and those who underwent urgent surgery during the surge. Materials and methods: This was a retrospective study from a single tertiary center in the Northeast of the US. Patients whose elective surgeries were delayed, or who underwent urgent surgery for diverticulitis during the first COVID-19 surge (3/16/2020 to 8/1/2020) were included. A cohort from 2019 was used for comparison. Variables were compared between groups including: procedure, death, length of stay, disposition, stoma rate, technique for surgery, and leak rate. Results: Forty-five patients were included in the COVID-19 group and 44 patients in the 2019 group. Twenty-seven patients had elective surgeries delayed during the COVID-19 surge. Ten (37%) required more urgent surgery, 80% with complicated disease. Six (22%) were admitted to the hospital and 13 (48%) required additional antibiotics. Eight (30%) patients postponed their surgeries indefinitely and 7 (26%) had surgery once permitted. There were no observed differences between the two groups in the rate of complicated disease, leaks, technique for surgery or stoma rate. Conclusions: During the first COVID-19 surge, over 1/3 of patients whose elective diverticulitis surgeries were postponed required urgent surgery, a majority of whom had complicated disease. There were no apparent differences in outcomes when compared to a pre-pandemic cohort, highlighting the importance of a triage system with the ability to escalate surgery in a timely manner.

How to Get Ahead: Early-Career Colorectal Surgeons Reflect on Their First Few Years in Practice.

OBJECTIVE: To identify strategies and barriers to career progression in early-career colorectal surgeons. DESIGN: Qualitative research study performed via semi-structured interviews with early-career, board-certified colon, and rectal surgeons. Responses were analyzed, coded, and categorized to understand strategies towards career progression, perceived barriers to career progression, beliefs about case mix, and referral patterns. SETTING: Interviews conducted in person and via telephone across the United States and Canada. PARTICIPANTS: Early-career board-certified colorectal surgeons RESULTS: Twenty-two board-certified colorectal surgeons currently employed in 14 states and 1 foreign country were interviewed. Fourty-five percent were female. Their current practice environment was described as academic (77%), private practice (18%), or military (5%). Seventy-seven percent of surgeons were satisfied with their career progression. Seventy-two percent were satisfied with the case volume. Seventy-two percent were satisfied with their case mix. When asked about strategies for career progression, surgeons made 77 comments focused on three main themes: optimization of their job search, optimization of relationships while on the job, and efforts to augment individual achievement. When asked about barriers to career advancement, surgeons most frequently commented on a lack of time and a lack of mentors. When asked about case mix, 63% of surgeons felt that they had no control over it. They were evenly divided between believing that a broad case mix or a niche specialized case mix was more instrumental for career progression. CONCLUSIONS: Early-career colorectal surgeons were mostly satisfied with their career progression, volume, and case mix. In discussing their careers, many have developed a number of strategies focused on growth as an individual as well as relationship building. They also identified a number of barriers including lack of time and lack of mentorship. Early-career surgeons may be able to utilize these strategies and anticipate barriers prior to starting their first job, leading to greater likelihood of career satisfaction.

What do Young Colorectal Surgeons Value From Their CRS Residency Training?

OBJECTIVE: Colorectal surgery (CRS) training has seen many changes over the years. This study sought to identify aspects of CRS residency curriculum that were most valued by recent graduates and what changes could be made to improve training. DESIGN: Semistructured interviews were performed with board-certified colorectal surgeons 2 to 7years removed from their CRS residency. Interview responses were qualitatively analyzed and converted to coded, categorizable data. Subjects were recruited via a snowball sampling method. SETTING: Interviews were conducted in person and via telephone with surgeons in a variety of practices across the United States and Canada. Analysis was performed by a team at Lahey Clinic, Burlington, MA, an academic, tertiary care center. PARTICIPANTS: Board certified colorectal surgeons 2 to 7years removed from CRS residency. RESULTS: Twenty surgeons from 11 different CRS residencies were interviewed. At the time of the interview, surgeons were employed in 13 states and 1 foreign country. When asked what aspects of their CRS residency were of value, surgeons produced 74 comments emphasizing: volume of cases (65% of subjects), variety of cases (55%), development of technical skills (40%), management of specific diseases (35%), faculty (30%), mentorship (30%), and practice management (15%). With regard to technical skills, surgeons cited pelvic surgery (40%) and minimally invasive techniques (45%) as the exposures that helped them become successful. When discussing what could be added to training, subjects made 54 comments identifying: more robotic exposure (35%), more anorectal disease (30%), more pelvic floor exposure (25%), and practice management/billing (35%) as items to incorporate. Sixty five percent of subjects believed that "nothing" should be eliminated from their training. CONCLUSIONS: Young colon and rectal surgeons valued their training highly and strongly declined to eliminate any substantial part of the existing curriculum. They also expressed a strong desire to add more elements to the CRS residency including further robotic training, more anorectal, more pelvic floor, and further training in practice management.