Efficacy of Anal Sphincter Division During Fistulotomy in Anal Fissure-Associated Fistula.

BACKGROUND: A subset of chronic anal fissures beget focal infection, leading to concomitant fistula. The optimal management of fissure-associated fistula is unknown. OBJECTIVE: This study aimed to characterize healing rates and effects of fistulotomy in fissure-associated fistula. DESIGN: Retrospective study. SETTING: Urban tertiary center. PATIENTS: Adults who underwent fistulotomy for a fistula associated with a chronic anal fissure were included in the study. However, those with Crohn's disease, a history of lateral internal sphincterotomy, and a fistula not amenable to fistulotomy were excluded. INTERVENTIONS: Patients were managed with fistulotomy. Fissures were otherwise managed conservatively with a step-up approach. MAIN OUTCOME MEASURES: The primary end point was healing, defined as resolution of symptoms and both fistula and fissure wounds within 1 year. Subgroup analysis compared those who underwent subcutaneous fistulotomy (group A) with those who underwent fistulotomy involving anal sphincter fibers (group B). RESULTS: Twenty-four of 38 patients (63%) healed with a median overall follow-up of 6.6 months (4.2-14.1). The overall median time to healing was 4.4 months (2.2-6.0). No clinical or pathologic factors predicted healing. In subgroup analysis, overall subcutaneous fistulotomy healing rates were nonstatically lower at 46% (6/13) compared to fistulotomy involving anal sphincter fibers at 72% (18/25; p = 0.16). There was no difference in time to healing (subcutaneous fistulotomy, 6.7 mo [5.2-8.4] vs fistulotomy involving sphincter, 5.1 mo [2.1-7.0]; p = 0.36). LIMITATIONS: The limitations include treatment bias, with increased utilization of chemical sphincter-relaxing agents in those who did not heal. Findings are not applicable to complex fistulas, Crohn's disease, or atypical fissures. CONCLUSIONS: Patients presenting with chronic fissure and associated subcutaneous, intersphincteric, or low transphincteric fistula are successfully managed with fistulotomy. Patients with a subcutaneous fistula tract exhibited nonstatistically significantly lower rates of healing. See Video Abstract at http://links.lww.com/DCR/C145 . EFICACIA DE LA DIVISIN ESFINTRICA DURANTE LA FISTULOTOMA EN CASOS DE FSTULA ASOCIADA A FISURA ANAL: ANTECEDENTES: Ciertos subgrupos de fisuras anales crónicas ocasionan infección localizada, induciendo la aparición de una fístula anal concomitante. Se desconoce el manejo óptimo de la fístula concomitante a una fisura anal.OBJETIVO: Se trata de caracterizar las tasas de curación y el efecto de la fistulotomía en el tratamiento de la fístula concomitante a la fisura anal.DISEÑO: Estudio retrospectivo.EMPLAZAMIENTO: Centro terciario urbano.PACIENTES: Adultos sometidos a fistulotomía por una fístula concomitante a una fisura anal crónica. Se excluyeron la enfermedad de Crohn, el antecedente de una esfinterotomía lateral interna y las fístulas no susceptibles de fistulotomía.INTERVENCIONES: Los pacientes fueron manejados con una fistulotomía clasica. Por lo demás, las fisuras se trataron de forma conservadora con un enfoque médico escalonado.PRINCIPALES MEDIDAS DE RESULTADO: El criterio principal de valoración fué la cura definitiva, determinada como la resolución completa de los síntomas y de las heridas tanto de la fístula como de la fisura en el plazo de un año. El análisis de los subgrupos comparó los que se sometieron a una fistulotomía subcutánea (grupo A) versus una fistulotomía que involucró las fibras del esfínter anal interno (grupo B).RESULTADOS: 24/38 pacientes (63%) curaron con una mediana de seguimiento global de 6,6 meses (4,2-14,1). El tiempo medio general de curación fue de 4,4 meses (2,2-6,0). Ningún factor clínico o patológico predijo la cura. En el análisis de subgrupos, las tasas generales de cura de la fistulotomía subcutánea no fueron estadísticamente más bajas de 46 % (6/13) comparados con la fistulotomía que involucró las fibras del esfínter anal interno en 72 % (18/25; p = 0,16). No hubo diferencia en el tiempo de cicatrización [fistulotomía subcutánea 6,7 meses (5,2-8,4) conparada a la fistulotomía y esfínterotomía parcial interna a 5,1 meses (2,1-7,0); p = 0,36].LIMITACIONES: Sesgo del tratamiento, con mayor utilización de agentes químicos relajantes de la musculatura esfínteriana en aquellos pacientes que no sanaron. No aplicable a fístulas complejas, enfermedad de Crohn o fisuras atípicas.CONCLUSIÓNES: Los pacientes que presentan fisura crónica y fístula subcutánea, inter-esfintérica o trans-esfintérica baja concomitante se manejan con éxito con una fistulotomía. Los pacientes con un trayecto de fístula subcutánea exhibieron tasas de curación más bajas y no estadísticamente significativas. Consulte Video Resumen en http://links.lww.com/DCR/C145 . (Traducción-Dr. Xavier Delgadillo ).

A Prospective Randomized Trial of Surgeon-Administered Intraoperative Transversus Abdominis Plane Block With Bupivacaine Against Liposomal Bupivacaine: The TINGLE Trial.

BACKGROUND: Transversus abdominis plane blocks are increasingly used to achieve opioid-sparing analgesia after colorectal surgery. Traditionally, bupivacaine was the long-acting analgesic of choice, but the addition of dexamethasone and/or epinephrine to bupivacaine may extend block duration. Liposomal bupivacaine has also been suggested to achieve an extended analgesia duration of 72 hours but is significantly more expensive. OBJECTIVE: The purpose of this study was to compare pain control between laparoscopic transversus abdominis plane blocks using liposomal bupivacaine versus bupivacaine with epinephrine and dexamethasone. DESIGN: This was a parallel-group, single-institution, randomized clinical trial. SETTINGS: The study was conducted at a single tertiary medical center. PATIENTS: Consecutive patients between October 2018 to October 2019, ages 18 to 90 years, undergoing minimally invasive colorectal surgery with multimodal analgesia were included. INTERVENTIONS: Patients were randomly assigned 1:1 to receive a laparoscopic transversus abdominis plane block with liposomal bupivacaine or bupivacaine with epinephrine and dexamethasone. MAIN OUTCOME MEASURES: The primary outcome was total oral morphine equivalents administered in the first 48 hours postoperatively. Secondary outcomes included pain scores, time to ambulation and solid diet, hospital length of stay, and complications. RESULTS: A total of 102 patients (50 men) with a median age of 42 years (interquartile range, 29-60 y) consented and were randomly assigned. The primary end point, total oral morphine equivalents administered in the first 48 hours, was not significantly different between the liposomal bupivacaine group (median = 69 mg) and the bupivacaine with epinephrine and dexamethasone group (median = 47 mg; difference in medians = 22 mg, (95% CI, -17 to 49 mg); p = 0.60). There were no significant differences in pain scores, time to ambulation, time to diet tolerance, time to bowel movement, length of stay, overall complications, or readmission rate between groups. There were no treatment-related adverse outcomes. LIMITATIONS: This study was not placebo controlled or blinded. CONCLUSIONS: This first randomized trial comparing laparoscopic transversus abdominis plane block with liposomal bupivacaine or bupivacaine with epinephrine and dexamethasone showed that a liposomal bupivacaine block does not provide superior or extended analgesia in the era of standardized multimodal analgesia protocols.See Video Abstract at http://links.lww.com/DCR/B533. ESTUDIO PROSPECTIVO Y RANDOMIZADO DE BLOQUEO DEL PLANO MUSCULAR TRANSVERSO DEL ABDOMEN REALIZADO POR EL CIRUJANO CON BUPIVACANA VERSUS BUPIVACANA LIPOSOMAL ESTUDIO TINGLE: ANTECEDENTES:El bloqueo anestésico del plano muscular transverso del abdomen se utiliza cada vez más para lograr una analgesia con menos consumo de opioides después de cirugía colorrectal. Tradicionalmente, la Bupivacaína era el analgésico de acción prolongada de elección, pero al agregarse Dexametasona y/o Adrenalina a la Bupivacaína se puede prolongar la duración del bloqueo. También se ha propuesto que la Bupivacaína liposomal logra una duración prolongada de la analgesia de 72 horas, pero es significativamente más cara.OBJETIVO:Comparar el control del dolor entre bloqueo laparoscópico del plano de los transversos del abdomen usando Bupivacaína liposomal versus Bupivacaína con Adrenalina y Dexametasona.DISEÑO:Estudio clínico prospectivo y randomizado de una sola institución en grupos paralelos.AJUSTE:Centro médico terciario único.PACIENTES:Todos aquellos pacientes entre 18 y 90 años sometidos a cirugía colorrectal mínimamente invasiva con analgesia multimodal, entre octubre de 2018 a octubre de 2019 incluidos de manera consecutiva.INTERVENCIONES:Los pacientes fueron seleccionados aleatoriamente 1:1 para recibir un bloqueo laparoscópico del plano de los transversos del abdomen con Bupivacaína liposomal o Bupivacaína con Adrenalina y Dexametasona.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el total de equivalentes de morfina oral administradas en las primeras 48 horas después de la operación. Los resultados secundarios incluyeron puntuaciones de dolor, inicio de dieta sólida, tiempo de inicio a la deambulación, la estadía hospitalaria y las complicaciones.RESULTADOS:Un total de 102 pacientes (50 hombres) con una mediana de edad de 42 años (IQR 29-60) fueron incluidos aleatoriamente. El criterio de valoración principal, equivalentes de morfina oral total administrada en las primeras 48 horas, no fue significativamente diferente entre el grupo de Bupivacaína liposomal (mediana = 69 mg) y el grupo de Bupivacaína con Adrenalina y Dexametasona (mediana = 47 mg; diferencia en medianas = 22 mg, IC del 95% [-17] - 49 mg, p = 0,60). No hubo diferencias significativas en las puntuaciones de dolor, tiempo de inicio a la deambulación, el tiempo de tolerancia a la dieta sólida, el tiempo hasta el primer evacuado intestinal, la duración de la estadía hospitalaria, las complicaciones generales o la tasa de readmisión entre los grupos. No hubo resultados adversos relacionados con el tratamiento.LIMITACIONES:Este estudio no fue controlado con placebo ni de manera cegada.CONCLUSIONES:Este primer estudio prospectivo y randomizado que comparó el bloqueo del plano de los músculos transversos del abdomen por vía laparoscópica, utilizando Bupivacaína liposomal o Bupivacaína con Adrenalina y Dexametasona, demostró que el bloqueo de Bupivacaína liposomal no proporciona ni mejor analgesia ni un efecto mas prolongado.Consulte Video Resumen en http://links.lww.com/DCR/B533.

Challenges in Ki-67 assessments in pulmonary large-cell neuroendocrine carcinomas.

AIMS: To gather the best available evidence regarding Ki-67% values in large-cell neuroendocrine carcinoma (LCNEC) and determine whether certain cut-off values could serve as a prognostic feature in LCNEC. METHODS AND RESULTS: Aperio ScanScope AT Turbo, eSlide Manager and ImageScope software (Leica Biosystems) were used to measure Ki-67% in 77 resected LCNEC diagnosed by World Health Organisation (WHO) criteria. Cases were stratified into six classes by 10% Ki-67 increments. Using the Kaplan-Meier method, overall (OS) and disease-free survivals (DFS) were compared by AJCC stage, by six Ki-67% classes and with Ki-67% cut-points ≥20% and ≥40%. Tumours were from 0.9 to 11.5 cm and pathological stages 1-3. The system measured Ki-67% positivity using 4072-44 533 tumour nuclei per case (mean 16610 ± 8039). Ki-67% ranged from 1 to 64% (mean = 26%; median = 26%). Only 16 (21%) tumours had Ki-67% ≥40%. OS ranged from 1 to 298 months (median follow-up = 25 months). DFS ranged from 1 to 276 months (median follow-up = 9 months). OS and DFS differed across AJCC stage (overall log-rank P = 0.038 and P = 0.037). However, neither OS nor DFS significantly correlated with Ki-67% when six or two classes were used with either ≥20% Ki-67 or ≥40% Ki-67 as cut-point. A literature review identified 14 reports meeting our inclusion criteria with ≥10 LCNEC. Reported Ki-67% ranged from 2% to 100%. Problems contributing to variability in Ki-67% measurements are discussed. CONCLUSION: Our findings caution against a blanket use of 20%, 40% or other Ki-67% cut-points for LCNEC diagnosis or prognostication.

Randomized Clinical Trial Comparing Laparoscopic Versus Ultrasound-Guided Transversus Abdominis Plane Block in Minimally Invasive Colorectal Surgery.

BACKGROUND: Transversus abdominis plane block may improve analgesia after colorectal surgery; however, techniques remain unstandardized and results are conflicting. OBJECTIVE: The purpose of this study was to compare laparoscopic and ultrasound-guided transversus abdominis plane block with no block in minimally invasive colorectal surgery. DESIGN: This was a randomized controlled trial. SETTINGS: The study was conducted at an urban teaching hospital. PATIENTS: Patients undergoing laparoscopic colorectal surgery were included. INTERVENTIONS: The intervention included 2:2:1 randomization to laparoscopic, ultrasound-guided, or no transversus abdominis plane block. MAIN OUTCOME MEASURES: Morphine use in the first 24 hours after surgery was measured. RESULTS: The study cohort included 107 patients randomly assigned to laparoscopic (n = 41), ultrasound-guided (n = 45), or no transversus abdominis plane block (n = 21). Mean age was 50.4 years (SD ± 18 y), and 50 patients (47%) were men. Laparoscopic transversus abdominis plane block was superior to ultrasound-guided (p = 0.007) and no transversus abdominis plane block (p = 0.007), with median (interquartile range) total morphine used in the first 24 hours postoperatively of 17.6 mg (6.6-33.9 mg), 34.0 mg (16.4-44.4 mg), and 31.6 mg (18.4-44.4 mg). At 48 hours, laparoscopic transversus abdominis plane block remained superior to ultrasound-guided (p = 0.03) and no transversus abdominis plane block (p = 0.007) with median (interquartile range) total morphine used at 48 hours postoperatively of 26.8 mg (15.5-45.8 mg), 44.0 mg (27.6-70.0 mg), and 60.8 mg (34.8-78.8 mg). Mean hospital stay was 5.1 ± 3.1 days without any intergroup differences. Overall complications were similar between groups. LIMITATIONS: Treatment teams were not blinded and there was operator dependence of techniques and variable timing of the blocks. CONCLUSIONS: Laparoscopic transversus abdominis plane block is superior to ultrasound-guided and no transversus abdominis plane block in achieving pain control and minimizing opioid use in the first 24 hours after colorectal surgery. A large, multicenter, randomized trial is needed to confirm our findings. See Video Abstract at http://links.lww.com/DCR/A822.

Comparison of Magee and Oncotype DX Recurrence Scores in estrogen receptor positive breast cancers.

Data from pathology reports of estrogen receptor positive (ER+) breast cancers with Ki67 < 14% (luminal-A; n = 128) and Ki67 ≥ 14% (luminal-B; n = 100) were entered into the automatic recurrence score (RS) calculator accessible at the University of Pittsburgh Department of Pathology website. Using RS obtained with Magee equations #1 and #3, an average modified Magee recurrence score (AMM RS) was calculated for each tumor. The AMM RS and the Oncotype DX RS (Onco RS) were compared per tumor and associated with follow-up. AMM RS and Onco RS agreed in 64.9% (148 of 228) breast cancers (70.3% luminal-A and 58% luminal-B). There was only one two-step (low risk by Onco/high risk by AMM) RS disagreement. This luminal-B patient is alive without recurrence and free of tumor at 46 months postdiagnosis. Low-risk/intermediate-risk disagreements comprised 94.7% (36 of 38) and 69% (29 of 42) of the RS disagreements in the luminal-A and luminal-B groups, respectively (P = 0.004). In luminal-A, there were only two intermediate/high-risk disagreements; both high-risk ratings were by Onco RS. In luminal-B, there were 12 intermediate/high-risk disagreements; 11 of the high-risk ratings were by Onco RS. 100% (3 of 3) luminal-A tumors and 75% (6 of 8) luminal-B tumors that were high risk by AMM RS were also high risk by Onco RS. Eight tumors recurred and/or metastasized. AMM RS and Onco RS disagreed in only two of these eight tumors. The high percentage of tumors scored as intermediate risk (50% by AMM RS and 39% by Onco RS) is a major limitation of both scoring algorithms.

Comparison of endoscopic ultrasound guided fine needle aspiration and PET/CT in preoperative diagnosis of pancreatic adenocarcinoma.

BACKGROUND: Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the procedure of choice to investigate and sample pancreatic masses for the preoperative diagnosis of pancreatic ductal adenocarcinoma (PDAC). The role of 18fluoro-deoxyglucose positron emission tomography/computed tomography (PET/CT) in PDAC is debated. This study evaluates the role of EUS-FNA as compared to PET/CT in the preoperative evaluation of PDAC. METHODS: Preoperative evaluation by PET/CT and EUS-FNA was performed on 25 patients with pancreatic solid lesions, who underwent a subsequent Whipple procedure or partial pancreatic resection. RESULTS: This series included 19 PDACs and 6 non-PDACs including 1 metastatic breast ductal adenocarcinoma, 2 low grade neuroendocrine tumors, 2 chronic pancreatitis and 1 gastrointestinal tumor abutting the pancreas. EUS-FNA correctly diagnosed 18 of 19 PDACs, 1 metastatic breast ductal adenocarcinoma and all 5 of the other non-PDAC cases. One case of well differentiated PDAC was negative on EUS-FNA. PET/CT provided excellent size and was positive in 14 of 19 PDACs and the metastatic breast ductal adenocarcinoma. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for EUS-FNA in diagnosis of selected pancreatic tumors were 91%, 100%, 100%, 50% and 92%, respectively, while they were 65%, 100%, 100%, 20% and 68% for PET/CT, respectively. CONCLUSIONS: Compared to PET/CT, EUS-FNA has a higher sensitivity and accuracy for preoperative diagnosis of PDAC. However, PET/CT provides excellent size, volume and stage information. A combination of both PET/CT and EUS will better help guide diagnosis and treatment of pancreatic adenocarcinoma.

Pathologic Staging and Survival of Patients With Synchronous Bilateral Lung Carcinomas.

OBJECTIVES: To compare survival data in patients with resected bilateral synchronous pulmonary carcinomas with survival data from patients with lung cancer in pStages I through IV and to evaluate the usefulness of comprehensive histologic evaluation (CHE) of tumor histologic patterns to distinguish between synchronous primaries and intrapulmonary metastases. METHODS: Ten-year overall survival (OS) data from 18 patients with 44 resected synchronous bilateral lung cancers, classified as "synchronous primaries" or "metastases" using CHE, were compared with survival data of 2,879 patients with lung cancer in pStages I through IV. RESULTS: Forty and four tumors from 16 and two patients, respectively, were classified as synchronous primaries and metastases. There were no significant differences in survival between these 18 patients and pStage I controls or between the synchronous primaries and the metastases patient groups. However, there were significant differences in survival between the patients with resected synchronous bilateral tumors and each of the pStage II through IV control groups (P < .05). CONCLUSIONS: Patients with resected synchronous bilateral lung cancers had similar 10-year OS to patients with stage I disease, regardless of CHE data. Most resected tumors were synchronous primaries by CHE.

Follicular variant of papillary thyroid carcinoma (FVPTC): histological features, BRAF V600E mutation, and lymph node status.

PURPOSE: Follicular variant of papillary thyroid carcinoma (FVPTC) is currently treated like conventional papillary thyroid carcinoma (cPTC). Recent reports indicate that encapsulated FVPTC behaves like follicular adenomas, while infiltrative FVPTC behaves like cPTC. This raises the possibility that histology and/or mutation status might help personalize management of FVPTC regarding extent of surgery, intensity of follow-up, and targeted therapy. This study correlates histological features, immunoreactivity for CK19, HBME, and Gal, and BRAF V600E mutation with lymph node (LN) metastasis and follow-up in FVPTC. METHODS: Forty-eight FVPTC (21 with regional lymph node metastasis [LN+] and 27 with negative lymph nodes [LN-]) were reviewed. Demographics, tumor focality, size, circumscription, follicular architecture, lymphovascular invasion, extrathyroidal extension (ETE), and margin status were charted. Macrodissected formalin-fixed paraffin-embedded sections from 47 (21 LN+ and 26 LN-) cases were analyzed for BRAF V600E (1799T>A) mutation using real-time PCR. Correlations between the variables and LN status were calculated. RESULTS: Sixty-two percent of cases with ETE demonstrated LN metastasis, while 59 % of cases with circumscribed tumors were LN-. In multivariable analysis, ETE and tumor size ≥1 cm were the best predictors of LN+ status, whereas in cases without ETE, the infiltrative pattern and tumor size provided the "best fit." Immunostains and BRAF mutation status were not helpful. All four tumors that recurred were LN+, with infiltrative borders, and lacked the BRAF mutation. CONCLUSIONS: Tumor circumscription, extrathyroidal extension, and tumor size ≥ 1.0 cm are predictors of lymph node status in FVPTC.

Survival and quality of life for nonagenarians after cardiac surgery.

BACKGROUND: Reports of cardiac surgery in the elderly have focused primarily on septuagenarians and octogenarians. There are very limited data regarding risk-adjusted models in nonagenarians. METHODS: From 1983 to 2011, patients with age 90 years or greater at the time of coronary artery bypass grafting (CABG) or valve surgery (aortic or mitral) were retrieved from a prospective institutional database. A Cox proportional hazard model was used to determine significant predictors of 5-year survival. In addition, a 12-month assessment of quality of life was conducted. RESULTS: The CABG-only (n = 46), valve-only (n = 55), or CABG-valve (n = 53) surgery was conducted in 154 patients. Demographic characteristics were similar in all groups except for congestive heart failure, which was more prominent in the valve-only or CABG-valve groups (p < 0.0001). The 30-day mortality was 8.8%, 12.8%, and 18.9% in the CABG-only, valve-only, and CABG-valve groups, respectively, without significant difference among groups (p = 0.35). At 5-years follow-up, the Kaplan-Meier survival curves do not show a difference among groups (p = 0.62). Cox proportional hazard model for 5-year survival identified age (hazard ratio [HR] = 1.25, confidence interval [CI] 1.09 to 1.43, p = 0.001, for 1-year increase), prior surgery (HR = 2.23, CI 1.23 to 4.64, p = 0.007), and prior stroke (HR = 2.39, CI 1.25 to 3.98, p = 0.01), as significant predictors of mortality. The 12-month quality of life questionnaire revealed an improvement in 83% of the patients, whereas only 4% reported a decline in cardiac status. CONCLUSIONS: Survival in nonagenarians is comparable after CABG or valve surgery. Redo surgery, stroke, and increasing age are significant hazards for mortality. Nonagenarians can undergo cardiac surgery with acceptable mortality and quality of life.

Value of Islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of pancreatic origin.

Neuroendocrine tumors can present as liver metastases before discovery of the primary tumor. Islet 1 and PAX8 have recently been proposed as markers for neuroendocrine tumors of pancreatic origin. In this study, we compared the utility of Islet 1 and PAX8 in distinguishing pancreatic neuroendocrine tumors from neuroendocrine tumors of other sites and determined the usefulness of an immunohistochemical panel, including TTF1, CDX2, Islet 1 and/or PAX8, in identifying metastatic pancreatic neuroendocrine tumors. A total of 110 primary neuroendocrine tumors (33 pancreatic, 31 pulmonary, 23 ileal, 14 rectal, and 9 gastric) and 73 metastatic neuroendocrine tumors (28 pancreatic, 5 pulmonary, 37 ileal, 1 rectal, 1 colonic, and 1 duodenal) were studied. Islet 1 and PAX8 were positive in 27/33 (82%) and 29/33 (88%), respectively, of primary pancreatic neuroendocrine tumors, and in 19/28 (68%) and 15/28 (54%), respectively, of metastatic pancreatic neuroendocrine tumors. No cases of primary (0/23) or metastatic (0/37) ileal neuroendocrine tumors were positive with either Islet 1 or PAX8. There was Islet 1 positivity in 2/31 (6%) primary pulmonary, 12/14 (86%) primary rectal, and 1/1 metastatic rectal neuroendocrine tumors, and PAX8 positivity in 7/31 (23%) primary pulmonary, 11/14 (79%) primary rectal, and 2/9 (22%) primary gastric neuroendocrine tumors. ROC curve analysis incorporating sensitivity and specificity data of immunohistochemical panels for metastatic pancreatic neuroendocrine tumors showed that a four-stain panel, including Islet 1, PAX8, TTF1, and CDX2 significantly outperformed a three-stain panel composed of PAX8, TTF1, and CDX2 (P=0.019), and also showed a trend for better performance compared with a three-stain panel composed of Islet 1, TTF1, and CDX2 (P=0.072). Both Islet 1 and PAX8 are reliable immunohistochemical markers for pancreatic neuroendocrine tumors and would be useful adjuncts to other markers (TTF1, CDX2) currently used to work up a metastatic neuroendocrine tumor of unknown primary.

Predictive accuracy of SYNTAX score for predicting long-term outcomes of unprotected left main coronary artery revascularization.

The American College of Cardiology/American Heart Association recently updated recommendations for percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) disease from class III to II(b) according to the results of the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) trial. The SYNTAX score is an angiographic tool using solely the coronary anatomy. We studied the effect of co-morbidities (Parsonnet's score) on the ability of the SYNTAX score to predict long-term outcomes in patients with ULMCA disease treated by revascularization. A total of 328 patients underwent revascularization of ULMCA from April 2003 to February 2007. Of the 328 patients, 120 underwent PCI (median follow-up 973 days) and 208 underwent coronary artery bypass grafting (CABG) (median follow-up 1,298 days). The ability of the SYNTAX score to predict outcomes was assessed using the Cox proportional hazards model. The outcomes between the PCI and CABG groups were compared by propensity analysis. The median SYNTAX score was 26 in the PCI and 28 in the CABG group (p = 0.5). In the PCI group, greater quartiles were associated with worse survival (62.1% at SYNTAX score of ≥36 vs 82.4% at SYNTAX score of <36, p = 0.03) and all-cause mortality, myocardial infarction, cerebrovascular events, and target vessel revascularization-free (MACCE) survival (47.7%, SYNTAX score ≥20 vs 76.6%, SYNTAX score <20, p = 0.02). Using the Parsonnet score as a covariate, the SYNTAX score continued to be an independent predictor of MACCE and demonstrated a trend toward predicting mortality in the PCI group. In contrast, the SYNTAX score did not predict the outcomes for the CABG group. No difference was found in mortality between the PCI and CABG groups for ULMCA disease, regardless of coronary complexity; although greater SYNTAX scores were associated with increased MACCE rates with PCI compared to CABG. Both the coronary anatomy (SYNTAX score) and co-morbidities (Parsonnet's score) predicted long-term outcomes for PCI of ULMCA disease. In contrast, the SYNTAX score did not predict the outcomes after CABG. In conclusion, the ideal scoring system to guide an appropriate revascularization decision for ULMCA disease should take into account both the coronary anatomy and the co-morbidities.

The utility of oral glucose tolerance testing for diagnosis and assessment of treatment outcomes in 166 patients with acromegaly.

CONTEXT: GH suppression after oral glucose load [oral glucose tolerance test (OGTT)] and normal age- and gender-matched IGF-I levels reflect biochemical control of acromegaly. The OGTT is the gold standard for determining control of GH secretion at diagnosis and after surgical treatment, but the usefulness of performing an OGTT in patients treated with medical therapy has not been determined. OBJECTIVE: Our objective was to assess relationships between basal GH levels (basal GH), GH responses to OGTT [GH nadir (GHn)], and IGF-I levels. DESIGN: This was a retrospective electronic database review. SETTING: This study was performed at a tertiary outpatient pituitary center. PATIENTS: A total of 166 patients with acromegaly (79 females, 87 males) were included in the study. Four categories of testing were performed: diagnosis, postoperative assessment without medication, testing during somatostatin analog (SA) therapy, and testing during dopamine agonist (DA) therapy. MAIN OUTCOME MEASURES: Basal serum GH and IGF-I levels and GH levels 2 h after 75 g OGTT were measured. RESULTS: A total of 482 simultaneous OGTT and IGF-I measurements were observed from 1985--2008. Discordant results of oral glucose tolerance testing (GHn and IGF-I) were observed 33, 48, and 18% in postoperative assessment without medication, SA, and DA categories, respectively. In the SA category, 42% of tests were discordant with normal IGF-I and nonsuppressed GHn. In contrast, 4% of tests were discordant with normal IGF-I and nonsuppressed GH in those treated with DA. No significant differences in discordance were observed when basal GH was used. CONCLUSIONS: Both basal and GHn levels are highly discordant with IGF-I levels during medical therapy with SAs. The OGTT is not useful in assessing biochemical control in these subjects.

Comparison of coronary artery bypass surgery and percutaneous drug-eluting stent implantation for treatment of left main coronary artery stenosis.

OBJECTIVES: The purpose of this study was to compare outcomes for drug-eluting stents (DES) and coronary artery bypass graft (CABG) surgery in patients with unprotected left main coronary artery (ULMCA) stenosis. BACKGROUND: Expert guidelines recommend coronary artery bypass graft (CABG) surgery for the treatment of significant stenosis of the unprotected left main coronary artery (ULMCA) if the patient is eligible for CABG; however, treatment by percutaneous coronary intervention (PCI) is common. METHODS: Details of patients (n = 343, ages 69.9 +/- 11.9 years) undergoing coronary revascularization for ULMCA stenosis (April 2003 to January 2007) were recorded. A total of 223 patients were treated with CABG (mean [interquartile range]: follow-up 600 [226 to 977) days) and 120 by PCI (follow-up 362 [192 to 586) days). The hazard ratios (HRs) for death and major adverse cardiovascular and cerebrovascular events (MACCE) were calculated incorporating propensity score adjustment. Survival comparisons were conducted in propensity-matched subjects (n = 134), and in low- and high-risk subjects for CABG. RESULTS: Patients treated by PCI were more likely to be >or=75 years of age (49% vs. 33%; p = 0.005), and of greater surgical risk (Parsonnet score 17.2 +/- 11.2 vs. 13.0 +/- 9.3; p < 0.001) than patients treated by CABG. Overall, the propensity-adjusted HR for death was not statistically different (HR 1.93, 95% confidence interval [CI] 0.89 to 4.19, p = 0.10), but MACCE was greater in the PCI group (HR 1.83, 95% CI 1.01 to 3.32, p = 0.05). In propensity-matched individuals, neither survival nor MACCE-free survival were different. Survival was equivalent among low-risk candidates, but PCI had a tendency to inferior survival in high-risk candidates (Ellis category IV, log-rank p = 0.05). Interaction testing, however, failed to demonstrate a difference in outcomes of the 2 revascularization techniques as a function of baseline risk assessment. CONCLUSIONS: Overall, the propensity-adjusted risk of mortality for treatment of ULMCA disease does not differ between PCI- and CABG-treated groups. There appears to be sufficient equipoise that a randomized clinical trial to compare the techniques would not be ethically contraindicated.

Impact of erythropoietin on allogenic blood exposure in orthopedic surgery.

Joint reconstruction surgery is associated with significant blood loss, and patients often require perioperative transfusions. Recombinant human erythropoietin (epoetin) can be used in anemic patients scheduled for elective, noncardiac, nonvascular surgery to reduce the need for transfusions. In the study reported here, patients with a preoperative hemoglobin level of 10 to 13 g/dL were treated with epoetin. Our analysis showed that transfusions were given to 3 (8%) of the 38 patients who received epoetin before surgery and 20 (57%) of the 35 historical controls (P<.001) and that length of hospital stay did not differ significantly between the 2 groups. Our results provide further support for use of epoetin as an effective strategy for reducing exposure to allogenic blood in orthopedic surgery.

The Akt pathway in human breast cancer: a tissue-array-based analysis.

The Akt pathway, an important regulator of cell proliferation and survival, is deregulated in many cancers. The pathway has achieved considerable importance due to the development of kinase inhibitors that are able to successfully reduce tumor growth. This study was conducted to determine the status of the Akt pathway in human breast cancers and to study the relationship between the different component proteins. Expression levels of PTEN, phosphorylated forms of the constituent proteins (Akt, FKHR, mTOR, and S6) and cyclin D1 were evaluated by immunohistochemistry, on consecutive sections from a tissue microarray containing 145 invasive breast cancers and 140 pure ductal carcinomas in-situ. Aberrant expression was correlated statistically with tumor characteristics and disease outcome. The Akt pathway was found to be activated early in breast cancer, in the in-situ stage. In all, 33, 15, 32, and 60% of ductal carcinoma in-situ showed overexpression of Akt, FKHR, mTOR, and cyclin D1. PTEN loss did not correlate statistically with expression of AKT or any of the other proteins with the exception of S6, indicating that Akt activation was not a result of PTEN loss. Expression levels of PTEN and S6 were significantly different in in-situ and invasive cancers, indicating association with disease progression. Loss of PTEN was noted in 11% of in-situ as compared to 26% of invasive cancers, while S6 overexpression was seen in 47% in-situ and in 72% invasive cancers. High-grade carcinomas were associated with PTEN loss, while low-grade carcinomas with good prognostic features showed cyclin D1 overexpression and were associated with longer disease free survival. Additionally, cancers with mTOR overexpression showed a three times greater risk for disease recurrence. Overall, a large proportion of in-situ and invasive breast cancers overexpressed cyclinD1 and S6. Our results may have significant implications in the development and application of targeted therapy.

The prognostic significance of intranodal isolated tumor cells and micrometastases in patients with non-small cell carcinoma of the lung.

OBJECTIVE: To study whether isolated tumor cells and micrometastases, as defined by the current American Joint Committee on Cancer criteria for extrapulmonary neoplasms, have prognostic value for patients with resected non-small cell carcinoma of the lung. METHODS: Intrathoracic lymph nodes (n = 1063) from 60 patients with non-small cell carcinoma of the lung were studied for the presence of metastases with serial histologic sections and keratin immunostains. Metastases were classified as isolated tumor cells, pN1mi, pN1, pN2mi, and pN2. Isolated tumor cells were smaller than 0.2 mm, while pN1mi and pN2mi measured 0.2 mm to 2 mm. Survival analysis was performed, stratifying by nodal status and stage. RESULTS: Isolated tumor cells were detected in 11 lymph nodes from 5 of 33 pN0 patients and in 9 pN1 and pN2 patients. The lymph nodes from 3 patients were reclassified as pN1mi. No pN2mi were detected. A survival model based on a stratification of the cohort into stages I to III was significant (chi-square = 7.426, df = 2, P =.024) but demonstrated considerable overlap between the survival curves of stage I and II patients. A model stratifying isolated tumor cells and pN1mi into stage I disease was significant (chi-square = 7.985, df = 2, P =.018) and showed no overlap between the survival curves of stage I and II patients. There were no significant survival function differences between patients with pN0, isolated tumor cells, and pN1mi. CONCLUSIONS: Patients with non-small cell carcinoma of the lung with isolated tumor cells and pN1mi have similar survivals to those with pN0, consistent with the findings reported for breast cancer patients. Future larger studies of patients with non-small cell carcinoma of the lung are needed to confirm whether current American Joint Committee on Cancer staging criteria should be modified to include the pN1mi category.