Outcomes of Simultaneous Versus Staged Resection for Stage IV Colorectal Cancer with Synchronous Liver Metastases.

INTRODUCTION: Management of stage IV colorectal cancer with synchronous liver metastases remains debated, as colorectal and liver resections can be performed simultaneously or staged apart. OBJECTIVE: This study aims to determine any demographic or outcome differences between simultaneous and staged resection. PARTICIPANTS: Retrospective review was performed on patients diagnosed with synchronous colorectal primary and liver metastases within Southern California Kaiser Permanente (KP) hospitals between 2010 and 2020. Patients with other metastases on diagnosis or those who did not receive both primary and liver resections were excluded. Demographic and outcome data were collected and analyzed. RESULTS: Of the 113 patients who met criteria, 72 (63.7%) received simultaneous and 41 (36.3%) received staged resection. Demographic data were comparable between simultaneous and staged resection, respectively, including median age of diagnosis, sex, and race. Both groups had similar median length of stay, percentage of major colorectal resection, and percentage of major liver resection. Both groups also had similar rates of radiation therapy, chemotherapy, and immunotherapy. There were no statistically significant difference in complications rates, median follow-up time, median overall survival, and median disease-free survival. CONCLUSIONS: Practice patterns within Southern California KP hospitals favor minor colorectal and liver resections. However, there were no significant differences in demographics, treatment rates, or outcomes between simultaneous and staged resection. While not statistically significant, our findings of a 11.9% higher major liver resection rate and 7.5-month longer median disease-free survival in the staged resection group may benefit from further study with higher power datasets.

Total Neoadjuvant Therapy Significantly Increases Complete Clinical Response.

BACKGROUND: Increased experience with total neoadjuvant therapy for rectal cancer suggests significantly more tumor regression and increased rates of complete clinical response as measured by pathological complete response and clinical complete response. OBJECTIVE: This study aimed to assess outcomes after total neoadjuvant therapy versus standard neoadjuvant chemoradiotherapy for patients with locally advanced rectal cancer. DESIGN: This is a retrospective cohort study. SETTINGS: A database of patients with rectal cancer from 2015 to 2019 at a large integrated health care system was reviewed. PATIENTS: Demographics of the 2 groups revealed no significant difference in clinical stage or patient characteristics. Of 465 patients, 66 patients underwent total neoadjuvant therapy and 399 underwent standard neoadjuvant chemoradiotherapy. Fifty-six patients underwent consolidation chemotherapy, and 10 underwent induction chemotherapy. MAIN OUTCOME MEASURES: Complete clinical response, disease-free survival, proctectomy-free survival, and organ preservation rates were the main outcome measures. RESULTS: Complete clinical response was achieved in 36 patients (58.1%) versus 59 patients (14.8%; p < 0.001), favoring the total neoadjuvant therapy group. Three-year overall survival was similar between groups (85.6% standard neoadjuvant chemoradiotherapy versus 86.0% total neoadjuvant therapy). Three-year distant metastasis-free survival was 67.4% in the total neoadjuvant therapy group compared to 77.7% in the standard neoadjuvant chemoradiotherapy group. Three-year proctectomy-free survival was 44% in the total neoadjuvant therapy group compared to 6% in the standard neoadjuvant chemoradiotherapy group. Twenty-two patients (37.3% of complete clinical responders) in the standard neoadjuvant chemoradiotherapy group elected to pursue organ preservation, whereas 31 patients (86.1% of complete clinical responders) from the total neoadjuvant therapy group chose organ preservation. LIMITATIONS: This study is limited by its retrospective nature with a shorter follow-up of 3 years. CONCLUSIONS: Total neoadjuvant therapy for rectal cancer significantly increased complete clinical response. This allowed patients to have greater organ preservation with no significant difference in overall survival or disease control. See Video Abstract at http://links.lww.com/DCR/B934 . LA TERAPIA NEOADYUVANTE TOTAL AUMENTA SIGNIFICATIVAMENTE LA RESPUESTA CLNICA COMPLETA: ANTECEDENTES:La mayor experiencia con la terapia neoadyuvante total para el cáncer de recto sugiere una regresión tumoral significativamente mayor y mayores tasas de respuesta clínica completa, medidas por respuesta patológica completa y respuesta clínica completa.OBJETIVO:Este estudio evaluó los resultados después de la terapia neoadyuvante total versus la quimiorradioterapia neoadyuvante estándar para pacientes con cáncer de recto localmente avanzado.DISEÑO:Este es un estudio de cohorte retrospectivo.ESCENARIO:Se revisó una base de datos de pacientes con cáncer de recto de 2015 a 2019 en un sistema de salud integrado grande.PACIENTES:La demografía de los dos grupos no revela diferencias significativas en el estadio clínico o las características de los pacientes. De 465 pacientes, 66 pacientes recibieron terapia neoadyuvante total y 399 quimiorradioterapia neoadyuvante estándar. Cincuenta y seis se sometieron a quimioterapia de consolidación mientras que 10 pacientes a quimioterapia de inducción.PRINCIPALES MEDIDAS DE RESULTADO:Se midieron la respuesta clínica completa, la sobrevida libre de enfermedad, la sobrevida libre de proctectomía y las tasas de preservación de órgano.RESULTADOS:Se logró una respuesta clínica completa en 36 pacientes (58.1 %) frente a 59 pacientes (14.8 %) (p < 0,001) a favor del grupo de terapia neoadyuvante total. La sobrevida general a tres años fue similar entre los grupos (85.6 % quimiorradioterapia neoadyuvante estándar frente a 86.0 % terapia neoadyuvante total). La sobrevida libre de metástasis a distancia a los tres años fue del 67.4 % en el grupo de terapia neoadyuvante total y del 77.7 % en el grupo de quimiorradioterapia neoadyuvante estándar. La sobrevida sin proctectomía a los tres años fue del 44 % en el grupo de terapia neoadyuvante total frente al 6 % en el grupo de quimiorradioterapia neoadyuvante estándar. Veintidós pacientes (37.3 % con respuesta clínica completa) en el grupo de quimiorradioterapia neoadyuvante estándar optaron por la preservación de órgano, mientras que 31 pacientes (86.1 % respuesta clínica completa) del grupo de terapia neoadyuvante total eligieron la preservación de órgano.LIMITACIONES:Este estudio es un estudio retrospectivo con un seguimiento más corto de 3 años.CONCLUSIONES:La terapia neoadyuvante total para el cáncer de recto aumentó significativamente la respuesta clínica completa. Esto permitió a los pacientes tener una mayor preservación de órgano sin diferencias significativas en la sobrevida general o el control de la enfermedad. Consulte Video Resumen en http://links.lww.com/DCR/B934 . (Traducción-Dr. Jorge Silva Velazco ).

Clinical Validation of a Circulating Tumor Cell Assay Using Density Centrifugation and Automated Immunofluorescence Microscopy.

OBJECTIVES: The US Food and Drug Administration (FDA)-approved CELLSEARCH assay (Menarini Silicon Biosystems) for circulating tumor cells (CTCs) relies on expression of an epithelial cell adhesion molecule to enrich for CTCs. We sought to validate a CTC assay (RareCyte) for clinical use that instead collects a buffy coat preparation enriched for CTCs. METHODS: Normal peripheral blood specimens spiked with cultured breast and prostate cancer cells and 47 clinical samples were used to validate assay performance. Specimens were enriched for buffy coat cells and applied onto 8 glass slides. The slides were immunofluorescently stained and imaged by automated microscopy and computer-aided image analysis. RESULTS: The assay was 100% specific for detecting spiked tumor cells. For samples spiked with 25, 50, and 125 cells, the percentage coefficients of variation were 42%, 21%, and 3.7%, respectively. Linearity studies demonstrated a slope of 0.99, an intercept of 1.6, and R2 of 0.96. Recoveries at the 25-, 50-, and 125-cell levels were 92%, 111%, and 100%, respectively. Clinical samples run on both CELLSEARCH and RareCyte correlated with an R2 of 0.8 after log-transformation and demonstrated 87.5% concordance using the CELLSEARCH criteria for predicting adverse outcomes. CONCLUSIONS: The RareCyte CTC assay has comparable performance to the FDA-cleared method and is ready for further clinical validation studies.

Robotic Versus Laparoscopic Surgery for Rectal Cancer: A Comprehensive Review of Oncological Outcomes.

The treatment of rectal cancer is complex and involves specialized multidisciplinary care, although the tenet is still rooted in a high-quality total mesorectal excision. The robotic platform is one of many tools in the arsenal to assist dissection in the low pelvis. This article is a comprehensive review of the oncological outcome comparing robotic vs laparoscopic rectal cancer resection, with a particular focus on total mesorectal excision. There is no statistical difference in total mesorectal grade, circumferential margin, distal margin, and lymph node harvest. Survival data are less mature, but there is also no difference in disease-free or overall survival between the two techniques. Although additional randomized trials are still needed to validate these findings, both techniques are currently acceptable in the minimally invasive treatment of rectal cancer, and surgeon preference is paramount to safe and optimal resection.

Adjuvant Chemotherapy Does Not Improve Recurrence-Free Survival in Patients With Stage 2 or Stage 3 Rectal Cancer After Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision.

BACKGROUND: Current guidelines for locally advanced stage 2/3 rectal cancer recommend neoadjuvant chemoradiotherapy followed by total mesorectal excision and adjuvant chemotherapy. The oncologic benefit of adjuvant chemotherapy has not been consistently demonstrated. OBJECTIVE: The purpose of this study was to evaluate disease recurrence and survival in patients with rectal cancer who received adjuvant chemotherapy after chemoradiotherapy and total mesorectal excision. DESIGN: This was a retrospective review of patients with stage 2/3 rectal cancer after chemoradiotherapy and surgery, based on receipt of adjuvant chemotherapy. SETTINGS: The study was conducted at the Kaiser Permanente Southern California system of 14 hospitals and associated clinics. PATIENTS: A total of 862 patients with stage 2/3 rectal cancer diagnosed and treated between January 1, 2005, and December 31, 2016, were included in this study. INTERVENTIONS: The study involved neoadjuvant chemoradiotherapy followed by total mesorectal excision with or without adjuvant chemotherapy. MAIN OUTCOME MEASURES: The primary end point was recurrence-free survival. RESULTS: A total of 348 stage 2 and 514 stage 3 patients were included; 660 patients (76.6%) underwent adjuvant chemotherapy. Mean patient follow-up after surgery was 63.0 months (range, 3-160). Multivariable analysis showed that yp stage (HR for yp stage 2 = 4.74; yp stage 3 = 8.83) and en bloc resection (HR = 1.76) were the only variables that significantly predicted disease recurrence. Neither pretreatment tumor stage nor receipt of adjuvant chemotherapy was significantly associated with recurrence-free survival. Log-rank testing failed to demonstrate significant recurrence-free survival improvement after receipt of adjuvant chemotherapy in any patient subgroup. LIMITATIONS: The study was limited by selection bias attributed to the nature of a retrospective study without patient randomization or predefined treatment protocol. CONCLUSIONS: In stage 2/3 rectal cancer treated with chemoradiotherapy and surgery, the addition of adjuvant chemotherapy was not associated with decreased recurrence-free survival in the entire cohort or in any subgroup, whereas tumor response to chemoradiotherapy is closely associated with disease recurrence. These findings have important consequences for treatment and surveillance decisions for patients with rectal cancer. Presurgical efforts that maximize tumor downstaging, such as total neoadjuvant therapy, may produce better oncologic outcomes than traditional adjuvant chemotherapy. See Video Abstract at http://links.lww.com/DCR/B134. LA QUIMIOTERAPIA ADYUVANTE NO MEJORA LA SOBREVIDA LIBRE DE RECURRENCIA EN PACIENTES CON CÁNCER DE RECTO ESTADÍOS II O III DESPUÉS DE RADIO-QUIMIOTERAPIA NEOADYUVANTE Y ESCISIÓN TOTAL DEL MESORRECTO: Las guías actuales para el tratamiento de cáncer rectal en estadio II-III localmente avanzado, recomiendan la radio-quimioterapia neoadyuvante con escisión total del mesorrecto seguidas de quimioterapia adyuvante. El beneficio oncológico de la quimioterapia adyuvante no ha sido demostrado de manera fehaciente.Evaluar la recurrencia y sobrevida a la enfermedad en pacientes con cáncer rectal que recibieron quimioterapia adyuvante después de radio-quimioterapia y escisión total del mesorrecto.Revisión retrospectiva de pacientes con cáncer rectal en estadios II-III después de radio-quimioterapia y cirugía, basada en la recepción de quimioterapia adyuvante.Sistema Permanente de Kaiser Sur-Californiano de 14 hospitales y clínicas asociadas.862 pacientes con cáncer rectal en estadio II-III diagnosticados y tratados entre el 1 de Enero 2005 y el 31 de Diciembre 2016.Radio-quimioterapia neoadyuvante seguida de escisión total del mesorrecto +/- quimioterapia adyuvante.El objetivo primario fue la sobrevida libre de recurrencia.Fueron incluidos 348 pacientes en estadio II y 514 en estadio III. 660 pacientes (76,6%) se sometieron a quimioterapia adyuvante. El seguimiento medio de cada paciente después de la cirugía fué de 63.0 meses (rango, 3-160). El análisis multivariable mostró que la etapa yp (Cociente de riesgo para estadío yp II = 4.74 y estadío yp III = 8.83) y la resección en bloque (Cociente de riesgo = 1.76) fueron las únicas variables que predijeron significativamente la recurrencia de la enfermedad. Ni el estadío tumoral previo al tratamiento ni la recepción de quimioterapia adyuvante se asociaron significativamente con la sobrevida libre de recurrencia. Las pruebas de rango logarítmico no pudieron demostrar una mejoría significativa de la sobrevida libre de recurrencia después de recibir quimioterapia adyuvante en cualquier subgrupo de pacientes.Sesgo de selección, debido al estudio retrospectivo sin aleatorización de los pacientes o protocolo de tratamiento predefinido.En casos de cáncer de recto estadíos II-III tratados con radio-quimioterapia y cirugía, la adición de quimioterapia adyuvante no se asoció con una disminución de la sobrevida libre de recurrencia en toda la cohorte o en ningún subgrupo, mientras que la respuesta tumoral a la radio-quimioterapia está estrechamente asociada con la recurrencia de la enfermedad. Estos hallazgos tienen consecuencias importantes en la decisión del tratamiento y la vigilancia en pacientes con cáncer de recto. Los esfuerzos pre-quirúrgicos que maximizan la reducción del tamaño del tumor, como la terapia neoadyuvante total, pueden producir mejores resultados oncológicos que la quimioterapia adyuvante tradicional. Consulte Video Resumen en http://links.lww.com/DCR/B134.

A population-based study comparing laparoscopic and robotic outcomes in colorectal surgery.

BACKGROUND: Current data addressing the role of robotic surgery for the management of colorectal disease are primarily from single-institution and case-matched comparative studies as well as administrative database analyses. The purpose of this study was to compare minimally invasive surgery outcomes using a large regional protocol-driven database devoted to surgical quality, improvement in patient outcomes, and cost-effectiveness. METHODS: This is a retrospective cohort study from the prospectively collected Michigan Surgical Quality Collaborative registry designed to compare outcomes of patients who underwent elective laparoscopic, hand-assisted laparoscopic, and robotic colon and rectal operations between July 1, 2012 and October 7, 2014. We adjusted for differences in baseline covariates between cases with different surgical approaches using propensity score quintiles modeled on patient demographics, general health factors, diagnosis, and preoperative co-morbidities. The primary outcomes were conversion rates and hospital length of stay. Secondary outcomes included operative time, and postoperative morbidity and mortality. RESULTS: A total of 2735 minimally invasive colorectal operations met inclusion criteria. Conversion rates were lower with robotic as compared to laparoscopic operations, and this was statistically significant for rectal resections (colon 9.0 vs. 16.9%, p < 0.06; rectum 7.8 vs. 21.2%, p < 0.001). The adjusted length of stay for robotic colon operations (4.00 days, 95% CI 3.63-4.40) was significantly shorter compared to laparoscopic (4.41 days, 95% CI 4.17-4.66; p = 0.04) and hand-assisted laparoscopic cases (4.44 days, 95% CI 4.13-4.78; p = 0.008). There were no significant differences in overall postoperative complications among groups. CONCLUSIONS: When compared to conventional laparoscopy, the robotic platform is associated with significantly fewer conversions to open for rectal operations, and significantly shorter length of hospital stay for colon operations, without increasing overall postoperative morbidity. These findings and the recent upgrades in minimally invasive technology warrant continued evaluation of the role of the robotic platform in colorectal surgery.

Robotic-laparoscopic rectal cancer excision versus traditional laparoscopy.

BACKGROUND AND OBJECTIVES: Robotic surgery has been advocated for the radical excision of rectal cancer. Most data supporting its use have been reported from European and Asian centers, with a paucity of data from the United States documenting clear advantages of the robotic technique. This study compares the short-term outcome of robotic versus laparoscopic surgery. METHODS: Consecutive patients who underwent laparoscopic (group 1) or robotic (group 2) rectal cancer excision at a single institution over a 2-year period were retrospectively reviewed. The main outcome measures were operative time, blood loss, conversion rates, number of lymph nodes, margin positivity, length of hospital stay, complications, and readmission rates. RESULTS: Forty-two patients were analyzed. The median operative time was shorter in group 1 than that in group 2 (240 minutes vs 260 minutes, P=.04). No difference was noted in blood loss, transfusion rates, intraoperative complications, or conversion rates. There was no difference in circumferential or distal margin positivity. The median length of stay was shorter in group 1 (5 days vs 6 days, P=.05). The 90-day complication rate was similar in both groups (33% vs 43%, P=.75), but there was a trend toward more anastomotic leaks in group 1 (14% vs 0%, P=.23). Similarly, a non-statistically significant trend toward a higher readmission rate was noted in group 1 (24% vs 5%, P=.18). CONCLUSION: Robotic rectal cancer excision yielded a longer operative time and hospital length of stay, although immediate oncologic results were comparable. The need for randomized data is critical to determine whether the added resource utilization in robotic surgery is justifiable.

Screening carotid artery duplex in patients undergoing cardiac surgery.

BACKGROUND: We sought to determine the prevalence of carotid artery stenosis (CAS)>50% in a large, multi-institutional health maintenance organization found during duplex ultrasonography screening before cardiac surgery and to identify risk factors to increase the yield of a preoperative screening program. METHODS: This retrospective review study was conducted on 722 patients who had undergone duplex ultrasonography screening of the carotid artery before cardiac surgery between June 2008 and February 2011. The primary outcome was CAS>50% detected on duplex ultrasonography screening. RESULTS: Seven hundred twenty-two patients (66.2% men; median age: 71 years) underwent duplex ultrasonography screening of the carotid artery before cardiac surgery. The main indications for cardiac surgery were valvular disease (39.5%) and coronary artery disease (36.3%). One hundred eighteen patients (16.3%) had CAS≥50%. Among the patients found to have carotid stenosis, 38 patients (32.2%) had bilateral stenosis>50% and 37 patients (31.4%) had at least 70% unilateral stenosis. The presence of peripheral vascular disease (odds ratio [OR]: 2.93 [95% confidence interval {CI}: 1.87-4.60]; P<0.001), and history of cerebrovascular disease within 12 months (OR: 4.57 [95% CI: 1.18-17.77]; P=0.028) were risk factors associated with CAS. Patients who have coronary artery disease with cardiac catheterization showing left main disease (OR: 6.80 [95% CI: 3.02-15.29]; P<0.001), 3-vessel disease or more (OR: 2.78 [95% CI: 1.43-5.43]; P=0.003), or both (OR: 4.13 [95% CI: 1.89-9.06]; P<0.001) were found to be significantly more likely to have CAS>50%. CONCLUSIONS: Independent risk factors that are predictive of the presence of CAS are peripheral vascular disease, having had a previous cerebrovascular accident, and coronary artery disease with left main or 3-vessel disease. Routine carotid duplex ultrasonography scanning may not be necessary for all patients undergoing cardiac surgery, and selective carotid screening programs may be considered in patients with symptomatic atherosclerosis disease or advanced coronary artery disease.

Perforation following colorectal endoscopy: what happens beyond the endoscopy suite?

BACKGROUND: The risk factors for perforation from colorectal endoscopy have been well studied, but little is known about clinical outcomes beyond the immediate event. OBJECTIVE: To evaluate short- and long-term outcomes of iatrogenic colorectal perforation following colorectal endoscopy. DESIGN: Retrospective review over 16 years at a single tertiary care institution. MAIN OUTCOME MEASURES: Treatment interventions, morbidity and mortality rates, hospital length of stay, stoma closure rate, and long-term complications. RESULTS: Of 132,259 colorectal endoscopies, 26 patients (0.02%) had a perforation (54% males; mean age, 67 years). The rectosigmoid colon was the most common site of perforation (65%). Thirty-eight percent of the perforations were recognized at the time of procedure, 31% presented within 24 hours, and 31% presented beyond 24 hours. Operative repair was undertaken in 85% of the patients, and 15% were managed with inpatient hospital observation. Primary repair was performed in 68% (defunctioning stoma in 18%). Mean hospital length of stay was 10.1 days. The overall postoperative complications rate was 55%, and wound complications were noted in 45%. The 30-day mortality rate was 19%. No death was observed beyond the first month. American Society of Anesthesiologists physical status Classes 3 and 4 were associated with mortality (p = 0.004). Of 7 patients who received a stoma, only 2 patients (29%) had stoma reversal. Long-term complications included incisional hernia (10%) and small-bowel obstruction (5%). CONCLUSIONS: Perforation following colorectal endoscopy was uncommon in this study but was associated with significant morbidity and mortality. An increased risk of death was noted with higher American Society of Anesthesiologists physical status class.

Successful salvage of late failure of hepatic portocholecystostomy (gallbladder Kasai) with Roux-en-Y cholecystojejunostomy.

The hepatic portoenterostomy (HPE) is the accepted initial operation for biliary reconstruction for biliary atresia, but in a select group of patients with patent distal extrahepatic bile ducts (PDEBD), a hepatic portocholecystostomy (HPC) may also be considered. A10 year old boy presented with sudden onset of jaundice following a successful HPC at 2 months of age. Radiographic evaluation revealed excretion into a distended gallbladder with distal biliary obstruction. He underwent a successful Roux-en-Y cholecystojejunostomy and remains jaundice-free two years later. Cholecystojejunostomy is an effective salvage operation for patients who develop late distal biliary obstruction after an HPC.

Defunctioning loop ileostomy for pelvic anastomoses: predictors of morbidity and nonclosure.

OBJECTIVE: The aim of this study was to determine the morbidity of a defunctioning loop ileostomy and the subsequent closure rate, and to identify the predictors of complications and nonclosure of stoma. DESIGN: This study is a retrospective review of a single-institution experience. PATIENTS: All patients who underwent a planned temporary defunctioning loop ileostomy performed synchronously with a pelvic anastomosis during a 6-year period were included. MAIN OUTCOME MEASURES: The primary outcome measures were the ileostomy complication rate for the entire spectrum of care, readmission and reoperation rates to treat ileostomy complications, and subsequent closure rate. Patient and treatment factors were evaluated for their independent effect on complications and closure rate with the use of multivariable logistic regression. RESULTS: One hundred twenty-three patients were identified (median age, 51 years). Of these patients, 64.2% developed ≥1 minor or major ileostomy complications (13.8% during index hospitalization, 52.8% as outpatient, and 23.4% after closure). Readmitted for dehydration following ileostomy formation were 11.4% of patients. The ileostomy was closed in 76.4% of patients with 8.6% requiring a midline laparotomy. The overall ileostomy-related reoperation rate was 10.4% (2.4% during index hospitalization, 1.6% at readmission, and 6.4% following ileostomy closure). Obesity (BMI ≥30 kg/m) was associated with a higher overall ileostomy complication rate (OR 8.56, 95% CI 1.64-44.74) and outpatient complication rate (OR 7.69, 95% CI 2.48-23.81). Age >65 years (OR 53.34, 95% CI 4.21-676.14) and hypertension (OR 8.36, 95% CI 1.09-64.43) increased the risks of high ileostomy output and dehydration. Obesity (OR 4.61, 95% CI 1.14-18.54) and smoking (4.47, 95% CI 1.43-13.98) decreased the likelihood of ileostomy closure. LIMITATION: This study was limited by its retrospective nature. CONCLUSIONS: The morbidity of a defunctioning loop ileostomy remains significant. Obesity is an independent predictor of ileostomy complications. Older age and hypertension increase the risks of high-output stoma and dehydration. Almost one quarter of patients never have the ileostomy closed. Obesity and smoking are associated with less likelihood of a subsequent ileostomy closure.

Microsatellite instability in saliva from patients with hereditary non-polyposis colon cancer and siblings carrying germline mismatch repair gene mutations.

Microsatellites are short tandem repeats of deoxyribonucleic acid (DNA) sequences which are distributed throughout the genome. Tumors in patients with Lynch syndrome tend to accumulate mutations in microsatellites at a much higher rate than other sequences in the genome resulting in microsatellite instability (MSI). This is due to germline mutations in mismatch repair (MMR) genes. Using small pool-polymerase chain reaction (SP-PCR), previous studies have shown that mutant alleles can be detected in microsatellites of DNA from peripheral blood lymphocytes (PBLs) of Lynch syndrome patients at frequencies that were low, but significantly higher than frequencies in PBLs of age-matched non-Lynch syndrome controls. In the present study, SP-PCR detection of frequency of mutant MSI alleles (FMMA) was performed on PBLs and saliva samples from four sets of families. Each family set consisted of a mutation carrying affected proband (initial tumor bearer), a germline mutation-carrier sibling without tumors, and an age-matched normal control, either related (for 3 family sets) without mutation carrier status or unrelated (for 1 family set) without mutation carrier status. FMMAs of saliva and PBL DNA were compared between each proband, sibling and control for each family set, and between family sets. In all five statistically significant saliva comparisons identified between germline mutation carriers (FMMA: 0.080-0.261) and normal controls (FMMA: 0.003-0.087), the measured FMMAs were always higher in the carriers (p < 0.05). A logistic regression model of the data showed a significant increase in FMMAs in saliva DNA from siblings with MMR mutation compared to the normal controls (p < 0.001). These results indicated that the increased FMMAs observed in the saliva DNA as well as PBL DNA of MMR gene mutation carriers compared to normal controls are real and repeatable. Furthermore, the logistic regression also indicated that the FMMAs seen in saliva were nearly double those seen in PBLs (p < 0.001). Saliva testing, a less-invasive procedure than PBL testing, is more sensitive and appears to be a viable alternative for identifying MSI in carriers with MMR mutations.

Examining Hedgehog pathway genes GLI3, SHH, and PTCH1 and the p53 target GLIPR1/GLIPR1L1/GLIPR1L2 gene cluster using fluorescence in situ hybridization uncovers GLIPR1/GLIPR1L1/GLIPR1L2 deletion in 9% of patients with multiple myeloma.

Mutations in genes regulating cell cycle and apoptosis are considered major culprits for the malignant transformation of cancer cells. Aberrant activation of the Hedgehog (HH) signaling pathway which primarily regulates genes involved in cell growth, proliferation, survival and apoptosis has been demonstrated in multiple myeloma. Mutations resulting in defective components of the p53 pathway, which serves a critical role in mediating cellular stress response by triggering DNA repair, cell cycle arrest, senescence and apoptosis, have also been identified. This study focuses on detecting copy number variations for the GLIPR1/GLIPR1L1/GLIPR1L2 gene cluster of the p53 pathway and three elements of the HH pathway, SHH, PTCH1 and GLI3 in multiple myeloma (MM) using fluorescence in situ hybridization (FISH). In eighteen samples, there was no evidence of abnormal copy number for PTCH1, GLI3 or SHH. Thus, it is unlikely that copy number variations of these genes are linked to multiple myeloma. However, a deletion of the GLIPR1/GLIPR1L1/ GLIPR1L2 gene cluster, all p53 targets, was found in three of 32 samples (9.4%) indicating that these deleted genes may have significant implications in MM. Further studies should be performed to determine the role of the GLIPR1/GLIPR1L1/GLIPR1L2 gene cluster in the pathogenesis of multiple myeloma.

Should barium enema be the next step following an incomplete colonoscopy?

INTRODUCTION: Double contrast barium enema (DCBE) is used to screen and diagnose colorectal disease and is often recommended following an incomplete colonoscopy. The purpose of this study was to determine the value of DCBE following an incomplete colonoscopy. MATERIALS AND METHODS: A retrospective review was conducted of all patients who had an incomplete colonoscopy at Kaiser Permanente, Los Angeles in a 6-year period. Patient data was extracted from the endoscopy and radiology databases. Variables collected included demographics, indication for colonoscopy, reason for incompletion, findings of DCBE, and findings of repeat colonoscopy if subsequently performed. RESULTS: The incomplete colonoscopy rate was 1.6%. The mean age was 62 years with a predominance of females. The most common indication for colonoscopy was screening. The most frequent reason attributed to an incomplete colonoscopy was patient discomfort. Two hundred thirty three patients underwent DCBE and 42 patients underwent a repeat colonoscopy without DCBE; 13.3% of the DCBE were of poor quality and could not be interpreted. A repeat colonoscopy following DCBE was performed in 7% of patients. In 50% of these patients, the repeat colonoscopy revealed significant findings not noted on the DCBE or ruled out positive DCBE findings. In patients who had repeat colonoscopy without DCBE, completion rate was 95%. CONCLUSION: The rate of incomplete colonoscopy in a high-volume modern endoscopy unit is extremely low. DCBE following incomplete colonoscopy has limited value. A repeat colonoscopy under deeper sedation and/or better bowel preparation may be the preferred next step.

Ultrasound for primary confirmation of mechanical capture in emergency transcutaneous pacing.

Clinical confirmation of mechanical capture in emergency transcutaneous pacing is sometimes difficult because of weak pulse volume or interference from skeletal muscle contractions. This report is of a case of using bedside ultrasound for primary confirmation of emergency transcutaneous pacemaker capture, and for differentiating between causes of persistent hypotension despite successful pacing. The technique of ultrasound-guided transcutaneous pacing is described.