ABSTRACT
BACKGROUND AND OBJECTIVES: Breast-conserving surgery (BCS) is followed by reoperations in approximately 25%. Reoperations lead to an increased risk of infection and wound healing problems as well as a worse cosmetic outcome. Several technical approaches for an intraoperative margin assessment to decrease the reoperation rate are under evaluation, some of them are still experimental. METHODS: A prospective single-arm post-marketing study with 60 patients undergoing BCS for ductal carcinoma in situ (DCIS) and invasive breast cancer was conducted. The specimen was intraoperatively examined by the ClearSight™ system, a mobile magnetic resonance imaging system that is based on a diffusion-weighted imaging protocol. However, the results were blinded to the surgeon. RESULTS: The ClearSight™ system was performed for both ductal and lobular breast cancer and DCIS, with a sensitivity of 0.80 (95% confidence interval [CI]: 0.44-0.96) and a specificity of 0.84 (95% CI 0.72-0.92), with an overall diagnostic accuracy of 80%. CONCLUSION: Had the ClearSight™ been known to the surgeon intraoperatively, the reoperation rate would have been reduced by 83% for invasive carcinoma, from 10% to 2%, and 50% for DCIS, from 30% to 15% reoperations. A trial designed to examine the impact on reoperation rates is currently ongoing.
Subject(s)
Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/surgery , Intraoperative Care , Magnetic Resonance Imaging , Margins of Excision , Adult , Aged , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging , Carcinoma, Intraductal, Noninfiltrating/pathology , Female , Humans , Mastectomy, Segmental , Middle Aged , Product Surveillance, Postmarketing , Prospective Studies , Sensitivity and SpecificityABSTRACT
BACKGROUND AND OBJECTIVES: One of the major unmet needs in Breast Conserving Surgery (BCS) is a rapid and accurate margin assessment of the lumpectomy specimen. This study evaluates the ability of a novel MRI system (prototype of the ClearSight™ system; Clear-Cut Medical Ltd., Rehovot, Israel) to distinguish malignant and non-malignant tissues in freshly excised breast specimen by comparing MR measurements to histopathology results. METHODS: Seventy-seven samples were obtained from 22 patients undergoing BCS enrolled in the study. A T2* (T2 Star) value in milliseconds (ms) was calculated for each sample and correlated with histopathology results. RESULTS: Of the 77 samples, 35 samples were classified by histopathology as malignant and 42 as non-malignant. T2* values were significantly higher in malignant samples compared to non-malignant samples (15.3 ± 2.72 ms and 10.6 ± 1.47 ms, respectively [P < 0.00001]). Analysis for a determined cutoff of 11.7 ms revealed 91% sensitivity, 93% specificity, and 92% accuracy. ROC curve analysis yielded AUC of 0.97. CONCLUSIONS: This study demonstrates that the system is sensitive and specific in differentiating malignant and non-malignant tissues in freshly excised breast specimen. The system has the potential to be used for breast specimen margin assessment during BCS, with the goal of decreasing the need for re-operation. J. Surg. Oncol. 2016;114:22-26. © 2016 Wiley Periodicals, Inc.
Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/surgery , Magnetic Resonance Imaging , Margins of Excision , Mastectomy, Segmental/methods , Adult , Aged , Breast Neoplasms/pathology , Female , Humans , Intraoperative Period , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Middle Aged , Outcome Assessment, Health Care , ROC Curve , Sensitivity and SpecificityABSTRACT
The purpose of this study was to assess pathological complete response and whether it serves a surrogate for survival among patients receiving neo-adjuvant doxorubicin-cyclophosphamide followed by paclitaxel for triple-negative breast cancer with respect to BRCA1 mutation status. From a neo-adjuvant systemic therapy database of 588 breast cancer cases, 80 triple-negative cases who had undergone BRCA genotyping were identified. Logistic regression model was fitted to examine the association between BRCA1 status and pathological complete response. Survival outcomes were evaluated using Kaplan-Meier method, differences between study groups calculated by log-rank test. Thirty-four BRCA1 carriers and 43 non-carriers were identified. The BRCA1 carriers had pathological complete response rate of 68 % compared with 37 % among non-carriers, p = 0.01. Yet this did not translate into superior survival for BRCA1 carriers compared with non-carriers. No difference in relapse-free survival were noted among those with or without pathological complete response in BRCA1 carriers regardless of pathological complete response status (Log-rank p = 0.25), whereas in the non-carrier cohort, relapse-free survival was superior for those achieving pathological complete response (Log-rank p < 0.0001). Response to neo-adjuvant systemic therapy differed in BRCA1-associated triple-negative breast cancer compared with triple-negative non-carriers, with a higher rate of pathological complete response. However, compared with non-carrier triple-negative breast cancer, pathological complete response was not a surrogate for superior relapse-free survival in BRCA1 patients. Future studies using specific chemotherapy regimens may provide further improvements in outcomes.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , BRCA1 Protein/genetics , Cyclophosphamide/administration & dosage , Paclitaxel/administration & dosage , Triple Negative Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Female , Humans , Middle Aged , Mutation , Neoadjuvant Therapy , Paclitaxel/therapeutic use , Survival Analysis , Treatment Outcome , Triple Negative Breast Neoplasms/genetics , Young AdultABSTRACT
BACKGROUND: Surgical margin involvement is a major cause for local recurrence of breast cancer. In many cases, surgical margin involvement entails re-operation in order to achieve clean margins. The "MarginProbe" device uses radiowave spectroscopy to identify malignant tissue in excised tumor specimens. The current paper describes our experience with "MarginProbe" to evaluate the margin status during surgery. METHODS: MarginProbe was used consecutively to evaluate margin involvement of histology-proven breast cancer patients. The excised tumor specimen was assessed visually as well as by palpation and specimen radiography. RESULTS: Forty-five patients who underwent breast preserving surgery were assessed with "MarginProbe" during surgery. Ten patients (22%) underwent re-excisions during the operation as indicated by the probe, which led to clear margins as the end result of surgery. In 2 patients (4.4%) additional surgery was performed at a later date to clear the margins. No adverse effects were noted due to the use of the probe. SUMMARY AND CONCLUSIONS: Use of the "MarginProbe" during breast preserving surgery helps identify involved margins and assists in reaching clear margins following tumor excision. Probe use was effective for infiltrating as well as in situ cancers. Routine use of the probe may contribute to a decreased re-operation rate for involved margins.
Subject(s)
Breast Neoplasms/surgery , Mastectomy, Segmental/methods , Radio Waves , Spectrum Analysis/methods , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Reoperation/statistics & numerical dataABSTRACT
Carriers of germline mutations in the BRCA1 gene have a significant increased lifetime risk for being diagnosed with breast cancer. The incomplete penetrance of BRCA1 suggests that environmental and/or genetic factors modify the risk and incidence among mutation carriers. Nutrition and particular micronutrients play a central role in modifying the phenotypic expression of a given genotype by regulating chromatin structure and gene expression. The active form of vitamin D, 1α,25-dihydroxyvitamin D3, is a potent inhibitor of breast cancer growth. Here we report that two non-calcemic analogues of 1α,25-dihydroxyvitamin D3, seocalcitol (EB1089) and QW-1624F2-2, collaborate with BRCA1 in mediating growth inhibition of breast cancer cells and breast cancer stem-like cells. EB1089 induces a G1/S phase growth arrest that coincides with induction of p21waf1 expression only in BRCA1-expressing cells. A complete knockdown of BRCA1 or p21waf1 renders the cells unresponsive to EB1089. Furthermore, we show that in the presence of ligand, BRCA1 associates with vitamin D receptor (VDR) and the complex co-occupies vitamin D responsive elements (VDRE) at the CDKN1A (p21waf1) promoter and enhances acetylation of histone H3 and H4 at these sites. Thus, BRCA1 expression is critical for mediating the biological impact of vitamin D3 in breast tumor cells.
Subject(s)
BRCA1 Protein/metabolism , Breast Neoplasms/pathology , Cell Proliferation , Cholecalciferol/metabolism , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Neoplastic Stem Cells/pathology , Promoter Regions, Genetic , Acetylation , BRCA1 Protein/genetics , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor , Cholecalciferol/pharmacology , Chromatin Immunoprecipitation , Cyclin-Dependent Kinase Inhibitor p21/genetics , Flow Cytometry , Fluorescent Antibody Technique , Histones/metabolism , Humans , Immunoblotting , Immunoprecipitation , Neoplastic Stem Cells/metabolism , Promoter Regions, Genetic/genetics , Receptors, Calcitriol/metabolism , Reverse Transcriptase Polymerase Chain Reaction , TransfectionSubject(s)
Biomedical Technology/trends , Health Care Sector/trends , Operating Rooms/trends , Patient Safety , Specialties, Surgical , Surgical Equipment/trends , Biomedical Technology/economics , Coercion , Conflict of Interest , Endoscopy/adverse effects , Evaluation Studies as Topic , Health Care Sector/economics , Health Care Sector/standards , Humans , Patient Selection , Physician-Patient Relations , Physicians/economics , Remuneration , Societies, Medical , Surgical Instruments/trends , Treatment OutcomeABSTRACT
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an accepted bariatric procedure. Swallow studies (SS) after LSG are not uniform and display different patterns with regard to contrast passage through the gastric sleeve. The impact of immediate postoperative contrast transit time on weight loss has not been studied. The influence of immediate fluid tolerance on weight loss after LSG is herein reported. METHODS: Ninety-nine patients after LSG were included. There were 67 females, mean age 41 (range 17-67), mean BMI 44.4 (range 37-75). A routine SS was performed on postoperative day (POD) 1. Pattern of contrast transit was noted. Patients were followed-up in our bariatric clinic. RESULTS: Percent excess weight loss was significantly lower in the patients with rapid contrast passage (Group 1, n = 50) than those with delayed passage (Group 2, n = 49). Group 1 achieved 62, 58, and 53 % at 1, 2, and 3 years, respectively, while Group 2 attained 69, 74, and 75 % at the same time points (p = 0.05, 0.001, and 0.04, respectively). Group 1 patients displayed a negative weight loss trend after 1 year whereas Group 2 patients plateaued after 2 years. CONCLUSIONS: Tolerance of fluid intake after LSG is crucial for patient recovery and discharge. Distinct radiologic appearance on POD 1 helps predict this behavior. Mid-term weight loss after LSG appears to be dependent on immediate postoperative contrast transit time, whereas patients with slow contrast passage tend to lose more weight. Long-term follow-up will reveal whether this finding will hold true.
Subject(s)
Deglutition , Gastrointestinal Transit , Gastroplasty , Obesity, Morbid/physiopathology , Weight Loss , Adolescent , Adult , Aged , Body Mass Index , Female , Follow-Up Studies , Gastroplasty/methods , Humans , Laparoscopy , Male , Middle Aged , Obesity, Morbid/surgery , Postoperative Period , Predictive Value of Tests , Retrospective Studies , Treatment OutcomeABSTRACT
Tumor-infiltrating lymphocytes (TILs) are produced by resecting tumor tissue and growing and expanding ex vivo large quantities of autologous T cells. Once the TILs are ready for infusion, the patient undergoes a non-myeloablative lympho-depleting course of chemotherapy and subsequent TIL infusion with high-dose bolus IL-2. This study reviews the surgical experience of the TIL program at the Chaim Sheba Cancer Research Center in Israel. Eligible patients underwent surgical consultation to determine what tumorectomy would be beneficial for harvesting appropriate tissue. Factors involved in the decision included tumor mass size, location and morbidity of the procedure. Between January 2006 and May 2010, 44 patients underwent 47 procedures of adoptive transfer of TILs. Three patients underwent the procedure twice for recurrence after initial good responses, including an additional surgical procedure to produce fresh tumor. Thirty-seven excisions were with general anesthesia and 10 were with local anesthesia. Of the 37 general anesthesia procedures, 27 were open procedures involving a thoracotomy, a laparotomy or dissection of a major lymph node basin. Ten used minimally invasive techniques such as thorascopy or laparoscopy. Tumorectomy sites included 18 lymph node metastasis, 13 subcutaneous nodules, 11 lung specimens and 5 abdominal visceral metastasis including 2 liver lesions. Surgical mortality and major morbidity was 0%. Minor morbidity included only wound complications. Maximal number of TILs were derived from lymph node specimens, while liver metastasis procured the fewest TILs. Adoptive cell transfer technology affords a maximal tumor response with minimal surgical morbidity in metastatic patients.
ABSTRACT
Chk1 phosphorylation by the PI3-like kinases ATR and ATM is critical for its activation and its role in prevention of premature mitotic entry in response to DNA damage or stalled replication. The breast and ovarian tumor suppressor, BRCA1, is among several checkpoint mediators that are required for Chk1 activation by ATM and ATR. Previously we showed that BRCA1 is necessary for Chk1 phosphorylation and activation following ionizing radiation. BRCA1 has been implicated in S-phase checkpoint control yet its mechanism of action is not well characterized. Here we report that BRCA1 is critical for Chk1 phosphorylation in response to inhibition of replication by either cisplatin or hydroxyurea. While Chk1 phosphorylation of S317 is fully dependent on BRCA1, additional proteins may mediate S345 phosphorylation at later time points. In addition, we show that a subset of phosphorylated Chk1 is released from the chromatin in a BRCA1-dependent manner which may lead to the phosphorylation of Chk1 substrate, Cdc25C, on S216 and to S-phase checkpoint activation. Inhibition of Chk1 kinase by UCN-01 or expression of Chk1 phosphorylation mutants in which the serine residues were substituted with alanine residues abrogates BRCA1-dependent cell cycle arrest in response replication inhibition. These data reveal that BRCA1 facilitates Chk1 phosphorylation and its partial chromatin dissociation following replication inhibition that is likely to be required for S-phase checkpoint signaling.
Subject(s)
BRCA1 Protein/metabolism , Cell Cycle Checkpoints , Chromatin/metabolism , Protein Kinases/metabolism , S Phase , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/radiation effects , Cell Line, Tumor , Checkpoint Kinase 1 , Chromatin/drug effects , DNA Damage , DNA Replication/drug effects , DNA Replication/radiation effects , Enzyme Activation/drug effects , Enzyme Activation/radiation effects , Humans , Hydroxyurea/pharmacology , Mutant Proteins/metabolism , Phosphorylation/drug effects , Phosphorylation/radiation effects , Phosphoserine/metabolism , Radiation, Ionizing , S Phase/drug effects , S Phase/radiation effects , Signal Transduction/drug effects , Signal Transduction/radiation effects , Stress, Physiological/drug effects , Stress, Physiological/radiation effectsABSTRACT
OBJECTIVES: To investigate the ability of parametric diffusion tensor imaging (DTI), applied at 3 Tesla, to dissect breast tissue architecture and evaluate breast lesions. MATERIALS AND METHODS: All protocols were approved and a signed informed consent was obtained from all subjects. The study included 21 healthy women, 26 women with 33 malignant lesions, and 14 women with 20 benign lesions. Images were recorded at 3 Tesla with a protocol optimized for breast DTI at a spatial resolution of 1.9 × 1.9 × (2-2.5) mm3. Image processing algorithms and software, applied at pixel resolution, yielded vector maps of prime diffusion direction and parametric maps of the 3 orthogonal diffusion coefficients and of the fractional anisotropy and maximal anisotropy. RESULTS: The DTI-derived vector maps and parametric maps revealed the architecture of the entire mammary fibroglandular tissue and allowed a reliable detection of malignant lesions. Cancer lesions exhibited significantly lower values of the orthogonal diffusion coefficients, λ1, λ2, λ3, and of the maximal anisotropy index λ1-λ3 as compared with normal breast tissue (P < 0.0001) and to benign breast lesions (P < 0.0009 and 0.004, respectively). Maps of λ1 exhibited the highest contrast-to-noise ratio enabling delineation of the cancer lesions. These maps also provided high sensitivity/specificity of 95.6%/97.7% for differentiating cancers from benign lesions, which were similar to the sensitivity/specificity of dynamic contrast-enhanced magnetic resonance imaging of 94.8%/92.9%. Maps of λ1-λ3 provided a secondary independent diagnostic parameter with high sensitivity of 92.3%, but low specificity of 69.5% for differentiating cancers from benign lesions. CONCLUSION: Mapping the diffusion tensor parameters at high spatial resolution provides a potential novel means for dissecting breast architecture. Parametric maps of λ1 and λ1-λ3 facilitate the detection and diagnosis of breast cancer.
Subject(s)
Algorithms , Breast Neoplasms/pathology , Breast/pathology , Diffusion Magnetic Resonance Imaging/methods , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Adult , Aged , Female , Humans , Middle Aged , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: Appendiceal carcinoid tumor is the most common type of primary appendiceal malignant lesion. Nonetheless; it is an exceedingly rare diagnosis; found in only about .3% to .9% of appendectomy specimens. We report the clinical and pathologic characteristics of carcinoids found with long-term follow-up evaluation. METHODS: Data of patients who were histologically reported to have carcinoid tumor of the appendix; in a single center; during a 16-year period were collected retrospectively. In addition; patients were contacted for current follow-up information. RESULTS: A total of 44 patients were diagnosed with appendiceal carcinoid during the study period. The median follow-up period for the cohort was 7 years. No evidence of any recurrent disease or other noncarcinoid neoplasm was found. CONCLUSIONS: Our data confirm the good prognosis as seen in earlier reports. The long-term significance of having a carcinoid; and whether this poses a risk for future neoplasms; need even longer-term studies.
Subject(s)
Appendectomy , Appendiceal Neoplasms/diagnosis , Carcinoid Tumor/diagnosis , Adolescent , Adult , Aged , Appendiceal Neoplasms/epidemiology , Appendiceal Neoplasms/surgery , Carcinoid Tumor/epidemiology , Carcinoid Tumor/surgery , Child , Diagnosis, Differential , Disease-Free Survival , Female , Follow-Up Studies , Humans , Incidence , Israel/epidemiology , Male , Middle Aged , Prognosis , Retrospective Studies , Time Factors , Young AdultABSTRACT
BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is an effective bariatric procedure with low morbidity and mortality. Unfortunately, it is fraught with high failure rates in long-term follow-up. Laparoscopic sleeve gastrectomy (LSG) is an emerging procedure, quickly gaining momentum in the arsenal of bariatric practice as a first step toward gastric bypass/biliopancreatic diversion or as a stand-alone operation. Recently, it has been described as a revisional option for previous bariatric surgery failures. We report our early experience with LSG as a revisional procedure for failed LAGB. METHODS: From January 2007 to April 2010, 46 patients, who had undergone LAGB, underwent LSG. Patient demographics, reason for band removal, interval between removal and LSG, operative times, estimated blood loss, complications, length of hospital stay, and percent of excess weight loss were collected. RESULTS: Of the 46 patients, 20 (43%) had their bands removed before LSG (median time interval, 2 years; range, 2 months to 9 years); the rest had concomitant band removal and LSG. Twelve patients were men (26%). Mean age and BMI were 40 (range, 20-60) years and 43.1 kg/m(2) (range, 33-57), respectively. In two cases, surgery was converted to an open procedure due to extensive adhesions related to previous surgeries. Median operative time, estimated blood loss, and length of hospital stay were 118 (range, 70-250) minutes, 41 (range, 5-600) ml, and 3 (range, 1-100) days, respectively. Major morbidity was encountered in three patients (6%; leak in 2 and bleeding in 1). There were no mortalities. Mean follow-up time for our cohort is 17 (range, 1-39) months. Percent of excess weight loss at 2, 6, 12, 24, and 36 months was 24, 37, 53, 51, and 48%, respectively. CONCLUSIONS: Our results suggest that LSG is safe, feasible, and effective as a revisional procedure for failed LAGB and can be considered as an appealing option in these cases. Larger series and longer follow-up are needed to confirm this.
Subject(s)
Gastrectomy/methods , Gastroplasty , Laparoscopy , Adult , Female , Humans , Male , Middle Aged , Reoperation , Retrospective Studies , Treatment Failure , Young AdultABSTRACT
INTRODUCTION: In patients receiving pre-operative anthracyclines for locally advanced breast cancer, early cardiotoxicity is a well-recognised complication that may interfere with surgery. The aim of this study was to assess the safety of breast surgery after neoadjuvant treatment with Doxorubicin. PATIENTS AND METHODS: A retrospective study of breast cancer patients treated with Doxorubicin as part of their neoadjuvant protocol. All patients were subsequently operated in our institution. Intra-operative and postoperative haemodynamic, cardiac or respiratory events were collected. RESULTS: A total of 83 patients were included. All patients had a normal left ventricular ejection fraction before starting on chemotherapy. Doxorubicin was given in conjunction with Cyclophosphamide and Paclitaxel. The cumulative dose of Doxorubicin was 240 mg/m(2). All patients completed their chemotherapy less than a year before surgery and were clinically asymptomatic. Of the patients, 2.3% displayed a significant reduction in cardiac function to meet cardiotoxicity criteria, although not clinically apparent. No complications occurred intra-operatively or postoperatively. CONCLUSIONS: Breast surgery can be safely performed after breast neoadjuvant chemotherapy with Doxorubicin. The risk of early cardiotoxicity does not mandate a cardiac function assessment after completion of treatment. Work-up should be individualised according to the anthracycline regimen, patient's cardiac risk factors and functional status before surgery.
Subject(s)
Antibiotics, Antineoplastic/adverse effects , Breast Neoplasms/surgery , Doxorubicin/adverse effects , Heart Diseases/chemically induced , Preoperative Care/methods , Adult , Aged , Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant , Doxorubicin/administration & dosage , Echocardiography , Female , Heart Diseases/prevention & control , Humans , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: Up to 4% of breast cancer cases occur in women younger than 35 years. Studies have suggested an association between breast cancer at a young age, poorer outcome, and adverse clinical and pathologic characteristics. It is unclear whether age is an independent prognostic factor. OBJECTIVES: To characterize the prognostic significance of young age at diagnosis through comparison of disease characteristics of "less-young" (born between 1958-1962 and aged 37-44 years) and "very-young" (born after 1967 and aged ≤35 years) premenopausal patients. METHODS: Consecutive patients with breast cancer born after 1967 treated at Sheba Medical Centre between January, 1999 and October, 2002 were identified and their files reviewed. This cohort was identified as "very-young" and was compared with a group of "less-young" patients. The clinico-pathologic characteristics and survival data were compared. RESULTS: Sixty-one very young and 94 less-young patients were identified. The mean age at diagnosis was 29.9 (range, 23-34 years) and 40.5 years (range, 37-44 years) for the very young and less young patients, respectively (P < 0.0001). Significantly more very young patients had metastatic disease at presentation (20% vs. 3%, respectively, P = 0.0007). The very young patients were more likely to have high grade, endocrine nonresponsive tumors than the less young patients. After controlling for stage and tumor grade, very-young age was not shown to be an independent risk factor for reduced survival. CONCLUSIONS: Very young age among Israeli women with breast cancer is associated with higher stage at diagnosis, adverse pathologic characteristics and adverse outcome but is not an independent prognostic factor for survival.
Subject(s)
Breast Neoplasms/pathology , Adult , Age Factors , Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Chi-Square Distribution , Female , Humans , Israel/epidemiology , Neoplasm Staging , Premenopause , Risk Factors , Survival Analysis , Treatment OutcomeABSTRACT
Germline mutations in the BRCA1 and BRCA2 genes are associated with a significantly increased lifetime risk for developing breast and/or ovarian cancer. However, incomplete penetrance and substantial variability in age of disease onset among carriers of the same mutation suggests the involvement of additional modifier genes and/or environmental factors. Somatic inactivating mutations in the p53 gene and genes of the p53 pathway often accompany BRCA1/2-associated tumors. Therefore, we assessed whether these genes are modifiers of penetrance. We genotyped Jewish-Ashkenazi women for functional single-nucleotide polymorphisms (SNPs) in the AKT1 (C>T rs3730358) and the PERP (C>T rs2484067) genes that affect p53-mediated apoptosis, as well as two tag-SNPs in the CHEK2 (C>T rs743184) and the ZBRK1/ZNF350 (G>A rs2278414) genes that encode for proteins involved in growth arrest following DNA damage. The study population included 138 healthy women, 148 breast/ovarian cancer BRCA1/2 mutation carriers, 121 asymptomatic BRCA1/2 mutation carriers, and 210 sporadic noncarrier breast cancer patients. Utilizing lambda(2) and Kaplan-Meier analysis revealed a hazard ratio (HR) of 3.23 (95% CI: 1.44-54, P = 0.0184) for the TT genotype of AKT (rs3730358), HR = 2.105 (95% CI: 1.049-7.434, P = 0.039) for CHEK2 CC genotype (rs743184), and HR = 2.4743 (95% CI: 1.205-11.53, P = 0.022) for the AG genotype of ZBRK1/ZNF350 (rs2278414). No significant association between PERP variants and cancer was identified HR = 0.662 (95% CI: 0.289-1.324, P = 0.261). Our results suggest that genes that act upstream of p53, or participate in the DNA damage response, may modify the risk of cancer in women with mutant BRCA1/2 alleles.
Subject(s)
Breast Neoplasms/genetics , Genes, BRCA1 , Genes, BRCA2 , Genes, p53 , Ovarian Neoplasms/genetics , Polymorphism, Single Nucleotide , Adult , Breast Neoplasms/ethnology , Female , Genetic Predisposition to Disease , Humans , Jews/genetics , Middle Aged , Mutation , Ovarian Neoplasms/ethnologyABSTRACT
BACKGROUND: We present data acquired in our institution about the incidence of incidental appendiceal carcinoids over a period of 16 years. The possibility of occult carcinoids raises the question of appendectomy of a noninflamed appendix during diagnostic laparoscopy for suspected appendicitis. METHODS: We performed a retrospective chart analysis of the surgical registry of a university-affiliated tertiary care center of a major population area for the past 16 years. Data were collected on all patients (n = 7592) who underwent appendectomy for the presumed diagnosis of acute appendicitis. Outcome measures were the incidence of incidental carcinoids of the appendix found during appendectomies and whether the introduction of laparoscopic appendectomy should alter the surgical management of a normal-appearing appendix. RESULTS: A total of 20 carcinoid appendices were resected by open surgery and 17 by laparoscopy. The diagnosis of a carcinoid tumor was not suspected in any patient before the operation, nor was a tumor identified at the time of the operation. In 6 (16%) patients the appendix appeared normal at the time of the operation. CONCLUSIONS: It has long been the standard of care to remove any appendix found in laparotomy for suspected appendicitis, but it is not clear what should be done during laparoscopy for suspected appendicitis when the appendix appears normal. Our data confirm the presence of occult carcinoids in normal-appearing appendices. Further studies are needed to determine the clinical significance of this finding.
Subject(s)
Appendectomy/methods , Appendiceal Neoplasms/epidemiology , Appendiceal Neoplasms/surgery , Carcinoid Tumor/epidemiology , Carcinoid Tumor/surgery , Laparoscopy/methods , Adolescent , Adult , Appendiceal Neoplasms/pathology , Carcinoid Tumor/pathology , Child , Female , Humans , Incidence , Incidental Findings , Male , Middle Aged , Registries , Retrospective StudiesABSTRACT
PURPOSE: Prevention of blood loss in liver resections is essential for reducing postoperative morbidity. The main method to control bleeding during surgery of the left hemiliver is occlusion of the left portal pedicle. This may be accomplished by hilar, fissural or posterior intrahepatic techniques. However, these techniques may injure transposed vessels or bile ducts from the right portal pedicle to the left. The purpose of this study was to describe the anatomical aspects of the posterior intrahepatic ligamentum venosum approach to the left portal pedicle. METHODS: Anatomical study was carried out on 215 isolated adult livers. In 57 specimens, sections of the extra- and intrahepatic portions of the left portal pedicle were prepared under stereoscopic microscopy. RESULTS: The ligamentum venosum is the anatomical landmark between the medial and lateral portions of the left portal vein. The convergence of the ligamentum venosum along the left portal pedicle is where the left portal sheath reaches its maximal thickness and these connections are tight. In 8-12%, the medial portion of the left portal pedicle includes a transposed right paramedian vein or right-sided bile ducts. CONCLUSIONS: According to our anatomical study, we believe that it is possible to use the ligamentum venosum as an anatomical guide to achieve a controlled approach of the left portal pedicle during left-sided hepatectomies. Moreover, ligation of the left portal pedicle at its convergence with the ligamentum venosum may prevent erroneous injury of transposed right paramedian vessels or bile ducts.
Subject(s)
Hepatectomy/methods , Ligaments/anatomy & histology , Liver/blood supply , Adolescent , Adult , Aged , Aged, 80 and over , Blood Loss, Surgical/prevention & control , Cadaver , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is gaining popularity as an additional bariatric procedure, either as a first step for biliopancreatic diversion or gastric bypass or as a stand-alone option for selected patients. Early postoperative fluid tolerance varies between patients and influences the length of hospital stay. Swallow studies after LSG are not uniform and display different patterns with regard to contrast passage through the gastric sleeve. METHODS: The 55 patients (40 women) in this study underwent LSG during 18 months. These patients had a mean age of 38.2 years (range: 17-61 years) and a mean body mass index (BMI) of 44.8 kg/m(2) (range: 39-75 kg/m(2)). The LSG procedure was performed using a four-port technique to resect the greater curvature of the stomach around a bougie. The mean operative time was 120 min (range: 45-240 min). A routine swallow study was performed on postoperative day 1, and clear fluids were initiated if no leak was detected. Patients were discharged when they could tolerate a daily fluid intake of 2 l. RESULTS: No mortalities, obstructions, or leaks occurred in the study cohort. Two main patterns of contrast passage were identified: type 1 (immediate unhindered flow through the sleeve to the antrum with a slight delay before continuation of the contrast to the duodenum) and type 2 (contrast filling of the proximal sleeve with delay of flow distally toward the duodenum). Patients with rapid contrast passage (group 1, n = 24) tolerated clear fluids better than those with delayed flow (group 2, n = 31) and were discharged earlier than their counterparts (mean length of hospital stay, 2.5 vs. 3.4 days; p < 0.001). CONCLUSIONS: Tolerance of fluid intake after LSG is crucial for patient recovery and discharge. A distinct radiologic appearance on postoperative day 1 helps to predict this behavior. The different patterns could be related to gastric sleeve construction or to possible postoperative sleeve spasm, hindering fluid passage. The influence of immediate fluid tolerance on weight loss after LSG is currently under investigation.
Subject(s)
Bariatric Surgery/methods , Gastrectomy/methods , Gastric Emptying , Gastric Stump/diagnostic imaging , Laparoscopy/methods , Adolescent , Adult , Body Mass Index , Contrast Media , Enteral Nutrition , Female , Humans , Male , Middle Aged , Postoperative Period , Radiography , Retrospective Studies , Surgical Stapling , Young AdultABSTRACT
BACKGROUND: Patients with thick melanomas > 4 mm deep are at great risk for regional and distant metastatic disease. Historically, the appropriate management of thick melanomas has remained unclear and there is no consensus in the literature. Many have taken the nihilistic view that surgical intervention to excise regional nodal basins is not justified in light of the poor overall prognosis and risk of occult distant disease. OBJECTIVES: To review the outcome of patients with thick node negative melanoma treated at a multidisciplinary academic center METHODS: We retrospectively reviewed a database of melanoma patients to identify patients with thick melanomas, > 4 mm, who were either clinically or sentinel node biopsy negative, staged T4N0, stage IIb or IIc. The charts of these patients were reviewed and updated, with a median follow-up of 4 years. RESULTS: We identified 23 patients who fit these criteria. Of these, 18 (78%) remain alive with a median follow-up of 4 years. Five patients died of metastatic disease. Of the 18 surviving patients, 14 remained with no evidence of disease after initial resection of their primary lesions. The majority of the recurrences were non-nodal. CONCLUSIONS: The overall survival of patients in our study remains above 75% at median follow-up of 4 years, even with thick initial index tumor depths. Most of the failures were due to hematogenous spread with lymphatic sparing. Tumor biology that may inhibit lymphatic spread could be a target of future investigation.