Liat Appelbaum

Dilated Upper Sleeve Can be Associated with Severe Postoperative Gastroesophageal Dysmotility and Reflux

BackgroundLaparoscopic sleeve gastrectomy (LSG) is an effective bariatric procedure, and it can be done as an isolated LSG or in conjunction with biliopancreatic diversion bypass/duodenal switch (laparoscopic duodenal switch; LDS). Gastroesophageal reflux after LSG has been described, but the mechanism is unknown and the treatment in the severest cases has not been discussed. We describe a cohort of patients who have underwent an LSG or LDS, and have suffered from a severe postoperative gastroesophageal motility disorder and/or reflux, report on their treatment, and discuss possible underlying mechanisms.MethodsSeven hundred and six patients underwent an LSG by two of the authors (AK, AB). Sixty nine patients underwent laparoscopic sleeve gastrectomy in Hadassah Medical Center, Jerusalem, Israel (January, 2006 and December 2008; 55 isolated LSG, 14 with LDS), and 637 (212 isolated LSG, 425 LDS) in Clinica San Jorge and Alcoy Hospital in Alcoy, Spain, (January 2002 and November 2008).ResultsOf them, eight patients who has suffered from a gastroesophageal dysmotility and reflux disease postoperatively and needed a specific treatment besides regular proton pump inhibitors (PPIs) were identified (1.1%).ConclusionA combination of dilated upper part of the sleeve with a relative narrowing of the midstomach, without complete obstruction, was common to all eight patients who suffered from a severe gastroesophageal dysmotility and reflux. The sleeve volume, the bougie size, and the starting point of the antral resection do not seem to have an effect in this complication. Operative treatment was needed in only one case out of eight; in the rest of the patients, medical modalities were successful. More knowledge is required to understand the underlying mechanisms.

US Findings after Irreversible Electroporation Ablation: Radiologic-Pathologic Correlation

PURPOSE To characterize ultrasonographic (US) findings after irreversible electroporation (IRE) to determine the utility of these findings in the accurate assessment of ablation margins. MATERIALS AND METHODS The institutional animal care and use committee approved the study. IRE ablation (n = 58) was performed in vivo in 16 pig livers by using two 18-gauge electroporation electrodes with 2-cm tip exposure, 1.5- or 2.0-cm interelectrode spacing, and an electroporation generator. Energy deposition was applied at 2250-3000 V (pulse length, 50-100 μsec; pulse repetition, 50-100). Ablations were performed under US guidance. Images were obtained during ablation and at defined intervals from 1 minute to 2 hours after the procedure. Zones of ablation were determined at gross and histopathologic examination of samples obtained from animals sacrificed 2-3 hours after IRE. Dimensions of the histologic necrosis zone and US findings were compared and subjected to statistical analysis, including a Student t test and multiple linear regression. RESULTS Within 20-50 pulse repetitions of IRE energy, the ablation zone appeared as a hypoechoic area with well-demarcated margins. During the next 8-15 minutes, this zone decreased in size from 3.4 cm ± 0.5 to 2.5 cm ± 0.4 and became progressively more isoechoic. Subsequently, a peripheral hyperechoic rim measuring 2-7 mm (mean, 4 mm ± 1) surrounding the isoechoic zone developed 25-90 minutes (mean, 41 minutes ± 19) after IRE. The final length of the treatment zone, including the rim, increased to 3.3 cm ± 0.6. The final dimensions of the outer margin of this rim provided greatest accuracy (1.7 mm ± 0.2) and tightest correlation (r(2) = 0.89) with gross pathologic findings. Histologic examination demonstrated widened sinusoidal spaces that progressively filled with spatially distributed hemorrhagic infiltrate on a bed of hepatocytes with pyknotic nuclei throughout the treatment zone. CONCLUSION US findings in the acute period after IRE are dynamic and evolve. The ablation zone can be best predicted by measuring the external hyperechoic rim that forms 90-120 minutes after ablation. This rim is possibly attributable to evolving hemorrhagic infiltration via widened sinusoids.

CT Features of Adnexal Torsion

OBJECTIVE Adnexal torsion is most commonly a clinical diagnosis, often aided by sonographic findings. At times, the clinical presentation can mimic nongynecologic causes of acute lower abdominal pain. In these cases, CT may be the initial imaging study. The purpose of this study was to define the CT features associated with adnexal torsion. CONCLUSION On CT, a well-defined adnexal mass abnormally located in the pelvis with ipsilateral deviation of the uterus in a woman or girl with lower abdominal pain should raise the suspicion of adnexal torsion. Inflammatory signs on CT suggest the presence of necrosis.

Characterization of Irreversible Electroporation Ablation in In Vivo Porcine Liver

OBJECTIVE The purpose of this study was to prospectively characterize and optimize irreversible electroporation ablation to determine the best parameters to achieve the largest target zones of coagulation for two electrodes. MATERIALS AND METHODS Ultrasound-guided irreversible electroporation ablation (n=110) was performed in vivo in 25 pig livers using two 18-gauge electroporation electrodes and an irreversible electroporation generator. Five variables for energy deposition and electrode configuration were sequentially studied: number of electrical pulses (n=20-90), length of pulses (20-100 microseconds), generator voltage (2250-3000 V), interelectrode spacing (1.5-2.5 cm), and length of active electrode exposure (1.0-3.0 cm). Zones of ablation were determined at gross pathology and histopathology 2-3 hours after irreversible electroporation. Dimensions were compared and subjected to statistical analysis. RESULTS For 1.5-cm spacing and 2-cm electrode exposure at 2250 V, there was no statistical difference in the size of coagulation when varying the number or length of pulses from 50 to 90 repetitions or 50-100 microseconds, respectively, with each parameter combination yielding 3.0±0.4×1.7±0.4×3.0±0.6 cm (width, depth, and height, respectively). Yet, increasing the pulse width or number over 70 caused increased hyperechogenic or gas and coagulation around the electrode. Increasing the voltage from 2250-3000 V for 70 pulses of 70 microseconds increased coagulation to 3.1±0.4×2.0±0.2 cm (p<0.01 for depth). Greater coagulation width of 3.9±0.5 cm (p<0.01) was achieved at 2-cm interelectrode spacing (with similar depth of 1.9±0.4 cm). However, consistent results required 90 repetitions and a 100-microsecond pulse width; 2.5-cm spacing resulted in two separate zones of ablation. Although electrode exposure did not influence width or depth, a linear correlation (r2=0.77) was noted for height, which ranged from 2.0±0.2-5.0±0.8 cm (for 1- and 3-cm exposures, respectively). CONCLUSION Predictable zones of tissue destruction can be achieved for irreversible electroporation. Ablation dimensions are sensitive to multiple parameters, suggesting that precise technique and attention to detail will be particularly important when using this modality.

Irreversible Electroporation: Treatment Effect Is Susceptible to Local Environment and Tissue Properties

PURPOSE To study the effects of the surrounding electrical microenvironment and local tissue parameters on the electrical parameters and outcome of irreversible electroporation (IRE) ablation in porcine muscle, kidney, and liver tissue. MATERIALS AND METHODS Animal Care and Use Committee approval was obtained, and National Institutes of Health guidelines were followed. IRE ablation (n = 90) was applied in muscle (n = 44), kidney (n = 28), and liver (n = 18) tissue in 18 pigs. Two electrodes with tip exposure of 1.5-2 cm were used at varying voltages (1500-3000 V), pulse repetitions (n = 70-100), pulse length (70-100 µsec), and electrode spacing (1.5-2 cm). In muscle tissue, electrodes were placed exactly parallel, in plane, or perpendicular to paraspinal muscle fibers; in kidney tissue, in the cortex or adjacent to the renal medulla; and in liver tissue, with and without metallic or plastic plates placed 1-2 cm from electrodes. Ablation zones were determined at gross pathologic (90-120 minutes after IRE) and immunohistopathologic examination (6 hours after) for apoptosis and heat-shock protein markers. Multivariate analysis of variance with multiple comparisons and/or paired t tests and regression analysis were used for analysis. RESULTS Mean (± standard deviation) ablation zones in muscle were 6.2 cm ± 0.3 × 4.2 cm ± 0.3 for parallel electrodes and 4.2 cm ± 0.8 × 3.0 cm ± 0.5 for in-plane application. Perpendicular orientation resulted in a cross-shaped zone. Orientation significantly affected IRE current applied (28.5-31.7A for parallel, 29.5-39.7A for perpendicular; P = .003). For kidney cortex, ovoid zones of 1.5 cm ± 0.1 × 0.5 cm ± 0.0 to 2.5 cm ± 0.1 × 1.3 cm ± 0.1 were seen. Placement of electrodes less than 5 mm from the medullary pyramids resulted in treatment effect arcing into the collecting system. For liver tissue, symmetric 2.7 cm ± 0.2 × 1.4 cm ± 0.3 coagulation areas were seen without the metallic plate but asymmetric coagulation was seen with the metallic plate. CONCLUSION IRE treatment zones are sensitive to varying electrical conductivity in tissues. Electrode location, orientation, and heterogeneities in local environment must be considered in planning ablation treatment. Online supplemental material is available for this article.

Irreversible Electroporation Ablation: Creation of Large-Volume Ablation Zones in in Vivo Porcine Liver with Four-Electrode Arrays

PURPOSE To prospectively determine optimal parameters with which to achieve defined large target zones of coagulation by using irreversible electroporation (IRE) with four-electrode arrays and the time needed to achieve this treatment effect in an in vivo animal model. MATERIALS AND METHODS This study was approved by the animal care and use committee. Ultrasonography (US)-guided IRE ablation (n = 90) was performed in vivo in 69 pig livers with an array of four electrodes (18 gauge) and an electroporation generator. Cardiac-gated 100-µsec IRE pulses were applied sequentially between the six sets of electrode pairs at 2250-3000 V. Multiple algorithms of energy deposition and electrode configuration were studied, including interelectrode spacing (1.5-2.5 cm), number of IRE pulses applied consecutively to each electrode pair (10, 20, 50, and 100), and number of times per cycle each electrode pair was activated (one to 10). Resultant zones of treatment were measured with US 1.5-3 hours after IRE and confirmed at gross and histopathologic examination. Data and ablation times were compared to determine the optimal algorithms with which to achieve 4-7-cm areas of treatment effect in the shortest time possible. In addition, the IRE current applied was correlated with ablation size. Data were analyzed by using analysis of variance with multiple comparisons, t tests, or nonparametric statistics. RESULTS For 2.5-cm spacing, ablation diameter was increased by increasing either the overall time of energy application or the number of cycles of 20 pulses (P < .01 for both). IRE application of less than four cycles (or continuous IRE application of 100 pulses) did not result in contiguous ablation. However, sequentially increasing the number of cycles of IRE from four to 10 increased both the electrical current applied (from 14.4 A ± 0.4 to 17.6 A ± 0.7, P = .0004) and ablation diameter (from 5.6 cm ± 0.3 to 6.6 cm ± 0.3, P = .001). Although division of application into cycles did not alter coagulation at 2.0- and 1.5-cm spacing, application of energy to diagonal electrode pairs increased coagulation. Thus, one 100-pulse cycle (11.0 minutes ± 1.4) produced 4.8 cm ± 0.3 of ablation for 2.0-cm spacing with diagonal pairs but only 4.1 cm ± 0.3 of ablation without diagonal pairs (7.5 minutes ± 1.0, P < .03 for both). CONCLUSION With four-electrode arrays, IRE can create large contiguous zones of treatment effect in clinically acceptable ablation times; parameters can be tailored to achieve a wide range of ablation sizes. Cyclical deposition of IRE application is beneficial, particularly for larger interprobe spacing, most likely owing to alterations of electrical conductivity that occur after successive applications of IRE energy.

Complete remission, in BRCA2 mutation carrier with metastatic pancreatic adenocarcinoma, treated with cisplatin based therapy.

Carriers of a germline mutation in the BRCA genes, in particular BRCA2, have an increased risk of developing pancreatic adenocarcinoma when compared with the general population. While the addition of cisplatin to gemcitabine did not produce survival benefit compared to single-agent gemcitabine in prospective trials it is postulated that the addition of DNA cross-linking agent such as cisplatin to standard gemcitabine chemotherapy should be considered in known BRCA mutation carriers. We report a case of pancreatic adenocarcinoma arising in a 60-year-old carrier of a rare BRCA2 (1153insertionT) germline mutation. The patient received gemcitabine without any response and actually progression of the disease had occurred. Therefore cisplatin was added in combination with gemcitabine. A dramatic complete response to therapy was encountered with no evidence of disease in both CT scans and markers (CA19-9). In conclusion, in patients with known BRCA mutation associated pancreatic adenocarcinoma, the addition of a DNA cross-linking agent such as cisplatin should be considered. Physicians should consider BRCA mutation testing when the diagnosis of pancreatic cancer is established, especially when the patient belongs to an ethnic group where founder mutations exist, and/or there is strong personal or family history of cancer. This may be applied also to other metastatic tumors diagnosed in BRCA1/2 carriers.

Evaluation of an electromagnetic image-fusion navigation system for biopsy of small lesions: assessment of accuracy in an in vivo swine model.

PURPOSE To evaluate the accuracy of a novel combined electromagnetic (EM) navigation/image fusion system for biopsy of small lesions. MATERIALS AND METHODS Using ultrasound (US) guidance, metallic (2 × 1 mm) targets were imbedded in the paraspinal muscle (n = 28), kidney (n = 18), and liver (n = 4) of four 55- to 65-kg pigs. Baseline helical computed tomography (CT) imaging (Brilliance; Philips) identified these biopsy targets and six and nine cutaneous fiducial markers. CT data were imported into a MyLab Twice system (Esaote, Genoa, Italy) for CT/US image fusion. After verification of successful image fusion, baseline registration error and respiratory motion error were assessed by documenting deviation of the US and CT position of the targets in real time. Biopsy targeting was subsequently performed under conditions of normal respiratory using 15-cm 16G eTrax needles (Civco). To mimic the conditions of poor US visualization, only reconstructed CT information was displayed during biopsy. Accuracy of targeting was measured by repeat CT scanning as the distance of the needle tip to the target center. Targeting accuracy of free-hand vs. guided technique, and electromagnetic (EM) sensor positioning (ie, on the hub or within the needle stylus tip) were evaluated. RESULTS In muscle, needle registration error was 0.9 ± 1.2 mm and respiratory motion error 4.0 ± 1.0 mm. Target accuracy was 4.0 ± 3.2 mm when an EM sensor was imbedded in the needle tip. Yet, with the EM sensor back on the needle hub, greater targeting accuracy was achieved using an US guide (3.2 ± 1.6 mm) vs. freehand (5.7 ± 3.2 mm, P = .04). For kidney, registration error was 1.8 ± 1.7 mm and respiratory motion error 4.9 ± 1.0 mm. For the deeper kidney targets, target accuracy was 4.4 ± 3.2 mm with a tip EM sensor, which was an improvement over the hub EM sensor positioning (9.3 ± 4.6 mm; P < .01). An additional source of fusion error was noted for liver. Beyond 17 ± 1 mm of respiratory motion, targets were observed to move >3 cm with US transducer/needle compression resulting in 14 ± 1.4 mm targeting accuracy. CONCLUSIONS A combined image-fusion/EM tracking platform can provide a high degree of needle placement accuracy (<5 mm) when targeting small lesions. Results fall within accuracy of respiratory error; with best results obtained by incorporating an EM sensor into the tip of the biopsy system.

Is radical cystectomy mandatory in every patient with variant histology of bladder cancer.

Urothelial carcinomas have an established propensity for divergent differentiation. Most of these variant tumors are muscle invasive but not all. The response of non muscle invasive variant tumors to intravesical immunotherapy with BCG is not established in the literature, and is reported here. Between June 1995 and December 2007, 760 patients (mean age of 67.5 years) underwent transurethral resection of first time bladder tumors in our institution. Histologically variant tumors were found in 79 patients (10.4%). Of these 57 patients (72%) of them had muscle-invasive disease or extensive non-muscle invasive tumors and remaining 22 patients (28%) were treated with BCG immunotherapy. These included 7 patients with squamous differentiation, 4 with glandular, 6 with nested, 4 with micropapillary and 1 patient with sarcomatoid variant. The response of these patients to immunotherapy was compared with that of 144 patients having high-grade conventional urothelial carcinomas. Median follow-up was 46 months. The 2 and 5-year progression (muscle-invasion) free survival rates were 92% and 84.24% for patients with conventional carcinoma compared to 81.06% and 63.16% for patients with variant disease (P=0.02). The 2 and 5-year disease specific survival rates were 97% and 91.43% for patients with conventional carcinoma compared to 94.74 % and 82% for patients with variant disease (P=0.33). 5 patients (22.7%) of variant group and 13 patients (9.03%) of conventional group underwent cystectomy during follow-up (P=0.068). Patients with non-muscle invasive variants of bladder cancers can be managed with intravesical immunotherapy if tumor is not bulky (>4 cm). Although progression to muscle invasive disease is more common than in conventional group and occurs in about 40% of the patients, life expectancy is similar to patients with conventional high-grade urothelial carcinomas provided that follow-up is meticulous.

Differentiating benign from malignant thyroid nodules using micro ribonucleic acid amplification in residual cells obtained by fine needle aspiration biopsy

BACKGROUND Fine needle aspiration biopsy (FNAB) is the most commonly used diagnostic tool to differentiate benign from malignant thyroid nodules. Nevertheless, some FNAB cytology results are not definite. In such cases diagnostic thyroid lobectomy is performed with malignancy rate on final histopathology ranging at 15%-75%. The aim of this study was to improve on the accuracy of FNAB-based cytology by amplification of microRNAs (micro ribonucleic acids [miRs]) from the residual cells left in the FNAB needle after submission for cytology. METHODS Residual cells were collected from the needle cup after FNAB cytology of 77 consecutive patients with thyroid nodules. miR-enriched RNA was extracted for all patients with cytology showing either follicular lesion or suspicion for malignancy (n=11). The expression of miR-21, -31, -146b, -187, -221, and -222 was determined using real-time polymerase chain reaction. Results were compared with final surgical histopathology. RESULTS RNA was successfully extracted from all FNAB specimens. Five patients had FNAB cytology suspicious for malignancy. The miR panel was positive in all five (100%). Six patients had follicular lesions on FNAB. The miR panel was positive in three of four patients (75%) with confirmed malignancy and was negative in two of two (0%) patients with benign pathology results. This corresponded to a specificity of 100%, sensitivity of 88%, and accuracy of 90%. CONCLUSIONS RNA extraction from FNAB residual cells is feasible, and a miR panel amplified from the extracted RNA seems like a promising diagnostic tool in this limited number of patients.