Combined hepatocellular-cholangiocarcinoma: what the radiologist needs to know about biphenotypic liver carcinoma

Combined hepatocellular-cholangiocarcinoma (CHC), also referred to as primary liver carcinoma (PLC) with biphenotypic differentiation, is an increasingly recognized subtype of malignant PLC encompassing varying morphologic forms thought to arise either from progenitor cell lineage or dedifferentiation of mature liver cells. Tumor cells express both biliary and hepatocellular markers by immunohistochemistry, and may also express progenitor cell and stem cell markers. Due to the relative rarity of this tumor type, little is known about the risk factors, imaging appearance, or prognosis. Few studies have demonstrated risk factors that overlap with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), though not all appear to arise in the background of cirrhosis. The imaging appearances of these tumors may overlap with those of HCC and CC and discriminating features such as classic enhancement patterns and biliary ductal dilation are not universally present. Serum tumor markers, such as alpha-fetoprotein and carbohydrate antigen 19-9, may be helpful when they are discordant with imaging or if both are elevated to a significant degree. In regards to management and prognosis, most studies demonstrate worse outcomes compared with HCC or CC. In the United States, the diagnosis of HCC is frequently made with imaging alone, and subsequent management decisions, including organ allocation for transplantation, rely upon the radiological diagnosis. Given the importance of radiological diagnosis, awareness of this tumor type is essential for appropriate management.     

Risk factors for failure of 5-fluorouracil needling revision for failed conjunctival filtration blebs

PURPOSE: To investigate the risk factors for failure of 5-fluorouracil (5-FU) needling revision, a useful procedure for restoring a failed filtration bleb. DESIGN: Interventional case series.METHODS: Retrospectively conducted study. SETTING: Institutional. STUDY POPULATION: Sixty-four eyes of 64 consecutive glaucoma patients that underwent 5-FU needling revisions for failed filtering bleb following either trabeculectomy or phaco-trabeculectomy with or without adjunctive mitomycin C (MMC). OBSERVATION PROCEDURES: Goldmann applanation tonometry, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. MAIN OUTCOME MEASURES: Successful outcome of the initial 5-FU needling revision, arbitrarily defined as target intraocular pressure (IOP) control with not more than two topical glaucoma medications and no additional 5-FU needling or other surgical procedures, was analyzed by Kaplan-Meier survival analysis, and risk factors for failure of the initial 5-FU needling revision were analyzed by Cox proportional hazards regression analysis. RESULTS: The cumulative success rate of the initial 5-FU needling revision was 45% at 1 year, 33% at 2 years, and 28% at 4 years. Failure of the initial 5-FU revision correlated significantly with preneedling IOP > 30 mm Hg (P =.0003), lack of MMC use during the previous filtration surgery (P =.013), and IOP >10 mm Hg immediately following needling revision (P =.0012) according to Cox's proportional hazards regression analysis.CONCLUSIONS: Pre-needling IOP > 30 mm Hg, lack of MMC use during the previous filtration surgery, and IOP > 10 mm Hg immediately after needling were found to be significant risk factors for failure of the initial 5-FU needling procedure. Therefore, it is important to monitor IOP closely following needling revision in those patients with such risk factors. They are more likely to require additional therapeutic interventions, including repeat needling revisions.     

Differential Association of BRCA1 and BRCA2 Genes with Some Breast Cancer–Associated Genes in Early and Late Onset Breast Tumors

Background: Accumulating evidence indicating more aggressive features of breast carcinoma (BC) in young women than their older counterparts have raised the question of whether these differences are present at the genetic level.Methods: For this purpose, we performed a comparative analysis of the frequency of deletions of BRCA1, BRCA2, BRCAX, TP53, ATM, and RB1 and amplification of Cyclin D1 and also studied the interrelation and prognostic significance of these genetic alterations in 30 early onset (40 years) and 33 late onset (>40 years) cases of BC. These gene alterations were also studied in 11 other types of breast lesions.Results: A differential pattern of alterations (deletion/amplification) was observed in the two age groups, with the sequence in younger women being BRCA1 (72%), TP53 (71%), ATM (64%), BRCA2 (62%), RB1 (60%), Cyclin D1 (43%), and BRCAX (24%) and that in the older group being TP53 (66%), RB1 (63%), BRCA1 (56%), ATM (53%), BRCA2 (45%), Cyclin D1 (24%), and BRCAX (23%). Similar, differential correlations were also seen with several clinicopathological parameters, prognosis, and combinations of alterations among these genes in the two age groups.Conclusions: Differential frequencies and interrelationships of genetic alterations and prognoses in these two age groups indicate that the molecular pathways for the development of tumors in both age groups may not be similar, though the ultimate effect is deregulation of cell cycle checkpoints and defects in the DNA repair pathway.     

Evaluation of efficacy of four laparoscopic needle drivers.

INTRODUCTION: To evaluate the impact of needle driver design on laparoscopic suturing skills by experts and novices. METHODS: Three experienced laparoscopic surgeons and 3 novice junior residents were asked to perform a fixed set of suturing tasks in a laparoscopic pelvic-trainer. The laparoscopic needle drivers compared were (1) the Ethicon driver (E 705R), (2) Karl Storz (KS) pistol grip (26173 KC), (3) KS finger grip (26167 SK), and (4) KS palm grip (26173 ML). Times were recorded for each operator to grasp and position a needle for suturing in a particular angle, as well as to throw a horizontal and a vertical stitch and tie a single square knot using 2-0 Vicryl suture with a taper CT-1 needle. Subsequently, participants were asked to complete a subjective questionnaire rating the drivers. RESULTS: The average suturing time provided the most discriminatory power in comparing the needle drivers. For experienced operators, the KS pistol grip allowed faster suturing times than did the KS finger grip and the KS palm grip but not the Ethicon driver. For novice users, the Ethicon driver allowed faster suturing times than did the KS finger grip but not the KS pistol grip or the KS palm grip. In the subjective questionnaire, the KS pistol grip received the highest scores, and the KS finger grip received the lowest scores. CONCLUSION: Novice laparoscopists performed best with the KS pistol grip as well as the Ethicon laparoscopic needle drivers while experienced laparoscopists performed best with the pistol grip KS needle driver.     

Is there a role for postimplant dosimetry after real-time dynamic permanent prostate brachytherapy?

PURPOSE: To evaluate the correlation of real-time dynamic prostate brachytherapy (RTDPB) dosimetry and traditional postimplant dosimetry for permanent prostate brachytherapy. METHODS AND MATERIALS: A total of 164 patients underwent RTDPB for clinically confined prostate cancer. Of these 164 patients, 45 were implanted with 103Pd and 119 with 125I. Additionally, 44 patients underwent combined external beam radiotherapy and brachytherapy and 120 patients underwent brachytherapy alone. The postimplant dosimetry with computed tomography was performed at 4 weeks and compared with the RTDPB dose plan using the intraclass correlation coefficient. The millicurie/gram of the prostate volume and the percentage of the minimal dose to 90% of the prostate relative to the prescribed implant dose (D90%) of the RTDPB patients was compared with 400 patients treated with a free-seed technique. RESULTS: The mean D90% achieved in the operating room and on the 3-week dose plan was 109% (range, 93-139%) and 105% (range, 88-140), respectively. The mean percentage of prostate volume receiving 100% of the prescribed minimal peripheral dose (V100) achieved in the operating room and on the 3-week dose plan was 93% (range, 78-98%) and 91% (range, 64-98%), respectively. The intraclass correlation coefficient for each calculated relationship was 0.586 for D90 (p<0.001), 1.19 for V100 (p=0.135), 0.692 for the urethral D90 (p<0.001), 0.602 for the maximal rectal dose (p<0.001), 0.546 for D90 with 125I (p<0.001), and 0.565 for D90 with 103Pd (p<0.001). A 12% decrease was noted in the millicurie/gram of the isotope, with a 2.5% increase in the D90 comparing RTDPB and the free-seed technique. CONCLUSION: The results of this study demonstrated a correlation between the dose assessment obtained intraoperatively and postoperatively at 3 weeks. With reliable dose data available in the operating room, our results question the need for routine postimplant dose studies. Furthermore, patients treated with RTDPB received less radioactivity per gram of the prostate with a corresponding small increase in the D90. Future analyses will assess variations in the inverse dose planning rules and the clinical correlation of patients undergoing RTDPB vs. older techniques for toxicity and biochemical outcomes.     

Genomic instabilities in squamous cell carcinoma of head and neck from the Indian population

Intrinsic genomic instability of an incipient tumor cell drives the development of cancer. In colorectal cancer, an inverse relationship between microsatellite instability (MIN) and chromosomal instability (CIN) has been reported. The relationship between MIN and CIN in head and neck squamous cell carcinoma (HNSCC) is uncertain. In the present study, we examined these two types of instabilities in HNSCC using microsatellite markers and arbitrary primed PCR (APPCR) technique. HNSCC tumors showed high frequency of MIN and loss of heterozygosity (LOH). We observed that, in contrast to colorectal tumors, the frequency of LOH increased with the increase in MIN. There was no significant difference between MIN- and MIN+ groups of HNSCC tumors in the extent of overall genomic alterations; rather higher MIN+ tumors exhibited higher incidence of deletion. Thus, in sporadic HNSCC, both MIN and CIN pathways operate simultaneously to drive tumor formation.