Determining tolerance levels for quality assurance of 3D printed bolus for modulated arc radiotherapy of the nose.

Given the existing literature on the subject, there is obviously a need for specific advice on quality assurance (QA) tolerances for departments using or implementing 3D printed bolus for radiotherapy treatments. With a view to providing initial suggested QA tolerances for 3D printed bolus, this study evaluated the dosimetric effects of changes in bolus geometry and density, for a particularly common and challenging clinical situation: specifically, volumetric modulated arc therapy (VMAT) treatment of the nose. Film-based dose verification measurements demonstrated that both the AAA and the AXB algorithms used by the Varian Eclipse treatment planning system (Varian Medical Systems, Palo Alto, USA) were capable of providing sufficiently accurate dose calculations to allow this planning system to be used to evaluate the effects of bolus errors on dose distributions from VMAT treatments of the nose. Thereafter, the AAA and AXB algorithms were used to calculate the dosimetric effects of applying a range of simulated errors to the design of a virtual bolus, to identify QA tolerances that could be used to avoid clinically significant effects from common printing errors. Results were generally consistent, whether the treatment target was superficial and treated with counter-rotating coplanar arcs or more-penetrating and treated with noncoplanar arcs, and whether the dose was calculated using the AAA algorithm or the AXB algorithm. The results of this study suggest the following QA tolerances are advisable, when 3D printed bolus is fabricated for use in photon VMAT treatments of the nose: bolus relative electron density variation within [Formula: see text] (although an action level at [Formula: see text] may be permissible); bolus thickness variation within [Formula: see text] mm (or 0.5 mm variation on opposite sides); and air gap between bolus and skin [Formula: see text] mm. These tolerances should be investigated for validity with respect to other treatment modalities and anatomical sites. This study provides a set of baselines for future comparisons and a useful method for identifying additional or alternative 3D printed bolus QA tolerances.

Acute Myocardial Infarction in a Young Bodybuilder: A Case Report and Review of the Literature.

BACKGROUND Misuse of androgenic anabolic steroids (AAS) is a current practice associated with vigorous bodybuilding for muscular hypertrophy, especially among gym practitioners and bodybuilders, influenced by the culture of body image. In addition to liver, psychiatric, genital, urinary, dermatological, and musculoskeletal complications, AAS misuse reportedly can lead to development of cardiovascular complications, such as hypertension, dyslipidemia, cardiac hypertrophy, and early coronary disease, and potentially acute myocardial infarction (AMI) and sudden death. CASE REPORT A 26-year-old male farmer who was also an amateur bodybuilder developed an extensive Killip Class I AMI in the anterior wall while using AAS. A few days before the acute event, his lipid and hormone levels were measured and found to be significantly elevated. The patient was asymptomatic after left anterior descending branch angioplasty, but he had significant electrocardiographic sequelae and ventricular dysfunction. CONCLUSIONS We describe the case of a young male bodybuilder using AAS who presented with AMI and was treated with primary angioplasty. Documentation of high levels of lipids and hormones 1 week before the acute event suggests some relationship between AAS and cardiovascular disease. The main effects of using these steroids on the cardiovascular system are reviewed. It is time for a new global warning about the risks of misusing AAS to obtain muscle hypertrophy. Based on current medical knowledge, these hormones should not be prescribed without a clear indication for their use.

Clinical implementation of a Monte Carlo based independent TPS dose checking system.

The increase in complexity of treatment plans over time through modalities such as intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) has often not been met with an increase in capability of the secondary dose calculation checking systems typically used to verify the treatment planning system. Monte Carlo (MC) codes such as EGSnrc have become easily available and are capable of performing calculations of highly complex radiotherapy treatments. This educational note demonstrates a method for implementing and using a fully automated system for performing and analysing full MC calculations of conformal, IMRT and VMAT radiotherapy plans. Example calculations were based on BEAMnrc/DOSXYZnrc and are performed automatically after either uploading exported plan DICOM data through a Python-based web interface, or exporting DICOM data to a monitored network location. This note demonstrates how completed MC calculations can then be analysed using an automatically generated dose point comparison report, or easily re-imported back into the treatment planning system. Agreement between the TPS and MC calculation was an improvement on agreement between RadCalc and the TPS, with differences ranging from 1.2 to 5.5% between RadCalc and the treatment planning system (TPS), and 0.1-1.7% between MC and TPS. Comparison of the dose-volume histogram (DVH) parameters [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] for the example VMAT plans showed agreement for the mean planning target volume dose within [Formula: see text], [Formula: see text] and [Formula: see text] generally within [Formula: see text] with the exception of a brain case, and [Formula: see text] within [Formula: see text]. Overall, this note provides a demonstration of a system that has been integrated well into existing clinical workflow, and has been shown to be a valuable additional tool in the secondary checking of treatment plan calculations.

Quasi-simultaneous 3D printing of muscle-, lung- and bone-equivalent media: a proof-of-concept study.

3D printing is a promising solution for the production of bespoke phantoms and phantom components, for radiotherapy dosimetry and quality assurance (QA) purposes. This proof-of-concept study investigated the use of a dual-head printer to deposit two different filaments (polylactic acid (PLA) and StoneFil PLA-concrete (Formfutura BV, Nijmegen, Netherlands)) at several different in-fill densities, to achieve quasi-simultaneous 3D printing of muscle-, lung- and bone-equivalent media. A Raise 3D Pro 3D printer (Raise 3D Technologies Inc, Irvine, USA) was used to print one thoracic and one cranial phantom slab. Analysis using in-house 3D print QA software showed that the two humanoid phantom slabs geometrically matched the stereolithography (STL) files on which they were based, within 0.3 mm, except in one area of the thoracic slab that was affected by thermal warping by up to 3.4 mm. The 3D printed muscle, lung and bone materials in the two humanoid phantom slabs were approximately radiologically-equivalent to human muscle, lung and bone. In particular, the use of StoneFil with a nominally constant in-fill density of 100% resulted in regions that were approximately inner-bone-equivalent, at kV and MV energies. These regions were bounded by walls that were substantially denser than inner bone, although generally not dense enough to be truly cortical-bone-equivalent. This proof-of-concept study demonstrated a method by which multiple tissue-equivalent materials (eg. muscle-, lung- and bone-equivalent media) can be deposited within one 3D print, allowing complex phantom components to be fabricated efficiently in a clinical setting.

Predisposing factors of diminished survival in simultaneous liver/kidney transplantation.

Since the adoption of the Model for End-Stage Liver Disease, simultaneous liver/kidney transplants (SLKT) have substantially increased. Recently, unfavorable outcomes have been reported yet contributing factors remain unclear. We retrospectively reviewed 74 consecutive adult SLKT performed at our center from 2000 to 2010 and compared with kidney transplant alone (KTA, N = 544). In SLKT, patient and death-censored kidney graft survival rates were 64 ± 6% and 81 ± 5% at 5 years, respectively (median follow-up, 47 months). Multivariable analyses revealed three independent risk factors affecting patient survival: hepatitis C virus positive (HCV+, hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.1-7.9), panel reactive antibody (PRA) > 20% (HR 2.8, 95% CI 1.1-7.2) and female donor gender (HR 2.9, 95% CI 1.1-7.9). For death-censored kidney graft survival, delayed graft function was the strongest negative predictor (HR 8.3, 95% CI 2.5-27.9), followed by HCV+ and PRA > 20%. The adjusted risk of death-censored kidney graft loss in HCV+ SLKT patients was 5.8 (95% CI 1.6-21.6) compared with HCV+ KTA (p = 0.008). Recurrent HCV within 1 year after SLKT correlated with early kidney graft failure (p = 0.004). Careful donor/recipient selection and innovative approaches for HCV+ SLKT patients are critical to further improve long-term outcomes.

Activation of Notch1 signaling in stromal fibroblasts inhibits melanoma growth by upregulating WISP-1.

The tumor microenvironment is emerging as an important target for cancer therapy. Fibroblasts (Fbs) within the tumor stroma are critically involved in promoting tumor growth and angiogenesis through secretion of soluble factors, synthesis of extracellular matrix and direct cell-cell interaction. In this work, we aim to alter the biological activity of stromal Fbs by modulating the Notch1 signaling pathway. We show that Fbs engineered to constitutively activate the Notch1 pathway significantly inhibit melanoma growth and tumor angiogenesis. We determine that the inhibitory effect of 'Notch-engineered' Fbs is mediated by increased secretion of Wnt-induced secreted protein-1 (WISP-1) as the effects of Notch1 activation in Fbs are reversed by shRNA-mediated blockade of WISP-1. When 'Notch-engineered' Fbs are co-grafted with melanoma cells in SCID mice, shRNA-mediated blockade of WISP-1 reverses the tumor-suppressive phenotype of the 'Notch-engineered' Fbs, significantly increases melanoma growth and tumor angiogenesis. Consistent with these findings, supplement of recombinant WISP-1 protein inhibits melanoma cell growth in vitro. In addition, WISP-1 is modestly expressed in melanoma-activated Fbs but highly expressed in inactivated Fbs. Evaluation of human melanoma skin biopsies indicates that expression of WISP-1 is significantly lower in melanoma nests and surrounding areas filled with infiltrated immune cells than in the adjacent dermis unaffected by the melanoma. Overall, our study shows that constitutive activation of the Notch1 pathway confers Fbs with a suppressive phenotype to melanoma growth, partially through WISP-1. Thus, targeting tumor stromal Fbs by activating Notch signaling and/or increasing WISP-1 may represent a novel therapeutic approach to combat melanoma.

Regulation of heat-induced apoptosis by Mcl-1 degradation and its inhibition by Hsp70.

Cellular stress eliminates irreversibly damaged cells by initiating the intrinsic death pathway. Cell stress is sensed by pro- and antiapoptotic members of the Bcl-2 protein family, which regulate the release of apoptogenic factors, such as cytochrome c, from mitochondria. Exposure of cells to hyperthermia results in the activation of the proapoptotic Bcl-2 family protein Bax, which plays an essential role in cytochrome c release. Heat directly affects Bax activity in vitro; however, antiapoptotic Bcl-2 family proteins, such as Bcl-xL, can suppress this activation, suggesting that a second heat-sensitive step must be breached before apoptosis ensues in cells exposed to hyperthermia. Here we show that heat shock causes the loss of Mcl-1 protein. Depletion of Noxa by short hairpin RNA protected cells from hyperthermia by preventing Mcl-1 degradation. Heat shock caused the dissociation of Noxa from Mcl-1, which allowed binding of the BH3-containing ubiquitin ligase Mule followed by Mcl-1 ubiquitination and degradation. Overexpression of Hsp70, which prevents heat-induced Bax activation, stabilized Mcl-1 protein levels in heat-shocked cells. This resulted from reduced Mule binding and ubiquitination as well as enhanced Mcl-1 expression compared with cells without Hsp70. Our results demonstrate that loss of Mcl-1 is a critical heat-sensitive step leading to Bax activation that is controlled by Hsp70.

Thin-layer ablation of human esophageal epithelium using a bipolar radiofrequency balloon device.

BACKGROUND: The goal of this study was to determine the optimal treatment parameters for the ablation of human esophageal epithelium using a balloon-based bipolar radiofrequency (RF) energy electrode. METHODS: Immediately prior to esophagectomy, subjects underwent esophagoscopy and ablation of two separate, 3-cm long, circumferential segments of non-tumor-bearing esophageal epithelium using a balloon-based bipolar RF energy electrode (BARRX Medical, Inc., Sunnyvale, CA, USA). Subjects were randomized to one of three energy density groups: 8, 10, or 12 J/cm2. RF energy was applied one time (1x) proximally and two times (2x) distally. Following resection, sections from each ablation zone were evaluated using H&E and diaphorase. Histological endpoints were complete epithelial ablation (yes/no), maximum ablation depth, and residual ablation thickness after tissue slough. Outcomes were compared according to energy density group and 1x vs 2x treatment. RESULTS: Thirteen male subjects (age, 49-85 years) with esophageal adenocarcinoma underwent the ablation procedure followed by total esophagectomy. Complete epithelial removal occurred in the following zones: 10 J/cm2 (2x) and 12 J/cm2 (1x and 2x). The maximum depth of injury was the muscularis mucosae: 10 and 12 J/cm2 (both 2x). A second treatment (2x) did not significantly increase the depth of injury. Maximum thickness of residual ablation after tissue slough was only 35 microm. CONCLUSIONS: Complete removal of the esophageal epithelium without injury to the submucosa or muscularis propria is possible using this balloon-based RF electrode at 10 J/cm2 (2x) or 12 J/cm2 (1x or 2x). A second application (2x) does not significantly increase ablation depth. These data have been used to select the appropriate settings for treating intestinal metaplasia in trials currently under way.

Gastric carcinoids: a temporal increase with proton pump introduction.

BACKGROUND: Recent reports have indicated a rising incidence of gastric carcinoids. This study aimed to evaluate the incidence pattern of gastric carcinoids in two large population-based cancer registries. METHODS: The Florida Cancer Data System (FCDS), Florida's statewide cancer registry, and the Surveillance, Epidemiology, and End Results (SEER) program were used. The study population was defined as all cases of gastric carcinoid identified in either database from January 1981 to December 2000. Descriptive statistics and age-adjusted incidence rates were calculated. RESULTS: There were 326 (FCDS) and 594 (SEER) cases of invasive gastric carcinoid during the 20-year study period. The mean age of the patients was 65 years (range, 21-96 years), and the male:female ratio was 1:1. The age-adjusted incidence rate in FCDS increased from 0.04 (per 100,000 age-adjusted to the 2000 U.S. standard population) to 0.18 in the year 2000. The estimated annual percentage change in incidence was 8.17 in FCDS and 9.17 in SEER (p < 0.05). A decrease in gastric cancer was noted during this same period (from 8.64 to 11.14 cases per 100,000 in FCDS and from 11.14 to 8.06 cases per 100,000 in SEER). CONCLUSIONS: This study documented a statistically significant eight- or ninefold increase in the incidence of gastric carcinoids in two large databases. The temporal increase in incidence correlates with the introduction and widespread use of proton pump inhibitors since the late 1980s. Other explanations include improved detection with wider application of upper endoscopy. Further epidemiologic studies are warranted.

Assessment in vitro of a novel therapeutic strategy for glioma, combining herpes simplex virus HSV1716-mediated oncolysis with gene transfer and targeted radiotherapy.

Genetically engineered herpes simplex virus ICP34.5 null mutants replicate only in dividing cells and have shown potential for the treatment of malignant disease, including glioma. Phase I trials have demonstrated the safety of these viruses in various clinical settings but it is envisaged that for full efficacy they will be used in combination with other therapeutic modalities. To enhance virus-induced tumour cytotoxicity, we have engineered an ICP34.5 null mutant (HSV1716) of HSV1 which expresses the noradrenaline transporter gene (NAT). This virus is designated HSV1716/NAT. We have shown previously that introduction of the NAT gene into a range of tumour cells, via plasmid-mediated transfection, conferred the capacity for active uptake of the radiopharmaceutical [131I]MIBG and resulted in dose-dependent toxicity. In this study, combination therapy utilising HSV1716/NAT and [131I]MIBG was assessed in vitro by the MTT assay. We demonstrate that the NAT gene, introduced by HSV1716/NAT into cultured glioma cells, was expressed 1 h after viral infection, enabling active uptake of [131I]MIBG. The combination of viral oncolysis and induced radiopharmaceutical uptake resulted in significantly enhanced cytotoxicity compared to either agent alone and the response was dose- and time-dependent. These studies show that the combination of oncolytic HSV therapy with targeted radiotherapy has the potential for effective tumour cell kill and warrants further investigation as a treatment for malignant glioma.

Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of prostate.

A targeted radiotherapy/gene therapy approach for prostate cancer, using the radiopharmaceutical [(131)I]meta-iodobenzylguanidine ([(131)I]MIBG), would restrict the effects of radiotherapy to malignant cells, thereby increasing efficacy and decreasing morbidity of radiotherapy. Prostate cancer cells were transfected with a transgene encoding the noradrenaline transporter (NAT) under the control of tumour-specific telomerase promoters, enabling them to actively take up [(131)I]MIBG. This led to tumour-specific cell kill. This strategy has the advantage of generating a radiological bystander effect, leading to the destruction of neighbouring tumour cells that have escaped transfection. This targeted approach could be a promising tumour-specific treatment option for prostate cancer.

Esophageal carcinoma: current controversial topics.

Worldwide, esophageal carcinoma is a common gastrointestinal cancer with a high mortality. The incidence of adenocarcinoma of the esophagus is increasing in the western world, but squamous cell carcinoma remains dominant in the underdeveloped parts of the world. Both types of esophageal carcinoma remain equally virulent. Currently, there are no optimal preventative screening programs available and most patients present with advanced or metastatic disease. Although many options are available for improving diagnostic accuracy, a single method has not displayed significant advantages over the others. In addition, selecting a superior treatment regimen has not surfaced. Preferred resection techniques exist, but one method has not illustrated improvements in survival over the others. A lack of improved survival rates with single modality therapies has led to a multi modality approach. However, developments in neoadjuvant and adjuvant therapies have led to mixed conclusions. Collectively, past studies have not shown an optimal neoadjuvant or adjuvant regimen in terms of survival benefit. This review highlights existing staging modalities and treatment regimens for esophageal carcinoma, in an effort to illustrate the controversial nature surrounding its management.

Virus replication in engineered human cells that do not respond to interferons.

The V protein of the paramyxovirus simian virus 5 blocks interferon (IFN) signaling by targeting STAT1 for proteasome-mediated degradation. Here we report on the isolation of human cell lines that express the V protein and can no longer respond to IFN. A variety of viruses, particularly slow-growing wild-type viruses and vaccine candidate viruses (which are attenuated due to mutations that affect virus replication, virus spread, or ability to circumvent the IFN response), form bigger plaques and grow to titers that are increased as much as 10- to 4,000-fold in these IFN-nonresponsive cells. We discuss the practical applications of using such cells in vaccine development and manufacture, virus diagnostics and isolation of newly emerging viruses, and studies on host cell tropism and pathogenesis.

Massive hemorrhage and infarction complicating focal nodular hyperplasia of the liver.

BACKGROUND: Spontaneous infarction or hemorrhage of focal nodular hyperplasia (FNH) has rarely been reported in the literature. CASE OUTLINE: A 43-year-old woman presented with upper abdominal pain and anemia. CT scan showed an enormous perihepatic hematoma. Trisegmentectomy successfully dealt with the problem. CONCLUSION: Although conservative management of FNH is often adopted, this case illustrates that these lesions can undergo massive bleeding.

Transfectant mosaic spheroids: a new model for evaluation of tumour cell killing in targeted radiotherapy and experimental gene therapy.

BACKGROUND: We describe an in vitro tumour model for targeted radiotherapy and gene therapy that incorporates cell population heterogeneity. MATERIALS AND METHODS: Transfectant mosaic spheroids (TMS) and transfected mosaic monolayers (TMM) are composed of two cell populations derived from a single cell line. The cells of one population were transfected with the noradrenaline transporter gene (NAT), allowing active uptake of a radiolabelled targeting agent meta-[131I]iodobenzylguanidine ([131I]MIBG); the other population of cells was derived from the same parent line and transfected with a marker gene - green fluorescent protein (GFP). After treatment with [131I]MIBG, cell kill was determined in TMM by clonogenic assay and in TMS by clonogenic assay and spheroid growth delay. RESULTS: We have used the TMS model to assess the 'radiological bystander effect' (radiation cross-fire) conferred by the beta-emitting radiopharmaceutical [131I] MIBG whose cellular uptake is facilitated by the transfected gene encoding NAT. We show that cell killing by [131I]MIBG in both TMS and TMM cultures increased in direct proportion to the fraction of NAT-transfected cells and that the degree of cell killing against fraction transfected was greater in TMS, suggestive of a greater bystander effect in the three-dimensional culture system. CONCLUSIONS: TMS provide a useful model for assessment of the effectiveness of targeted radiotherapy in combination with gene therapy when less than 100% of the target cell population is expressing the NAT transgene. Further, this novel model offers the unique opportunity to investigate radiation-induced bystander effects and their contribution to cell cytotoxicity in radiotherapy and other gene therapy applications.

Expression in UVW glioma cells of the noradrenaline transporter gene, driven by the telomerase RNA promoter, induces active uptake of [131I]MIBG and clonogenic cell kill.

One of the most effective ways to kill cancer cells is by treatment of tumours with radiation. However, the administered dose of radiation to the tumour is limited by normal tissue toxicity. Strategies which decrease normal tissue exposure relative to tumour dose are urgently sought. One such promising scheme involves gene transfer, leading to the introduction of transporters specific for pharmaceuticals which can be labelled with radionuclides. We have previously demonstrated in vitro, that transfer of the noradrenaline transporter (NAT) gene, under viral promoter control, induces in host cells the active accumulation of the radiopharmaceutical [131I]meta-iodobenzylguanidine ([131I]MIBG) which results in kill of clonogens. We now report 17-fold enhancement of [131I]MIBG uptake by UVW glioma cells transfected with the NAT gene whose expression is driven by the human telomerase RNA (hTR) promoter (70% the uptake achieved by the strong viral promoter). Multicellular spheroids composed of hTR-NAT-transfected UVW cells exhibited dose-dependent susceptibility to treatment with [131I]MIBG. This was demonstrated by decreased survival of clonogens and complete sterilization of clonogens derived from spheroids and also failure of spheroids to regrow after administration of 7 MBq/ml [131I]MIBG. These data suggest hTR regulated expression of NAT may be an effective gene therapy strategy.

Dilatation of biliary strictures through the afferent limb of a Roux-en-Y choledochojejunostomy in patients with sclerosing cholangitis.

Repeated dilatation of biliary strictures in patients with sclerosing cholangitis through a subcutaneously placed afferent limb of a choledochojejunostomy is technically feasible and safe. This study is a prospective 15-year evaluation of 36 patients treated by repeat dilatation through this jejunal limb. There was one operative death and one major complication of dilatation. The 5-year survival of all patients was 74%. If patients with cirrhosis or unproven cholangiocarcinoma at the time of operation are not included, the 5-year survival is 86%. The 15-year survival of all patients was 30%; it was 64% if those with cirrhosis and unproven cholangiocarcinoma at the time of operation are not included. Six patients are presently alive with an average survival of 159 months. The study suggests that a combination of repeated dilatations combined with transplantation is the approach of choice in selected patients.

Management of hilar bile duct carcinoma.

BACKGROUND/AIMS: Hilar cholangiocarcinoma is a rare tumor with a dismal prognosis. Because proximal bile duct cancers are uncommon, outcomes related to various therapeutic interventions are not well defined. METHODOLOGY: Between 1985 and 1997, 55 patients with bile duct cancers involving the proximal third of the extrahepatic bile ducts were seen. The management of patients with resectable and unresectable disease was retrospectively reviewed. All but four patients were followed until the time of death. RESULTS: Forty patients underwent laparotomy following preoperative assessment of extent of disease and 19 patients (35%) ultimately underwent resection with curative intent. Survival was significantly longer in patients who underwent resection (2-year survival 47% vs. 18%; P = 0.027). Of those patients whose disease was resected, 11 patients received adjuvant radiotherapy. Survival for this group was not significantly different from that seen in patients who did not receive adjuvant radiotherapy. Similarly, in patients with unresectable disease, administration of radiotherapy was not associated with an improved outcome. CONCLUSIONS: Locoregional extent of disease is the greatest problem in cases of proximal bile duct cancers. Resection provides the best hope for long-term survival, but new adjuvant strategies are needed.

Neoadjuvant therapy for esophageal cancer: standard of care or elusive myth?

Although surgical resection as the sole treatment modality for esophageal carcinoma has historically been associated with poor survival rates, improvements have recently been reported using varied neoadjuvant chemo-radiation protocols. This study evaluates the outcome of patients undergoing surgery for esophageal carcinoma at the University of Miami/Jackson Memorial Hospital between July 1991 and June 1996. Seventy-two patients underwent esophageal resection; 51 males and 21 females with a median age of 62.5 years (range = 42-82). Histology was equally distributed between adenocarcinoma (36 patients; 50%) and squamous cell carcinoma (36 patients; 50%). Pathological stage distribution consisted of 6 stage 0 (8%), 10 stage I (14%), 23 stage II (32%), 31 stage III (43%), and 2 stage IV (3%) lesions. Patients were divided into three groups according to the type of preoperative treatment; Group 1 (n = 44); surgery alone; Group 2 (n = 18); neoadjuvant 5-fluorouracil based chemotherapy, and Group 3 (n = 9); neoadjuvant 5-fluorouracil based chemotherapy in conjunction with external beam radiation (XRT). One patient received preoperative XRT alone. All survivors were followed for a minimum of 1 year and statistical analysis was performed using Kaplan-Meier curves, log-rank, and chi-square tests. In the 28 patients receiving any form of neoadjuvant therapy only one patient had a pathological complete response (CR) (3.5%). The overall 5 year and median survival rates were 18 per cent and 20.5 months (range = 0-73), respectively. Individual treatment group survival rates at 5 years were 28% for Group 1; 21% for Group 2; and 0% for Group 3, showing no survival difference between Groups 1 and 2; Group 3 fared significantly worse than the other two, probably as a result of the high operative mortality in this group. These results indicate that surgical resection continues to be an important treatment modality for esophageal carcinoma. Neoadjuvant chemotherapy in our experience failed to improve these survival rates and pre-operative chemoradiation was associated with a high perioperative mortality rate. Chemotherapy regimens with higher CRs may further improve these survival rates.

Large cystic lesions of the liver in adults: a 15-year experience in a tertiary center.

BACKGROUND: Cystic lesions of the liver consist of a heterogeneous group of disorders and may present a diagnostic and therapeutic challenge. Large hepatic cysts tend to be symptomatic and can cause complications more often than smaller ones. STUDY DESIGN: We performed a retrospective review of adults diagnosed with large (> or = 4 cm) hepatic cystic lesions at our center, over a period of 15 years. Polycystic disease and abscesses were not included. RESULTS: Seventy-eight patients were identified. In 57 the lesions were simple cysts, in 8 echinococcal cysts, in 8 hepatobiliary cystadenomas, and in 1 hepatobiliary cystadenocarcinoma. In four patients, the precise diagnosis could not be ascertained. Mean size was 12.1 cm (range, 4 to 30 cm). Most simple cysts were found in women (F:M, 49:8). Bleeding into a cyst (two patients) and infection (one patient) were rare manifestations. Percutaneous aspiration of 28 simple cysts resulted in recurrence in 100% of the cases within 3 weeks to 9 months (mean 4(1/2) months). Forty-eight patients were treated surgically by wide unroofing or resection (laparoscopically in 18), which resulted in low recurrence rates (11% for laparoscopy and 13% for open unroofing). Four of the eight patients with echinococcal cysts were symptomatic. All were treated by open resection after irrigation of the cavity with hypertonic saline. There was no recurrence during a followup period of 2 to 14 years. Hepatobiliary cystadenomas occurred more commonly in women (F:M, 7:1) and in the left hepatic lobe (left:right, 8:0). Seven were multiloculated. All were treated by open resection, with no recurrence, and none had malignant changes. Cystadenocarcinoma was diagnosed in a 77-year-old man, and was treated by left hepatic lobectomy. CONCLUSIONS: Large symptomatic simple cysts invariably recur after percutaneous aspiration. Laparoscopic unroofing can be successfully undertaken, with a low recurrence rate. Open resection after irrigation with hypertonic saline is a safe and effective treatment for echinococcal cysts. Hepatobiliary cystadenomas have predilection for women and for the left hepatic lobe. Malignant transformation is an uncommon but real risk. Open resection is a safe and effective treatment for hepatobiliary cystadenoma, and is associated with a low recurrence rate.