The Effect of Season and Weather on Orthopaedic Trauma: Consult Volume Is Significantly Correlated with Daily Weather.

INTRODUCTION: On-call orthopedic clinicians have long speculated that daily consult volume is closely correlated with weather. While prior studies have demonstrated a relationship between weather and certain fracture types, the effect of weather on total orthopaedic consult volume has not yet been examined. The aim of this study was to investigate this relationship. METHODS: We retrospectively reviewed orthopaedic consult data from 405 consecutive days at an urban, level one trauma center. The number, mechanism of injury, and type of consult were collected, along with daily weather data (temperature, wind, and precipitation). Statistical analysis was then performed to determine the relationship between weather and orthopaedic trauma consults. RESULTS: A total of 4543 consults were received during the study period. There was a significant difference in total number of consults between months of the year (p<0.001). A post hoc analysis revealed that this was due to increased volume in the summer months relative to the winter months (i.e., August 13.7 consults/day; January 9.3 consults/day). Average daily temperature and consult volume were also positively correlated (p<0.001, r= 0.30). While there was no significant association between precipitation and total consult volume, when there was over 0.25 inches of rain, there were less penetrating trauma (p=0.034) and motorcycle collision consults (p=0.013). CONCLUSION: Weather parameters, specifically average temperature and precipitation, were found to be associated with daily orthopedic consult type and volume. Additionally, consult volume varies significantly between months of the year. Because trauma centers are often resource scarce, this is an important relationship to understand for proper resource allocation.

Low CHD5 expression activates the DNA damage response and predicts poor outcome in patients undergoing adjuvant therapy for resected pancreatic cancer.

The DNA damage response (DDR) promotes genome integrity and serves as a cancer barrier in precancerous lesions but paradoxically may promote cancer survival. Genes that activate the DDR when dysregulated could function as useful biomarkers for outcome in cancer patients. Using a siRNA screen in human pancreatic cancer cells, we identified the CHD5 tumor suppressor as a gene, which, when silenced, activates the DDR. We evaluated the relationship of CHD5 expression with DDR activation in human pancreatic cancer cells and the association of CHD5 expression in 80 patients with resected pancreatic adenocarcinoma (PAC) by immunohistochemical analysis with clinical outcome. CHD5 depletion and low CHD5 expression in human pancreatic cancer cells lead to increased H2AX-Ser139 and CHK2-Thr68 phosphorylation and accumulation into nuclear foci. On Kaplan-Meier log-rank survival analysis, patients with low CHD5 expression had a median recurrence-free survival (RFS) of 5.3 vs 15.4 months for patients with high CHD5 expression (P=0.03). In 59 patients receiving adjuvant chemotherapy, low CHD5 expression was associated with decreased RFS (4.5 vs 16.3 months; P=0.001) and overall survival (OS) (7.2 vs 21.6 months; P=0.003). On multivariate Cox regression analysis, low CHD5 expression remained associated with worse OS (HR: 3.187 (95% CI: 1.49-6.81); P=0.003) in patients undergoing adjuvant chemotherapy. Thus, low CHD5 expression activates the DDR and predicts for worse OS in patients with resected PAC receiving adjuvant chemotherapy. Our findings support a model in which dysregulated expression of tumor suppressor genes that induce DDR activation can be utilized as biomarkers for poor outcome.

Genetic diversity and response to IFN of the NS3 protease gene from clinical strains of the hepatitis C virus.

The N-terminal one-third of the hepatitis C virus nonstructural gene 3 (NS3) codes for a serine protease. To investigate natural genetic diversity of this enzyme a nested PCR reaction was developed to obtain NS3 protease sequence data directly from patient strains. This data was used to determine genetic diversity, phylogenetic and evolutionary rates, and selection of variants by interferon therapy. The potential effect of genetic diversity on enzyme structure using molecular modeling was also attempted. Results show significant variability in clinical HCV strains at both the nucleotide (30.2% for 1a and 25.8% for 1b) and amino acid sequences (11.0% for 1a and 9.9% for 1b). Phylogenic analysis shows two distinct clades with two HCV isolates grouping as a sister clade to 1b. Structural analysis reveals that most mutations lie in the N-terminus of the enzyme. When strains were sorted as to whether or not the patient had received antiviral therapy, no difference was found in the number or locations of mutations in 1a strains. However, 1b strains demonstrated an overall drop in the number of positions that were mutated. This study demonstrates significant differences among natural strains that may pose a problem for structure based drug development.

Genetic approaches to studying protein synthesis: effects of mutations at Psi516 and A535 in Escherichia coli 16S rRNA.

A genetic system for the study of ribosomal RNA function and structure was developed. First, the ribosome binding sequence of the chloramphenicol acetyltransferase gene and the message binding sequence of 16S ribosomal RNA were randomly mutated and alternative highly functional sequences were selected and characterized. From this set of mutants, a single clone was chosen and subjected to a second round of mutagenesis to optimize the specificity of the system. In the resulting system, plasmid-encoded ribosomes efficiently and exclusively translate specific mRNA containing the appropriate ribosome binding sequences. This system allows facile isolation and analysis of mutations that would normally be lethal and allows direct selection of rRNA mutants with predetermined levels of ribosome function. The system was used to examine the effects of mutations at the sole pseudouridine (Psi) in Escherichia coli 16S rRNA which is located at position 516 of the conserved 530 loop. The nucleotide opposite Psi516 in the hairpin, A535, was also mutated. The data show that a pyrimidine (Psi or C) is required at position 516, while substitutions at position 535 reduce ribosome function by < 50%. A requirement for base pair formation between Psi516 and A535 was not indicated.

Comparison of results generated by serotyping, pulsed-field restriction analysis, ribotyping, and repetitive-sequence PCR used to characterize penicillin-resistant pneumococci from the United States.

One hundred forty-seven isolates of Streptococcus pneumoniae with high-level penicillin resistance collected during a national surveillance program in the United States were characterized by serotyping, pulsed-field restriction analysis, ribotyping, and repetitive-sequence (BOX element) PCR. The results generated by each method were compared by frequency of association to examine whether relationships existed between the various typing methods and statistically to determine association with the geographic source of the isolate or the age of the patient from whom the isolate was obtained. When the data were examined by pairwise analysis of individual strain classifications produced by each typing method, no statistically significant relationships between strain type, geographic location, or patient age were identified, suggesting that distinct clones of penicillin-resistant S. pneumoniae have been widely distributed throughout the United States. However, we did observed shared expression of two or three typing markers at a high frequency (>50%) among clusters of strains, indicating a certain level of concordance between the various typing methods used to classify penicillin-resistant S. pneumoniae.

Aerobic activity of Escherichia coli alcohol dehydrogenase is determined by a single amino acid.

Expression of the alcohol dehydrogenase gene, adhE, in Escherichia coli is anaerobically regulated at both the transcriptional and the translational levels. To study the AdhE protein, the adhE(+) structural gene was cloned into expression vectors under the control of the lacZ and trp(c) promoters. Wild-type AdhE protein produced under aerobic conditions from these constructs was inactive. Constitutive mutants (adhC) that produced high levels of AdhE under both aerobic and anaerobic conditions were previously isolated. When only the adhE structural gene from one of the adhC mutants was cloned into expression vectors, highly functional AdhE protein was isolated under both aerobic and anaerobic conditions. Sequence analysis revealed that the adhE gene from the adhC mutant contained two mutations resulting in two amino acid substitutions, Ala267Thr and Glu568Lys. Thus, adhC strains contain a promoter mutation and two mutations in the structural gene. The mutant structural gene from adhC strains was designated adhE*. Fragment exchange experiments revealed that the substitution responsible for aerobic expression in the adhE* clones is Glu568Lys. Genetic selection and site-directed mutagenesis experiments showed that virtually any amino acid substitution for Glu568 produced AdhE that was active under both aerobic and anaerobic conditions. These findings suggest that adhE expression is also regulated posttranslationally and that strict regulation of alcohol dehydrogenase activity in E. coli is physiologically significant.

Laparoscopic harvesting of jejunal free flaps for esophageal reconstruction.

Endoscopic harvest of the jejunum is indicated for the reconstruction of complex defects of the head and neck and specifically the reconstruction of circumferential defects of the esophagus. However, open laparotomies are associated with systemic and local morbidity and are often seen as prohibitively invasive procedures. Laparoscopy for intra-abdominal procedures is a proven technique that yields less morbidity and provides an anatomical exposure similar to that of the open approach. We report on 11 consecutive clinical cases of free jejunal flap harvesting with the laparoscopic technique and show that the procedure is feasible.

Comparison of NNA agar culture and selective broth culture for detection of group B streptococcal colonization in women.

In 1996, the Centers for Disease Control and Prevention recommended the use of a selective broth culture for the improved detection of genital tract or anorectal carriage of group B streptococci (GBS) in pregnant women. In order to verify this recommendation in our laboratory, we compared the sensitivity of Todd-Hewitt medium with gentamicin and nalidixic acid (SBM) with our current method of direct plating on blood agar medium containing neomycin and nalidixic acid (NNA). Five hundred consecutive cervicovaginal and anorectal specimens submitted for GBS culture were included in the study. Swabs were plated onto NNA and the swabs were immersed in SBM, followed by overnight incubation at 35 degrees C. On the following day, the NNA plates were examined for colonies typical of GBS and the organisms were identified by the CAMP test or by latex agglutination. SBM cultures were subcultured onto blood agar and CNA agar plates, and the plates were reincubated for 24 h. Negative specimens from either medium were incubated for an additional 24 h and were examined again before finalization of the results. GBS were recovered from 78 specimens by both methods; from SBM only for 17 specimens (sensitivity, 86%) and from NNA only for 16 specimens (sensitivity, 85%). A moderate to heavy growth of Enterococcus faecalis was observed on plates containing NNA-positive, SBM-negative specimens. Competitive growth studies suggested that E. faecalis suppressed the growth potential of GBS in SBM. Our study suggests that direct plating on NNA, as a single method, is equivalent in sensitivity to SBM for the recovery of GBS, and the results are often available 24 h sooner. However, it appears that both direct plating and selective broth amplification techniques are required for the maximum level of identification of colonization with GBS in pregnant women.

Culture and characterization of sinusoidal endothelial cells isolated from human liver.

Although most vascular models use large vessel endothelial cells from human umbilical veins, there is marked heterogeneity among endothelial cells from different vascular beds and organs. More accurate modeling of endothelial involvement in liver diseases, including metastasis, may result from the use of human hepatic sinusoidal endothelial cells. Liver resection specimens were sectioned, then treated with a 1.2 U/ml dispase solution. The tissue slurry was mechanically disaggregated and separated by centrifugation on a Percoll density gradient. Cells were then cultured in an endothelial-specific media with growth factors. These techniques resulted in a homogeneous monolayer consistent with endothelial cells by light microscopy. An endothelial origin was further confirmed by the expression of Factor VIII, binding of Ulex lectin, and uptake of acetylated low density lipoprotein. Electron microscopy showed transcellular fenestrations consistent with a sinusoidal origin. These human hepatic sinusoidal endothelial cells were then studied for expression of the adhesion molecules CD31/PECAM, CD34, E-selectin, ICAM-1, L-selectin, LFA-3, P-selectin, and VCAM-1 plus the binding of wheat germ agglutinin lectin. The patterns of adhesion molecule expression and lectin binding by these cells are characteristic of hepatic sinusoidal endothelia. In this paper, we have described a method for isolation and culture of human cells with the morphologic and phenotypic characteristics of hepatic sinusoidal endothelia.

Down-regulation of vascular endothelial growth factor in a human colon carcinoma cell line transfected with an antisense expression vector specific for c-src.

Vascular endothelial growth factor (VEGF) is implicated in the angiogenesis of human colon cancer. Recent evidence suggests that factors that regulate VEGF expression may partially depend on c-src-mediated signal transduction pathways. The tyrosine kinase activity of Src is activated in most colon tumors and cell lines. We established stable subclones of the human colon adenocarcinoma cell line HT29 in which Src expression and activity are decreased specifically as a result of a transfected antisense expression vector. This study determined whether VEGF expression is decreased in these cell lines and whether the smaller size and reduced growth rate of antisense vector-transfected cell lines in vivo might result, in part, from reduced vascularization of tumors. Northern blot analysis of these cell lines revealed that VEGF mRNA expression was decreased in proportion to the decrease in Src kinase activity. Under hypoxic conditions, cells with decreased Src activity had a <2-fold increase in VEGF expression, whereas parental cells had a >50-fold increase. VEGF protein in the supernatants of cells was also reduced in antisense transfectants compared with that from parental cells. In nude mice, subcutaneous tumors from antisense transfectants showed a significant reduction in vascularity. These results suggest that Src activity regulates the expression of VEGF in colon tumor cells.

Regulation of vascular endothelial growth factor expression in human colon carcinoma cells by activity of src kinase.

BACKGROUND: The c-src protooncogene encodes a protein tyrosine kinase, pp60c-src, that is a mediator in many signal transduction pathways. One pathway in which pp60c-src protein tyrosine kinase activity is implicated involves regulation of vascular endothelial growth factor (VEGF), an angiogenic factor important to neovascularization of growing tumors. Recently we demonstrated that decreased activity of pp60c-src in colon tumor cells contributes to decreased expression of VEGF. This study examined the relationship between pp60c-src activation, cell density, and VEGF production in a colon tumor cell line. METHODS: Parental HT-29 colon adenocarcinoma cells and stable subclones created by transfection with c-src antisense and sense (control) expression vectors were plated under sparse (2 x 10(4) cells/cm2) and confluent (20 x 10(4) cells/cm2) conditions and grown for 36 hours. Protein and RNA were extracted from cells to determine pp60c-src levels, c-Src tyrosine kinase activity, and VEGF mRNA expression. RESULTS: The pp60c-src kinase activity of HT-29 cells and control sense-transfected clones grown under confluent conditions was increased threefold to fivefold compared with cells grown under sparse conditions. In contrast, the ability of confluent culture conditions to increase pp60c-src activity was blunted in antisense transfectants. By regression analysis, VEGF expression was found to vary directly with pp60c-src levels (r2 = 0.886). CONCLUSIONS: Cell density contributes to the regulation of c-src kinase activity and VEGF expression in HT-29 cells. When the steady-state level of pp60c-src is reduced in antisense transfectants, not only is the steady-state level of VEGF reduced, but the ability of confluence to stimulate pp60c-src activity and VEGF production is too. These data suggest that c-src may be an intermediary of both constitutive and inducible pathways for VEGF production in colon tumor cells.

Decreased tumorigenicity of a human colon adenocarcinoma cell line by an antisense expression vector specific for c-Src.

In greater than 80% of colon tumors and established cell lines, the specific activities of the protein tyrosine kinases pp60(c-src) and pp62(c-yes) are increased with respect to normal colonic epithelial cells. However, no mutations in either gene have been identified in colon tumors. Therefore, the possible biological consequences of activations of these protein tyrosine kinases in colon tumors have been unclear. To determine if pp60(c-src) activation affects growth and tumorigenicity of established colon tumor cell lines, an antisense expression vector that specifically reduces pp60(c-src) expression was constructed. The vector was transfected into HT 29 cells, an established colon tumor cell line in which both pp60(c-src) and pp62(c-yes) are activated. Two stable subclones were isolated in which pp60(c-src) but not pp62(c-yes) expression and activity were reduced. These established cell lines proliferated more slowly than parental cells proportionately to reduction in pp60(c-src) expression. When injected into nude mice, antisense transfected cells formed slow-growing tumors; however, the rate of tumor growth was reduced far greater than would be predicted from decreased proliferation rates in tissue culture. In contrast, stable subclones transfected with a comparable "sense" expression vector were unaltered in growth rates in tissue culture and in nude mice with respect to parental HT 29 cells. These data demonstrate that the activation of pp60(c-src) alone contributes to the tumorigenicity of HT 29 cells, a cell line widely used as a model for biological properties of colon carcinoma. Furthermore, because pp60(c-src) and pp62(c-yes) appear redundant to the growth regulation of normal colonic epithelial cells, the data suggest that src-specific inhibitors might be of therapeutic value for colon cancer.

Genetic analysis of the Shine-Dalgarno interaction: selection of alternative functional mRNA-rRNA combinations.

The interaction of bacterial mRNAs with the small ribosomal subunit is strongly promoted by Watson-Crick base pairing between a purine-rich consensus ribosomal RNA-binding sequence (RBS) on mRNA and its complementary message-binding sequence (MBS) on rRNA known as the Shine-Dalgarno interaction. To identify and characterize components of the Shine-Dalgarno interaction that contribute to translation initiation, we simultaneously and randomly mutated both the MBS of the 16S rRNA gene from Escherichia coli and the RBS of the chloramphenicol acetyl transferase (CAT) gene and selected chloramphenicol-resistant mutant combinations. Nucleotide distribution in both mutated sequences of the survivors was nonrandom and the MBSs of the surviving clones showed a preference for purines. In addition, strong interactions between specific nucleotide pairs within each of the mutated sequences were indicated. Although the contribution of free energy of duplex formation between rRNA and mRNA was highly significant (P < 0.001), only 23% of the observed activity in all of the mutants could be attributed to this variable. MBSs that were lethal upon expression were also isolated. These sequences may cause overtranslation of specific messages in the cell. These data indicate that specific sequence constraints exist (primarily within the MBS) that are necessary to establish a functional threshold for translation and that only after establishment of this threshold is the level of expression significantly affected by the free energy of MBS-RBS duplex formation.

Anti-metastatic prostacyclins inhibit the adhesion of colon carcinoma to endothelial cells by blocking E-selectin expression.

Prostacyclins have long been shown to have anti-metastatic activity. One hypothesis is their modulation of cell adhesion molecule (CAM) expression by target organ endothelial cells. We have postulated that prostacyclin, its analogs, and mechanistic mimics decrease colon carcinoma adhesion to cytokine-stimulated endothelial cells by blocking endothelial expression of the adhesion molecule E-selectin, but not the vascular cell adhesion molecule-1 (VCAM-1). Cultured human microvascular endothelial cells (HDMEC) were pre-incubated with prostacyclin (PGI2), dibutyrl-cAMP (dbcAMP), forskolin (FOR), and/or iso-methylbutylxanthine (IBMX) for 15 min, then co-incubated with the cytokine tumor necrosis factor (TNF) for 4 h. HDMEC surface expression of E-selectin and VCAM-1 was evaluated by flow cytometry and ELISA. Adherence of 51Cr-labeled colon carcinoma cells to HDMEC monolayers was then determined. In parallel assays, HDMECs were incubated with anti-E-selectin and anti-VCAM-1 monoclonal antibody (1:100) prior to the addition of tumor cells. Prostacyclins, its analogs, and mimics significantly reduced E-selectin expression by HDMEC, while the reduction of VCAM-1 expression was much less pronounced. Prostacyclins also significantly decreased colon carcinoma adherence to stimulated HDMECs. The inhibition of E-selectin expression, but not VCAM-1 expression, corresponded to the reduction of tumor cell adherence. Prostacyclin's effects on tumor adhesion were nullified by pre-incubation with E-selectin antibody. The inhibition of colon carcinoma adherence to cytokine-stimulated endothelial cells treated with prostacyclin, its analogs, and mimics appears to result from blocking endothelial E-selectin, but not VCAM-1, expression. These data support the hypothesis that prostacyclins may exert their anti-metastatic effect, in part, by inhibiting CAM-mediated adherence of colon carcinoma to endothelial cells in metastatic target organs.

The need for standardized pathologic staging of pancreaticoduodenectomy specimens.

A standardized method for pathologic evaluation and staging of pancreaticoduodenectomy (PD) specimens is critical for accurate reporting of the number and location of lymph nodes and margins of resection. We examined the impact of standardized pathologic evaluation (SPE) of PD specimens on the identification of regional lymph nodes and describe our detailed system for the pathologic analysis of the PD specimen. Forty consecutive patients underwent PD for histologically confirmed adenocarcinoma of the pancreatic head between April 1990 and August 1993. Fifteen consecutive specimens were examined before the introduction of the SPE, and 25 consecutive specimens underwent SPE. Resection margins were evaluated by frozen-section analysis, and then the specimen was divided into six regions on an anatomic dissection board for lymph node identification. The 25 specimens examined according to the SPE had a significantly increased number of lymph nodes identified (P = 0.0001) compared with the 15 specimens examined without the SPE. Twelve of the 25 specimens contained positive lymph nodes, 6 of which were confined to the pancreaticoduodenal region. No positive nodes were found in the periaortic region. There were no differences in pathologic variables between patients found to have negative and those with positive regional lymph nodes. SPE of PD specimens provides a method for improved lymph node identification, ensures accurate prospective evaluation of margins of resection, and provides a complete analysis of potentially important pathologic variables. We offer this system as a standardized model for groups engaged in protocol-based clinical research examining innovative multimodality treatment strategies for patients with resectable pancreatic cancer.

Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence. Pancreatic Tumor Study Group.

OBJECTIVE: Tumor invasion of the superior mesenteric-portal vein (SMPV) confluence is often considered a contraindication to pancreaticoduodenectomy for patients with malignant tumors of the pancreas or periampullary region. The authors sought to determine whether pancreaticoduodenectomy with en bloc resection of the SMPV confluence could be safely performed and whether tumors involving the SMPV confluence were associated with pathologic parameters suggesting poor prognosis. SUMMARY BACKGROUND DATA: Several centers have reported high rates of retroperitoneal margin positivity after pancreaticoduodenectomy for tumors of the pancreatic head and periampullary region. Positive-margin or incomplete resection is associated with early tumor recurrence and no survival benefit compared with palliative therapy. Tumor adherence to the lateral of posterior wall of the SMPV confluence often represents the only barrier to complete tumor resection at the time of pancreaticoduodenectomy. METHODS: Data on all patients undergoing pancreaticoduodenectomy for adenocarcinoma of the pancreas or periampullary region over a 3.5-year period were entered prospectively in a pancreatic tumor database. To be considered for surgery, patients were required to fulfill the following computed tomography criteria for resectability: 1) the absence of extrapancreatic disease, 2) no tumor encasement of the superior mesenteric artery or celiac axis, and 3) a patent SMPV confluence. Tumor adherence to the superior mesenteric vein or SMPV confluence was assessed intraoperatively, and en bloc venous resection was performed when necessary to achieve complete tumor extirpation. Data on operative characteristics, morbidity, mortality, tumor size, nodal metastases, margin positivity, perineural invasion, and tumor DNA content were compared for patients who did and did not receive venous resection. RESULTS: Fifty-nine patients underwent pancreaticoduodenectomy, 36 without venous resection and 23 with en bloc resection of the SMPV confluence. No differences in median hospital stay, morbidity, mortality, tumor size, margin positivity, nodal positivity, or tumor DNA content were observed between groups. CONCLUSIONS: When necessary, segmental resection of the SMPV confluence may be performed safely during pancreaticoduodenectomy for periampullary malignant tumors. Tumors invading the SMPV confluence are not associated with histologic parameters suggesting a poor prognosis. Our data suggest that venous involvement is a function of tumor location rather than an indicator of aggressive tumor biology.

Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for adenocarcinoma of the pancreatic head.

BACKGROUND: Local recurrence in the bed of the resected pancreas is the most common site of tumor recurrence following a standard pancreaticoduodenectomy (PD) for adenocarcinoma of the pancreatic head. In an attempt to improve local and regional disease control and thereby enhance the quality and length of survival in patients undergoing potentially curative PD, we have used a protocol of preoperative multimodality therapy. PATIENTS AND METHODS: All patients were treated with external-beam radiation (30.0 or 50.4 Gy) and concomitant 5-fluorouracil (300 mg/m2 per day) prior to PD. Electron-beam intraoperative radiation therapy was given to the bed of the resected pancreas before reconstruction. Patients were assessed for recurrence by physical examination, chest roentgenography, and computed tomography scan performed at 3-month intervals following treatment. RESULTS: Thirty-nine patients completed all therapy; 1 perioperative death occurred. Thirty-eight tumor recurrences have been documented in 29 patients at a median of 11 months from the date of diagnosis; 23 patients died of disease. The liver was the most frequent site of recurrence, and liver metastases were a component of treatment failure in 53% of patients. Isolated local or peritoneal recurrences were documented in only 4 patients (11%). The only significant clinical or pathologic variable predictive of local-regional recurrence was a previous laparotomy and intraoperative biopsy. The median survival of all 39 patients was 19 months, and the 4-year actuarial survival rate was 19%. CONCLUSIONS: Preoperative chemoradiation, PD, and electron-beam intraoperative radiation therapy for adenocarcinoma of the pancreatic head have resulted in improved local-regional tumor control, with distant metastatic disease becoming the predominant site of tumor recurrence. Future treatment strategies should incorporate effective multimodality therapy for local-regional disease as demonstrated in this study. Major improvements in overall survival will likely await the development of systemic or regional therapy for liver metastases.

Laparoscopic intracorporeal harvest of jejunal tissue for autologous transplantation.

Our goal in this study was to assess the feasibility and safety of performing an intracorporeal laparoscopic jejunal harvest. The initial technique was developed and refined in a pig and then a dog model. In the animal studies, careful dissection of the jejunal flap with its feeding vessel was accomplished along with an intracorporeal anastomosis. The laparoscopic dissection was facilitated by temporarily anchoring the jejunal flap to the anterior abdominal wall and transilluminating the mesentery. We present the first case report of a patient who underwent a laparoscopic jejunal harvest, intracorporeal small bowel anastomosis, and a microvascular anastomosis in the neck for reconstruction of the laryngopharynx.