Use of a Pfannenstiel incision in minimally invasive colorectal cancer surgery is associated with a lower risk of wound complications.

BACKGROUND: The Pfannenstiel incision, widely used in gynecological surgery, has been reported to be associated with lower rates of wound complications than midline incisions in open surgery. However, its effect on wound complications in minimally invasive surgery (MIS) is not well understood. We hypothesize that use of a Pfannenstiel incision in MIS colorectal cancer resections would be associated with fewer short-term wound complication rates. METHODS: A retrospective cohort study was performed on 171 patients who had undergone MIS colorectal cancer surgery requiring a specimen extraction/hand-access site, divided into a Pfannenstiel and a midline group depending on the type of incision used. Wound complications compared included disruption, infection, dehiscence, evisceration, and fistula formation. The Mann-Whitney U and Fisher's exact tests were used to analyze differences in risk factors between the groups. Logistic regression was performed to determine factors associated with prevention of wound complications. RESULTS: Patients in the Pfannenstiel group had significantly lower rates of wound disruption (0 vs. 13%, p = 0.02), superficial surgical site infection (7 vs. 22%, p = 0.03), and overall wound complications (13 vs. 30%, p = 0.04). Using multivariate logistic regression, Pfannenstiel incisions and colon rather than rectal resections were significant predictors of prevention of wound complications. CONCLUSIONS: The use of a Pfannenstiel incision in MIS colorectal cancer resections is associated with a decreased risk of short-term wound complications.

Early predictors of anastomotic leaks after colectomy.

BACKGROUND: An anastomotic leak after colorectal surgery is associated with significant morbidity and decreased survival. Our aim was to identify the early predictors of anastomotic leaks. METHODS: The records of patients undergoing restorative resection for colorectal disease from January 2000 to November 2005 were reviewed. Demographics, clinical events, and laboratory parameters were recorded. RESULTS: A total of 311 patients were included. An anastomotic leak was identified in 25 patients (8%). A leak was suspected and diagnosis confirmed at a mean of 10+/-1 days postoperatively. More respiratory and neurological events occurred in patients with an anastomotic leak (p<0.001). These events occurred early in the postoperative course and were usually the first signs and symptoms of a leak. More patients with a leak had absence of bowel activity by postoperative day 6 compared to patients without a leak (p<0.0001). Elevations of the white blood cell count or temperature were a late finding. CONCLUSION: The earliest clinical predictors of an anastomotic leak are pulmonary and/or neurological. Awareness of these findings might help in early diagnosis and treatment of an anastomotic leak.

Transformation of intestinal epithelial cells by chronic TGF-beta1 treatment results in downregulation of the type II TGF-beta receptor and induction of cyclooxygenase-2.

The precise role of TGF-beta in colorectal carcinogenesis is not clear. The purpose of this study was to determine the phenotypic alterations caused by chronic exposure to TGF-beta in non-transformed intestinal epithelial (RIE-1) cells. Growth of RIE-1 cells was inhibited by >75% following TGF-beta1 treatment for 7 days, after which the cells resumed a normal growth despite the presence of TGF-beta1. These 'TGF-beta-resistant' cells (RIE-Tr) were continuously exposed to TGF-beta for >50 days. Unlike the parental RIE cells, RIE-Tr cells lost contact inhibition, formed foci in culture, grew in soft agarose. RIE-Tr cells demonstrated TGF-beta-dependent invasive potential in an in vitro assay and were resistant to Matrigel and Na-butyrate-induced apoptosis. The RIE-Tr cells were also tumorigenic in nude mice. The transformed phenotype of RIE-Tr cells was associated with a 95% decrease in the level of the type II TGF-beta receptor (TbetaRII) protein, a 40-fold increase in cyclooxygenase-2 (COX-2) protein, and 5.9-fold increase in the production of prostacyclin. Most RIE-Tr subclones that expressed low levels of TbetaRII and high levels of COX-2 were tumorigenic. Those subclones that express abundant TbetaRII and low levels of COX-2 were not tumorigenic in nude mice. A selective COX-2 inhibitor inhibited RIE-Tr cell growth in culture and tumor growth in nude mice. The reduced expression of TbetaRII, increased expression of COX-2, and the ability to form colonies in Matrigel were all reversible upon withdrawal of exogenous TGF-beta1 for the RIE-Tr cells.

Atraumatic hemobilia arising from a cirrhotic liver.

Biliary hemorrhage may occur in a variety of clinical settings, but spontaneous hemobilia has not been reported from a cirrhotic liver. We describe a case of major hepatic hemobilia in a patient with cirrhosis and no history of trauma. A 50-year-old woman had abdominal pain, melena, and profound anemia. An extensive workup did not show the site of bleeding but did show a mass in the gallbladder. Cholecystectomy was performed, and at operation the patient was found to have cirrhosis and portal hypertension. The gallbladder "mass" was simply an organized clot, and hemorrhage recurred postoperatively. On reoperation, bleeding from the ampulla of Vater was observed, confirming the diagnosis of hemobilia. She was treated with angiographic interruption of hepatic arterial flow, at which time bleeding ceased. Her total transfusion requirements included 46 units of blood. Through 16 months of follow-up the patient has had no recurrent bleeding and no evidence of encephalopathy. This case demonstrates that spontaneous hemobilia may indeed arise from a cirrhotic liver. Proximal interruption of arterial flow is usually not recommended for hemobilia, especially in the presence of portal hypertension and cirrhosis, but may be life-saving in selected patients.

Multifactor evaluations of surgical trainees and teaching services.

Surgical education has been exposed to increasing challenges as students have moved from the highly structured environment of a university hospital into a variety of clinical settings within the community. Presented with a general surgical service that uses ten relatively autonomous teaching services in seven hospitals, we have developed a computer-based evaluation system designed to provide quality control and a feed-back loop for trainee, teacher, and service. Trainees were rated by comparing them to their peers, with the chief resident as a reference standard. Profiles of each teaching service also were developed and compared one to the other. The results of both studies over a one year period are presented.

Thrombospondin-1 and transforming growth factor-beta l promote breast tumor cell invasion through up-regulation of the plasminogen/plasmin system.

BACKGROUND: Pericellular proteolysis is crucial in tumor cell invasion. The plasminogen/plasmin system is one of the main protease systems involved in cancer progression. Thrombospondin-1 (TSP-1), through activation of transforming growth factor-beta 1 (TGF-beta 1), up-regulates the main plasminogen activator, the urokinase-type plasminogen activator (uPA). The objectives of this study were to determine the role of TSP-1 and TGF-beta 1 in the localization of the plasminogen/plasmin system to the tumor cell surface by the uPA receptor (uPAR) and to determine its effect in breast tumor cell invasion. METHODS: The effect of TSP-1 and TGF-beta 1 in uPAR expression was determined in MDA-MB-231 human breast cancer cells by enzyme-linked immunosorbent assay and Western blot analysis. Their effect and the role of the plasminogen/plasmin system in breast tumor cell invasion were studied with a Boyden Chamber assay. RESULTS: uPAR expression was up-regulated more than twofold by both TSP-1 and TGF-beta 1. The effect of TSP-1 involved its receptor and the activation of TGF-beta 1 by TSP-1. Breast tumor cell invasion was up-regulated sevenfold to eightfold by both TSP-1 and TGF-beta 1 compared with the control group. Antibodies against uPA or uPAR neutralized the TSP-1- and TGF-beta 1-promoted breast tumor cell invasion. CONCLUSIONS: TSP-1, through the activation of endogenous TGF-beta 1, up-regulates the plasminogen/plasmin system and promotes tumor cell invasion in breast cancer cells.

Transforming growth factor-beta 1 inhibits generation of angiostatin by human pancreatic cancer cells.

BACKGROUND: Angiostatin, a proteolytic fragment of plasminogen, is a potent inhibitor of angiogenesis. We have previously shown that the human pancreatic cancer cell line ASPC-1 produces enzymatic activity capable of generating angiostatin. In this study we sought to determine whether angiostatin production by ASPC-1 cells was regulated by the growth factor transforming growth factor-beta 1 (TGF-beta 1), a key mediator of tumor angiogenesis. METHODS: ASPC-1 cells were grown to 70% to 80% confluence in 20% fetal calf serum-RPMI. Medium was changed to serum free. TGF-beta 1 was added at concentrations of 0, 1, 5, and 10 ng/mL with or without plasminogen activator inhibitor type-1 (PAI-1) at concentrations of 0, 5, 10, 50, and 100 micrograms/mL. Cells were then cultured for an additional 24 hours. The serum-free conditioned medium was obtained. Angiostatin generation was determined by incubating 20 micrograms of plasminogen with 100 microL of serum-free conditioned medium for 0, 1, 2, 3, 6, 12, and 24 hours. Samples were run on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred. The membrane was probed with a monoclonal antibody to the kringle 1-3 fragment of plasminogen and developed using enhanced chemiluminescence. RESULTS: TGF-beta 1 and PAI-1 inhibited the conversion of plasminogen into angiostatin in a time- and dose-dependent manner. Antibody to PAI-1 completely blocks TGF-beta 1 mediated angiostatin inhibition. CONCLUSIONS: TGF-beta 1 inhibits the generation of the antiangiogenic molecule angiostatin by human pancreatic cancer cells in a time- and dose-dependent manner. This effect is mediated through modulation of the plasminogen/plasmin system.

Cyclooxygenase-2 alters transforming growth factor-beta 1 response during intestinal tumorigenesis.

BACKGROUND: Recent investigation suggests that cyclooxygenase-2 plays an important role in colorectal carcinogenesis. Transforming growth factor-beta1 (TGF-beta 1) is one of the most potent stimulators of cyclooxygenase-2 expression. A key step in intestinal tumorigenesis involves alteration of the normal cellular response to TGF-beta 1. We have hypothesized that overexpression of cyclooxygenase-2 alters intestinal epithelial response to TGF-beta 1. METHODS: RIE-1 cells were stably transfected with rat cyclooxygenase-2 complementary DNA in either the sense (RIE-S) or antisense (RIE-AS) orientation. Tumor cell invasion was assessed with a modified Boyden collagen type I invasion assay in the presence of TGF-beta 1, antibody to urokinase plasminogen activator (uPA), or the selective cyclooxygenase-2 inhibitor SC-58125. Expression of uPA, uPA receptor, and plasminogen activator inhibitor-1 were determined by Western blot and enzyme-linked immunosorbent assay. RESULTS: RIE-1 and RIE-AS did not invade although RIE-S cells were minimally invasive at baseline. TGF-beta 1 had no effect on RIE-1 or RIE-AS invasion; however, TGF-beta 1 significantly upregulated RIE-S cell invasion. All 3 RIE cell lines produce minimal uPA under basal conditions. TGF-beta 1 upregulated uPA production only in the RIE-S cells. Both antibody to uPA and SC-58125 reversed TGF-beta-mediated RIE-S cell invasion. SC-58125 inhibited TGF-beta-mediated RIE-S uPA production. CONCLUSIONS: These results demonstrate that overexpression of cyclooxygenase-2 alters intestinal epithelial response to TGF-beta 1, which may be a mechanism by which cyclooxygenase-2 promotes colon carcinogenesis.

Thrombospondin-1 and transforming growth factor beta-1 upregulate plasminogen activator inhibitor type 1 in pancreatic cancer.

Controlled degradation of the extracellular matrix by proteases is crucial in tumor cell invasion. We have shown that thrombospondin-1 (TSP-1), through activation of transforming growth factor beta-1 (TGF-beta1), regulates the plasminogen/plasmin protease system in breast cancer. To determine whether this occurred in other epithelial neoplasms, we studied the role of TSP-1 and TGF-beta1 in the regulation of the plasminogen/plasmin system in pancreatic cancer. ASPC-1 and COLO-357 pancreatic cancer cells were treated with TSP-1 or TGF-beta1 at varying concentrations. The TSP-1 and TGF-beta1-treated cells were also treated with either anti-TSP-1, anti-TSP-1 receptor, or anti-TGF-beta1 antibodies. Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression was determined by enzyme-linked immunosorbent assay. TSP-1 and TGF-beta1 promoted a dose-dependent upregulation of ASPC-1 and COLO-357 PAI-1 expression. The TSP-1 effect could be blocked with anti-TSP-1 or anti-TGF-beta1 antibodies. The TGF-beta1 effect could be blocked only with anti-TGF-beta1 antibody. Anti-TSP-1 receptor antibody blocked the TSP-1 effect on PAI-1 expression but had no effect on TGF-beta1-mediated PAI-1 expression. Neither TSP-1 nor TGF-beta1 had an effect on uPA production. We conclude that TSP-1, in a receptor-mediated process that involves the activation of TGF-beta1, upregulates PAI-1 expression in pancreatic cancer without an effect on uPA production.

Measuring and predicting the performances of practicing physicians: an overview of two decades of research at the University of Utah.

This paper presents the major findings of research carried out by a team of investigators at the University of Utah School of Medicine in the 1960s and 1970s (1) to better understand the multidimensional and complex aspects of practicing physicians' performances, and (2) to investigate relationships between assessments of students in medical school and physicians' performances. The major research began in the 1960s, and data were assembled from a variety of sources to identify factors of physicians' performances. The original study sampled 507 practicing physicians, classified into four highly diverse and representative groups. The team also investigated to what degree these physicians' medical school performances (measured by grades) were predictors of their practice performances. Factor analysis of the data on the physicians' performances resulted in the identification of 25 to 29 factors within each of the four groups. A representative profile of the performances of each physician studied showed how well the physician performed on each of the factors appropriate to his or her specialty and background. Correlation analysis demonstrated that these physicians' performances in medical school, as measured by grade-point averages (GPAs), were almost completely independent of their later performances in their practices, a disturbing finding and one that the team maintained cannot be dismissed by arguments of "restriction of range." In the teams' later studies, 61 measures of physicians' performances were correlated to medical school GPAs in the two basic science years and the two clinical science years. No association beyond chance was observed, and nonsignificant relationships held up regardless of the physicians' specialties or years of experience.(ABSTRACT TRUNCATED AT 250 WORDS)

Preoperative selection of patients for lumbar sympathectomy by use of the Doppler index.

Yao and Bergan [8] have shown that an ankle systolic index of more than 0.25 is associated with a high rate of success from lumbar sympathectomy. This association has been borne out in our small series. We have also suggested that diseases that obviously compromise collateral circulation might be a relative contraindication to sympathectomy. Although incomplete, literature on collateral flow in relation to sympathectomy tends to confirm this idea. Consideration of such diseases as a contraindication to sympathectomy might further increase the success rate after sympathectomy. Regardless, ankle systolic index alone appears to be a reliable objective, non-invasive method of selecting patients with an increased chance of success from lumbar sympathectomy.

Spontaneous hepatic rupture in pregnancy.

Hepatic rupture as a late complication of toxemic pregnancy is a rare yet lethal condition requiring rapid recognition and surgical management. The clinical triad of toxemia, right upper quadrant pain, and sudden hypotension is the diagnostic hallmark of presentation. Most patients present near the time of delivery and are found to have subcapsular hematomas of the right hepatic lobe with free rupture into the peritoneal cavity and resultant exsanguinating hemorrhage. The association of toxemia and disseminated intravascular coagulation with secondary microembolic damage to the liver and other organs has been discussed. Basic surgical principles in the managment of hepatic subcapsular hematomas, and the prolonged postoperative course and frequent complications in these patients have been stressed.

Computer-assisted image analysis of tumor sections for a new thrombospondin receptor.

BACKGROUND: A cell surface receptor (50 kd) has been recently identified in malignant cells that recognizes the tumor cell adhesive domain (ie, cysteine-serine-valine-threonine-cysteine-glycine [CSVTCG]) of thrombospondin (TSP). This CSVTCG-specific TSP receptor can be considered as a new tumor marker, and its concentration on the cell surface may correlate directly with the capacity of tumor cells to invade and metastasize. MATERIALS AND METHODS: Six patients with primary, stages III and IV squamous cell carcinomas of the head and neck were studied. Tumor sections were specifically stained for this receptor with immunohistochemical techniques. The stained specimens were then subjected to computer-assisted image analysis. The area of positive staining and the heterogeneity of the pattern of staining were compared to peritumoral angiogenesis and clinical outcome of the patients. RESULTS: The results indicate that those patients with a high and homogenous positive stain score (mean +/- standard error [SE] 78 +/- 5%) for the CSVTCG-specific TSP receptor had high microvessel density and died from metastatic disease within 12 months of initial treatment (correlation coefficients = 0.95 and 1, respectively). Patients with a low and heterogenous positive stain score for receptor (mean +/- SE 8 +/- 2%; P < 0.001) had low microvessel counts and remained disease-free for at least 2 years. There was no relationship between receptor density and histologic classification of the primary tumors. CONCLUSION: The CSVTCG-specific TSP receptor, quantified through image analysis of immunohistochemical stained tissue sections, is highly predictive of clinical outcome in patients with squamous cell carcinomas of the head and neck.

Anaphylactic reactions to isosulfan blue dye during sentinel lymph node biopsy for breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an alternative to axillary dissection for many breast cancer patients. Cases of anaphylactic reaction to the isosulfan blue dye used during SLNB have recently been reported. No study on the incidence of serious anaphylactic reactions during SLNB for breast cancer has been reported. METHODS: We reviewed 639 consecutive SLNBs for breast cancer performed at our institution. Sentinel lymph node biopsy was performed using both isosulfan blue dye and technetium-99m sulfur colloid. Cases of anaphylaxis were reviewed in detail. RESULTS: Overall, 1.1% of patients had severe anaphylactic reactions to isosulfan blue requiring vigorous resuscitation. No deaths or permanent disability occurred. In patients with anaphylaxis, hospital stay was prolonged by a mean of 1.6 days. In 1 patient, the anaphylactic reaction required termination of the operation. CONCLUSIONS: Prompt recognition and aggressive treatment of anaphylactic reactions to isosulfan blue are critical to prevent an adverse outcome. Lymphatic mapping with blue dye should be performed in a setting where personnel are trained to recognize and treat anaphylaxis.

Embolic and occlusive complications from thrombosed femorofemoral grafts.

Five episodes of acute arterial occlusions associated with thrombosed femorofemoral grafts are reported. Four of these occlusions were directly associated with trauma to the graft and were thought to be embolic. All patients had thrombus extending from the thrombosed graft into the femoral artery, threatening the survival of the lower extremity. We recommend that when a graft thrombectomy is not performed, or is not successful, the thrombosed femorofemoral graft should be detached or excised as prophylaxis against embolic and occlusive complications.