Is interval appendectomy indicated after non-operative management of acute appendicitis in patients with cancer? A retrospective review from a single institution.

Interval appendectomy (IA) is a controversial subject, with little consensus on its use in patients undergoing treatment for malignancy. We sought to determine the frequency of recurrent appendicitis in cancer patients managed nonoperatively (NOM) during index hospitalization (IHA) for acute appendicitis (AA). Clinical presentation, cancer treatment, and follow-up were collected from electronic medical records of patients with CT scan-confirmed AA treated at a single institution between August 1999 and August 2009. Seventy-two of 109 AA patients underwent appendectomy during IHA; 34 of these 109 were NOM during IHA. Median index length of NOM patients' stay was six days (0-55), median age was 59 (18-80) years. Indications for NOM were presence of abscess or phlegmon (14), mild symptoms (13), high surgical risk (3), end-stage cancer (3), and patient declining surgery (1). Eight NOM patients underwent percutaneous drainage of abdominal abscess (median total duration of intravenous + oral antibiotics = 12 days [0-55]). There were six deaths (1 IHA, 5 NOM): four sepsis and two cancer progression. At a median of 19-month follow-up (range 1-103), four NOM patients surviving IHA had recurrent AA (11.7%) at two (n = 2) and three months (n = 2) after the first episode. Overall, six had IA (17.6%) one to seven months post AA; 25 remained asymptomatic, without IA. In conclusion, among NOM patients at a cancer center at IHA for AA, recurrent AA was early (<4 months) but uncommon. IA should be offered to those with recurrent symptoms, but appears to have a very limited role after several months of asymptomatic follow-up.

Lymph node yield after colectomy for cancer: is absence of mismatch repair a factor?

BACKGROUND: Nodal staging is crucial in determining the use of adjuvant chemotherapy for colon cancer. The number of metastatic lymph nodes has been positively correlated with the number of lymph nodes examined. Current guidelines recommend that at minimum 12 to 14 lymph nodes be assessed. In some studies, mismatch repair deficiency has been associated with lymph node yield. OBJECTIVE: The purpose of this work was to determine whether mismatch repair-deficient colorectal tumors are associated with increased lymph node yield. DESIGN: We queried an institutional database to analyze colectomy specimens with immunohistochemistry for mismatch repair genes in patients treated for colorectal cancer between 1999 and 2012. Before 2006, immunohistochemistry was performed at the request of an oncologist or surgeon. After 2006, it was routinely performed for patients <50 years of age. We measured the association of clinical and pathologic features with lymph node quantity. Fourteen predictors and confounders were jointly analyzed in a multivariable linear regression model. SETTINGS: The study was conducted at a single tertiary care institution. PATIENTS: Tissue specimens from 256 patients were reviewed. MAIN OUTCOME MEASURES: The correlation of tumor, patient, and operative variables to the yield of mesenteric lymph nodes was measured. RESULTS: Of 256 colectomy specimens reviewed, 94 had mismatch repair deficiency. On univariate analysis, mismatch repair deficiency was associated with lower lymph node yield, older patient age, right-sided tumors, and poor differentiation. The linear regression model identified 5 variables with independent relationships to lymph node yield, including patient age, specimen length, lymph node ratio, perineural invasion, and tumor size. A positive correlation was observed with tumor size, specimen length, and perineural invasion. Tumor location had a more complex, nonlinear, quadratic relationship with lymph node yield; proximal tumors were associated with a higher yield than more distal lesions. Mismatch repair deficiency was not independently associated with lymph node yield. LIMITATIONS: Mismatch repair immunohistochemistry based on patient age, family history, and pathologic features may reduce the generalizability of these results. Our sample size was too small to identify variables with small measures of effect. The retrospective nature of the study did not permit a true assessment of the extent of mesenteric resection. CONCLUSIONS: Patient age, length of bowel resected, lymph node ratio, perineural invasion, tumor size, and tumor location were significant predictors of lymph node yield. However, when controlling for surgical and pathologic factors, mismatch repair protein expression did not predict lymph node yield.

Surgical skills assessment of applicants to general surgery residency.

BACKGROUND: Manual skill proficiency is not currently employed in selecting residents for general surgery training programs. The study objective was to assess whether the technical skill levels of applicants to a general surgery residency program are higher than those of internal medicine residents. MATERIAL AND METHODS: Forty-two applicants to a community general surgery program underwent manual skill testing on interview day. Four laparoscopic tasks on a virtual reality (VR) simulator (LapSim, Goteborg, Sweden) were tested. Performance scores were computer-generated. Participants' previous experience with other manual dexterity activities was assessed via a questionnaire. Applicants' self-perception of their surgical skills was correlated with their skill dexterity scores on the simulator. Candidates' simulator scores were also compared with those of a group of internal medicine interns (n = 9) and a group of mid-level surgical residents, PGY 2-3 (n = 7). RESULTS: Simulator scores of the applicants were significantly lower than those of mid-level surgical residents in all VR tasks (P < 0.05). The internal medicine interns scored higher that the surgery candidates in three of four simulator tasks. Participation in other manual dexterity activities was not associated with increased dexterity scores. CONCLUSION: This study suggests that surgical dexterity levels do not correlate with the self-assessed skill levels or with previous experience with other manual dexterity activities. Moreover, there appears to be no self-selection of applicants for surgery residency based on actual surgical skills. Selection criteria for surgical training, which incorporate technical proficiency skills, may potentially better discriminate those applicants with an aptitude for a surgical specialty.

Eph-B4 prevents venous adaptive remodeling in the adult arterial environment.

Eph-B4 determines mammalian venous differentiation in the embryo but is thought to be a quiescent marker of adult veins. We have previously shown that surgical transposition of a vein into the arterial environment is characterized by loss of venous identity, as indicated by the loss of Eph-B4, and intimal thickening. We used a mouse model of vein graft implantation to test the hypothesis that Eph-B4 is a critical determinant of venous wall thickness during postsurgical adaptation to the arterial environment. We show that stimulation of Eph-B4 signaling, either via ligand stimulation or expression of a constitutively active Eph-B4, inhibits venous wall thickening and preserves venous identity; conversely, reduction of Eph-B4 signaling is associated with increased venous wall thickness. Stimulated Eph-B4 associates with caveolin-1 (Cav-1); loss of Cav-1 or Eph-B4 kinase function abolishes inhibition of vein graft thickening. These results show that Eph-B4 is active in adult veins and regulates venous remodeling. Eph-B4-Cav-1-mediated vessel remodeling may be a venous-specific adaptive mechanism. Controlled stimulation of embryonic signaling pathways such as Eph-B4 may be a novel strategy to manipulate venous wall remodeling in adults.

Elevated monocytes in patients with critical limb ischemia diminish after bypass surgery.

BACKGROUND: Mononuclear cells (MNC) increase neovascularization and ulcer healing after injection into an ischemic extremity. Circulating MNC are composed of lymphocytes (85%), monocytes (15%), and endothelial progenitor cells (EPC; 0.03%). We hypothesized that ischemic limbs secrete paracrine signals to recruit bone marrow-derived monocytes and EPC into the circulation, such that patients with critical limb ischemia (CLI) have increased circulating monocytes compared with control patients. We also hypothesized that circulating monocytes and EPC recruitment decrease after resolution of ischemia with successful revascularization. METHODS: We reviewed the records of all patients at the VA Connecticut Healthcare System undergoing primary, functionally successful, lower extremity peripheral bypass surgery between 2002 and 2007, but only including patients with both preoperative and postoperative (>4 mo) complete blood counts with differentials. RESULTS: Patients with CLI (n = 24) had elevated preoperative monocyte counts compared with control patients (n = 8) (0.753 ± 0.04 versus 0.516 ± 0.05; P = 0.0046), whereas the preoperative lymphocyte counts were not significantly different. After revascularization, ischemic patients had decreased monocyte counts compared with control patients (-20% versus + 55%; P = 0.0003), although lymphocyte counts were unchanged in both groups. Diabetic patients also had reduced postoperative monocyte counts (-32% versus + 13%; P = 0.035). Multivariable logistic regression demonstrated that the only factor that independently predicted reduced postoperative monocyte count was preoperative CLI (P = 0.038). CONCLUSIONS: Patients with CLI have increased numbers of circulating monocytes, and the monocyte number decreases with resolution of ischemia after successful revascularization. Circulating monocytes may be a clinically useful perioperative marker in patients with CLI undergoing vascular surgery.

Is gender related to the stage of colorectal cancer at initial presentation in young patients?

BACKGROUND: The incidence of colorectal cancer (CRC) in young adults is rising, and young age is a predictor of poor survival. The purpose of this study was to examine factors leading to increased mortality in patients ≤ 50 years of age, and to examine this population for characteristics that could lead to benefit from CRC screening. METHODS: Charts of patients 50 years of age and under, diagnosed with CRC from 1998 through 2007, at our community teaching hospital, were reviewed retrospectively. Demographics, social and family history, staging, treatment and death were evaluated. Mann Whitney, Fisher Exact, and χ(2) tests were used with P <0.05 considered statistically significant. RESULTS: Forty-five young patients with CRC were identified. Twenty-five patients were female and 20 male; the mean age was 43.6 y. Most patients presented with rectal bleeding. Right-sided cancers had a higher presenting stage (P < 0.05). Men had both a higher presenting stage (P = 0.35) and a higher incidence of smoking compared with women (P = 0.001). Female patients were more likely to have left-sided CRC (65%) compared with men (35%). Ninety-six percent of patients underwent surgical resection; 14 patients died. CONCLUSIONS: CRC in young adults is not common, but is often advanced when discovered. Diagnostic efforts should be aggressive in young patients who have rectal bleeding, especially young male smokers. Sigmoidoscopy is not adequate for comprehensive diagnosis of CRC in young patients, as the majority have right-sided colon cancers, which often result in subsequent presentation of the disease at a higher stage, risk, and mortality rate.

Cervical spine injuries; an outcome analysis.

Cervical spine injury (CSI) in octogenarians continues to carry a high morbidity and mortality rate. The incidence of CSI among individuals who are below the age of 80 is declining, whereas the incidence of CSI for those 80 years and above is rising.The aim of the study was to evaluate outcomes of cervical spine injuries in octogenarians caused by different mechanisms: motor vehicle accidents, compared to a fall.Material and methods. The National Trauma Data Bank (NTDB) was queried for patients ages 80 and above, who sustained a cervical spine injury via motor vehicle collision and falls. Patient demographics, mechanism of injury, Glasgow Coma Score (GCS), injury severity score (ISS), days in Intensive Care Unit, Temperature on arrival, blood pressure on arrival, CT Scan of head results, complications, sex, and mortality.Results. Three-thousand three hundred seventy-five patients, 80 years of age and older with CSI were included in the study; fifteen percent of these octogenarians with cervical spine injuries died. It was observed that patients in the motor vehicle accident (MVA) group have 1.737 (95% CI 1.407, 2.144 p-value < 0.0001) times the odds of dying, compared to those in the fall group. Patients over the age of 80 who were in a MVA have 1.209 (95% CI 0.941, 1.554 p-value = 0.1372) times the odds of having a positive head CT, compared with people over the age of 80 who experienced a fall. Patients involved in a motor vehicle accident with associated CSI were more likely to be a younger age, have a lower GCS on arrival, have a longer length of stay in the Intensive Care Unit, and a higher ISS (p<0.05).Conclusions. Cervical spine injury in octogenarians carries a high mortality regardless of mechanism. Elderly patients who suffer cervical spine injuries in motor vehicle accidents have a lower SBP, a higher ISS and are nearly twice as likely to die as those who were injured in a fall.

Papillary adenocarcinoma of the urachus presenting as an umbilical mass.

A 53-year-old Caucasian female presented with an erythematous, tender, fluctuant mass in the periumbilical region. A computerized tomography scan of the abdomen and pelvis suggested a large tumor extending from the umbilicus to the dome of the bladder with elements of tissue within the bladder consistent with a malignancy of either bladder or urachal origin. The patient subsequently underwent a cystoscopic biopsy which was positive for papillary adenocarcinoma arising in a villous adenoma. Metastatic workup revealed multiple hepatic and bilateral pulmonarynodules. Palliative laparotomywithlysis of adhesions, smallbowel resection, partial cystectomy, omentectomy, abdominal wall and umbilical resection were performed.

Surgically implantable magnetic resonance angiography coils improve resolution to allow visualization of blood flow dynamics.

BACKGROUND: Magnetic resonance angiography (MRA) is clinically useful but of limited applicability to small animal models due to poor signal resolution, with typical voxel sizes of 1 mm(3) that are insufficient to analyze vessels of diameter <1 mm. We determined whether surgically implantable, extravascular MRA coils increase signal resolution adequately to examine blood flow dynamics METHODS: A custom MRA coil was surgically implanted near the carotid artery of a New Zealand White rabbit. A stenosis was created in the carotid artery to induce complicated, non-laminar flow. Phase contrast images were obtained on multiple axial planes with 3T MRA and through-plane velocity profiles were calculated under laminar and complicated flow conditions. These velocity profiles were fit to a laminar flow model using ordinary least squares in order to quantify the degree of flow complication (Matlab). Flow was also measured with a Doppler flow probe; vessel diameters and flow velocities were compared with duplex ultrasound RESULTS: Carotid artery blood flow was 24.7 +/- 2.6 ml/min prior to stenosis creation and reduced to 12.0 +/- 1.7 ml/min following injury (n=3). An MRA voxel size of 0.1 x 0.1 x 5 mm was achieved. The control carotid artery diameter was 1.9 +/- 0.1 mm, and cross-sectional images containing 318 +/- 22 voxels were acquired (n=26). Velocity profiles resembled laminar flow proximal to the stenosis, and then became more complicated just proximal and distal to the stenosis. Laminar flow conditions returned downstream of the stenosis CONCLUSION: Implantable, extra-vascular coils enable small MRA voxel sizes to reproducibly calculate complex velocity profiles under both laminar and complicated flow in a small animal model. This technique may be applied to study blood flow dynamics of vessel remodeling and atherogenesis.

A woman's influence to choose mastectomy as treatment for breast cancer.

INTRODUCTION: Over a 10-y period at our community hospital, more than 50% of women 40 y of age and younger underwent a mastectomy as first line breast cancer treatment. These results catapulted a study to identify personal and physical implications of a mastectomy and to determine if, in women of all ages, breast conservation therapy with close follow-up is a better alternative to mastectomy. METHODS: Six hundred eight women underwent a mastectomy for breast cancer from 1989 to 2005 at our teaching institution; 77% (n = 120) of 156 successfully contacted women agreed to participate in the study, and 70% (n = 84) of them completed a questionnaire. RESULTS: Most women discovered their breast cancer through mammography or self breast examination, 31% and 28%, respectively. Five patients were diagnosed at Stage 0, 35 at Stage 1, 26 at Stage 2, 8 at Stage 3, 1 at Stage 4, and 9 patients had an unknown stage of disease. Sixty-three patients primarily discussed their treatment plan with a surgeon; 80 were satisfied with the time spent discussing their treatment. Twenty-four patients underwent various reconstruction procedures; most (75%) were satisfied with their treatment and reconstruction choices. CONCLUSIONS: Mastectomy as a treatment choice for breast cancer did not have the negative personal and physical outcome that we had predicted. Personal choice and a surgeon's advice were the primary influencing factors on the women's treatment choice of mastectomy. Adequate preoperative discussion time and a multimodality cancer team can be most helpful in providing comprehensive treatment options for all women with breast cancer.

Limb ischemia after iliac ligation in aged mice stimulates angiogenesis without arteriogenesis.

OBJECTIVE: Older patients are thought to tolerate acute ischemia more poorly than younger patients. Since aging may depress both angiogenesis and arteriogenesis, we determined the effects of age on both angiogenesis and arteriogenesis in a model of severe acute limb ischemia. METHODS: Young adult (3-months-old) and aged (18-months-old) C57BL/6 mice underwent right common iliac artery and vein ligation and transection. Data were collected on days 0, 7, and 14. Perfusion was measured with a laser Doppler scan and compared to the contralateral limb. Functional deficits were evaluated with the Tarlov scale. Capillary density and endothelial progenitor cell (EPC) number were determined by direct counting lectin-positive/alpha-actin-negative cells and VEGFR2/CXCR4 dually-positive cells, respectively; angiography was performed to directly assess arteriogenesis. RESULTS: Young adult and aged mice had a similar degree of decreased perfusion after iliac ligation (young, n = 15: 20.4 +/- 1.9%, vs aged, n = 20: 19.6 +/- 1.3%; P = .72, analysis of variance [ANOVA]); however, young mice recovered faster and to a greater degree than aged mice (day 7, 35 +/- 6% vs 17 +/- 4%, P = .046; day 14, 60 +/- 5% vs 27 +/- 7%, P = .0014). Aged mice had worse functional recovery by day 14 compared to young mice (2.3 +/- 0.3 vs 4.3 +/- 0.4; P = .0021). Aged mice had increased capillary density (day 7, 12.9 +/- 4.4 vs 2.8 +/- 0.3 capillaries/hpf; P = .02) and increased number of EPC incorporated into the ischemic muscle (day 7, 8.1 +/- 0.9 vs 2.5 +/- 1.9 cells; P = .007) compared to young mice, but diminished numbers of collateral vessels to the ischemic limb (1 vs 9; P = .01), as seen on angiography. CONCLUSION: After severe hind limb ischemia, aged animals become ischemic to a similar degree as young animals, but aged animals have significantly impaired arteriogenesis and functional recovery compared to younger animals. These results suggest that strategies to stimulate arteriogenesis may complement those that increase angiogenesis, and may result in improved relief of ischemia.

Laminar shear stress stimulates vascular smooth muscle cell apoptosis via the Akt pathway.

Vascular smooth muscle cells (SMC) may be directly exposed to blood flow after an endothelial-denuding injury. It is not known whether direct exposure of SMC to shear stress reduces SMC turnover and contributes to the low rate of restenosis after most vascular interventions. This study examines if laminar shear stress inhibits SMC proliferation or stimulates apoptosis. Bovine aortic SMC were exposed to arterial magnitudes of laminar shear stress (11 dynes/cm(2)) for up to 24 h and compared to control SMC (0 dynes/cm(2)). SMC density was assessed by cell counting, DNA synthesis by (3)[H]-thymidine incorporation, and apoptosis by TUNEL staining. Akt, caspase, bax, and bcl-2 phosphorylation were assessed by Western blotting; caspase activity was also measured with an in vitro assay. Analysis of variance was used to compare groups. SMC exposed to laminar shear stress had a 38% decrease in cell number (n = 4, P = 0.03), 54% reduction in (3)[H]-thymidine incorporation (n = 3, P = 0.003), and 15-fold increase in TUNEL staining (n = 4, P < 0.0001). Akt phosphorylation was reduced by 67% (n = 3, P < 0.0001), whereas bax/bcl-2 phosphorylation was increased by 1.8-fold (n = 3, P = 0.01). Caspase-3 activity was increased threefold (n = 5, P = 0.03). Pretreatment of cells with ZVAD-fmk or wortmannin resulted in 42% increased cell retention (n = 3, P < 0.01) and a fourfold increase in apoptosis (n = 3, P < 0.04), respectively. Cells transduced with constitutively-active Akt had twofold decreased apoptosis (n = 3, P < 0.002). SMC exposed to laminar shear stress have decreased proliferation and increased apoptosis, mediated by the Akt pathway. These results suggest that augmentation of SMC apoptosis may be an alternative strategy to inhibit restenosis after vascular injury.

Hybrid verrucous-squamous cell carcinoma of the ovary with synchronous squamous cell carcinoma of the endometrium.

Verrucous carcinoma, a variant of well-differentiated squamous cell carcinoma, is usually described in the literature as arising in the oral cavity, skin, and larynx. The reports on verrucous carcinoma arising in the genital tract, usually originating in the vagina, vulva, or uterine cervix, are few. Verrucous carcinoma arising in the ovary has not been previously reported. In this article, a unique hybrid carcinoma, a large aggressive verrucous carcinoma in combination with squamous carcinoma of the left ovary and synchronously occurring with a squamous cell carcinoma in the endometrium, is presented. This unique case of a hybrid carcinoma includes the first-known case of this type of carcinoma involving the ovary. The negative cervical evaluation findings, together with the histologic patterns of the tumors in the uterus and the ovary, support the conclusion that these 2 carcinomas are synchronous, one arising in the left ovary and the other arising in the uterus.

Endothelial nitric oxide synthase stimulates aneurysm growth in aged mice.

BACKGROUND/AIMS: Age-associated changes in endothelial nitric oxide synthase (eNOS) expression have not been definitively linked to the pathophysiology of aortic aneurysms. We examined the role of eNOS in human patients and an age-appropriate mouse model. METHODS: eNOS transcripts and immunodetectable protein were assessed by quantitative PCR and immunohistochemistry in human ascending thoracic aneurysms (n = 29) and referent aortae (n = 31). Carotid aneurysms were induced with CaCl2 in young adult (3 months) and aged (18 months) C57BL/6 and eNOS-knockout (eNOS-KO) mice. RESULTS: eNOS transcripts and protein were reduced in human aneurysms compared with controls, although aortic eNOS expression also decreased with patient age. Aged wild-type mice had significantly larger aneurysm diameter than young adult mice. Aged wild-type mice had reduced eNOS transcripts and protein compared with young adult mice. Aged eNOS-KO mice had smaller aneurysms compared with aged wild-type mice but similar size aneurysms compared with young eNOS-KO and young wild-type mice. CONCLUSION: eNOS expression is reduced in both aged human and aged mouse endothelium and eNOS expression is linked to aneurysm expansion in aged but not young adult mice. These findings support the relevance of age-associated changes in eNOS expression in clinical aneurysmal disease.

Control of blood vessel identity: from embryo to adult.

Arteries and veins have been historically defined by the direction of blood flow and oxygen tension within the vessel, in addition to their functional, hemodynamic, and anatomical differences. It is now known that the molecular identity of these vessels is genetically predetermined, with specific molecular pathways activated during the development of arteries and veins. Eph-B4 is a determinant of venous differentiation and Ephrin-B2 is a determinant of arterial differentiation. Placement of a vein into the higher pressure and flow of the arterial circulation results in adaptation of the vein to the arterial environment. There is selective loss of Eph-B4 expression without induction of Ephrin-B2 expression during vein graft adaptation. These findings suggest that loss of venous identity is the crucial mechanism in vein graft adaptation and that developmentally critical determinants of vessel identity are plastic during adult life.

Endothelial progenitor cells: a primer for vascular surgeons.

Endothelial progenitor cells (EPCs) participate in vascular healing during both acute injury and chronic disease. The quantity and quality of circulating EPCs correlate inversely with the severity of vascular disease, such that reduced number and/or function of EPCs are significant independent risk factors for impaired healing capacity, dysfunctional endothelium, and progression of atherosclerosis and vascular disease. EPC therapy assists healing of cardiac and limb ischemia and has great potential for improving the quality of life and longevity of patients with severe cardiovascular and peripheral vascular disease who are not candidates for conventional revascularization procedures. In addition, EPCs can be used to promote vascular graft patency. This review focuses on the characterization of EPCs, positive and negative regulators of EPCs, the role of EPCs in vascular disease, and the potential for EPC therapy to ameliorate the sequelae of severe peripheral vascular disease.