A Novel Cause of Bowel Obstruction in a Patient with Long-Standing Crohn's Disease.

Solitary fibrous tumors are rare tumors of mesenchymal origin. Although most often observed in the lung pleura, they have been reported in varied extrapleural sites. A 70-year-old male with complicated Crohn's disease presented with 3 days of nausea, emesis, constipation, and abdominal pain. Computed Tomography (CT) demonstrated mucosal thickening of the middescending colon, consistent with fibrosing stricture. Surgical excision revealed an unusual, 5 cm mass originating in the subserosa. Histopathology of the lesion was notable for a proliferation of cells with spindle and stellate-shaped nuclei and no appreciable mitotic figures, which extended into the muscularis and submucosa. Immunohistochemistry was STAT6 nuclear positive and cytoplasmic CD34 positive, diagnostic for solitary fibrous tumor (SFT). In this case, the SFT infiltrating into the muscularis propria and subserosa caused the stricture and bowel obstruction. This illustrates that while fibrosing strictures are usually the etiology of bowel obstruction in the setting of Crohn's disease, other rare possible causes should be considered.

Randomized clinical trial of accelerated enhanced recovery after minimally invasive colorectal cancer surgery (RecoverMI trial).

BACKGROUND: Minimally invasive surgery (MIS) and enhanced recovery protocols (ERPs) have improved postoperative recovery and shortened length of hospital stay (LOS). Telemedicine technology has potential to improve outcomes and patient experience further. This study was designed to determine whether the combination of MIS, ERP and a structured telemedicine programme (TeleRecovery) could shorten total 30-day LOS by 50 per cent. METHODS: This was a phase II prospective RCT at a large academic medical centre. Eligible patients aged 18-80 years undergoing minimally invasive colorectal resection using an ERP were randomized after surgery. The experimental arm (RecoverMI) included accelerated discharge on postoperative day (POD) 1 with or without evidence of bowel function and a televideoconference on POD 2. The control arm was standard postoperative care. The primary endpoint was total 30-day LOS (postoperative stay plus readmission/emergency department/observation days). Secondary endpoints included patient-reported outcomes measured by EQ-5D-5L™, Brief Pain Inventory (BPI) and a satisfaction questionnaire. RESULTS: Thirty patients were randomized after robotic (21 patients) or laparoscopic (9) colectomy, including 14 patients in the RecoverMI arm. Median 30-day total LOS was 28·3 (i.q.r. 23·7-43·6) h in the RecoverMI arm and 51·5 (43·8-67·0) h in the control arm (P = 0·041). There were no differences in severe adverse events or EQ-5D-5L™ score between the study arms. The BPI revealed low pain scores regardless of treatment arm. Satisfaction was high in both arms. CONCLUSION: In patients having surgery for colorectal neoplasms, the trimodal combination of MIS, ERP and TeleRecovery can reduce 30-day LOS while preserving patients' quality of life and satisfaction. Registration number: NCT02613728 ( https://clinicaltrials.gov).

ANTECEDENTES: La cirugía mínimamente invasiva (minimally invasive surgery, MIS) y los protocolos de recuperación intensificada (enhanced recovery protocols, ERP) han mejorado la recuperación postoperatoria y acortan la duración de la estancia (length of stay, LOS). La tecnología de la telemedicina tiene potencial para mejorar aún más los resultados y la experiencia del paciente. Este estudio se diseñó para determinar si la combinación de MIS, ERP y un programa estructurado de telemedicina (TeleRecovery) podría acortar la LOS total a los 30 días en un 50%. MÉTODOS: Se efectuó un ensayo controlado aleatorizado, prospectivo, de fase II en un gran centro médico académico. Los pacientes elegibles de 18-80 años de edad que se sometieron a resección colorrectal MIS mediante ERP se asignaron al azar después de la resección quirúrgica. El brazo experimental (RecoverMI) incluyó el alta acelerada en el día 1 del postoperatorio (postoperative day, POD) con o sin evidencia de recuperación del tránsito intestinal y una televideoconferencia en el día 2 POD. Los pacientes en el grupo control recibieron los cuidados postoperatorios habituales. El criterio de valoración principal fue la LOS total (estancia postoperatoria más reingreso/estancia en urgencias/días de observación) a los 30 días. Los criterios de valoración secundarios incluyeron los resultados referidos por los pacientes medidos por los cuestionarios EQ-5D-5L, el Cuestionario Breve del Dolor (Brief Pain Inventory, BPI) y un cuestionario de satisfacción. RESULTADOS: Treinta pacientes fueron aleatorizados después de una colectomía robótica (21) o laparoscópica (9), incluidos 14 pacientes en el grupo de RecoverMI. La mediana de la LOS total a los 30 días fue de 28,3 horas (rango intercuartílico, RIQ 23,7-43,6) en el grupo de RecoverMI y de 51,5 horas (RIQ 43,8-67,0) en el grupo control (P = 0,04). No hubo diferencias entre los grupos de estudio en los eventos adversos graves o en las puntuaciones del EQ-5D-5L. El BPI mostró puntuaciones bajas de dolor independientemente del grupo de tratamiento. La satisfacción fue alta en ambos grupos. CONCLUSIÓN: Entre los pacientes que se someten a cirugía por cáncer colorrectal, la combinación trimodal de MIS, ERP y TeleRecovery puede reducir la LOS a los 30 días, preservando la calidad de vida y la satisfacción del paciente.

Superior Mesenteric Vein-First Approach to Robotic Complete Mesocolic Excision for Right Colectomy: Technique and Preliminary Outcomes.

INTRODUCTION: There is growing evidence supporting complete mesocolic excision as the optimal surgical approach for right-sided colon cancer to improve oncologic outcomes in comparison with conventional surgical resection. Although the feasibility of a minimally invasive approach to complete mesocolic excision has been reported, obesity has been associated with increased difficulty for finding the correct plane for dissection and delineating the vascular anatomy. We describe a novel approach with early identification of and dissection along the superior mesenteric vein during robotic complete mesocolic excision surgery, for all patients, regardless of BMI. TECHNIQUE: The dissection is initiated with identification of the superior mesenteric vein as the starting point. Then, the vascular dissection is performed along the anterior superior mesenteric vein plane while observing complete mesocolic excision principles. The anterior superior mesenteric vein plane is an optimal and safe dissection plane because there are no anterior tributaries. The ileocolic vein and artery are ligated separately at their junction with the superior mesenteric vein and superior mesenteric artery. The dissection is then continued cephalad along the superior mesenteric vein, identifying additional colic arteries, including the middle colic arterial trunk as well as the venous tributaries to the superior mesenteric vein such as the gastrocolic trunk. The superior right colic vein is then ligated at the gastrocolic confluence and the middle colic vessels are ligated. After the vascular dissection is completed, the colon is then mobilized. RESULTS: A total of 66 patients received the "superior mesenteric vein-first" approach for robotic colectomy between 2013 and 2018, including 40.9% patients with BMI >30 kg/m. Median lymph node yield was 32 (interquartile range, 25-40). The median distance to the high vascular tie was 12 cm (interquartile range, 7-19). Median estimated blood loss was 33 mL (interquartile range, 25-50). Overall rate of grade ≥3 complications was 3.0%. CONCLUSIONS: Using the superior mesenteric vein-first approach, robotic complete mesocolic excision for right colectomy can be performed on patients with high or low BMI with excellent short-term oncologic outcomes and acceptable morbidity. See Video Abstract at http://links.lww.com/DCR/A960.

Perioperative Considerations in Crohn Disease and Ulcerative Colitis.

The management of inflammatory bowel disease (IBD) is medically and surgically complex. Numerous patient- and disease-oriented factors must be considered in treating patients with IBD, including nutritional replenishment/support, effect of immunosuppressive medications, extent of resection, and use of proximal diversion. Perioperative planning and optimization of the patient is imperative to ensuring favorable outcomes and limiting morbidity. These perioperative considerations in Crohn disease and ulcerative colitis are reviewed here.

Retrograde jejunogastric intussusception due to suture concretion.

We describe a patient who presented with acute small bowel obstruction five years after Roux-en-Y reconstruction. Computed tomography and operative exploration showed a retrograde intussusception at the gastrojejunostomy due to an intraluminal suture concretion. We describe the preoperative imaging, endoscopic and intraoperative findings, and review the literature.

In vivo progression of LAPC-9 and LNCaP prostate cancer models to androgen independence is associated with increased expression of insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR).

Androgen deprivation therapies for metastatic prostate cancer are useful initially, but progression to androgen independence usually results in relapse within 2 years. The molecular mechanisms underlying the clinically important transition from androgen dependence to androgen independence are poorly described. Several lines of investigation have suggested that insulin-like growth factors (IGFs) are involved in the biology of prostate cancer, but little is known about their relevance to progression to androgen independence. We used three in vivo models of androgen-dependent (AD) human prostate cancer to study this issue. Progression to androgen-independent (AI) growth was associated with a 60-fold increase in expression of IGF-I mRNA in LAPC-9 xenografts and a 28-fold increase in IGF-I expression in LNCAP xenografts, relative to the initial AD neoplasms. IGF type I receptor (IGF-IR) mRNA levels were approximately 2.5-fold and approximately 5-fold higher, respectively, in AI LAPC-9 and LNCaP tumors compared with the original AD neoplasms. AI growth of these xenografts was also associated with significant reductions in IGF binding protein-3 expression. LAPC-4 xenografts, which previously have been shown to exhibit molecular pathology related to HER-2/neu expression with progression to AI, showed relatively minor changes in expression of the genes investigated, but we nevertheless found evidence of increased IGF-IR phosphorylation with progression to androgen independence in this model. Taken together with prior observations, our results suggest that deregulation of expression of genes related to any one of several critical receptor tyrosine kinase regulatory systems, including IGF signaling, may confer androgen independence.

Bicalutamide (Casodex)-induced prostate regression involves increased expression of genes encoding insulin-like growth factor binding proteins.

OBJECTIVES: To examine the effects of bicalutamide (Casodex), a pure antiandrogen with high specificity for the androgen receptor, on insulin-like growth factor binding protein (IGFBP) expression and apoptotic regression of the rat ventral prostate. METHODS: Rats were treated daily with 10 mg/kg body weight bicalutamide or vehicle alone. Ventral prostates were collected at various days of treatment. Northern blot analysis was performed to quantitate expression of genes encoding IGFBPs, and the TUNEL method was used to determine the extent of apoptosis in ventral prostate. RESULTS: In rats treated daily with bicalutamide, increases in mRNA levels of IGFBP-2, -3, -4, and -5 were detectable by Northern blotting by 6 hours and reached 6 to 10-fold of control levels after 5 days of treatment. The time-course of induction of apoptosis in the ventral prostate by bicalutamide, as detected in situ by the TUNEL method, corresponded to the time-course of induction of IGFBP expression. CONCLUSIONS: We demonstrate that apoptotic regression of the ventral prostate during bicalutamide treatment is accompanied by increased expression of IGFBP-2, -3, -4, and -5. Rapid induction of IGFBPs, which can limit access of insulin-like growth factors (IGFs) to the IGF-I receptor, may play a role in the induction of apoptosis by antiandrogens, particularly in view of the increasing evidence that IGF-I inhibits apoptosis. These results document a previously unrecognized effect of antiandrogens and extend our previous studies relating IGF physiology to prostate biology. Together with evidence that a strong positive correlation exists between plasma IGF-I levels and prostate cancer risk, our data suggest that IGF physiology may play a key role in prostate cancer biology and is strongly influenced by androgen-targeting therapies.

Castration-induced apoptosis of androgen-dependent shionogi carcinoma is associated with increased expression of genes encoding insulin-like growth factor-binding proteins.

Insulin-like growth factor (IGF)-I has well-characterized mitogenic and antiapoptotic effects that are essential for maintenance of the normal prostate and may be important during regression of the normal prostate and/or prostate tumors induced by androgen-targeting therapies for prostate cancer. IGF-I activity is modulated by IGF-binding proteins (IGFBPs). Here we examine IGFBP expression during regression of androgen-dependent Shionogi carcinoma tumors after castration. In this model, we observe a 90% reduction in Shionogi tumors by 10 days postcastration. Northern blotting of RNA from tumors collected at various times after castration indicates a rapid induction of IGFBP-5 concomitant with apoptotic regression of tumors, as detected by Apoptag staining of tumor sections after castration. IGFBP-5 mRNA was not detectable in tumors from control animals, but levels increased 120-fold in tumors 3 days after castration. The mRNAs for IGFBP-3 and 4 were abundant in Shionogi tumors from intact mice and decreased to -33% and -20% of control, respectively. Castration had no significant effect on IGFBP-2 expression. Treatment with calcium channel blockers inhibited castration-induced apoptosis and tumor regression and also significantly inhibited up-regulation of IGFBP-5 after castration. These data provide strong evidence for a functional role of IGFBP-5 expression in mediating the apoptosis induced by androgen deprivation in androgen-dependent neoplasia.

Regression of DMBA-induced breast carcinoma following ovariectomy is associated with increased expression of genes encoding insulin-like growth factor binding proteins.

Insulin-like growth factor I (IGF-I) has well characterized mitogenic and antiapoptotic effects in both normal and neoplastic mammary epithelial cells which are mediated through the IGF-I receptor. IGF activity is modulated by a family of high affinity IGF binding proteins (IGFBPs 1-6). Here we show that gene expression of IGFBP-2, -3, -4 and -5 increases rapidly in DMBA-induced rat mammary tumors following ovariectomy. We observed a 90% reduction in volume of DMBA-induced rat mammary tumors by 14 days post-ovariectomy. The time course of maximal tumor regression was associated with increased gene expression of IGFBPs, as detected by Northern blot analysis. IGFBP-2, -3, -4 and -5 mRNA levels increased from 2- to 16-fold of control by 14 days of estrogen-ablation. These results are compatible with the hypothesis that response of DMBA-induced mammary tumors to estrogen deprivation therapies involves reduction of IGF bioactivity secondary to upregulation of expression of IGF binding proteins.

Vitamin D analogue EB1089-induced prostate regression is associated with increased gene expression of insulin-like growth factor binding proteins.

Vitamin D analogues have an antiproliferative effect on prostate cancer cells in vitro and thus have been proposed as candidates for chemoprevention of prostate cancer. Insulin-like growth factor (IGF)-I has been shown to protect cells from apoptosis and plays an essential role in normal prostate physiology. We have studied the effects of the 1,25-dihydroxyvitamin D3 analogue EB1089 on the IGF system in the prostate in vivo. Treatment of rats with EB1089 for 14 days caused a 25% decrease in ventral prostate weight. Apoptosis was detected in prostate sections of EB1089-treated rats by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and histologic examination of hematoxylin/eosin stained tissue sections indicated that secretory epithelial cells were flattened, a characteristic of cells undergoing pressure-induced atrophy. Ventral prostate regression was associated with 15- to 25-fold increases in gene expression of IGF-binding proteins (IGFBPs)-2,-3,-4 and -5. We also observed a 40-fold increase in prostatic IGF-I mRNA levels in response to EB1089. Although we have previously shown that castration of rats leads to upregulation of IGFBPs in the ventral prostate, EB1089 treatment had no effect on serum levels of dihydrotestosterone or free testosterone. These results suggest that prostate regression induced by EB1089 may be related to alterations in availability of IGF-I as a result of increased production of IGFBPs.

Castration-induced apoptosis in the rat ventral prostate is associated with increased expression of genes encoding insulin-like growth factor binding proteins 2,3,4 and 5.

Insulin-like growth factor binding proteins (IGFBPs) have recently been demonstrated to act as regulators of apoptosis in vitro in both prostate and breast cancer cell lines. We show here that gene expression of IGFBP-2,-3,-4 and -5 increase rapidly in the rat ventral prostate following castration. Increases in IGFBP mRNA levels were detectable by Northern blotting by 6 hours and reached 5 to 10 fold of control levels at 72 hours after castration. Apoptosis in the ventral prostate, as detected in situ by the TUNEL method, was also induced as early as 6 hours after castration. TRPM-2/clusterin, a gene known to be associated with involution of the prostate, was not detected in sham castrated controls but was expressed by 24 hours following androgen ablation. IGF-I mRNA levels increased to 160% of control values within 6 hours following castration, then decreased gradually over the next 72 hours to 35% of control. Affinity labelling experiments demonstrated that IGF-I receptor levels increased initially after castration with peak binding at 24 hours, then declined to levels lower than control. These results suggest that rapid induction of IGFBPs in the rat ventral prostate following androgen ablation may play a role in apoptosis and involution of the prostate gland.

Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells.

Insulin-like growth factors (IGFs) are known to have potent antiapoptotic activity. The antiestrogen ICI 182,780 (ICI) is a potent inhibitor of MCF7 human breast cancer cell growth and has recently been reported to act as an antiproliferative agent in part via upregulation of expression of insulin-like growth factor binding proteins (IGFBPs) -3 and -5, which attenuate the bioactivity of IGFs in many experimental systems. We show here that ICI and IGFBP-3 induce apoptosis in MCF7 cells. Treatment of MCF7 cells with 10 nM ICI or 36 nM recombinant human IGFBP. 3 for 72 hours increased apoptosis approximately 3.5-fold relative to control as quantitated by a cell death ELISA which measures DNA fragmentation. Long R3 IGF-I, an IGF-I analogue with greatly reduced affinity for IGFBPs yet similar affinity for IGF-I receptors, was a more potent inhibitor of IGFBP-3-induced and ICI-induced apoptosis than IGF-I. These results suggest that IGFBP-3 enhances apoptosis by reducing bioavailability of ligands for the IGF-I receptor and suggest that modulation of IGFBP-3 expression by ICI contributes to apoptosis induced by this compound. More generally, the data suggest that IGFBPs are regulators of apoptosis.

Regulation of insulin-like growth factor I receptor expression by the pure antiestrogen ICI 182780.

Insulin-like growth factor I (IGF-I) is a mitogen for human breast cancer cells both in vivo and in vitro. We demonstrate here that the antiestrogen ICI 182780 (ICI) at 10(-8) m decreases IGF-I receptor (IGF-IR) mRNA levels by 70% after treatment for 48 h. Measurements of mRNA stability indicate that the half-life of IGF-IR mRNA is approximately 3 h. Estradiol treatment increases the half-life of the IGF-IR mRNA to approximately 6 h and the level of IGF-IR gene transcription by 1.8-fold, whereas ICI treatment not only decreases the IGF-IR transcription rate by 50% but also decreases the IGF-IR mRNA half-life to less than 3 h. Affinity labeling studies with [125I]-IGF-I show 35% increased labeled IGF-I to MCF-7 cell membrane following estradiol treatment and 40% decreased labeling following ICI treatment. We also demonstrate that ICI attenuates IGF-I-stimulated growth. Our data suggest that attenuation of IGF-I responsivity by ICI may be due in part to reducing the IGF-IR expression.

Infectious peritonitis in a cat that subsequently developed a myeloproliferative disorder.

The effusive form of feline infectious peritonitis was diagnosed clinically and serologically in a 3-year-old male domestic cat. The cat responded to treatment for 9 months, then developed a myeloproliferative disorder with cytologic characteristics of reticuloendotheliosis.

Effect of alcohols on lactose solubility.

In tests of effects of high (70 to 90% volume/volume) and low (2 and 5% volume/volume) alcohol concentrations, solubility of lactose decreased with increased alcohol concentration and decreased as alcohol chain length increased. Since lactose has lower solubility in alcohol, crystallization would be expected to be speeded by increased supersaturation. Composition of precipitates formed by the action of ethanol changed with time; alpha-lactose precipitated more rapidly at first, then beta-lactose. Time of crystallization was related directly to the percentage of beta-lactose (therefore, the relation was inverse for total alpha). However, the percentage of alpha-hydrate increased with time and with water content. Agitation during crystallization increased production of beta-lactose. Composition of the lactose precipitate varied greatly with concentration of alcohol (ethanol). When ethanol concentration was low, only alpha-hydrate was precipitated whereas at higher concentrations stable anhydrous alpha lactose also was precipitated, with the percentage of total alpha decreasing while the percentage of beta-lactose increased. Crystal shape changed from prisms initially to partially or fully developed tomahawks as time went by or as the percentage of ethanol decreased, and crystal color increased with crystallization time and as ethanol percentage decreased. Choosing long-chain alcohols and controlling suitable parameters enabled recovery of greater amounts and more desirable forms of lactose.

Selection of strain, growth conditions, and extraction procedures for optimum production of lactase from Kluyveromyces fragilis.

Forty-one strains of Kluyveromyces fragilis (Jörgensen) van der Walt 1909 varied 60-fold in ability to produce lactase (beta-galactosidase). The four best strains were UCD No. 55-31 (Northern Regional Research Center NRRL Y-1196), UCD No. C21(-), UCD No. 72-297(-), and UCD No. 55-61 (NRRL Y-1109). Biosynthesis of lactase during the growth of K. fragilis strain UCD No. 55-61 was followed on both lactose and sweet whey media. Maximum enzyme yield was obtained at the beginning of the stationary phase of growth. Bets lactase yields from K. fragilis UCD No. 55-61 were obtained with 15% lactose and an aeration rate of at least .2 mmol oxygen/liter per min. Supplementary growth factors were unneccessary for good lactase yeilds when yeast was grown on whey media. Best extraction of lactase from fresh yeast cells was obtained by toluene autolysis (2% vol/vol) at 37 C in .1 M potassium phosphate buffer, pH 7.0, containing .1 mM manganese chloride and .5 mM magnesium sulfate. The enzyme was concentrated and purified partially by acetone precipitation. At least 95% of the enzyme activity of the concentrated solution was retained after storage for 7 days at 22 C, for 3 wk at 4 C, and for 6 wk at -20 C.