Penetrating colon trauma - outcomes related to single versus multiple colonic injuries.

INTRODUCTION: There is no conclusive evidence to guide surgical management in the presence of multiple colonic injuries as opposed to a single colonic injury, and whether multiple colonic suture lines are associated with worse outcomes than single suture lines. AIM: We reviewed the outcomes of penetrating colonic trauma in relation to whether patients had single versus multiple colonic suture lines (primary repair or anastomosis) following laparotomy. METHODS: A retrospective study was conducted at a major trauma centre in South Africa from 2012-2020 for all patients over 18 years who had sustained penetrating colon injury. RESULTS: 541 cases were included: 409 with single suture line and 54 with multiple suture lines. There were no differences between groups in terms of mechanism of injury (gunshot vs stab; p = 0.328), Injury Severity Score (p = 0.071), or Penetrating Abdominal Trauma Index (p = 0.396). Admission lactate was worse for multiple suture line patients (p = 0.049), but no other blood gas parameters were different, and there was no higher incidence of damage control surgery (p = 0.558) or ICU admission (p = 0.156) for this group. There was a higher rate of diversion in the multiple suture line group (p < 0.001). Univariable logistic regression did not show an increased risk of gastro-intestinal complications, suture line leak rate, or mortality for multiple suture lines compared to single. CONCLUSION: It appears that there is no appreciable difference in outcome between patients with a single colonic suture line compared to patients with more than one suture line following trauma laparotomy. In light of this, each injury should be treated on its own merit, in the context of the patient's overall physiological condition, without undue fear of leaving the patient with more than one colonic suture line. However, judicious use of diversion remains advisable.

Penetrating colon trauma-the effect of concomitant small bowel injury on outcome.

INTRODUCTION: There is limited evidence to suggest that patients with penetrating colon injury have higher complication rates when there is concomitant small bowel (SB) injury. AIM: We performed a retrospective study looking at outcomes of penetrating colonic trauma in patients with- and without concomitant SB injury. METHODS: We interrogated our electronic registry over an eight-year period (2012-2020) for all patients over 18 years who had sustained penetrating colon injury and who had survived beyond 72 h. Demographic data, admission physiology, and Injury Severity Score (ISS) were recorded. Two groups of patients were observed: those with colonic injury (no SB injury) and those with combined colon and SB injury. Outcomes observed included leak rates, length of Intensive Care Unit (ICU) stay, length of hospital stay (LOS), morbidity and mortality. RESULTS: A total of 450 patients were eligible for analysis, of which 257 had colon injury without SB injury and 193 had a combination of colon and SB injury. There was no difference in mechanism of injury between groups. Admission physiology was similar between groups but arterial blood gas values were worse in the combined group. Rates of damage control surgery and ICU admission were higher in the combined group. Primary repair was done in equal proportions between groups but anastomosis was more frequently performed in the combined group. There was no difference in complication rates, including gastro-intestinal complications and suture line leaks. Length of ICU stay, LOS, and mortality were similar between groups. Univariable analysis demonstrated that the presence of concomitant small bowel injury was not an independent risk factor for colonic suture line failure or death. CONCLUSION: There is no evidence from this data that the presence of a combined penetrating colon and SB injury should change management priorities. Each injury should be treated on its own merit, in the context of the patient's physiology.

Penetrating Colon Trauma-the Effect of Injury Location on Outcomes.

BACKGROUND: There is limited evidence to suggest that the more distal a penetrating colonic injury, the poorer its expected outcome, prompting consideration of diversion rather than anastomosis when faced with left colonic injury. The clinical outcomes of penetrating colonic trauma in relation to their anatomical location within the colon were reviewed. METHODS: A review was performed over eight years (2012-2020) of all patients over 18 years who had sustained penetrating colon injury and presented to our trauma centre in South Africa. Direct comparison was made between right colon vs left colon injuries. RESULTS: A total of 450 patients were included; right colon: 260, left colon: 190. Gunshots predominated in the right colon, and the PATI was higher in this group. There were minimal differences in admission physiology and blood gas parameters between groups, but higher damage control surgery and ICU admission rates for the right colon group. There were similar rates of primary repair, anastomosis, and stoma between groups. Leak rates were no different between the two groups, and although overall complication rates were higher for the right colon, there was no difference with regard to gastro-intestinal and other complications, nor for mortality. While regression analysis did identify PATI to be a risk factor for overall complications and mortality, it failed to do so for anastomotic leak. CONCLUSION: Our study did not demonstrate any difference in anastomotic leak rates or mortality between right vs left colonic injury. We recommend that all colonic injuries should be treated on their own merit, balanced against the patient's condition, regardless of anatomical location within the colon.

Skin-only closure as a temporary abdominal closure technique in a rural setting - exploring role and safety profile.

BACKGROUND: Acute laparotomy for trauma or sepsis often prevents definitive closure due to need for relook laparotomy or to prevent abdominal compartment syndrome. Skin-only closure is widely used in our setting. In this study, we review the safety and effectiveness of this technique. METHODS: Patients presenting with intra-abdominal pathology undergoing acute laparotomy and then subsequent skinonly closure using 2-0 prolene were included in the study and followed postoperatively for a three-month period for adverse events stratified by Clavien-Dindo grading, and rate of definitive closure. RESULTS: During the study period, twenty-five patients underwent emergent laparotomy and skin-only closure. The median age of patients undergoing skin-only closure was 27 years (standard deviation 9.1). Six patients presented with major trauma and 19 presented with sepsis. Twenty-one patients underwent subsequent fascial closure. One patient was unable to undergo fascial closure and was managed as a planned ventral hernia. Fourteen patients developed a postoperative complication. There were no deaths and no readmissions to intensive care. Three further patients developed a ventral hernia. CONCLUSION: Skin-only closure, in carefully selected patients, is a feasible alternative to other temporary abdominal closure techniques in a resource-constrained setting.

The Value of Navigators in Breast Cancer Management in a South African Hospital.

BACKGROUND: Specialist breast cancer nurses (BCNs) have improved the psychological care and follow-up rates of breast cancer (BC) patients. This study sought to determine if breast cancer research workers (BCRWs) as de facto BCNs impacted patients' adherence to treatment by comparing groups with and without these patient navigators; hence assessing our need for BCNs. METHODS: Two groups BC patients booked for primary chemotherapy compared. Study group 1 (SG1): no BCRWs/BCNs. Study group 2 (SG2): BCRWs involvement. Assessment of numbers completing primary chemotherapy, undergoing surgery post-neoadjuvant chemotherapy and BCRWs interventions. RESULTS: SG1: n = 281, 25-89y, mean 52.7y, Stage 4: 35.6%, Stage 3: 64.4%. SG2: n = 154, 21-85y, mean 52.6y, Stage 4: 47.4%, Stage 3: 43.3%, Stage 2: 9%. Primary chemotherapy not completed SG1: 40.2% (113) versus SG2: 13.5% (21); p < 0.00001. SG1: 88% not completing were lost to follow-up. Excluding peri-chemotherapy deaths and discontinuation: SG1: 37.1% did not complete chemotherapy versus SG2: 2.6%, p < 0.00001. SG2: BCRWs: 107 interventions for 58 (37.7%) patients. Therapeutic breast surgery SG1: 103/181 (56.9%) versus SG2: 66/81 (81.5%); p < 0.0001. SG1: main reasons for not having surgery: lost to follow-up during (n = 58) or after (n = 9) chemotherapy. Follow-up SG2: 12-43 months, mortality: 52% (80/154), no lost to follow-ups. SG1: No mortality data. CONCLUSIONS: In our setting, BC patients often do not attend or complete treatments. In this study, BCRWs as de-facto BCNs were beneficial for BC patient care, improving chemotherapy compliance and therapeutic surgical interventions. This highlights the need for BCNs for the management of BC patients in South Africa.

Endocannabinoids and endocannabinoid-like compounds modulate hypoxia-induced permeability in CaCo-2 cells via CB1, TRPV1, and PPARα.

BACKGROUND AND PURPOSE: We have previously reported that endocannabinoids modulate permeability in Caco-2 cells under inflammatory conditions and hypothesised in the present study that endocannabinoids could also modulate permeability in ischemia/reperfusion. EXPERIMENTAL APPROACH: Caco-2 cells were grown on cell culture inserts to confluence. Trans-epithelial electrical resistance (TEER) was used to measure permeability. To generate hypoxia (0% O2), a GasPak™ EZ anaerobe pouch system was used. Endocannabinoids were applied to the apical or basolateral membrane in the presence or absence of receptor antagonists. KEY RESULTS: Complete hypoxia decreased TEER (increased permeability) by ~35% after 4 h (recoverable) and ~50% after 6 h (non-recoverable). When applied either pre- or post-hypoxia, apical application of N-arachidonoyl-dopamine (NADA, via TRPV1), oleamide (OA, via TRPV1) and oleoylethanolamine (OEA, via TRPV1) inhibited the increase in permeability. Apical administration of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) worsened the permeability effect of hypoxia (both via CB1). Basolateral application of NADA (via TRPV1), OA (via CB1 and TRPV1), noladin ether (NE, via PPARα), and palmitoylethanolamine (PEA, via PPARα) restored permeability after 4 h hypoxia, whereas OEA increased permeability (via PPARα). After 6 h hypoxia, where permeability does not recover, only basolateral application PEA sustainably decreased permeability, and NE decreased permeability. CONCLUSIONS AND IMPLICATIONS: A variety of endocannabinoids and endocannabinoid-like compounds modulate Caco-2 permeability in hypoxia/reoxygenation, which involves multiple targets, depending on whether the compounds are applied to the basolateral or apical membrane. CB1 antagonism and TRPV1 or PPARα agonism may represent novel therapeutic targets against several intestinal disorders associated with increased permeability.

Straight to flexible sigmoidoscopy: rationalization of 2-week wait referrals in suspected colorectal cancer.

AIM: The 2-week wait pathway was designed to decrease the time from presentation to primary care of patients with 'red flag' symptoms of suspected cancer for review by a specialist for the diagnosis or exclusion of cancer. In our tertiary referral centre we have found that 968 colonoscopies per year are required to satisfy the demand for the 2-week wait, leading to limited colonoscopy availability for other services. We sought to determine the yield of colorectal cancer found at colonoscopy referred via the 2-week wait and referenced to the original red flag symptoms. This was in order to select the most efficacious alternative primary investigation based upon presenting symptoms. METHOD: Electronic records were retrospectively analysed. All patients who went through the 2-week wait for suspicion of colorectal cancer in 2013 and were found to have colorectal cancer on colonoscopy were included. Patients not undergoing colonoscopy as the first investigation were excluded. The splenic flexure was deemed to be within the range of a flexible sigmoidoscope. RESULTS: In all, 2950 referrals were made. 968 colonoscopies were performed as the primary investigation of which 35 were found to have colorectal cancer. No patients referred with rectal bleeding and another symptom had a tumour more proximal to the range of flexible sigmoidoscopy. 80% of tumours proximal to the splenic flexure were suitable for CT diagnosis alone. CONCLUSION: Our data support the use of flexible sigmoidoscopy alone as an initial investigation for patients presenting with rectal bleeding with or without additional colorectal symptoms. Patients with anaemia (without bleeding) or change in bowel habit (without bleeding) may be investigated with CT colonography alone; colonoscopy may then be used selectively prior to surgery.

What interval between colorectal cancer resection and first surveillance colonoscopy? An audit of practice and yield.

AIM: Colonoscopic follow-up after colorectal cancer resection (CRC) is recommended to screen for anastomotic recurrence and metachronous neoplasia, although guidelines vary in the timings of the first investigation. We aimed to quantify current practice and yield of neoplasia at first colonoscopy in relation to time from original resection. METHOD: We conducted a retrospective case note study of all CRCs treated with curative intent within our hospital between two time periods: 2001-2003 and 2006-2007. Variables collected were the extent of preoperative luminal imaging, tumour site, procedure, timing and findings of initial colonoscopy, postoperative CT findings and mortality. The first follow-up colonoscopy findings including neoplasia formation and recurrence rates were matched with rates of complete preoperative luminal imaging. Two-year and 5-year outcomes were sought. RESULTS: A total of 863 patients underwent CRC with curative intent within these two time periods (518 vs 345). Colonoscopic follow-up rates by 2 years were 32.8%vs 54.1%. Within the first cohort 63.5% of patients underwent colonoscopy by 5 years. Significant volumes of neoplasia and resectable recurrences were found before 2 years within these groups. Earlier detection of recurrent malignancy was associated with an improved patient outcome. Complete preoperative screening of the bowel was not associated with a lower incidence of neoplasia at first postoperative colonoscopy. CONCLUSION: Our study demonstrates significant colonoscopic detection rates of neoplasia within 2 years of CRC. Patient outcomes were improved with earlier detection. We would therefore suggest an interval of no more than 2 years between resection and first surveillance colonoscopy.

Effects of sequential implanting and ractopamine hydrochloride supplementation on carcass characteristics and longissimus muscle tenderness of calf-fed steers and heifers.

A 4 × 2 factorial arrangement of treatments (4 growth-enhancement treatments × 2 sex classes) was used to quantify effects of initial implanting (I-implant, d 0), terminal implanting (T-implant, d 63), and feeding ractopamine hydrochloride [RAC, 200 mg/(animal/d)] for the last 28 d on feed on carcass characteristics and LM shear force (WBSF) of calf-fed steers (n = 159) and heifers (n = 132). Growth-enhancement treatments included the following: TRT1, T-implant only; TRT2, I-implant and RAC; TRT3, I-implant and T-implant; TRT4, I-implant, T-implant, and RAC. Growth responses (BW and ADG) were measured in 3 segments of the finishing period: 1) d 0 to 63, 2) d 63 to 28 d before slaughter, and 3) final 28 d. Cattle were slaughtered after 152, 166, or 180 d of finishing; carcass data were collected after a 48-h chill; and LM WBSF was measured at 3, 7, 14, 21, and 28 d postmortem. A priori contrasts were constructed to test effects associated with use vs. exclusion of growth enhancement in each segment of the finishing period. The interaction between sex class and treatment was not significant (P > 0.05) for any trait tested, indicating that the 4 treatments elicited similar effects in both sexes. Initial implanting improved (P < 0.001) ADG from d 0 to 63 by 11.5%, terminal implanting improved (P < 0.001) ADG from d 63 to 28 d before slaughter by 15%, and supplementing twice-implanted cattle with RAC enhanced ADG during the final 28 d of finishing by 12%. Effects of I-implant, T-implant, and RAC resulted in LM area increases of 3 cm(2) (P = 0.015), 6 cm(2) (P < 0.001), and 3 cm(2) (P = 0.011), respectively, and HCW responses of 11 kg (P = 0.011), 16 kg (P = 0.001), and 6 kg (P = 0.195), respectively. Initial implanting resulted in a 20-point reduction (P = 0.097) in marbling, and T-implant reduced marbling by 25 points (P = 0.04), whereas marbling score was unaffected (P = 0.236) by RAC supplementation. Cattle that received only 1 implant (TRT1 and TRT2) produced carcasses with greater (P = 0.026) mean marbling scores and greater (P = 0.01) rates of conformity to beef carcass marketing specifications for HCW, quality grade, yield grade, and LM area than did cattle that were implanted twice (TRT3 and TRT4). Values for LM WBSF were not affected (P > 0.05) by initial or terminal implanting; however, RAC supplementation increased (P = 0.007) mean LM WBSF by 0.23 kg, which translated into a reduction (P = 0.007) in predicted consumer acceptance of LM steaks.

Does auxin binding protein 1 control both cell division and cell expansion?

The Auxin-Binding Protein 1 (ABP1) was identified over 30 years ago thanks to it's high affinity for active auxins. ABP1 plays an essential role in plant life yet to this day, its function remains 'enigmatic.' A recent study by our laboratory shows that ABP1 is critical for regulation of the cell cycle, acting both in G(1) and at the G(2)/M transition. We showed that ABP1 is likely to mediate the permissive auxin signal for entry into the cell cycle. These data were obtained by studying a conditional functional knock-out of ABP1 generated by cellular immunization in the model tobacco cell line, Bright Yellow 2.

The role of adrenal corticosteroids in induction of micronuclei by morphine.

It has previously been shown that morphine can increase the frequency of micronucleated splenocytes when administered to mice, but not when cells are exposed to the opiate in vitro. Morphine treatment is also known to increase circulating levels of glucocorticosteroids, which have been reported to produce genetic damage in vivo and in vitro. In order to determine whether adrenal hormones might mediate the genotoxic effects of morphine, adrenalectomized and sham-operated mice were treated with morphine sulfate. In sham-operated animals administration of morphine produced a dose-related increase in the frequency of micronucleated cells, whereas adrenalectomy abolished the effect. When plasma from morphine-treated mice was used to supplement growth medium of untreated splenocytes, the frequency of micronucleated cells increased, an effect partially blocked by the steroid antagonist RU 486. The N-methylmorphine, which does not stimulate the release of corticosterone from adrenal glands, induced micronuclei formation in splenocytes, and administration of metyrapone, an inhibitor of corticosterone biosynthesis, blocked the morphine-induced increase in corticosterone secretion, but had no effect on the frequency of micronuclei formation. These results indicate that basal levels of glucocorticosteroids are required for induction of micronuclei by morphine in murine splenocytes, but activation of the hypothalamo-pituitary-adrenal (HPA) axis by morphine does not contribute to the observed response.

Carcinoid metastasis to extraocular muscles: case reports and review of the literature.

Carcinoid tumors are slow growing, low-grade malignant neoplasms that are believed to originate from neuroendocrine cells, usually in the gastrointestinal mucosa. Metastasis of carcinoid tumor to the orbit is a rare occurrence. When metastasis does occur, the choroid is the most common ocular structure involved. We report two cases of unique involvement of extraocular muscles.

Orbital pachymengitis secondary to Pseudomonas aeruginosa.

Pachymengitis is a very rare disorder that can present with multiple cranial neuropathies. The etiology can be inflammatory, infective or a combination of both, resulting in a thickening of the cranial dura and an obliteration of the individual layers of the meninges. We present a rare case of Pseudomonas aeruginosa pachymeningitis in the orbit that resulted in severe and permanent visual loss, in a patient after extensive sinus surgery.

Carcinogenesis: basic principles.

Many steps are required to convert a normal cell into a cancerous one. The cancer cell must be able to multiply under conditions that a normal cell would not and to invade surrounding tissue and spread throughout the body. Both genetic changes, such as activation of oncogenes or inactivation of tumor suppressor genes, and epigenetic changes, such as stimulation of cell proliferation, contribute to the development of cancers. Chemical agents can increase the probability of malignant transformation by inducing mutations that can ultimately lead to tumor formation, by promoting the development of tumors in cells with preexisting genetic damage, or by increasing the rate of acquisition of malignant traits by benign tumors. Chemical carcinogens are structurally diverse, but all initiating agents are either already electrophiles or can be converted to electrophilic reactants through metabolic activation. Genetic and environmental factors can alter an individual's ability to metabolize carcinogens, to repair DNA damage, and to respond to mitogenic stimuli, all of which can alter susceptibility to chemical carcinogenesis. The incidence and time required for appearance of tumors appear to be dose-related, but the existence of no-effect doses of carcinogens remains controversial.

Continuous Measurement of Changes in Intracellular Calcium Concentration in Mouse Splenic T Cells Attached to a Glass Substrate.

Mitogen- and isoproterenol-induced changes of [Ca(2+)](i) in T cells attached to a glass substrate were examined. Murine (C57BL/6) splenic T cells were attached to coverslips or 35-mm dishes (MatTek) precoated with Cell Tak((R)) (3.5 &mgr;g/cm(2)). The cells were then loaded with fluorescent dye (2 &mgr;g/ml of fura2-AM or fluo3-AM) and changes in [Ca(2+)](i) in a population of cells (using a spectrofluorometer) or in single cells (using a confocal microscope) were measured during continuous superfusion. Population measurements of [Ca(2+)](i) demonstrated that concanavalin A (Con A, 2 or 5 &mgr;g/ml) caused an increase in [Ca(2+)](i) that rose to a peak and then declined to a steady state. The concentration-response relationship (0.05-5 &mgr;g/ml) had an EC(50) of approximately 0.3 &mgr;g/ml. Isoproterenol decreased the Con A-induced elevation of steady state [Ca(2+)](i). In single cell studies, the increase in [Ca(2+)](i) in response to Con A typically occurred in about 50% of the cells in a microscope field, and the delay before activation varied among cells. Taken together these data demonstrate that Cell Tak((R)) can be used to attach T cells to glass coverslips and will be useful for the study of signaling mechanisms in T cells. Copyright 1995 S. Karger AG, Basel

The clastogenicity of morphine sulfate in vivo.

An opioid analgesic, morphine, and an opioid peptide, beta-endorphin, have been shown to induce chromosome damage, as indicated by an increased frequency of micronucleated lymphocytes, following acute administration to mice. The genotoxic response is opioid receptor-mediated and is abolished in adrenalectomized animals. Further, plasma from morphine-treated animals also induces micronuclei formation in naive lymphocytes in vitro; this response is blocked by inclusion the steroid antagonist RU 486 in the incubation mixture. In addition to the steroid-mediated production of chromosome damage, morphine acts directly on lymphocytes to enhance the clastogenicity of acutely administered cyclophosphamide in manner consistent with depressed DNA repair capacity.