Colorectal Cancer Prevention in Lung Transplant Recipients: The Need for an Enhanced Surveillance Protocol.

BACKGROUND: Solid organ transplant recipients are at increased risk for noncutaneous neoplasms, including colorectal cancer (CRC). We evaluated precancerous lesions detected by post-transplant surveillance colonoscopy to infer the rate at which new adenomas develop in this population. STUDY DESIGN: We reviewed all patients who underwent lung transplant between January 2013 and August 2017 at our institution. Those with post-transplant survival <1 year, personal history of CRC, previous lung transplant, and lack of pretransplant colonoscopy were excluded. RESULTS: During the study period, 411 patients underwent lung transplant; 237 met inclusion criteria. Median age at transplant was 63.6 (interquartile range [IQR] 59.2-68.3) years. Most recipients were immunosuppressed with a combination of prednisone, tacrolimus, and mycophenolate mofetil. At least 1 adenoma was found in 92 patients (38.8%) pretransplant and in 118 patients (49.8%) from 1 to 5 years post-transplant, with 68.6% identified at 1 year. Most adenomas were identified proximal to the splenic flexure. Multiple (≥3) adenomas were found in 31.4% of positive colonoscopies. Within 5 years after transplant, patients with a positive pretransplant colonoscopy had significantly more positive post-transplant colonoscopies than patients with a negative pretransplant colonoscopy (63.0% vs 41.4%, p < 0.001). No de novo CRC was identified. CONCLUSIONS: Lung transplant recipients have a significantly higher risk of adenoma formation than average-risk adults (25%-30% national detection rate). This increase occurs in the early post-transplant period (within 3 years). An enhanced CRC surveillance protocol for lung transplant recipients is needed.

A Comprehensive Review of the Diagnosis, Treatment, and Management of Urologic Chronic Pelvic Pain Syndrome.

PURPOSE OF REVIEW: Urologic chronic pelvic pain syndrome (UCPPS) is a chronic, noncyclic pain condition which can lead to significant patient morbidity and disability. It is defined by pain in the pelvic region, lasting for greater than 3 to 6 months, with no readily identifiable disease process. The aim of this review is to provide a comprehensive update of diagnosis and treatment of UCPPS. RECENT FINDINGS: UCPPS encompasses chronic pelvic pain syndrome or chronic prostatitis (CP/CPPS) in men and interstitial cystitis or painful bladder syndrome (IC/PBS) in women. Underlying inflammatory, immunologic, and neuropathic components have been implicated in the pathogenesis of UCPPS. For optimal patient management, an individualized and multimodal approach is recommended. Medical management and physical therapy are the mainstays of treatment. Injection therapy may offer additional relief in medically refractory patients. Further minimally invasive management may include spinal cord and peripheral nerve stimulation, though evidence supporting efficacy is limited.

Perioperative Outcomes and Predictors of Mortality After Surgery for Sigmoid Volvulus.

BACKGROUND: Data on outcomes after surgery for sigmoid volvulus is limited. The aim of this study was to develop a model to predict need for emergent surgery and mortality after resection for sigmoid volvulus. METHODS: The NSQIP database was queried from 2012 to 2016 to identify patients undergoing segmental resection for sigmoid volvulus. Pre-, intra-, and post-operative variables were compared. Primary and secondary outcomes were emergent surgery and risk of mortality, respectively. Chi-square and Fischer's test for categorical variables and the Mann-Whitney test for continuous variables were used. Significant variables for each outcome were entered into a logistic regression model to predict the outcomes. RESULTS: 2086 patients met inclusion criteria. Factors associated with emergency surgery included female gender, relative hematocrit elevation, relative leukocytosis, acute kidney injury, preoperative sepsis, prior functional independence, and bleeding disorders. Laparoscopic resection and mechanical bowel preparation were more commonly used in the nonemergent setting. Patients having emergent resection were more likely to suffer from postoperative superficial surgical site infection, pneumonia, cardiac arrest, septic shock, myocardial infarction, and receive perioperative transfusion. No difference was seen in ileus, readmission or reoperation rates in the emergent and nonemergent groups. Factors predictive of postoperative mortality included increased age, systemic sepsis, and emergent surgery. Independence before illness, higher albumin levels, and lower BMI were shown to be protective. CONCLUSIONS: Emergent resection is independently associated with poor postoperative outcomes and mortality. Predictors of need for emergent resection and mortality identified in this study can be used to aid in shared decision-making for patients with sigmoid volvulus.

Current mismatch repair deficiency tumor testing practices and capabilities: A survey of Australian pathology providers.

AIM & METHODS: An electronic survey of the Royal College of Pathologists of Australasia accredited pathology services was conducted to assess Lynch syndrome tumor screening practices and to identify barriers and capabilities to screen newly diagnosed colorectal and endometrial tumors in Australia. RESULTS: Australia lacks a national policy for universal mismatch repair-deficient (dMMR) testing of incident colorectal and endometrial tumors cases. Routine Lynch syndrome tumor screening program for colorectal and/or endometrial tumors was applied by 95% (37/39) of laboratories. Tumor dMMR screening methods varied; MMR protein immunohistochemistry (IHC) alone was undertaken by 77% of 39 laboratories, 18% performed both IHC and microsatellite instability testing, 5% did not have the capacity to perform in-house testing. For colorectal tumors, 47% (17/36) reported following a universal approach without age limit, 30% (11/36) tested only "red flag" cases; 6% (3/36) on clinician request only. For endometrial tumors, 37% (12/33) reported clinician request generated testing, 27% (9/33) were screening only "red flag" cases, and 12% (4/33) carried out universal screening without an age criteria. BRAF V600E mutation testing of colorectal tumors demonstrating aberrant MLH1 protein expression by IHC was the most common secondary tumor test, with 53% of laboratories performing the test; 15% of laboratories also applied the BRAF V600E test to endometrial tumors with aberrant MLH1 expression despite no evidence for its utility. Tumor testing for MLH1 promoter methylation was performed by less than 15% laboratories. CONCLUSION: Although use of tumor screening for evidence of dMMR is widely available, protocols for its use in Australia vary widely. This national survey provides a snapshot of the current availability and practice of tumor dMMR screening and identifies the need for a uniform national testing policy.

G-CSF increases mesenchymal precursor cell numbers in the bone marrow via an indirect mechanism involving osteoclast-mediated bone resorption.

During the course of studies to investigate whether MPC circulate in response to G-CSF, the agent most frequently used to induce mobilization of hematopoietic progenitors, we observed that while G-CSF failed to increase the number of MPC in circulation (assayed in vitro as fibroblast colony-forming cells, CFU-F), G-CSF administration nevertheless resulted in a time-dependent increase in the absolute number of CFU-F within the BM, peaking at Day 7. Treatment of BM cells from G-CSF-treated mice with hydroxyurea did not alter CFU-F numbers, suggesting that the increase in their numbers in response to G-CSF administration is not due to proliferation of existing CFU-F. Given previous studies demonstrating that G-CSF potently induces bone turnover in mice, we hypothesized that the increase in CFU-F may be triggered by the bone resorption that occurs following G-CSF administration. In accord with this hypothesis, administration of an inhibitor of osteoclast differentiation, osteoprotegerin (OPG), prevented the increase of CFU-F numbers induced by G-CSF. In conclusion, these data indicate that the cytokine treatment routinely used to mobilize hematopoietic stem cells could provide a readily applicable method to induce in vivo expansion of MPC for clinical applications.

Angiotensin-converting enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal, and adult hematopoietic tissues.

Previous studies revealed that mAb BB9 reacts with a subset of CD34(+) human BM cells with hematopoietic stem cell (HSC) characteristics. Here we map BB9 expression throughout hematopoietic development and show that the earliest definitive HSCs that arise at the ventral wall of the aorta and surrounding endothelial cells are BB9(+). Thereafter, BB9 is expressed by primitive hematopoietic cells in fetal liver and in umbilical cord blood (UCB). BB9(+)CD34(+) UCB cells transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice contribute 10-fold higher numbers of multilineage blood cells than their CD34(+)BB9(-) counterparts and contain a significantly higher incidence of SCID-repopulating cells than the unfractionated CD34(+) population. Protein microsequencing of the 160-kDa band corresponding to the BB9 protein established its identity as that of somatic angiotensin-converting enzyme (ACE). Although the role of ACE on human HSCs remains to be determined, these studies designate ACE as a hitherto unrecognized marker of human HSCs throughout hematopoietic ontogeny and adulthood.

Membrane-bound stem cell factor is a key regulator in the initial lodgment of stem cells within the endosteal marrow region.

OBJECTIVE: The transmembrane isoform of stem cell factor (tm-SCF) has been implicated in the adhesion of hemopoietic stem cells to the extracellular matrix within the bone marrow microenvironment in vitro. In addition, in vivo SCF has been shown to play a role in cell mobilization and migration. The aim of this study was to determine if SCF is an integral component of the hemopoietic "niche" of the bone marrow in situ. MATERIALS AND METHODS: To analyze the role of tm-SCF in cell lodgment, purified populations of primitive progenitors and hemopoietic stem cells (HSC) were transplanted into a hemopoietic microenvironment devoid of tm-SCF, and the spatial distribution of engrafted cells was analyzed. In addition, populations of HSC were isolated using non-neutralizing and neutralizing antibodies to the SCF receptor c-kit, and their spatial distribution was analyzed post-transplant. RESULTS: The data demonstrated a significant impairment in the lodgment of transplanted cells within the endosteal marrow region in mice lacking tm-SCF, with a reduction of almost 30% by 15 hours post-transplant. The role of tm-SCF was confirmed by analyzing the spatial distribution of HSC isolated using a neutralizing antibody to c-kit. CONCLUSION: The data demonstrate that although tm-SCF does not appear to play a role in the homing of transplanted cells to the bone marrow, it is critical in the lodgment and detainment of HSC within their hemopoietic "niche."