Transcriptomic response of bioengineered human cartilage to parabolic flight microgravity is sex-dependent.

Spaceflight and simulated spaceflight microgravity induced osteoarthritic-like alterations at the transcriptomic and proteomic levels in the articular and meniscal cartilages of rodents. But little is known about the effect of spaceflight or simulated spaceflight microgravity on the transcriptome of tissue-engineered cartilage developed from human cells. In this study, we investigate the effect of simulated spaceflight microgravity facilitated by parabolic flights on tissue-engineered cartilage developed from in vitro chondrogenesis of human bone marrow mesenchymal stem cells obtained from age-matched female and male donors. The successful induction of cartilage-like tissue was confirmed by the expression of well-demonstrated chondrogenic markers. Our bulk transcriptome data via RNA sequencing demonstrated that parabolic flight altered mostly fundamental biological processes, and the modulation of the transcriptome profile showed sex-dependent differences. The secretome profile analysis revealed that two genes (WNT7B and WNT9A) from the Wnt-signaling pathway, which is implicated in osteoarthritis development, were only up-regulated for female donors. The results of this study showed that the engineered cartilage tissues responded to microgravity in a sex-dependent manner, and the reported data offers a strong foundation to further explore the underlying mechanisms.

Long-term results of ligation of intersphincteric fistula tract (LIFT) for fistula-in-ano.

BACKGROUND: Ligation of intersphincteric fistula tract is a novel surgical technique in the treatment of transsphincteric fistula-in-ano that has been shown to be successful in the short term. Median follow-up in current literature ranges from 5 to 9 months. However, the long-term success rate is unknown. OBJECTIVE: This study describes our long-term results in performing the ligation of intersphincteric fistula tract procedure. DESIGN: This study is a retrospective review. PATIENTS: Thirty-eight patients from August 2008 to October 2011 were evaluated. INTERVENTIONS: All patients underwent the ligation of intersphincteric fistula tract for fistula-in-ano. MAIN OUTCOME MEASURES: Patient and fistula characteristics, primary healing rate, secondary healing rate, previous treatments, and failures were reviewed. RESULTS: The median follow-up was 26 months (range, 3-44 months), and 26 patients (68%) were followed for greater than 12 months. The overall primary healing rate was 61% (23 of 38), and it was 62% (16 of 26) in patients followed for over 12 months. Eighty percent (12/15) of the failures are early failures (persistent symptoms or failure at ≤6 months), and 20% are late failures (>6 months) with 1 failure occurring 12 months postprocedure. Increase in length of fistula tract was associated with decreased healing (OR 0.55, 95% CI 0.34-0.88, p = 0.01). There were no intraoperative complications and no reported incontinence. CONCLUSION: Our study demonstrates favorable long-term results for the ligation of intersphincteric fistula tract procedure. It appears that long tracts negatively affect healing, and late failures can occur up to 12 months postoperatively. Understanding the type of failure can help guide subsequent treatment to maximize healing success.

Distribution of CD133 reveals glioma stem cells self-renew through symmetric and asymmetric cell divisions.

Malignant gliomas contain a population of self-renewing tumorigenic stem-like cells; however, it remains unclear how these glioma stem cells (GSCs) self-renew or generate cellular diversity at the single-cell level. Asymmetric cell division is a proposed mechanism to maintain cancer stem cells, yet the modes of cell division that GSCs utilize remain undetermined. Here, we used single-cell analyses to evaluate the cell division behavior of GSCs. Lineage-tracing analysis revealed that the majority of GSCs were generated through expansive symmetric cell division and not through asymmetric cell division. The majority of differentiated progeny was generated through symmetric pro-commitment divisions under expansion conditions and in the absence of growth factors, occurred mainly through asymmetric cell divisions. Mitotic pair analysis detected asymmetric CD133 segregation and not any other GSC marker in a fraction of mitoses, some of which were associated with Numb asymmetry. Under growth factor withdrawal conditions, the proportion of asymmetric CD133 divisions increased, congruent with the increase in asymmetric cell divisions observed in the lineage-tracing studies. Using single-cell-based observation, we provide definitive evidence that GSCs are capable of different modes of cell division and that the generation of cellular diversity occurs mainly through symmetric cell division, not through asymmetric cell division.

Early result of ligation of the intersphincteric fistula tract for fistula-in-ano.

PURPOSE: The ligation of the intersphincteric fistula tract is a new surgical procedure without any use of biologic material. The purpose of this study is to present our early results with this novel technique. METHODS: A retrospective review of patients who underwent the procedure for high transsphincteric fistulas was analyzed. The procedure was performed by a single surgeon. Patient and fistula characteristics, complications, and recurrences were reviewed. RESULTS: Twenty-five patients underwent the ligation of intersphincteric fistula tract procedure. All the patients had transsphincteric fistulas that were not suitable for fistulotomy. All patients underwent the procedure on an outpatient basis with a median follow-up of 24 weeks (range, 8-52 wk). Of the 25 patients, 17 (68%) healed completely and did not require any further surgical treatment. Eight of the 25 patients had persistent symptoms: 5 patients had a clear tract with an internal opening, 2 patients had a draining sinus without an identifiable internal opening, and 1 patient presented with an intersphincteric fistula, which was at the site of the intersphincteric groove incision. There were no statistically significant differences in recurrence rates with regard to the presence of a seton at the time of surgery, history of previous operations such as mucosal advancement flap, or seton placement. CONCLUSION: The ligation of intersphincteric fistula is a promising sphincter-preserving procedure that is simple and safe, and it does not require expensive biologic material. Our early data confirm a low recurrence rate with a primary healing rate of 68%.

Successful enhanced recovery program after colorectal surgery in a county institution.

Enhanced recovery programs after colorectal surgery have gained acceptance recently as they have shown a decrease length of hospital stay. However, these pathways require strict adherence to standardized programs with patient education and high compliance. This study was designed to assess the feasibility of such a program in a large county hospital. A retrospective review was performed of 54 consecutive patients who underwent laparoscopic or open segmental colorectal resection without an ostomy. The first 27 patients were treated in a conventional manner, whereas the latter 27 were treated using a protocol promoting early feeding and ambulation with decreased intravenous fluids and narcotic use. There were no baseline differences between the groups, however, there was a significant difference in the patients treated with the enhanced recovery program in terms of less intravenous fluids administered in surgery (P = 0.001), and over the subsequent 3 days (P = 0.0017), with a decrease in length of hospital stay of 4 compared with 6 days (P = 0.003). There were no differences in terms of complication and readmission rates. Based on this study, we conclude that strict adherence to a standard enhanced recovery program was effective in reducing hospital stay in patients undergoing colorectal resection without any increase in complications.

Role of water-soluble enema before takedown of diverting ileostomy for low pelvic anastomosis.

The integrity of a low pelvic anastomosis is often studied radiographically before takedown of a diverting ileostomy. The aim of this study is to determine the impact of routine water-soluble enema studies (WSE) in our patient population with low pelvic anastomosis. We retrospectively reviewed the operative database for a county teaching hospital from 1998 to 2008. All patients with low pelvic anastomosis (ultralow colorectal, coloanal, and ileoanal pouch anastomosis) with diverting ileostomy who underwent subsequent takedown were identified. Fifty patients met inclusion criteria. Thirty-eight patients were evaluated by WSE and 12 were not. Twenty-five patients (66%) were noted to have normal WSE studies before ostomy takedown. Thirteen patients (26%) were noted to have abnormalities on WSE. Two stenoses were clinically significant. Water-soluble enema study was 100 per cent sensitive and 69 per cent specific for detecting significant pathology. Digital rectal examination (DRE), colonoscopy, and flexible sigmoidoscopy were also 100 per cent sensitive in detecting substantial pathology. Routine use of WSE failed to demonstrate a significant impact on patients with low pelvic anastomosis undergoing ileostomy takedown. Routine DRE and rigid proctoscopy can be used to evaluate low pelvic anastomosis. WSE can be used selectively on patients with abnormal findings.

Characteristics of colorectal cancer in young patients at an urban county hospital.

Colorectal cancer (CRC) is a disease primarily affecting an older population. The incidence of CRC in young patients has been rising. The purpose of this study was to evaluate the characteristics of CRC in an ethnically diverse, young population. Two groups of patients with CRC (40 years old or younger and 60 years old or older) treated from 1998 to 2005 were retrospectively evaluated. Forty-one young patients with CRC were identified. Hispanics constituted 51 per cent of the young population. Forty-four per cent of the lesions were right-sided in the young group compared with 21 per cent in the older group (P = 0.004). Advanced tumor stage (T3 and T4) was noted in 87.8 per cent of the young and 63 per cent of the older patients (P = 0.002; OR, 4.08). Poorly differentiated tumor grade was more common in young patients (P = 0.003) as well as mucinous/ signet ring characteristics (P = 0.005). Young patients had an increased likelihood of a family history (P = 0.0001). Operative intervention and survival were similar for the two groups. Our study confirms, in an ethnically diverse young population, that CRC tends to be advanced stage, aggressive, and frequently nonoperable at the time of diagnosis. It is important for physicians to recognize the poor outcome of CRC in a younger population and consider an aggressive approach to diagnosis and early treatment.

Outcome analysis of patients undergoing colorectal resection for emergent and elective indications.

Despite advances in perioperative care and operative techniques, urgent colorectal operations are associated with higher morbidity and mortality. To evaluate our rate of complications in elective and urgent colorectal operations, we performed retrospective chart review of 209 consecutive patients who underwent colorectal resection between 1998 and 2002 at Harbor-UCLA Medical Center. One hundred, forty-three (71%) patients underwent elective colorectal resection. A total of 19 (13.3%) complications occurred in the elective group, compared with 24 (38.1%) in the urgent group (P = 0.003). Both right-sided and left-sided operations were associated with higher incidence of complications when performed urgently. Wound infection occurred in 7.7 per cent of patients undergoing an elective operation and 14.3 per cent in an urgent setting (P = 0.21). Intra-abdominal abscess occurred in 1.4 per cent of patients undergoing elective operation, compared with 11.1 per cent in the urgent operation group. Four (1.9%) patients developed wound dehiscence, 1 in elective and 3 in the urgent group (P = 0.09). Anastomotic leak occurred in 1.9 per cent of patients, 2 in each group (P = 0.6). There were six deaths, 3 in elective and 3 in urgent cases (P = 0.4). Urgent operation of the colon and rectum is associated with higher incidence of complications. Both right- and left-sided resections have a higher complication rate when performed in a nonelective setting.

Prevalence of left-sided colorectal cancer and benefit of flexible sigmoidoscopy: a county hospital experience.

The best way to evaluate the colon for both diagnosis of symptoms and surveillance is colonoscopy. However, access to colonoscopy is often restricted. Our objective was to assess the anatomic distribution and stage at presentation of colorectal cancer (CRC) in a county hospital population, the prevalence and distribution of CRC in younger patients, and the utility of flexible sigmoidoscopy for early diagnosis of left-sided cancers in this population. We performed a retrospective chart review of 151 patients who underwent colorectal resection from 2001 to 2003. Overall, 66.9 per cent of patients underwent resection for left-sided CRC. Forty-two (27.8%) of 151 were under age 50. In patients over 50, 66.1 per cent were found to have left-sided CRC compared with 69 per cent of patients under 50. Fifty per cent (50.3%) of patients had stage III or IV (advanced) disease. Forty-nine and a half per cent of patients over 50 and 52.3 per cent under 50 had advanced disease. Forty-eight and a half per cent of patients with left-sided CRC had advanced stage disease compared with 54% of patients with right-sided CRC. In patients under 50, the rates were 55.2 per cent and 46.1 per cent respectively. Two-thirds of the CRC occurred in the left side of the colon in both older and younger population. Flexible sigmoidoscopy should be considered as an early tool in the diagnosis of CRC.

Matrix metalloproteinase-7 modulates synaptic vesicle recycling and induces atrophy of neuronal synapses.

Matrix metalloproteinase-7 (MMP-7) belongs to a family of zinc dependent endopeptidases that are expressed in a variety of tissues including the brain. MMPs are known to be potent mediators of pericellular proteolysis and likely mediators of dynamic remodelling of neuronal connections. While an association between proteases and the neuronal synapse is emerging, a full understanding of this relationship is lacking. Here, we show that MMP-7 alters the structure and function of presynaptic terminals without affecting neuronal survival. Bath application of recombinant MMP-7 to cultured rat neurons induced long-lasting inhibition of vesicular recycling as measured by synaptotagmin 1 antibody uptake assays and FM4-64 optical imaging. MMP-7 application resulted in reduced abundance of vesicular and active zone proteins locally within synaptic terminals although their general levels remained unaltered. Finally, chronic application of the protease resulted in synaptic atrophy, including smaller terminals and fewer synaptic vesicles, as determined by electron microscopy. Together these results suggest that MMP-7 is a potent modulator of synaptic vesicle recycling and synaptic ultrastructure and that elevated levels of the enzyme, as may occur with brain inflammation, may adversely influence neurotransmission.

Selective treatment of rectal cancer with single-stage coloanal or ultralow colorectal anastomosis does not adversely affect morbidity and mortality.

BACKGROUND AND AIMS: The surgical treatment of low rectal cancer commonly includes low pelvic anastomoses with coloanal or ultralow colorectal anastomoses. Anastomotic leak rates in low pelvic anastomoses range from 4 to 26%. Many surgeons opt to routinely create a diverting ostomy to reduce the extent of morbidity should an anastomotic leak occur. The intent of our study was to determine if our policy of selected diversion is safe. MATERIALS AND METHODS: A retrospective chart review of 66 rectal cancer patients who underwent proctectomy and low pelvic anastomoses -- less than 6 cm from anal verge, with or without a diverting ostomy -- was undertaken. Temporary diverting stomas were utilized at the discretion of the attending surgeon primarily based on subjective criteria. The main outcome was postoperative complications. RESULTS/FINDINGS: Forty-nine patients (78% preoperatively irradiated) were treated with a one-stage operation, whereas 17 (53% preoperatively irradiated) underwent reconstruction with proximal diversion. The mean anastomotic height for patients with a single stage procedure was 3.8 cm above the anal verge versus 2.6 for patients with a two-stage procedure (p = 0.076). Complication rates were lower in patients who did not undergo diversion (29% vs 47%, p = 16). With regard to anastomotic-associated complications for single stage versus two stage, complication rates were 8% versus 18%, respectively (p = 0.27). INTERPRETATION/CONCLUSION: Low pelvic anastomoses in rectal cancer patients can be safely performed as a single-stage procedure, reserving the use of diversion for select cases.

The role of carcinoembryonic antigen as a predictor of the need for preoperative computed tomography in colon cancer patients.

A retrospective study of 117 patients with the diagnosis of colon cancer was performed to evaluate the clinical utility of the preoperative computed tomography (CT) scan and to assess the role of carcinoembryonic antigen (CEA) as a predictor of the need for CT scan in colon cancer patients. Forty-nine patients had a CT scan that altered their treatment. One hundred per cent of stage IV patients versus only 26.5 per cent of stage I, II, and III patients had their operative and/or treatment planning altered by the preoperative CT. The sensitivity of CT scan in predicting metastatic disease was 90.3 per cent. All patients with stage IV disease had an abnormal CEA (>3 ng/mL). There was 89.7 per cent of stage IV patients who had a CEA twice that of normal or above. By using a CEA level of 3.1 ng/mL or above as a prerequisite for preoperative tomography, 34 nonmetastatic patients would not have had preoperative CT scans. Using a prerequisite of 6.1 ng/mL or above, 49 nonmetastatic patients would not have had a preoperative CT scan, and 90 per cent of the stage IV patients would have been imaged. We recommend obtaining a preoperative CT scan on those patients with a CEA value twice that of normal or greater.

Number of lymph nodes examined and its impact on colorectal cancer staging.

The status of lymph nodes is the most important prognosticator in colorectal cancer patients. Patients with lymph node involvement have a lower survival rate and are candidates for adjuvant therapy. The purpose of our study was to determine the number of lymph nodes that needs to be examined to accurately detect nodal metastasis. We conducted a retrospective study of 151 patients who underwent colorectal cancer operation at Harbor-UCLA Medical Center. Data from the operative report and pathology report were collected and analyzed. Fourteen (33.3%) patients with five to nine nodes examined had positive nodes. Twenty-six (57.8%) patients with 10 to 14 nodes examined had positive nodes. Patients who had 10 to 14 nodes examined were significantly more likely to have positive lymph nodes (P = 0.03). Patients with advanced T stage had a significantly higher number of positive lymph nodes (78.1% in T4 vs 11.1% in T1, P < 0.0001). Patients with poorly differentiated cancer showed a trend toward a higher positive node rate. Tumor differentiation and T stage seem to correlate with higher nodal metastasis rate. A higher number of lymph nodes examined was associated with a higher nodal metastasis rate. Examination of at least 10 lymph nodes would increase the yield of positive lymph nodes and avoid under-staging of patients with colorectal cancer.

Factors affecting the successful management of intra-abdominal abscesses with antibiotics and the need for percutaneous drainage.

PURPOSE: There is no definite consensus on the management of intra-abdominal abscesses in adults. This retrospective study evaluated the use of antibiotic therapy and percutaneous image-guided drainage in adult patients with intra-abdominal abscesses. METHODS: A retrospective chart review of 114 patients with intra-abdominal abscesses was conducted. Data collected included patient demographics, presenting symptoms, radiographic interpretation, vital signs, antibiotic coverage, laboratory values, and details of the hospital course. Bivariate statistical tests were performed using the Wilcoxon rank-sum test, chi-squared test, or Fisher's exact test, where appropriate. RESULTS: Sixty-seven of 114 patients (59 percent) had intra-abdominal abscesses resulting from appendicitis, diverticulitis in 30 patients (26 percent), postoperative in 13 patients (11 percent), and undetermined in 4 patients (4 percent). Three patients (3 percent; 95 percent confidence interval, 1-8 percent) failed conservative management and underwent urgent operation. Sixty-one (54 percent; 95 percent confidence interval, 44-63 percent) patients improved with intravenous antibiotic therapy alone. Fifty patients (44 percent; 95 percent confidence interval, 35-54 percent) underwent image-guided percutaneous drainage after 48 to 72 hours of antibiotic therapy. Patients who improved on antibiotics alone had average abscess diameter of 4 cm, whereas patients who underwent percutaneous drainage had average diameter of 6.5 cm (P<0.0001). Maximal temperature at time of admission was 100.8 degrees F for antibiotic group and 101.2 degrees F for percutaneous drainage group (P=0.0067). CONCLUSIONS: The majority of the patients with intra-abdominal abscesses improved with antibiotic therapy alone. Those patients with an abscess diameter>6.5 cm and temperature at admission>101.2 degrees F have higher likelihood of failing conservative therapy with antibiotics alone and requiring percutaneous drainage.

Reoperation for stoma-related complications.

Stoma complications are common. Most do not require reoperation, but when surgery is indicated, numerous options are available. Complications can arise early or late, and they can vary from benign to life-threatening. Meticulous preoperative planning is crucial in preventing stoma complications. Good communication with the patient is important in the decision-making process.

Colonic histoplasmosis presenting as colon cancer in the nonimmunocompromised patient: report of a case and review of the literature.

Histoplasma capsulatum is an important pathogen that is the most commonly diagnosed endemic mycosis in the gastrointestinal tract of immunocompromised hosts. Failure to recognize and treat disseminated histoplasmosis in AIDS patients invariably leads to death. Gastrointestinal manifestations frequently involve the terminal ileum and cecum, and depending on the layer of bowel wall involved present as bleeding, obstruction, perforation, or peritonitis. Because they can be variable in appearance, they may be mistaken for Crohn's disease or malignant tumors. Four distinct pathologic patterns of GI histoplasmosis have been described that all have differing clinical presentations. We report a case of a non-AIDS patient who presented with a near-obstructing colonic mass suspicious for advanced malignancy but was found to have histoplasmosis on final pathology. The patient underwent successful operative resection, systemic anti-fungal therapy, and extensive workup for immunosuppressive disorders, which were negative. The patient was from an area in Mexico known to be endemic for histoplasmosis. This is the first report of a colonic mass lesion occurring in a non-AIDS patient, and review of the worldwide literature regarding GI histoplasmosis reveals excellent long-term survival with aggressive therapy. We discuss the surgical and medical management of colonic histoplasmosis in this report.

Diverticulitis: truly minimally invasive management.

The purpose of this study is to evaluate the treatment of patients with acute diverticulitis in the inpatient setting using minimal intervention. This was a retrospective study of 75 patients admitted over a 3-year period with acute diverticulitis as evidenced by computed tomography (CT) and clinical scenario. Of the patients enrolled, 24 (32%) had abscesses identified on their initial CT scan. An additional four patients had abscesses noted on a subsequent CT scan obtained because of lack of complete improvement with medical management, thus raising the total number of abscesses to 28 (37%). Of the patients with abscesses, 10 (36%) underwent drainage using a CT-guided percutaneous or ultrasound-guided transrectal approach an average of 6 days after admission. Of the 75 patients, five (7%) required operative intervention during the initial hospitalization for failure of medical management, two (40%) of whom had abscesses on presentation. The overall median length of hospitalization was 5 (interquartile range [IQR] 4-9) days, and 18 patients (24%) had recurrences during the study period. Our conservative approach to percutaneous and surgical intervention resulted in relatively low percutaneous drainage, a low operative rate, and a reasonable length of hospitalization and recurrence rate.