Valentine N. Nfonsam

Is It Time to Lower the Recommended Screening Age for Colorectal Cancer

BACKGROUND Overall, colorectal cancer (CRC) incidence in the US has decreased over the last 30 years, yet it has increased in patients younger than 50. Cancers in this population are more aggressive and advanced at diagnosis. Our goal was to determine if screening should begin at a younger age. To accomplish this, we analyzed the rates of change in CRC incidence, and compared the incidence with that of cervical cancer (CC), which is screened earlier. Locations of CRC were compared to determine the appropriate screening method. STUDY DESIGN Incidence statistics were obtained from the Cancer Query System of the SEER database. Data were obtained from 1987 to 2006 in age groups of 5-year increments from 0 to 4 years old to 85+ years old for incidences of colon, rectal, and overall CRC. Combined data from 2002 to 2006 were queried to determine the locations of tumors and the overall incidence of CRC and CC at different ages. RESULTS Across age groups 20 to 49, CRC incidence was higher in 2006 than in 1987. The most significant increase was from age 40 to 44, where CRC increased from a low of 10.7 per 100,000 in 1988 to 17.9 per 100,000 in 2006 (67%). Colon and rectal cancer increased 56% and 94%, respectively. People older than 50 had decreasing incidences. Approximately 30% of cancers in patients aged 35 to 49 occurred proximal to the splenic flexure. The incidence of CRC cancer equaled and subsequently surpassed CC in the 40 to 44 age group. CONCLUSIONS The most significant increase in CRC has occurred in patients ages 40 to 44. Patients over 50 continued to see a decline. Many of these cancers would be missed with sigmoidoscopy. Consideration should be given for age-based colonoscopic screening beginning at age 40, an age at which the incidence mirrors other accepted screened cancers.

The use of silver nylon in preventing surgical site infections following colon and rectal surgery

BACKGROUND: Patients who undergo colorectal surgery have up to a 30% chance of developing a surgical site infection postoperatively. Silverlon is a silver nylon dressing designed to prevent surgical site infections, but only anecdotal evidence has previously supported its efficacy. OBJECTIVE: The aim of this study was to evaluate the effect of silver nylon dressings in patients undergoing colorectal surgery. DESIGN: We performed a prospective, randomized, controlled trial comparing a silver nylon dressing with gauze dressings in patients undergoing elective colorectal surgery. SETTING: The study was performed at a university-based, tertiary referral center. PATIENTS: We studied patients undergoing elective colorectal surgery with an abdominal skin incision of at least 3 cm. INTERVENTION: Patients were randomly assigned to receive either a silver nylon or a gauze dressing. MAIN OUTCOME MEASURES: The primary end point was surgical site infection occurring within 30 days of surgery. RESULTS: One hundred ten patients were enrolled in the study and were randomly assigned to 1 of 2 treatment groups. After a 30-day follow-up period, the incidence of surgical site infection was lower in the silver nylon group compared with the control group (13% vs 33%, P = .011). Twenty-five patients in the study developed superficial surgical site infections, 5 in the silver nylon group and 14 in the control group (P = .021). Two patients in the study group developed deep wound infections compared with 4 in the control group (P = .438). Multivariate analysis revealed that patients in the control group had a 3-fold increase in risk of infection compared with patients in the silver nylon group (P = .013). LIMITATIONS: A limitation of this study is that the members of the surgical team were not blinded to the treatment groups. CONCLUSION: Silver nylon is safe and effective in preventing surgical site infection following colorectal surgery.

An extended paIn relief trial utilizing the infiltration of a long-acting Multivesicular liPosome foRmulation Of bupiVacaine, EXPAREL (IMPROVE): a Phase IV health economic trial in adult patients undergoing ileostomy reversal

Background Opioid analgesics are effective for postsurgical pain but are associated with opioid-related adverse events, creating a significant clinical and economic burden. Gastrointestinal surgery patients are at high risk for opioid-related adverse events. We conducted a study to assess the impact of an opioid-sparing multimodal analgesia regimen with liposome bupivacaine, compared with the standard of care (intravenous [IV] opioid-based, patient-controlled analgesia [PCA]) on postsurgical opioid use and health economic outcomes in patients undergoing ileostomy reversal. Methods In this open-label, multicenter study, sequential cohorts of patients undergoing ileostomy reversal received IV opioid PCA (first cohort); or multimodal analgesia including a single intraoperative administration of liposome bupivacaine (second cohort). Rescue analgesia was available to all patients. Primary outcome measures were postsurgical opioid use, hospital length of stay, and hospitalization costs. Incidence of opioid-related adverse events was also assessed. Results Twenty-seven patients were enrolled, underwent the planned surgery, and did not meet any intraoperative exclusion criteria; 16 received liposome bupivacaine-based multimodal analgesia and eleven received the standard IV opioid PCA regimen. The multimodal regimen was associated with significant reductions in opioid use compared with the IV opioid PCA regimen (mean, 20 mg versus 112 mg; median, 6 mg versus 48 mg, respectively; P < 0.01), postsurgical length of stay (median, 3.0 days versus 5.1 days, respectively; P < 0.001), and hospitalization costs (geometric mean,

Laparoscopic management of distal ventriculoperitoneal shunt complications

6482 versus

DNA Damage, DNA Repair and Cancer

9282, respectively; P = 0.01). Conclusion A liposome bupivacaine-based multimodal analgesic regimen resulted in statistically significant and clinically meaningful reductions in opioid consumption, shorter length of stay, and lower inpatient costs than an IV opioid-based analgesic regimen.

Epigenetic field defects in progression to cancer

AbstractBackgroundThe traditional management of hydrocephalus still is the placement of ventriculoperitoneal (VP) shunts. However, the majority of patients require one or more revisions over their lifetime. Revisions may be required for infections, proximal site malfunction, or distal catheter complications. The authors present their experience with distal catheter complications managed laparoscopically.MethodsPatients with recurrent symptoms of increased intracranial pressure or abdominal complaints were evaluated for shunt malfunction. Similar radiographic imaging was performed for all the patients, including computed tomography (CT) of the head and abdomen, shunt series, and/or ultrasound of the distal catheter.ResultsFrom April 2003 to July 2005, 13 patients with distal VP shunt complications were managed laparoscopically. On the basis of preoperative cerebrospinal fluid (CSF) cultures, all the patients were determined not to have an infection. Radiographic imaging showed the patients to have distal catheter problems. Preoperatively, five abdominal CT scans, six shunt series, and four abdominal ultrasounds were obtained. All studies singly and positively identified the appropriate abdominal catheter defect except in three patients who required multiple sequential radiographic studies for final determination of the diagnosis. In four patients (30.8%), the distal catheter was found to be in the extraperitoneal space. Another four patients (30.8%) had intraabdominal CSF pseudocysts. Five patients (38.4%) had issues with the position of the intraabdominal catheter: four of them subdiaphragmatic and one on the dome of the bladder. Laparoscopic repositioning was successful for all 13 patients. ConclusionRegardless of the patient’s presenting symptoms, appropriate imaging studies should be obtained preoperatively in a sequential manner. Distal VP shunt complications can be safely and effectively managed laparoscopically. This approach allows the intraabdominal portion of the catheter to be assessed and problems to be managed, thereby salvaging the existing shunt and avoiding the potential morbidity associated with additional VP shunt placement.

Ratio images and ultraviolet C excitation in autofluorescence imaging of neoplasms of the human colon

DNA damage is a change in the basic structure of DNA that is not itself replicated when the DNA is replicated. A DNA damage can be a chemical addition or disruption to a base of DNA (creating an abnormal nucleotide or nucleotide fragment) or a break in one or both chains of the DNA strands. When DNA carrying a damaged base is replicated, an incorrect base can often be inserted opposite the site of the damaged base in the complementary strand, and this can become a mutation in the next round of replication. Also DNA doublestrand breaks may be repaired by an inaccurate repair process leading to mutations. In addi‐ tion, a double strand break can cause rearrangements of the chromosome structure (possibly disrupting a gene, or causing a gene to come under abnormal regulatory control), and, if such a change can be passed to successive cell generations, it is also a form of mutation. Mu‐ tations, however, can be avoided if accurate DNA repair systems recognize DNA damages as abnormal structures, and repair the damages prior to replication. As illustrated in Figure 1, when DNA damages occur, DNA repair is a crucial protective process blocking entry of cells into carcinogenesis.

Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing

A field defect is a field of pre-malignant tissue in which a new cancer is likely to arise. Field defects often appear to be histologically normal under the microscope. Recent research indicates that cells within a field defect characteristically have an increased frequency of epigenetic alterations and these may be fundamentally important as underlying factors in progression to cancer. However, understanding of epigenetic field defects is at an early stage, and the work of Katsurano et al published this year, is a key contribution to this field. One question examined by Katsurano et al was how early could the formation of an epigenetic field defect be detected in a mouse colitis model of tumorigenesis. They highlighted a number of measurable epigenetic alterations, detected very early in normal appearing tissue undergoing histologically invisible tumorigenesis. They also documented the increasing presence of the epigenetic alterations at successive times during progression to cancer. In this commentary, we offer a perspective on the changes they observed within a broader sequence of epigenetic events that occur in progression to cancer. In particular, we highlight the likely central role of epigenetic deficiencies in DNA repair gene expression that arise during progression to cancer.

Short-term outcomes of the surgical management of acquired rectourethral fistulas: does technique matter?

Abstract. The accepted screening technique for colon cancer is white light endoscopy. While most abnormal growths (lesions) are detected by this method, a significant number are missed during colonoscopy, potentially resulting in advanced disease. Missed lesions are often flat and inconspicuous in color. A prototype ultraviolet spectral imager measuring autofluorescence (AF) and reflectance has been developed and applied in a study of 21 fresh human colon surgical specimens. Six excitation wavelengths from 280 to 440 nm and formulaic ratio imaging were utilized to increase lesion contrast and cause neoplasms to appear bright compared to normal tissue. It was found that in the subset of lesions which were most difficult to visualize in standard color photographs [low contrast lesions, (LCLs)] a ratio image (F340/F440) of AF images excited at 340 and 440 nm produced extraordinary images and was effective in about 70% of these difficult cases. Contrast may be due to increased levels of reduced nicotinamide adenine dinucleotide, increased hemoglobin absorption, and reduced signal from submucosal collagen. A second successful ratio image (R480/R555) combined two reflectance images to produce exceptional images especially in particular LCLs where F340/F440 was ineffective. The newly discovered ratio images can potentially improve detection rate in screening with a novel AF colonoscope.

Are there differences in outcome after elective sigmoidectomy for diverticular disease and for cancer? A national inpatient study.

Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ0 fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.