Biomedical subjects

Walter E Longo

Publications and source records attributed to Walter E Longo.

46 records · Page 3Linked to original sources

PubMed2003

Human intestinal epithelial and smooth muscle cells are potent producers of IL-6.

BACKGROUND: Interleukin-6 (IL-6), a pluripotent cytokine, has traditionally been considered the product of proinflammatory cells. However, many other cell types have been shown to produce IL-6. Since intestinal inflammation is commonly associated with a vigorous systemic inflammatory response, we hypothesized that intestinal epithelial and smooth muscle cells might contribute to that response by producing IL-6. We therefore studied the capacity of differentiated human intestinal epithelial and smooth muscle cell lines to produce IL-6 in response to various proinflammatory stimuli. MATERIALS AND METHODS: CCL-241, a human intestinal epithelial cell line, and HISM, a human intestinal muscle cell line, were grown to confluency and then treated for 24 h with various concentrations of lipopolysaccharide, Clostridium difficile culture extract containing both toxin A and toxin B, recombinant human tumor necrosis factor-alpha (TNF-alpha), or recombinant human interleukin-1 beta (IL-1beta). Supernatants were then collected for IL-6 determination using an enzyme-linked immunosorbent assay. Cell numbers were determined using a Coulter counter. For comparison, parallel studies were performed using phorbol ester-primed U-937 and THP-1 human macrophage cell lines. RESULTS: Both human intestinal epithelial and smooth muscle cells produced IL-6 under basal conditions. In HISM cells, but not in CCL-241 cells, IL-6 release was increased slightly by treatment with C. difficile culture extract containing both toxin A and toxin B and with lipopolysaccharide. In both cell lines, IL-6 production was profoundly stimulated by treatment with IL-1beta and less so with TNF-alpha. Combinations of high-dose TNF-alpha and IL-1beta may have a slightly additive, but not synergistic, effect on IL-6 release. The amount of IL-6 produced by IL-1-stimulated intestinal cell lines was 70-fold higher than that produced by stimulated macrophage cell lines. CONCLUSIONS; Both intestinal epithelial and smooth muscle cells demonstrate the ability to release significant amounts of IL-6. The profound response to IL-1beta and TNF-alpha stimulation by both cell lines suggests that human intestinal parenchymal cells, influenced by paracrine mediators liberated from proinflammatory cells, might significantly contribute to the overall systemic inflammatory response by producing IL-6.

Bacterial Proteins↗

PubMed2003

Risk factors for adverse outcomes after the surgical treatment of appendicitis in adults.

OBJECTIVE: To define risk factors that predict adverse outcomes after the surgical treatment of appendicitis in Department of Veterans Affairs Medical Centers. SUMMARY BACKGROUND DATA: Risk factors for adverse outcomes after the surgical treatment of appendicitis in adults are poorly defined. Accurate presurgical assessment of the risk of perioperative complications and death is important in planning surgical therapy. METHODS: The VA National Surgical Quality Improvement Program contains prospectively collected and extensively validated data on approximately 1,000,000 major surgical operations. All patients undergoing surgical intervention for appendicitis from 1991 to 1999 registered in this database were selected for study. Independent variables examined included 68 putative preoperative risk factors and 12 intraoperative process measures. Dependent variables were 21 specific adverse outcomes, including death. Stepwise logistic regression analysis was used to construct models predicting 30-day morbidity rate and the 30-day postoperative mortality rate. RESULTS: There were 4163 patients identified. The mean age was 50 years; 96% were male. Sixteen percent of patients had 1 or more complications after surgical intervention. Prolonged ileus, failure to wean from the ventilator, pneumonia, and both superficial and deep wound infection were the most frequently reported complications, accounting for the majority of the morbidity. The 30-day mortality rate was 1.8% (74 deaths). For >50% of the complications reported, the 30-day mortality rates were significantly higher (P < 0.01) for patients with complications than for those without. Thirty-day mortality rates for several complications exceeded 30%, including cardiac arrest, coma >24 hours, myocardial infarction, acute renal failure, bleeding requiring >4 units of red cells, and systemic sepsis. Four preoperative factors predicted a high risk of 30-day mortality in the logistic regression analysis: "completely dependent" functional status, bleeding disorder, steroid usage, and current pneumonia. "Threat to life" or "moribund" American Society of Anesthesiologists classification and more than a 10% weight loss in the 6 months before surgery were associated with a high risk of complications. CONCLUSIONS: Morbidity and mortality rates after the surgical treatment of appendicitis in VA hospitals are comparable with those reported in other large series. Most postsurgical complications are associated with an increased 30-day mortality rate. The models presented here are the most robust available in predicting 30-day morbidity and mortality for VA patients with appendicitis. Furthermore, they provide a starting point for the design of similar models to evaluate non-VA patients with appendicitis using the data the National Surgical Quality Improvement Program is currently gathering from private hospitals.

Adolescent↗

PubMed2003

Colovaginal fistulas. Etiology and management.

OBJECTIVE: To review the diagnosis and treatment of colovaginal fistulas from various causes. DATA SOURCES: Papers on colovaginal fistulas were identified using Ovid and PubMed. The search terms used were as follows: colovaginal fistulas, rectovaginal fistulas, diverticular disease and fistulas. METHODS OF STUDY: Articles were selected based on their relevance to colovaginal fistulas and were then further subdivided into epidemiology, etiology, presentation, diagnosis and management. RESULTS: English-language papers were selected based on their relevance to all aspects of colovaginal fistulas. CONCLUSION: Optimizing nutrition is paramount prior to surgery. Medical management rarely corrects the problem. Diverticular colovaginal fistulas arise in patients who have previously undergone a hysterectomy. Radiation-related fistulas often involve the distal sigmoid colon and rectum, and recurrent cancer must be ruled out. Often symptoms are associated with radiation cystitis and terminal ileitis. When indicated, restoration of intestinal continuity is preferred. Malignant fistulas carry a poor prognosis, and when surgical removal is not practical, they are treated palliatively with fecal diversion or an endoluminal stent. Those arising from inflammatory bowel disease most frequently arise due to Crohn's disease, and extirpation of diseased bowel and associated abscess will successfully treat the condition. Fistulas arising from ulcerative colitis can be malignant. There remains a small role for colostomy as a nondefinitive procedure to alleviate symptoms. Colovaginal fistulas require a multidisciplinary approach and focused diagnostics, successful treatment can dramatically improve the patient's quality of life.

Colonic Diseases↗

PubMed2003

The specialty of colon and rectal surgery: its impact on patient care and role in academic medicine.

The specialty of colon and rectal surgery, a specialty of general surgery, has evolved from the field of proctology. Clinical care has demonstrated decreased number of patients requiring intestinal stomas, improved quality of life in patients with benign anorectal disorders, and more favorable results in patients afflicted with primary and recurrent colorectal cancer. Basic science investigations have spawned from clinical questions such as the molecular biology of colorectal cancer, use of cyclooxygenase inhibitors and polyp regression, and novel cytokine antagonists in inflammatory bowel disease. Medical students are exposed to surgeons with expertise in anorectal anatomy and physiology, mechanisms of carcinogenesis and the importance of screening for detection of colorectal cancer, and novel therapies for inflammatory bowel disease. Surgical residents benefit by having a colorectal surgeon on the faculty by repetitive exposure to anorectal surgery, low pelvic anastomoses, stoma creation and closure, and surgery involving the small intestine. Senior colorectal surgeons will develop critical pathways for the healthcare delivery of patients afflicted with colorectal disease. The specialty of colorectal surgery will continue to translate into improved patient care and positively impact in academic medicine by providing expertise into student and resident training and generate highly sophisticated clinical and basic science investigations.

Colon↗

PubMed2002

Acute surgical emergencies in inflammatory bowel disease.

BACKGROUND: Acute surgical emergencies in patients with inflammatory bowel disease may carry a substantial morbidity, but fortunately today, a low mortality. The aim of this review is to delineate the treatment of acute surgical emergencies that occur in patients with ulcerative colitis and Crohn's disease. METHODS: Suitable English language reports were identified using PubMed search. RESULTS: Inflammatory bowel disease can present in numerous ways as an acute surgical emergency. These include toxic colitis, hemorrhage, perforation, intra-abdominal masses or abscesses with sepsis, and intestinal obstruction. Toxic colitis and perforation are best managed with intestinal resection and fecal diversion. Hemorrhage in ulcerative colitis initially requires colectomy with rectal preservation and ileostomy. In Crohn's disease hemorrhage is often focal and localization and segmental resection are performed. Intra-abdominal abscesses should initially be attempted by computed tomography-guided percutaneous drainage followed subsequently by definitive resection. Perianal disease requires abscess drainage with minimal tissue trauma. Intestinal obstruction should be initially managed nonoperatively, with surgery reserved for complete obstruction or intractability. CONCLUSIONS: Acute surgical emergencies in patients with inflammatory bowel disease are rare and can have a high morbidity. With a multidisciplinary approach, morbidity can be reduced and patients can have a rapid return and improved quality of life.

Abdominal Abscess↗

PubMed2002

Cholecystectomy in patients with previous spinal cord injury.

BACKGROUND: The number of people in the United States with spinal cord injury (SCI) is estimated at about 200,000. The prevalence of gallbladder disease in this population is about three times as high as in neurally intact people, but the results of surgical treatment have received little attention. METHODS: A retrospective, population-based study of patients with SCI who later received cholecystectomy for benign gallbladder disease was performed. National computer data sets of all patients receiving medical care in all Department of Veterans Affairs (DVA) medical centers for fiscal years 1994 to 1998 were used. Computer-based data were augmented with chart-based resources. RESULTS: During the period of interest, there were 21,849 patients with ICD-9-CM codes for SCI in the DVA computer system, among whom 367 had codes for cholecystectomy. After retrieval and review of data from individual charts, 118 were deemed evaluable. There were 68 who had successful laparoscopic cholecystectomy and 14 who required conversion to open cholecystectomy after laparoscopic efforts failed (conversion rate 14 of 82=17%). There were 36 who received planned open cholecystectomy. Patients under the age of 60 years were more likely to have a laparoscopic approach (P <0.05). Emergency cholecystectomies were more likely to be performed via the open route (P <0.01). The morbidity rate was 8 of 68 (12%) for successful laparoscopic cholecystectomy, 4 of 14 (29%) for failed laparoscopic surgery completed by conventional open technique, and 11 of 36 (31%) for planned open surgery. The mortality rate in the traditional surgery group was 1 of 36 (3%). There were no deaths in the other groups. CONCLUSIONS: We believe this series is the largest so far reported. The mortality rate of cholecystectomy in SCI patients is comparable to that in neurally intact individuals, but the morbidity rate is high. Contractures, stomas, heterotopic ossification, and other sequelae of SCI do not generally cause technical difficulties with surgery. If complications of cholecystectomy are indeed SCI-related, attention to perioperative SCI care could improve outcomes of cholecystectomy. Future research should continue to explore this important research topic.

Adult↗

PubMed2002

The preoperative assessment and postoperative surveillance of patients with colon and rectal cancer.

Many advances have been made in the field of colorectal cancer follow-up since the pioneering efforts of Wangensteen and others with second-look operations in the 1950s. The understanding of the biology and natural history of colorectal malignancy has been advanced. Diagnostic methods for detection of recurrent disease have also advanced tremendously with CEA monitoring, immunoscintigraphy. CT, MRI, and PET imaging. As has been discussed in this article, however, no strategy of postoperative follow-up has been shown unequivocally to produce improved survival benefit or cure rate. It is quite possible that benefit will be shown, but well-controlled trials will be required. Cost considerations will likely prove important, because the rate of detection of curable disease will likely.be low. Quality of life issues will also be important in such trials. Better treatment and outcome ol recurrent disease would provide a strong rationale for vigorous postoperative surveillance. New recommendations are currently evolving [54]. Early diagnosis seems likely to enhance the curability of both local and distant relapses and second primary tumors. Furthermore, there may be a survival and quality of life advantage that results from the early institution of chemotherapy, even for those tumors found to be inoperable [55]. In devising a plan for follow-up in patients, it is important to recognize the anatomic and temporal patterns of recurrence as well as their relationships to the initial tumor staging. Although there is little proof that the identification of recurrent disease in follow-up programs increases the likelihood of resectability, cure, or prolonged survival, many physicians have witnessed successful treatment of recurrent colorectal cancer. These anecdotal experiences, the unproven belief that follow-up is beneficial, and traditions imparted during training are among the likely motivating factors for most physicians caring for colorectal cancer patients.

Colorectal Neoplasms↗

PubMed2002

Morbidity and mortality of gastrectomy for cancer in Department of Veterans Affairs Medical Centers.

BACKGROUND: The purpose of this study was to define risk factors that predict 30-day morbidity and mortality after gastrectomy for cancer in Veterans Affairs (VA) Medical Centers. METHODS: The VA National Surgical Quality Improvement Program prospectively collected data on 708 patients undergoing gastrectomy for cancer in 123 participating VA medical centers from 1991 to 1998. Independent variables included 68 preoperative patient characteristics and 12 intraoperative variables; the dependent variables were 21 defined adverse outcomes and death. Predictive models for 30-day morbidity and mortality were constructed by using stepwise logistic regression analysis. RESULTS: The 30-day morbidity rate was 33.3% (236 of 708). The overall 30-day mortality rate was 7.6% (54 of 708). Significant positive predictors of morbidity (P <.05) included current pneumonia, American Society of Anesthesiologists class IV (threat to life), partially dependent functional status, dyspnea on minimal exertion, preoperative transfusion, extended operative time, and increasing age. Significant positive predictors of mortality (P <.05) included do not resuscitate status, prior stroke, intraoperative transfusion, preoperative weight loss, preoperative transfusion, and elevated preoperative alkaline phosphatase level. CONCLUSIONS: Risk factors predicting morbidity and mortality rates at VA hospitals after gastrectomy for gastric cancer are reported by using a prospectively collected, multi-institutional database. Assigning relative weights to factors associated with adverse outcomes may help improve patient care.

Adult↗

PubMedDate not supplied

Colorectal cancer presenting as surgical emergencies.

Colorectal Cancer (CRC) is a major cause of cancer morbidity and mortality. Surgery is considered the first line therapy for CRC, and is generally encountered by many surgeons under elective conditions. Unfortunately, colorectal cancer may present acutely as a surgical emergency. These conditions include, but are not limited to perforation, hemorrhage, and obstruction. The presentation of a patient with these conditions can lead to higher morbidity and mortality. The choice of operation depends mainly on the site of the disease (left-sided versus right-sided), the patient's physical condition, nutritional status, and age. The treatment for right-sided lesions is a right hemicolectomy. However, treatment of left-sided lesions is still undecided. There are many therapeutic options such as primary or staged resections, Hartman's procedure, subtotal colectomy, or colostomy. Other therapies involve non-operative techniques such as laser therapy, colonic stenting, emergency endoscopy, and comfort measures.

Colorectal Neoplasms↗

PubMedDate not supplied

Follow-up of colorectal cancer patients after resection with curative intent-the GILDA trial.

PURPOSE: Surgery remains the primary treatment of colorectal cancer. Data are lacking to delineate the optimal surveillance strategy following resection. A large-scale multi-center European study is underway to address this issue (Gruppo Italiano di Lavoro per la Diagnosi Anticipata-GILDA). METHODS: Following primary surgery with curative intent, stratification, and randomization at GILDA headquarters, colon cancer patients are then assigned to a more intensive or less intensive surveillance regimen. Rectal cancer patients undergoing curative resection are similarly randomized, with their follow-up regimens placing more emphasis on detection of local recurrence. Target recruitment for the study will be 1500 patients to achieve a statistical power of 80% (assuming an alpha of 0.05 and a hazard-rate reduction of >24%). RESULTS: Since the trial opened in 1998, 985 patients have been randomized from 41 centers as of February 2004. There were 496 patients randomized to the less intensive regimens, and 489 randomized to the more intensive regimens. The mean duration of follow-up is 14 months. 75 relapses (15%) and 32 deaths (7%) had been observed in the two more intensive follow-up arms, while 64 relapses (13%) and 24 deaths (5%) had been observed in the two less intensive arms as of February 2004. CONCLUSIONS: This trial should provide the first evidence based on an adequately powered randomized trial to determine the optimal follow-up strategy for colorectal cancer patients. This trial is open to US centers, and recruitment continues.

Adolescent↗