Comparison of endoscopic submucosal dissection with laparoscopic-assisted colorectal surgery for early-stage colorectal cancer: a retrospective analysis.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is increasingly being used to resect early colorectal carcinoma, despite the technical difficulties associated with the procedure. Laparoscopic-assisted colorectal surgery (LAC) is an alternative to open surgery for colorectal cancers, and ESD was recently introduced as another alternative. In this study, we compared ESD with LAC as minimally invasive treatments for early colorectal cancer. PATIENTS AND METHODS: The study included 589 patients (297 patients with colorectal intramucosal or slightly submucosal invasive cancers undergoing ESD; 292 patients with T1 colorectal cancers undergoing LAC) who were treated at National Cancer Center Hospital in Tokyo, Japan, between January 1998 and September 2008. The clinical outcomes of ESD and LAC were evaluated retrospectively and compared on the basis of data that were originally collected prospectively. RESULTS: In the ESD group, mean tumor size was 37 mm, mean procedure time was 106 minutes, and the en bloc and curative resection rates were 87 % and 80 %, respectively. There were 14 perforations (4.7%) and 5 cases of postprocedure bleeding (1.7%); all complications were successfully managed endoscopically except for one of the perforations, which required emergency surgery. In the LAC group, mean tumor size was 20 mm, mean operation time was 206 minutes, and complications included 31 wound infections, 2 pelvic abscesses, 3 anastomotic leakages, and 1 anastomotic bleed. Stomas were necessary in 93 % of the patients who underwent LAC for rectal cancers located below the peritoneal reflection. CONCLUSIONS: ESD was associated with a lower complication rate than LAC, with favorable en bloc and curative resection rates. The safety profile and possibility of curative treatment with colorectal ESD provide advantages for the treatment of early colorectal cancers with nul risk of lymph node metastasis.

Endoscopic red flags for the detection of high-risk serrated polyps: an observational study.

BACKGROUND AND STUDY AIMS: In routine practice, colonoscopy may fail to prevent colorectal cancer (CRC), especially in the proximal colon. A better endoscopic recognition of serrated polyps is important, as this pathway may explain some of the post-colonoscopy cancers. In this study, the endoscopic characteristics of serrated polyps were examined. PATIENT AND METHODS: This was a cross-sectional, single-center study of all consecutive patients referred for elective colonoscopy during 1 year. The endoscopists were familiarized with the detection and treatment of nonpolypoid colorectal lesions. Serrated polyps were classified into high risk serrated polyps, defined as dysplastic or large (≥ 6 mm) proximal nondysplastic serrated polyps, and low risk serrated polyps including the remaining nondysplastic serrated polyps. Advanced colorectal neoplasms were defined as multiple (at least three),≥ 10 mm in size, high grade dysplastic adenomas or CRC. RESULTS: A total of 2309 patients were included (46.1 % men, mean age 58.4 years), of whom 2.5 % (57) had at least one high risk serrated polyp and 13.9 % (322) had at least one advanced neoplasm. Overall, serrated polyps were more often nonpolypoid than adenomas (16.2 % vs. 11.1 %; P = 0.002). In total, 65 high risk serrated polyps were found, of which 43.1 % (28) displayed a nonpolypoid endoscopic appearance. Patients with advanced neoplasms were more likely to have synchronous high risk serrated polyps than patients without advanced neoplasms: OR 3.66 (95 % CI 2.03 - 6.61, P < 0.001). CONCLUSIONS: High risk serrated polyps are frequently nonpolypoid and are associated with synchronous advanced colorectal neoplasms. Advanced colorectal neoplasms may therefore be considered red flags for the presence of high risk serrated polyps. Detection, diagnosis, and treatment of high risk serrated lesions may be important targets to improve the quality of colonoscopic cancer prevention.

Water immersion versus standard colonoscopy insertion technique: randomized trial shows promise for minimal sedation.

BACKGROUND AND STUDY AIMS: Water immersion is an alternative colonoscopy technique that may reduce discomfort and facilitate insertion of the instrument. This was a prospective study to compare the success of colonoscopy with minimal sedation using water immersion and conventional air insufflation. PATIENTS AND METHODS: A total of 229 patients were randomized to either water immersion or the standard air insertion technique. The primary outcome was success of minimal sedation colonoscopy, which was defined as reaching the cecum without additional sedation, exchange of the adult colonoscope or hands-on assistance for trainees. Patient comfort and satisfaction were also assessed. RESULTS: Successful minimal-sedation colonoscopy was achieved in 51 % of the water immersion group compared with 28 % in the standard air group (OR, 2.66; 95 % CI 1.48 - 4.79; P = 0.0004). Attending physicians had 79 % success with water immersion compared with 47 % with air insufflation (OR, 4.19; 95 % CI 1.5 - 12.17; P = 0.002), whereas trainees had 34 % success with water compared with 16 % using air (OR, 2.75; 95 % CI 1.15 - 6.86; P = 0.01). Using the water method, endoscopists intubated the cecum faster and this was particularly notable for trainees (13.0 +/- 7.5 minutes with water vs. 20.5 +/- 13.9 minutes with air; P = 0.0001). Total procedure time was significantly shorter with water for both experienced and trainee endoscopists ( P < 0.05). Patients reported less intraprocedural pain with water compared with air (4.1 +/- 2.7 vs. 5.3 +/- 2.7; P = 0.001), with a similar level of satisfaction. There was no difference in the neoplasm detection rates between the groups. CONCLUSION: Colonoscopy insertion using water immersion increases the success rate of minimal sedation colonoscopy. Use of the technique leads to a decrease in discomfort, time to reach the cecum, and the amount of sedative and analgesic used, without compromising patient satisfaction.

Mutation of a major keratin phosphorylation site predisposes to hepatotoxic injury in transgenic mice.

Simple epithelia express keratins 8 (K8) and 18 (K18) as their major intermediate filament (IF) proteins. One important physiologic function of K8/18 is to protect hepatocytes from drug-induced liver injury. Although the mechanism of this protection is unknown, marked K8/18 hyperphosphorylation occurs in association with a variety of cell stresses and during mitosis. This increase in keratin phosphorylation involves multiple sites including human K18 serine-(ser)52, which is a major K18 phosphorylation site. We studied the significance of keratin hyperphosphorylation and focused on K18 ser52 by generating transgenic mice that overexpress a human genomic K18 ser52--> ala mutant (S52A) and compared them with mice that overexpress, at similar levels, wild-type (WT) human K18. Abrogation of K18 ser52 phosphorylation did not affect filament organization after partial hepatectomy nor the ability of mouse livers to regenerate. However, exposure of S52A-expressing mice to the hepatotoxins, griseofulvin or microcystin, which are associated with K18 ser52 and other keratin phosphorylation changes, resulted in more dramatic hepatotoxicity as compared with WT K18-expressing mice. Our results demonstrate that K18 ser52 phosphorylation plays a physiologic role in protecting hepatocytes from stress-induced liver injury. Since hepatotoxins are associated with increased keratin phosphorylation at multiple sites, it is likely that unique sites aside from K18 ser52, and phosphorylation sites on other IF proteins, also participate in protection from cell stress.

A randomised tandem colonoscopy trial of narrow band imaging versus white light examination to compare neoplasia miss rates.

OBJECTIVE: Colonoscopy, the "gold standard" screening test for colorectal cancer (CRC), has known diagnostic limitations. Advances in endoscope technology have focused on improving mucosal visualisation. In addition to increased angle of view and resolution features, recent colonoscopes have non-white-light optics, such as narrow band imaging (NBI), to enhance image contrast. We aimed to study the neoplasia diagnostic characteristics of NBI, by comparing the neoplasm miss rate when the colonoscopy was performed under NBI versus white light (WL). DESIGN: Randomised controlled trial. SETTING: US Veterans hospital. PATIENTS: Elective colonoscopy adults. INTERVENTION: We randomly assigned patients to undergo a colonoscopic examination using NBI or WL. All patients underwent a second examination using WL, as the reference standard. MAIN OUTCOME MEASURES: The primary end point was the difference in the neoplasm miss rate, and secondary outcome was the neoplasm detection rate. RESULTS: In 276 tandem colonoscopy patients, there was no significant difference of miss or detection rates between NBI or WL colonoscopy techniques. Of the 135 patients in the NBI group, 17 patients (12.6%; 95% confidence interval (CI) 7.5 to 19.4%) had a missed neoplasm, as compared with 17 of the 141 patients (12.1%; 95% CI 7.2 to 18.6%) in the WL group, with a miss rate risk difference of 0.5% (95% CI -7.2 to 8.3). 130 patients (47%) had at least one neoplasm. Missed lesions with NBI showed similar characteristics to those missed with WL. All missed neoplasms were tubular adenomas, the majority (78%) was < or = 5 mm and none were larger than 1 cm (one-sided 95% CI up to 1%). Nonpolypoid lesions represented 35% (13/37) of missed neoplasms. INTERPRETATION: NBI did not improve the colorectal neoplasm miss rate compared to WL; the miss rate for advanced adenomas was less than 1% and for all adenomas was 12%. The neoplasm detection rates were similar high using NBI or WL; almost a half the study patients had at least one adenoma. Clinicaltrials.gov identifier: NCT00628147.

Computer-assisted chest radiography reading for tuberculosis screening in people living with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a significant risk factor for tuberculosis (TB). We evaluated the performance of computer-aided detection for tuberculosis (CAD4TB) in people living with diabetes mellitus (PLWD) in Indonesia. METHODS: PLWD underwent symptom screening and chest X-ray (CXR); sputum was examined in those with positive symptoms and/or CXR. Digital CXRs were scored using CAD4TB and analysed retrospectively using clinical and microbiological diagnosis as a reference. The area under the receiver operator curve (AUC) of CAD4TB scores was determined, and an optimal threshold score established. Agreement between CAD4TB and the radiologist's reading was determined. RESULTS: Among 346 included PLWD, seven (2.0%) had microbiologically confirmed and two (0.6%) had clinically diagnosed TB. The highest agreement of CAD4TB with radiologist reading was achieved using a threshold score of 70 (κ = 0.41, P < 0.001). The AUC for CAD4TB was 0.89 (95%CI 0.73-1.00). A threshold score of 65 for CAD4TB resulted in a sensitivity, specificity, positive predictive value and negative predictive value of respectively 88.9% (95%CI 51.8-99.7), 88.5% (95%CI 84.6-91.7), 17.0% (95%CI 7.6-30.8) and 99.6% (95%CI 98.2-100). With this threshold, 48 (13.9%) individuals needed microbiological examination and no microbiologically confirmed cases were missed. CONCLUSIONS: CAD4TB has potential as a triage tool for TB screening in PLWD, thereby significantly reducing the need for microbiological examination.

Susceptibility to hepatotoxicity in transgenic mice that express a dominant-negative human keratin 18 mutant.

Keratins 8 and 18 (K8/18) are intermediate filament phosphoglycoproteins that are expressed preferentially in simple-type epithelia. We recently described transgenic mice that express point-mutant human K18 (Ku, N.-O., S. Michie, R.G. Oshima, and M.B. Omary. 1995. J. Cell Biol. 131:1303-1314) and develop chronic hepatitis and hepatocyte fragility in association with hepatocyte keratin filament disruption. Here we show that mutant K18 expressing transgenic mice are highly susceptible to hepatotoxicity after acute administration of acetaminophen (400 mg/Kg) or chronic ingestion of griseofulvin (1.25% wt/wt of diet). The predisposition to hepatotoxicity results directly from the keratin mutation since nontransgenic or transgenic mice that express normal human K18 are more resistant. Hepatotoxicity was manifested by a significant difference in lethality, liver histopathology, and biochemical serum testing. Keratin glycosylation decreased in all griseofulvin-fed mice, whereas keratin phosphorylation increased dramatically preferentially in mice expressing normal K18. The phosphorylation increase in normal K18 after griseofulvin feeding appears to involve sites that are different to those that increase after partial hepatectomy. Our results indicate that hepatocyte intermediate filament disruption renders mice highly susceptible to hepatotoxicity, and raises the possibility that K18 mutations may predispose to drug hepatotoxicity. The dramatic phosphorylation increase in nonmutant keratins could provide survival advantage to hepatocytes.

Transnasal small-caliber esophagogastroduodenoscopy for preoperative evaluation of the high-risk morbidly obese patient.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is an important facet of the preoperative evaluation for bariatric surgery. Morbidly obese patients are at high risk for airway complications during this procedure, and an attractive alternative is transnasal EGD. This report describes a series of patients evaluated successfully using this technique. METHODS: All patients undergoing preoperative transnasal small-caliber EGD for morbid obesity surgery between September 2004 and June 2005 at a Veterans Affairs Hospital were included in the analysis. The variables assessed were the adequacy of the examination, patient tolerance, the need for sedation, and the ability to perform interventions. RESULTS: The study enrolled 25 patients (17 men and 8 women) with an average age of 55 years (range, 44-63 years) and an average body mass index (BMI) of 47 kg/m2 (range, 38-69 kg/m2). All the patients met the 1991 National Institutes of Health (NIH) Consensus Conference Criteria for bariatric surgery and were undergoing preoperative evaluation. The most common comorbidities were hypertension (82%), diabetes mellitus (80%), and obstructive sleep apnea (68%). All 25 patients had successful cannulation of the duodenum's second portion with excellent tolerance. There were no sedation requirements for 23 (92%) of the 25 patients. Significant pathology was found in 14 (56%) of the 25 patients, including hiatal hernia (28%), gastritis (16%), esophageal intestinal metaplasia (16%), esophagitis (12%), gastric polyps (8%), gastric ulcer (4%) and esophageal varices (4%). Biopsies were indicated for 12 patients and successful for all 12 (100%). CONCLUSION: Transnasal small-caliber EGD is a feasible and safe alternative to conventional EGD for the preoperative evaluation of patients undergoing bariatric surgery. It requires minimal to no sedation in a population at high risk for complications in this setting. In addition, this technique is effective in identifying pathology that requires preoperative treatment and offers a complete examination with biopsy capabilities. This technique should be considered for all morbidly obese patients at high risk for airway compromise during EGD.

Use of a double balloon enteroscope facilitates caecal intubation after incomplete colonoscopy with a standard colonoscope.

BACKGROUND: Caecal intubation is a necessary step in the complete endoscopic evaluation of the colon. Studies have estimated that experienced colonoscopists may fail to reach the caecum in up to 10% of cases. AIMS: To evaluate the utility of the double balloon enteroscope used for complete examination of the colon in patients with incomplete standard colonoscopy. PATIENTS: Twenty consecutive patients with incomplete colonoscopies within the Veterans Affairs Palo Alto Health Care System. Mean age of 66 years (S.D.+/-12 years, range 46-84), 16 men. METHODS: Prospective single-centre case series on the caecal intubation rate using standard double balloon enteroscope technique in patients with previous incomplete conventional colonoscopy. RESULTS: Use of the standard double balloon enteroscope technique permitted complete colonoscopy to be achieved in 95% of the patients (19/20). Seven patients (35%) had significant pathology beyond the extent of the prior incomplete colonoscopy. We performed endoscopic mucosal resection, polypectomy or biopsy. The mean time to reach the caecum was 28 min (S.D.+/-20 min, range 6-90 min). The sedation was similar to conventional colonoscopy. No complications occurred. CONCLUSIONS: The double balloon enteroscope technology and technique can be used to complete examination of the colon in patients who were referred because of incomplete standard colonoscopy.

Esophageal submucosal gland duct adenoma.

An 81-year-old man with a 3-year history of dysphagia underwent endoscopic resection of a 1-cm-diameter distal esophageal mass. Examination revealed a submucosal neoplasm with a circumscribed growth pattern composed of tubules, cysts, and papillae in association with a marked interstitial lymphoid infiltrate. The cyst lumens and papillae were lined by two to six layers of cytologically bland cuboidal to columnar cells with rare mitotic figures. The basal layer of cells was uniformly positive for smooth-muscle actin. Mucin-positive intracytoplasmic lumens were focally present, but cytoplasmic mucin was not seen. There was no evidence of Barrett's metaplastic epithelium. These features are similar to those in two, possibly three, previously reported cases of esophageal adenomas and bear a resemblance to sialadenoma papilliferum, a rare neoplasm of the minor salivary glands. Their clinicopathologic and immunohistologic features suggest that these neoplasms derive from the submucosal gland ducts. Comparison with the previously reported cases indicates that although the proportions of the various components (tubules, cysts, and papillae) may vary, all cases appear to pursue a slowly growing, clinically indolent course with no evidence of recurrence after complete resection.

Automated computer interviews to elicit utilities: potential applications in the treatment of deep venous thrombosis.

OBJECTIVE: To assess the practicality of an automated computer interview as a method to assess preferences for use in decision making. To assess preferences for outcomes of deep vein thrombosis (DVT) and its treatment. STUDY DESIGN: A multimedia program was developed to train subjects in the use of different preference assessment methods, presented descriptions of mild post-thrombotic syndrome (PTS), severe PTS and stroke and elicited subject preferences for these health states. This instrument was used to measure preferences in 30 community volunteers and 30 internal medicine physicians. We then assessed the validity of subject responses and calculated the number of quality-adjusted life years (QALYs) for each individual for each alternative. RESULTS: All subjects completed the computerized survey instrument without assistance. Subjects generally responded positively to the program, with volunteers and physicians reporting similar preferences. Approximately 26.5% of volunteers and physicians had preferences that would be consistent with the use of thrombolysis. Individualization of therapy would lead to the most QALYs. CONCLUSIONS: Utilization of computerized survey instruments to elicit patient preferences appears to be a practical and valid approach to individualize therapy. Application of this method suggests that there may be many patients with DVT for whom treatment with a thrombolytic drug would be optimal.

Quality-of-life research on the Internet: feasibility and potential biases in patients with ulcerative colitis.

OBJECTIVE: The World Wide Web (WWW) is a new communications medium that permits investigators to contact patients in nonmedical settings and study the effects of disease on quality of life through self-administered questionnaires. However, little is known about the feasibility and, what is more important, the validity of this approach. An on-line survey for patients with ulcerative colitis (UC) and patients whose UC had been treated with surgical procedures was developed. To understand how patients on the WWW might differ from those in practice and the potential biases in conducting epidemiological research in volunteers recruited on the Internet, post-surgery patients who responded to the WWW survey were compared with those in a surgical practice. SETTING: The Internet and private practice surgical clinic. MAIN OUTCOMES: Scores from the Short form 36 (SF-36) Health Assessment Questionnaire and the Self-Administered Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: Over a 5-month period, 53 post-surgery patients enrolled in the Internet study; 47 patients from a surgical clinic completed the same computer-based questionnaire. Surgically treated patients on the WWW were younger than their clinic counterparts (median age category 35-44 years vs. 45-54 years, p = 0.01) but more ill with a lower summary IBDQ score (168 vs. 186, p = 0.019) and lower health status across almost all dimensions of the SF-36 (p = 0.016). CONCLUSIONS: It is feasible to conduct epidemiological research on the effects of UC on quality of life on the Web; however, systematic differences in disease activity between volunteer patients on the WWW and "in the clinic" may limit the applicability of results.

Endoscopic ultrasound-guided diagnosis and therapy in pancreatic disease.

The role of endoscopic ultrasound (EUS) in the detection and staging of pancreatic cancer is well established in medical literature. The development of EUS-guided fine needle aspiration (FNA) and subsequently EUS-guided fine needle injection (FNI) has expanded the clinical utility of EUS. These newer techniques made "interventional" EUS possible. Several recent applications of EUS-guided FNI include celiac nerve block, pseudocyst drainage, and drug delivery into pancreatic tumors. EUS is also gaining acceptance as an alternative diagnostic modality in the management of choledocholithiasis. The value of EUS in the diagnosis of early chronic pancreatitis is still being actively studied. This article reviews a number of recent developments in EUS-guided diagnosis and therapy with an emphasis on EUS-guided FNA and EUS-guided FNI.

Role of emerging technology in the era of cost containment.

In this era of cost containment, new technologies will play the same role that they did before, improvement in the quality of care. Application of these new technologies in medical practice, however, will be scrutinized much more closely. The previous requirement of proving that a new technology is efficacious and safe will no longer be adequate. Physicians will be required to provide data that reflect the costs and overall effectiveness of the new technology. This article briefly discusses some key concepts of cost-effectiveness analysis.

Endoscopic management of acute gallstone pancreatitis.

Urgent management of acute biliary pancreatitis has increasingly included early endoscopic intervention. Endoscopic intervention allows effective removal of the offending stone(s) and reestablishment of biliary drainage. Four randomized controlled trials involving more than 800 patients in Western and Asian countries have been completed. This article summarizes the findings of these studies and proposes a preferred approach to the management of acute biliary pancreatitis.

Expandable metal stents for gastric-outlet, duodenal, and small intestinal obstruction.

The treatment of patients who have malignant gastric-outlet, duodenal and small intestinal obstructions is difficult. The morbidity and mortality of palliative surgery in these patients is significant. It is not uncommon for patients to be treated with supportive therapy only, which unfortunately, neither relieves the severe nausea and vomiting, nor allows adequate food intake. Over the past few years, a number of studies have reported the safety and efficacy of self-expanding metal stents used to palliate malignant upper gastrointestinal obstruction. In this article, the authors focus on the use of self-expanding metal stents to treat malignant gastric-outlet, duodenal, and small intestinal obstructions.