Ectopic adrenocorticotropic hormone syndrome caused by neuroendocrine carcinoma of the colon.

A 48-year-old woman with a history of autoimmune hemolytic anemia and taking long-term corticosteroid therapy presented with a 3-month history of general fatigue, abdominal distension, and pigmentation. A computed tomography scan of the abdomen showed a tumor in the sigmoid colon and multiple metastatic nodules in the liver. A colonoscopy revealed an obstructing mass with the presence of an irregular ulcer in the sigmoid colon. Following biopsy and histopathological analysis, the patient was diagnosed with neuroendocrine carcinoma (NEC) of the colon. She received her first cycle of chemotherapy, with carboplatin and etoposide. During hospitalization, her pigmentation and hypertension worsened and hypokalemia was observed, all of which suggsted Cushing's syndrome. Her plasma adrenocorticotropic hormone (ACTH) and cortisol levels were high, and an ectopic ACTH-producing tumor was suspected. After a second chemotherapy cycle, she developed neutropenic fever and subsequently died. At autopsy, two histological types were found in the tumor: small cell carcinoma and large cell NEC. Immunohistochemical analysis revealed ACTH in the large cell NEC. This is the first reported case of an ectopic ACTH syndrome caused by NEC of the colon.

An alternative option for "resect and discard" strategy, using magnifying narrow-band imaging: a prospective "proof-of-principle" study.

BACKGROUND: The "resect and discard" strategy is beneficial for cost savings on screening and surveillance colonoscopy, but it has the risk to discard lesions with advanced histology or small invasive cancer (small advanced lesion; SALs). The aim of this study was to prove the principle of new "resect and discard" strategy with consideration for SALs using magnifying narrow-band imaging (M-NBI). METHODS: Patients undergoing colonoscopy at a tertiary center were involved in this prospective trial. For each detected polyp <10 mm, optical diagnosis (OD) and virtual management ("leave in situ", "discard" or "send for pathology") were independently made using non-magnifying NBI (N-NBI) and M-NBI, and next surveillance interval were predicted. Histological and optical diagnosis results of all polyps were compared. RESULTS: While the management could be decided in 82% of polyps smaller than 10 mm, 24/31 (77%) SALs including two small invasive cancers were not discarded based on OD using M-NBI. The sensitivity [90% confidence interval (CI)] of M-NBI for SALs was 0.77 (0.61-0.89). The risk for discarding SALs using N-NBI was significantly higher than that using M-NBI (53 vs. 23%, p = 0.02). The diagnostic accuracy (95% CI) of M-NBI in distinguishing neoplastic from non-neoplastic lesions [0.88 (0.86-0.90)] was significantly better than that of N-NBI [0.84 (0.82-0.87)] (p = 0.005). CONCLUSIONS: The results of our study indicated that our "resect and discard" strategy using M-NBI could work to reduce the risk for discarding SALs including small invasive cancer (UMIN-CTR, UMIN000003740).

Proposal of a new 'resect and discard' strategy using magnifying narrow band imaging: pilot study of diagnostic accuracy.

BACKGROUND AND AIM: A 'resect and discard' strategy using non-magnifying narrow band imaging (N-NBI) has been proposed for reducing screening colonoscopy costs, but it does not take into consideration advanced histology and magnifying NBI (M-NBI) that can potentially further improve the 'resect and discard' strategy. We conducted a pilot study to investigate the feasibility of M-NBI for the new 'resect and discard' strategy with consideration for advanced histology. METHODS: The present study involved 63 patients. For each polyp, optical diagnosis was independently made using N-NBI and M-NBI, a decision (discard or send for pathology) was made based on the M-NBI findings, and histological and optical diagnosis results were compared. RESULTS: Sensitivity, specificity and accuracy (95% confidence interval) of M-NBI for lesions with advanced histology were 1.00 (0.36-1.00), 0.92 (0.91-0.92) and 0.92 (0.90-0.92), respectively. Whereas the management of 86% of small polyps could be decided without formal histopathology, lesions with advanced histology were not discarded using M-NBI. The diagnostic accuracy of M-NBI in distinguishing neoplastic from non-neoplastic lesions was higher than that of N-NBI. CONCLUSIONS: We propose a new resect and discard strategy with advanced histology using M-NBI that is a promising strategy to reduce the costs of histopathology and to minimize the risk of discarding important lesions.

Randomized study of two endo-knives for endoscopic submucosal dissection of esophageal cancer.

OBJECTIVES: Settings for endoscopic submucosal dissection (ESD) of esophageal cancer have not been standardized, and no studies have directly compared ESD devices in humans. METHODS: We conducted a randomized study to compare the performances of two different endo-knives, the Flush knife and Mucosectom, for esophageal ESD in 48 lesions. All procedures were initiated by two endoscopists, who were assisted by senior endoscopists with verbal advice. In the Flush-knife group, mucosal incision with a 2-mm Flush knife was followed by submucosal dissection using a 1-mm Flush knife. In the Mucosectom group, mucosal incision with a 2-mm Flush knife was followed by submucosal dissection with a Mucosectom. The primary outcome variable was the procedure time required for submucosal dissection. The secondary outcome variables were total procedure time, self-completion rates, and adverse events. RESULTS: Total procedure time in the Mucosectom group was significantly shorter than in the Flush-knife group (57±21 vs. 83±27 min, respectively; P<0.001). The submucosal-dissection time in the Mucosectom group was significantly shorter than in the Flush-knife group (40±18 vs. 61±23 min, respectively; P<0.001). The self-completion rate in the Mucosectom group was slightly higher than in the Flush-knife group, but the difference was not significant (91.7% vs. 75%, respectively; P=0.25). One perforation and one postoperative bleeding occurred in the Flush-knife group, both of which were treated successfully by endoscopic treatment. CONCLUSIONS: The Mucosectom reduced the procedure and submucosal-dissection times of esophageal ESD, without increasing adverse events.

Clinical outcomes of endoscopic mucosal resection and endoscopic submucosal dissection as a transoral treatment for superficial pharyngeal cancer.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been introduced for the treatment of superficial pharyngeal cancer. METHODS: Sixty superficial pharyngeal cancers in 45 patients were treated by EMR or ESD. Resectability and curability, complications, and survival were analyzed retrospectively. RESULTS: The en bloc resection and curative resection rate were higher with ESD (100; 81.6%) than with EMR (59; 50%). In subgroup analysis with regard to tumor size ≤ 10 mm, both resection rates were comparative. All the patients had preserved larynx and swallowing, speech, and airway function. Two of the 45 patients died of other diseases, local recurrence was observed in 4 of 18 patients with noncurative resection with a median observation period of 38 months. No recurrence was observed in patients with curative resection. CONCLUSIONS: ESD or EMR for superficial pharyngeal cancer is minimally invasive treatment and lesions larger than 10 mm should be referred for ESD.

Histological features responsible for brownish epithelium in squamous neoplasia of the esophagus by narrow band imaging.

BACKGROUND AND AIM: Esophageal squamous neoplasias usually appear brown under narrow band imaging as a result of microvascular proliferation, and brownish color changes in the areas between vessels, referred to as brownish epithelium. However, the reasons for the development of this brownish epithelium and its clinical implications have not been fully investigated. METHODS: Patients with superficial esophageal neoplasias treated by endoscopic resection were included in the study. Areas of mucosa with brownish and non-brownish epithelia were evaluated histologically. RESULTS: A total of 68 superficial esophageal neoplasias in 58 patients were included in the analysis. Of the 68 lesions, 32 were classified in the brownish epithelium group, and 36 in the non-brownish epithelium group. Brownish epithelium was significantly associated with a diagnosis of high-grade intraepithelial neoplasia or invasive cancer (P < 0.0001). Thinning of the keratinous layer, thinning of the epithelium, and cellular atypia were significantly associated with brownish epithelium by univariate analysis, and thinning of the keratinous layer and thinning of the epithelium were confirmed to be independent factors by multivariate analysis. The odds ratios were 9.6 (95% confidence interval: 2.0-46.3) for thinning of the keratinous layer, and 4.6 (95% confidence interval: 1.1-19.4) for thinning of the epithelium. CONCLUSIONS: Brownish epithelium is an important finding in the diagnosis of esophageal squamous neoplasia, and may be related to thinning of the keratinous layer, caused by neoplastic cell proliferation, and thinning of the epithelium.

Safety and curative ability of endoscopic submucosal dissection for superficial esophageal cancers at least 50 mm in diameter.

BACKGROUND AND AIM: Limited data are available regarding the use of endoscopic submucosal dissection (ESD) for superficial esophageal cancers ≥ 50 mm in diameter. The aim of the present study was to investigate the safety and success of ESD for superficial esophageal cancers ≥ 50 mm. METHODS: A total of 39 patients with superficial esophageal squamous cell carcinoma ≥ 50 mm were treated with ESD at Osaka Medical Center for Cancer and Cardiovascular Diseases between January 2004 and April 2011, and were analyzed in a retrospective study. RESULTS: En bloc resection was achieved in all patients. One mediastinal emphysema without perforation occurred during the procedure. Stricture developed in 11 of 39 patients, requiring a median of five endoscopic balloon dilatation procedures. Thirty-three clinical epithelial or lamina propria mucosal cancers were treated by ESD with curative intent, of which invasion into the muscularis mucosa or deeper was detected in seven and lymphovascular involvement in three. The en bloc resection rate was 100% with a tumor-free margin achieved in 92% of lesions. The curative resection and complication rates during ESD were 70% and 2.5%, respectively. CONCLUSION: ESD achieved a high en bloc resection rate of 92% with a tumor-free margin. Curative resection rate of ESD in patients with clinical epithelial or lamina propria mucosal cancers was not low at 70%. However, the risk of stricture must be taken into account when considering the use of ESD in lesions ≥ 50 mm.

Factors predicting perforation during endoscopic submucosal dissection for gastric cancer.

BACKGROUND: Perforation is a common complication of endoscopic submucosal dissection (ESD), but little is known about the relevant risk factors. OBJECTIVE: To investigate the risk factors for perforation. DESIGN: Retrospective study. SETTING: A cancer referral center. PATIENTS: A total of 1795 early gastric tumors in 1500 patients treated by ESD from July 2002 to December 2010 were included in the analysis. MAIN OUTCOME MEASUREMENTS: The associations between the incidence of perforation and patient and lesion characteristics were investigated. RESULTS: Perforation during ESD occurred in 50 lesions (2.8%). Univariate analysis identified tumor location (upper, middle, or lower stomach), tumor diameter (≤ 20 or >20 mm), and treatment period (lesions treated in the first or second period) as predictors of perforation. Multivariate analysis identified tumor location (upper stomach), tumor diameter (>20 mm), and treatment period (first half) as independent risk factors for perforation. The odds ratios were 2.4 (95% CI, 1.3-4.7; P = .006) for lesions in the upper stomach and 1.9 (95% CI, 1.0-3.5; P = .04) for lesions larger than 20 mm. Perforation risks were 5.4% for lesions in the upper stomach and 4.4% for lesions larger than 20 mm. Three patients required emergency surgery, but the rest of the patients were successfully treated with endoscopic clipping. There was no perforation-related mortality. LIMITATIONS: Single-center, retrospective study design. CONCLUSIONS: Lesions in the upper stomach and lesions larger than 20 mm were independent risk factors for perforation during ESD. Patients should be made aware of the estimated high risks of these lesions before undergoing ESD.

Comprehensive investigation of areae gastricae pattern in gastric corpus using magnifying narrow band imaging endoscopy in patients with chronic atrophic fundic gastritis.

BACKGROUND: Barium radiographic studies have suggested the importance of evaluating areae gastricae pattern for the diagnosis of gastritis. Significance of endoscopic appearance of areae gastricae in the diagnosis of chronic atrophic fundic gastritis (CAFG) was investigated by image-enhanced endoscopy. MATERIALS AND METHODS: Endoscopic images of the corpus lesser curvature were studied in 50 patients with CAFG. Extent of CAFG was evaluated with autofluorescence imaging endoscopy. The areae gastricae pattern was evaluated with 0.2% indigo carmine chromoendoscopy. Micro-mucosal structure was examined with magnifying chromoendoscopy and narrow band imaging. RESULTS: In patients with small extent of CAFG, polygonal areae gastricae separated by a narrow intervening part of areae gastricae was observed, whereas in patients with wide extent of CAFG, the size of the areae gastricae decreased and the width of the intervening part of areae gastricae increased (p < 0.001). Most areae gastricae showed a foveola-type micro-mucosal structure (82.7%), while intervening part of areae gastricae had a groove-type structure (98.0%, p < 0.001). Groove-type mucosa had a higher grade of atrophy (p < 0.001) and intestinal metaplasia (p < 0.001) compared with foveola type. CONCLUSIONS: As extent of CAFG widened, multifocal groove-type mucosa that had high-grade atrophy and intestinal metaplasia developed among areae gastricae and increased along the intervening part of areae gastricae. Our observations facilitate our understanding of the development and progression of CAFG.

Predicting the effects of chemoradiotherapy for squamous cell carcinoma of the esophagus by induction chemotherapy response assessed by positron emission tomography: toward PET-response-guided selection of chemoradiotherapy or esophagectomy.

BACKGROUND: We have developed a treatment protocol for esophageal cancer involving a single course of induction chemotherapy followed by chemoradiotherapy. This study aimed to determine if it was possible to predict the effects of chemoradiotherapy on the basis of the response to induction chemotherapy, assessed by positron emission tomography (PET). METHODS: Sixteen patients with Stage II-IVA esophageal cancer were treated using this protocol from April 2007 to July 2010. Chemotherapy involved a fluorouracil and platinum-based combination regimen. All patients received PET scans before and 12-24 days after the beginning of induction chemotherapy. Associations between the response to induction chemotherapy assessed by PET and the effects of chemoradiotherapy were evaluated. RESULTS: Induction chemotherapy followed by chemoradiotherapy resulted in complete response (CR) in 10 of the 16 patients. The reduction in maximum standardized uptake value (SUV(max)) was 58 ± 12% in patients with CR (n = 10), compared with 14 ± 16% in patients without CR (n = 6) (P < 0.0001). Using a cut-off value of 55% for SUV(max) reduction rate, eight of 10 cancers with CR and six of six cancers without CR were correctly identified, providing a sensitivity and specificity of 80 and 100%, respectively. The overall 1-year survival rates for patients with an SUV(max) reduction rate >55% (responders) were 100%, compared with 60% for patients with an SUV(max) reduction rate ≤55% (non-responders), respectively. CONCLUSIONS: The response to a single course of induction therapy assessed by PET was significantly associated with the effects of chemoradiotherapy.

Autofluorescence imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia: a phase II study.

BACKGROUND AND AIM: Few prospective studies examining the efficacy of autofluorescence imaging (AFI) screening for esophageal cancer have been reported. This study aimed to investigate the diagnostic value of AFI endoscopy for the screening of squamous mucosal high-grade neoplasia of the esophagus, performed by experienced and less-experienced endoscopists. METHODS: Patients with a history of esophageal neoplasia or head and neck cancer underwent AFI endoscopic screening, followed by chromoendoscopy using iodine staining as the reference standard. The primary outcome was the sensitivity of AFI for detecting new squamous mucosal high-grade neoplasias. The secondary outcome was the positive predictive value (PPV) of AFI. RESULTS: Of a total 364 patients who underwent endoscopic examination, 43 new mucosal high-grade neoplasias were detected. The sensitivities of AFI in the experienced and less-experienced endoscopist groups were 71% (95% confidence interval [CI]: 55-87%) and 50% (95% CI: 32-68%), respectively. The PPV of AFI in the experienced and the less-experienced endoscopist groups were 25% (95% CI: 16-34%) and 26% (95% CI: 15-37%), respectively. The sensitivity of AFI in lesions ≤ 10 mm (31%, 5/16 lesions) was significantly lower than that in lesions > 10 mm (78%, 21/27 lesions) (P = 0.003). CONCLUSIONS: The sensitivity of AFI for the detection of new squamous mucosal high-grade neoplasias, and its PPV, were both low. Based on these results, a randomized study to compare AFI with standard techniques is not justified.

[Usefulness of endoscopic salvage treatment in a patient with local failure esophageal cancer after CRT].

Chemoradiotherapy (CRT) is widely used as non-surgical treatment for esophageal cancer in recent years. CRT is very useful, but it allows about 40% relapse. Salvage surgery after CRT, long-term survival can be expected, but perioperative mortality is high. In contrast, EMR for local failure after definitive CRT has been reported showing a 5-year survival rate of 49. 1%. If it can safely control of local failure, then we thought it's useful for long-term survival. If the depth of invasion was to the submucosal layer of the local failure lesion, we performed an endoscopic resection. If vertical margins are positive pathologically, we have added a photodynamic therapy. In cases of difficult endoscopic resection, PDT alone was performed. We experienced a case of recurrent esophageal cancer after CRT was useful for local treatment with PDT and EMR.

Autofluorescence imaging of early colorectal cancer.

Autofluorescence imaging (AFI) is expected to better detect colorectal neoplasms than the conventional white light imaging (WLI). The AFI image of colorectal cancer is different according to its macroscopic type. Protruded lesion, which is the most common macroscopic type of colorectal neoplasms, is revealed as magenta protruded lesion. Flat lesion, which is uncommon macroscopic type, is presented as distinct magenta area surrounding green mucosa using AFI. And depressed lesion, which is rare macroscopic type, is revealed as green area surrounded by magenta mucosa.

Autofluorescence imaging with a transparent hood for detection of colorectal neoplasms: a prospective, randomized trial.

BACKGROUND: Colonoscopy is one of the most reliable methods for detection of colorectal neoplasms, but conventional colonoscopy can miss some lesions. OBJECTIVE: To evaluate the efficacy of autofluorescence imaging (AFI) with a transparent hood (TH) for detection of colorectal neoplasms. DESIGN: A 2 × 2 factorial designed, prospective, randomized, controlled trial. SETTING: This study was conducted at the Osaka Medical Center for Cancer and Cardiovascular Diseases, a tertiary cancer center. PATIENTS: A total of 561 patients. INTERVENTIONS: Patients were allocated to 1 of 4 groups: (1) white light imaging (WLI) alone--colonoscopy using WLI without a TH; (2) WLI+TH--colonoscopy using WLI with a TH; (3) AFI alone--colonoscopy using AFI without a TH; and (4) AFI+TH--colonoscopy using AFI with a TH. Eight colonoscopists used each allocated method. MAIN OUTCOME MEASUREMENT: The difference in neoplasm detection rate (number of detected neoplasms per patient) between the WLI alone and AFI+TH groups. RESULTS: Neoplasm detection rate (95% confidence interval) in the AFI+TH group was significantly higher than in the WLI alone group (1.96 [1.50-2.43] vs 1.19 [0.93-1.44]; P = .023, Tukey-Kramer multiple comparison test). Relative detection ratios (95% confidence interval) for polypoid neoplasms based on Poisson regression model were significantly increased by mounting a TH (1.69 [1.34-2.12], P < .001), and relative detection ratios for flat neoplasms were significantly increased by AFI observation (1.83 [1.24-2.71], P = .002). LIMITATIONS: Open trial performed in single cancer referral center. CONCLUSION: AFI colonoscopy with a TH detected significantly more colorectal neoplasms than did conventional WLI colonoscopy without a TH.

Significance of each narrow-band imaging finding in diagnosing squamous mucosal high-grade neoplasia of the esophagus.

BACKGROUND AND AIM: Although narrow-band imaging (NBI) is used increasingly in clinical situations, the significance of each NBI finding has not been investigated. The primary endpoint of the present study was to identify the significant NBI findings to diagnose esophageal mucosal high-grade neoplasia. METHODS: Between August 2007 and January 2009, we detected 59 new superficial esophageal lesions. The video images of NBI were recorded digitally. NBI findings such as brownish dots (dilated intra-epithelial papillary capillary loop [IPCL]), tortuous IPCL, elongated IPCL, caliber change in IPCL, variety in IPCL shapes, demarcation line, brownish epithelium, and protrusion or depression were evaluated using the video images. The association between each NBI finding and diagnosis of mucosal high-grade neoplasia, and intra- and interobserver agreement was evaluated. RESULTS: In univariate analysis, brownish epithelium, brownish dots, tortuous IPCL, variety in IPCL shapes and demarcation line were associated significantly with diagnosis of mucosal high-grade neoplasia. In multivariate analysis, brownish epithelium and brownish dots were confirmed to be independent factors. Odds ratios were 25.5 (95% confidence interval [CI]: 2.4-268) for brownish epithelium and 19.3 (95% CI: 1.8-207.7) for brownish dots. Intraobserver agreement was substantial for brownish epithelium and brownish dots. Interobserver agreement was moderate in brownish epithelium and brownish dots. CONCLUSIONS: Brownish epithelium and brownish dots were confirmed to be significant and reproducible NBI findings in the diagnosis of squamous mucosal high-grade neoplasia of the esophagus. Initial assessment of esophageal lesions should be done based on these findings.