Evaluation of FOLFOX or CAPOX reintroduction with or without bevacizumab in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy (REACT study).

BACKGROUND: Chemotherapy in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of reintroducing modified FOLFOX6 (mFOLFOX6) or CAPOX with or without bevacizumab in recurrent colorectal cancer patients after oxaliplatin adjuvant chemotherapy. METHODS: Patients that participated in this trial had a medical history of adjuvant chemotherapy, including oxaliplatin with a cumulative dose greater than 400 mg/m2, and recurrence that was diagnosed more six months post adjuvant chemotherapy. Primary endpoints were response rate (RR) and disease control rate (DCR), while key secondary endpoints were time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 31 patients were enrolled between October 2012 and October 2016. Of the 29 eligible patients, 7 received mFOLFOX6 and 22 received CAPOX. The RR was 62.1% (95% confidence interval 42.3-79.3) and the DCR was 82.8% (95% confidence interval 64.2-94.2). The RR for oxaliplatin-free interval was 100.0% in months 6-12 and 56.0% after 12 months. Median TTF, PFS, and OS were 6.3, 10.8, and 28.7 months, respectively. Grade 3 or worse peripheral sensory neuropathy developed in 6.5%. Allergic reactions occurred in 12.9% of the patients, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. CONCLUSION: Reintroduction of oxaliplatin was feasible and achieved high RR or DCR in patients after more than 6 months post oxaliplatin adjuvant chemotherapy.

Prospective evaluation of the proportion of sessile serrated adenoma/polyps in endoscopically diagnosed colorectal polyps with hyperplastic features.

BACKGROUND AND STUDY AIMS: Sessile serrated adenoma/polyps (SSA/Ps) are considered precursors of colorectal cancers with microsatellite instability. However, it is still difficult to differentiate SSA/Ps from hyperplastic polyps endoscopically; therefore, the prevalence of SSA/Ps remains uncertain in clinical practice. This study aimed to clarify the proportion of SSA/Ps in endoscopically diagnosed colorectal polyps with hyperplastic features (E-HPs). PATIENTS AND METHODS: Patients aged ≥ 40 years undergoing colonoscopy for standard clinical indications at our center were prospectively enrolled between June 2013 and May 2014. During colonoscopy, 0.05 % indigo carmine dye was sprayed throughout the colorectum to highlight lesions. All detected lesions were diagnosed by high definition magnifying narrow-band imaging and were resected endoscopically or surgically, apart from rectosigmoid E-HPs ≤ 5 mm. The number of rectosigmoid E-HPs ≤ 5 mm was recorded, and some were resected for use as tissue samples. RESULTS: A total of 343 patients (male: 42.9 %; mean age: 61.5 years) were included. Among 3838 E-HPs (distal: 96.4 %) detected in 294 patients, 792 were resected and analyzed. All of 21 SSA/Ps identified in 17 patients were included in E-HPs, and the overall proportion of SSA/Ps in E-HPs was 2.7 %. However, this proportion increased with the size of E-HPs (≤ 5 mm: 0.7 %; 6 - 9 mm: 29.0 %; ≥ 10 mm: 70 %) and was higher in the proximal colon than in the distal colorectum (10.9 % vs. 0.9 %). In addition, no SSA/P was found in the rectum, and no SSA/P had cytological dysplasia. CONCLUSIONS: The overall proportion of SSA/Ps in E-HPs was 2.7 %, although this proportion was higher in the proximal colon and increased with the size of E-HPs. SSA/Ps were common in routine colonoscopy, with a prevalence of at least 5.0 %. STUDY REGISTRATION: UMIN000010832.

The addition of high magnifying endoscopy improves rates of high confidence optical diagnosis of colorectal polyps.

BACKGROUND AND STUDY AIMS: The real-time optical diagnosis of colorectal polyps with high confidence predictions can achieve high levels of accuracy. Increasing the rates of high confidence optical diagnosis can improve the clinical application of real-time optical diagnosis in routine practice. The primary aim of this prospective study was to evaluate whether high magnifying endoscopy improves the rates of high confidence narrow-band imaging (NBI) - based optical diagnosis for differentiating between neoplastic and non-neoplastic colorectal lesions according to the NBI international colorectal endoscopic (NICE) classification. PATIENTS AND METHODS: Consecutive adult patients undergoing colonoscopy with a high magnifying (maximum, × 80) colonoscope between April and August 2012 were recruited. The optical diagnosis for each polyp was evaluated during colonoscopy in two consecutive stages by the same endoscopist, who first used NBI with non-magnifying endoscopy (NBI-NME), then NBI with magnifying endoscopy (NBI-ME). A level of confidence was assigned to each prediction. RESULTS: The analysis included 124 patients (mean age, 56.4 years; male-to-female ratio, 72:52) with 248 polyps smaller than 10 mm. Of the 248 polyps, 210 were 1 to 5 mm in size and 38 were 6 to 9 mm in size; 77 polyps were hyperplastic, 4 were sessile serrated adenomas/polyps, 160 were low grade adenomas, 5 were high grade adenomas, and 2 were deep submucosal invasive carcinomas. The rate of high confidence optical diagnosis when NBI-ME was used was significantly higher than the rate when NBI-NME was used for diminutive (1 - 5 mm) polyps (92.9 % vs 79.5 %, P < 0.001) and for small (6 - 9 mm) polyps (94.7 % vs 84.2 %, P = 0.048). CONCLUSION: High magnifying endoscopy significantly improved the rates of high confidence NBI-based optical diagnosis of diminutive and small colorectal polyps. STUDY REGISTRATION: UMIN 000007608.

Feasibility of single-incision laparoscopic cholecystectomy for acute cholecystitis.

AIM: To assess the safety of single-incision laparoscopic cholecystectomy (SILC) for acute cholecystitis. METHODS: All patients who underwent SILC at Sano Hospital (Kobe, Japan) between January 2010 and December 2014 were included in this retrospective study. Clinical data related to patient characteristics and surgical outcomes were collected from medical records. The parameters for assessing the safety of the procedure included operative time, volume of blood loss, achievement of the critical view of safety, use of additional trocars, conversion to laparotomy, intraoperative and postoperative complications, and duration of postoperative hospital stay. Patient backgrounds were statistically compared between those with and without conversion to laparotomy. RESULTS: A total of 100 patients underwent SILC for acute cholecystitis during the period. Preoperative endoscopic treatment was performed for suspected choledocholithiasis in 41 patients (41%). The mean time from onset of acute cholecystitis was 7.7 d. According to the Updated Tokyo Guidelines (TG13) for the severity of cholecystitis, 86 and 14 patients had grade I and grade II acute cholecystitis, respectively. The mean operative time was 87.4 min. The mean estimated blood loss was 80.6 mL. The critical view of safety was obtained in 89 patients (89%). Conversion laparotomy was performed in 12 patients (12%). Postoperative complications of Clavien-Dindo grade III or greater were observed in 4 patients (4%). The mean duration of postoperative hospital stay was 5.7 d. Patients converted from SILC to laparotomy tended to have higher days after onset. CONCLUSION: SILC is feasible for acute cholecystitis; in addition, early surgical intervention may reduce the risk of laparotomy conversion.

Narrow-band imaging observation of colorectal lesions using NICE classification to avoid discarding significant lesions.

AIM: To assess the risk of failing to detect diminutive and small colorectal cancers with the "resect and discard" policy. METHODS: Patients who received colonoscopy and polypectomy were recruited in the retrospective study. Probable histology of the polyps was predicted by six colonoscopists by the use of NICE classification. The incidence of diminutive and small colorectal cancers and their endoscopic features were assessed. RESULTS: In total, we found 681 cases of diminutive (1-5 mm) lesions in 402 patients and 197 cases of small (6-9 mm) lesions in 151 patients. Based on pathology of the diminutive and small polyps, 105 and 18 were non-neoplastic polyps, 557 and 154 were low-grade adenomas, 18 and 24 were high-grade adenomas or intramucosal/submucosal (SM) scanty invasive carcinomas, 1 and 1 were SM-d carcinoma, respectively. The endoscopic features of invasive cancer were classified as NICE type 3 endoscopically. CONCLUSION: The risk of failing to detect diminutive and small colorectal invasive cancer with the "resect and discard" strategy might be avoided through the use of narrow-band imaging observation with the NICE classification scheme and magnifying endoscopy.

Manganese superoxide dismutase plays an important role in the inflammatory process and predicts disease severity and activity in patients with ulcerative colitis.

The aim of this study was to investigate the expression pattern of manganese superoxide dismutase (MnSOD) in relation to inflammatory factors in ulcerative colitis (UC) and characterize this enzyme as a newly identified biomarker potentially linked to disease pathogenesis of UC. MnSOD expression was analyzed immunohistochemically in 48 formalin-fixed and paraffin-embedded specimens from patients with UC who had undergone endoscopical biopsy. MnSOD expression was observed in vascular endothelium, macrophages, and polymorphonuclear leukocytes within lamina propria of inflamed mucosa. The patients who did not express MnSOD tended to have stabilization of symptoms, but accompanied with status of inflammation. The MnSOD expression pattern was strongly correlated with disease type. MnSOD was expressed in polymorphonuclear leukocytes of all disease types, but cases of chronically counting and exacerbation type had particularly high frequency of immunopositive cells. MnSOD expression in macrophages was frequently observed in cases of symptom remaining type. The cases with MnSOD expression in the vascular endothelium showed a tendency to express in relapse-remission and exacerbation of symptoms. Immunohistochemical evaluation for MnSOD expression may be useful for predicting disease severity and activity in patients with UC.

NBI and NBI Combined with Magnifying Colonoscopy.

Although magnifying chromoendoscopy had been a reliable diagnostic tool, narrow-band imaging (NBI) has been developed in Japan since 1999 and has now replaced the major role of chromoendoscopy because of its convenience and simplicity. In this paper, we principally describe the efficacy of magnifying chromoendoscopy and magnifying colonoscopy with NBI for detection, histological prediction, estimation of the depth of early colorectal cancer, and future prospects. Although some meta-analyses have concluded that NBI is not superior to white light imaging for detection of adenomatous polyps in screening colonoscopy, NBI with magnification colonoscopy is useful for histological prediction, or for estimating the depth of invasion. To standardize these diagnostic strategies, we will focus on the NBI International Colorectal Endoscopic (NICE) classification proposed for use by endoscopists with or without a magnifying endoscope. However, more prospective research is needed to prove that this classification can be applied with satisfactory availability, feasibility, and reliability. In the future, NBI might contribute to the evaluation of real-time histological prediction during colonoscopy, which has substantial benefits for both reducing the risk of polypectomy and saving the cost of histological evaluation by resecting and discarding diminutive adenomatous polyps (resect and discard strategy).

Diagnóstico de las lesiones neoplásicas y no-neoplásicas y predicción de la invasión submucosa del cáncer colorrectal temprano durante la colonoscopia / Diagnosis of neoplastic and non-neoplastic lesions and prediction of submucosal invasion of early cancer during colonoscopy

La cromoendoscopia de magnificación es una nueva y atractiva herramienta que permite un análisis detallado de la arquitectura morfológica de los orificios de las criptas de la mucosa. En esta revisión describimos, principalmente, la eficacia de la cromoendoscopia de magnificación y de la colonoscopia de magnificación con NBI para el diagnóstico diferencial de las lesiones colorrectales, incluyendo una distinción entre lesiones neoplásicas y no-neoplásicas y también entre cáncer temprano tratable endoscópicamente o no, basados en una revisión de la literatura. Hemos conducido un estudio prospectivo mostrando que una combinación de la colonoscopia de magnificación y la cromoendoscopia es actualmente un método más confiable que la colonoscopia convencional y la cromoendoscopia para la distinción entre lesiones neoplásicas y no-neoplásicas del colon y del recto. La colonoscopia de magnificación con NBI es tan precisa como la cromoendoscopia de magnificación. Nosotros utilizamos colonoscopia de magnificación con NBI más que la cromoendoscopia para distinguir de rutina los pólipos neoplásicos de los no-neoplásicos. Los colonoscopistas pueden predecir la profundidad de la invasión del cáncer colorrectal por medio de la cromoendoscopia de magnificación, la colonoscopia de magnificación con NBI y a través del signo de no-levantamiento. Entre estos métodos, la cromoendocopia de magnificación es el más confiable, con una exactitud, sensibilidad y especificidad de 98,8%, 85,6% y 99,4%, respectivamente. Aunque su confiabilidad depende de la habilidad del que hace la observación, la difusión de las aplicaciones de la técnica de magnificación podría influir en las indicaciones de biopsias de muestreo durante la colonoscopia y en las de mucosectomía.

Magnifying chromoendoscopy is an exciting new tool that allows detailed analysis of the morphological architecture of mucosal crypt orifices. In this review, we principally describe the efficacy of magnifying chromoendoscopy and magnifying colonoscopy with narrow band imaging (NBI) for differential diagnosis of colorectal lesions, including distinction between non-neoplastic and neoplastic lesions, and also between endoscopically treatable early invasive cancers and untreatable cancers, based on a review of the literature. We have conducted a prospective study showing that a combination of magnifying colonoscopy and chromoendoscopy is currently a more reliable method than conventional endoscopy and chromoendoscopy for separating non-neoplastic from neoplastic lesions of the colon and rectum. Magnifying colonoscopy with NBI is convenient and as accurate as chromoendoscopy with magnification. We principally use only magnifying colonoscopy with NBI, rather than chromoendoscopy, to routinely distinguish neoplastic from non-neoplastic polyps. Colonoscopists can predict the depth of invasion of early colorectal cancer by magnifying chromoendoscopy, magnifying colonoscopy with NBI and the non-lifting sign. Among these approaches, magnifying chromoendoscopy is diagnostically the most reliable, with an accuracy, sensitivity, and specificitiy of 98.8%, 85.6%, and 99.4%, respectively. Although its reliability depends on the skill of magnifying observation, widespread applications of the magnification technique could influence the indications for biopsy sampling during colonoscopy and the indications for mucosectomy.

Intraductal tubular carcinoma of the pancreas: case report with review of literature.

A 67-year-old man presented with leg edema. Laboratory data showed elevated blood glucose and carbohydrate antigen (CA) 19-9 levels, and anemia. Further imaging studies revealed a relatively clear-margined tumor totally occupying the main pancreatic duct (MPD) from the head to the tail of the pancreas (maximum diameter 10 cm) without mucin hypersecretion. Total pancreatectomy with splenectomy and regional lymphadenectomy were performed. Intraductal tubular carcinoma (ITC) was diagnosed by immunohistochemical staining and electron microscopic examination. Previous reports showed that this tumor is characterized by slow growth, with a favorable prognosis and intraductal nodular growth occupying the MPD and no macroscopic mucus. Whether ITC should be distinguished from other types of pancreatic neoplasm is controversial, and the accumulation of more ITC cases and multi-institutional analysis are necessary to establish the diagnostic criteria and characteristics of this histological entity.