Konservative versus chirurgische Therapie beim idiopathischen und sekundären Megakolon oder Megarektum im Erwachsenenalter - eine retrospektive multizentrische Kontrollstudie.

BACKGROUND: Idiopathic and secondary megacolon (MC) and megarectum (MR) in adults is associated with persistent bowel dilatation and reduced intestinal motility. Little is known about the optimal treatment of this rare disease. Therefore, we retrospectively analysed long-term data from these patients in 5 community and university hospitals, focusing on conservative versus surgical treatment. METHODS: Patient records from 7/2004 to 9/2021 were screened for colorectal diseases with severe constipation and persistent megacolon ≥ 9.0 cm and/or megarectum ≥ 6.5 cm. Follow up-data was collected through telephone interviews and written surveys. ClinicalTrialsgov NCT04340856. RESULTS: Sixty-seven patients with idiopathic (n=10) and secondary (n=57) MC or MR were identified with only 20 of 67 patients (29.9%) correctly diagnosed. Mean/median age was 64/69 (range 18-93) years. Thirty-two patients were treated with laxative regimens, and 35 underwent surgery (colostomy: n=12, segmental resection, or hemicolectomy: n=10, (sub)total colectomy: n= 13) after conservative treatment attempts in 32/35 (91.4%). The mean/median follow-up was 4.2/2.7 (range 0.1-17.0) years. The readmission rate for MC-associated symptoms was significantly higher after conservative treatment than after surgical therapy at 12 (0.84 vs. 0.36 per patient, p=0.036), 24 (1.00 vs. 0.52, p=0.048) and 36 (1.13 vs. 0.58, p=0.047) months, as was the number of patients with persistent laxative dependence (28/32 (87.5%) vs. 19/33 (57.6%); p = 0.007). Therapy-associated adverse events (Clavien-Dindo classification) were documented more often in surgically treated patients (11/35, 31.4%) (p=0.025). CONCLUSION: Surgical treatment may be considered earlier if idiopathic or secondary MC or MR is correctly diagnosed, and conservative treatment has been attempted.

[Influence of specialization on primary success and complication rate in ERCP. Proposal to improve the quality of ERCP]. / Einfluss der Spezialisierung auf primäre Erfolgs- sowie Komplikationsrate bei der ERCP. Vorschlag zur Verbesserung der Qualität der ERCP.

Endoscopic retrograde cholangiopancreatography [ERCP] is a complex procedure with a flat learning curve. It is associated with the risk of serious complications such as pancreatitis, bleeding, cholangitis and perforation. Endosonography should therefore also be offered for the precise indication of the higher-risk ERCP. Numerous factors influence the success of ERCP. In addition to structured training for the initial acquisition of skills and a minimum number of ERCPs of varying degrees of difficulty, maintaining a good quality of ERCP also requires a regular minimum number of examinations performed per year. There is extensive evidence that shows a significant correlation between ERCP volumes and primary success rates, lower lengths of hospital stay, fewer unwanted readmissions and fewer complications. The cut-offs for differentiating between high-volume and low-volume centers were chosen inconsistently in the studies, with the highest evidence for a cut-off value of 200 ERCPs/year. The question of specialization in ERCP has been given a relevance by the current developments in german hospital reform. Here, a minimum number of ERCPs should be defined for groups of different specialization. However, a minimum number alone will not be able to achieve good treatment quality. In terms of high-quality patient care, it is necessary to offer ERCPs in specialized gastroenterology center, which, in addition to a sufficient number of ERCPs for training and to maintain competence, offer an on-call service and complementary procedures such as EUS and which are embedded in appropriately accessible clinics that have the necessary resources for complication management.

[Structural, procedural, and personnel requirements for cross-sectoral provision of endoscopic gastroenterological procedures]. / Strukturelle, prozedurale und personelle Voraussetzungen für eine sektorenübergreifende Erbringung endoskopischer gastroenterologischer Leistungen.

Gastroenterology has made crucial advances in diagnostic and interventional endoscopic procedures, opening up improvements in the treatment of many patients. Thus, organ-preserving treatments are increasingly being made possible, replacing more invasive organ resecting surgical procedures. At the same time, the degree of complexity and risks varies widely between different endoscopic procedures. In many cases, simpler endoscopic procedures are now offered on an outpatient basis. Further potential for cross-sectoral performance of endoscopic procedures exists in the case of complex endoscopic procedures, which, however, require special structural, procedural and personnel requirements in order to provide quality-assured treatment, enable post-interventional monitoring and, if necessary, take measures to ensure the success of the treatment. We summarize the essential prerequisites and limitations for cross-sector performance of endoscopic procedures in gastroenterology.

Photochemical Internalization of Gemcitabine Is Safe and Effective in Locally Advanced Inoperable Cholangiocarcinoma.

BACKGROUND: Photochemical internalization (PCI) is a novel technology for light-induced enhancement of the local therapeutic effect of cancer drugs, utilizing a specially designed photosensitizing molecule (fimaporfin). The photosensitizing molecules are trapped in endosomes along with macromolecules or drugs. Photoactivation of fimaporfin disrupts the endosomal membranes so that drug molecules are released from endosomes inside cells and can reach their therapeutic target in the cell cytosol or nucleus. Compared with photodynamic therapy, the main cytotoxic effect with PCI is disruption of the endosomal membrane resulting in delivery of chemotherapy drug, and not to the photochemical reactions per se. In this study we investigated the effect of PCI with gemcitabine in patients with inoperable perihilar cholangiocarcinoma (CCA). METHODS: The in vitro cytotoxic effect of PCI with gemcitabine was studied on two CCA-derived cell lines. In a fimaporfin dose-escalation phase I clinical study, we administered PCI with gemcitabine in patients with perihilar CCA (n = 16) to establish a safe and tolerable fimaporfin dose and to get early signals of efficacy. The patients enrolled in the study had tumors in which the whole length of the tumor could be illuminated from the inside of the bile duct, using an optical fiber inserted via an endoscope (Fig. 1). Fimaporfin was administered intravenously at day 0; gemcitabine (i.v.) and intraluminal biliary endoscopic laser light application on day 4; followed by standard gemcitabine/cisplatin chemotherapy. RESULTS: Preclinical experiments showed that PCI enhanced the effect of gemcitabine. In patients with CCA, PCI with gemcitabine was well tolerated with no dose-limiting toxicities, and no unexpected safety signals. Disease control was achieved in 10 of 11 evaluable patients, with a clearly superior effect in the two highest dose groups. The objective response rate (ORR) was 42%, including two complete responses, while ORR at the highest dose was 60%. Progression-free survival at 6 months was 75%, and median overall survival (mOS) was 15.4 months, with 22.8 months at the highest fimaporfin dose. CONCLUSION: Photochemical internalization with gemcitabine was found to be safe and resulted in encouraging response and survival rates in patients with unresectable perihilar CCA.

Oral mannitol for bowel preparation: a dose-finding phase II study.

BACKGROUND: Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality. Nevertheless, there are no laxatives which combine effectiveness, safety, easy self-administration, good patient acceptance, and low cost. However, mannitol, a sugar alcohol, could be an attractive candidate for use in clinical practice if it is shown to demonstrate adequate efficacy and safety. AIMS: The present phase II dose-finding study compared three doses of mannitol (50, 100, and 150 g) to identify the best dose to be used in a subsequent phase III study. METHODS: The Boston Bowel Preparation Scale, caecal intubation rate, adherence, acceptability, and safety profile, including measurement of potentially dangerous colonic gas concentrations (CH4, H2, O2), were considered in all patients. A weighted algorithm was used to identify the best mannitol dose for use in the subsequent study. RESULTS: The per-protocol population included 60 patients in the 50 g group, 54 in the 100 g group, and 49 in the 150 g group. The 100 g dose was the best as it afforded optimal colon cleansing efficacy (94.4% of patients had adequate BP), adherence, acceptability, and safety, including negligible gas concentrations. CONCLUSIONS: The present study demonstrated that the colon cleansing efficacy and safety of mannitol were dose dependent. Conversely, gas concentrations were not dose dependent and negligible in all patients. Combined evaluation of efficacy, tolerability, and safety, using a weighted algorithm, determined that mannitol 100 g was the best dose for the phase III study.

[Quality management in the field of gastroenterology - Proposals of the Quality Commission of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) for Outpatient and Inpatient Quality Assurance]. / Qualität in der Gastroenterologie ­ "Vorschläge der Kommission Qualität der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten zur ambulanten und stationären Qualitätssicherung".

The quality of the medical care depends on numerous factors that can often be influenced by the doctor itself. It is a great challenge to follow the constant scientific progress in practice. Scientific standards in gastroenterology are defined in DGVS guidelines and regularly revised. The implementation of evidence-based recommendations in practice remains challenging. On the basis of the DGVS guidelines, the Quality Commission has therefore developed a selection of quality indicators with particular relevance using standardized criteria, the broad implementation of which could contribute to improved patient care in gastroenterology.

Diagnostic and therapeutic single-operator cholangiopancreatoscopy with SpyGlassDS™: results of a multicenter retrospective cohort study.

BACKGROUND AND AIMS: The aim of the study was to evaluate the usefulness and diagnostic and therapeutic outcome of the single-operator cholangiopancreatoscopy (SOC) with SpyGlassDS™. METHODS: In a retrospective multicenter study between November 2015 and January 2017, SpyGlassDS™ procedures were analyzed in participating centers. Indications, accuracy of SOC-guided biopsies, management of large bile duct stones, and complications were analyzed. Follow-up was 4 months. RESULTS: Two hundred and six patients out of 250 examinations were evaluated. Indications were biliary stones (n = 132), bile duct stenosis (n = 93), stones and stenosis combined (n = 24), and bile duct leakage (n = 1). Of the 117 cases which were suspicious of malignancy, in 99 cases the lesion could be stratified into benign (n = 55) or malignant (n = 44) indicating a sensitivity of 95.5% and a specificity of 94.5% for the indication tumor. SOC-guided biopsies revealed a sensitivity of 57.7% with a specificity of 100%. In 107 examinations, biliary stones were visualized and could be completely removed in 91.1% with a need of three procedures (range 1-6) to achieve final stone clearance. In 75 cases, lithotripsy was performed and was successful in 71 cases (95%). Four out of 45 patients (8.9%) underwent cholecystectomy with surgical bile duct revision as a final therapy. Adverse Event (AE) occurred in 33/250 patients (13.2%) and Serious Adverse Event (SAE) occurred in 1/250 patients (0.4%). Cholangitis was 1% (n = 102) after peri-interventional administration of antibiotics and 12.8% (n = 148) without antibiotic prophylaxis (p < 0.001). CONCLUSIONS: SOC with SpyGlassDS™ became a new standard for the diagnosis of indefinite biliary lesions and therapy of large bile duct stones. The diagnostic yield of SOC-guided biopsies facilitated a definite diagnosis in most cases and should be improved by standardized biopsy protocols. SOC-guided interventions allowed removal of large biliary stones by SOC-guided lithotripsy. The complication rate of 13.2% can be considerably reduced by use of a single-shot antibiotic treatment.

[German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) position statement on endoscopic decompression in acute Ileus]. / Positionspapier der DGVS zur endoskopischen Dekompression bei akutem Ileus.

In patients with ileus with dilated intestine in imaging studies, endoscopic decompression appears a feasible option. However, its use is often uncritical and without scientific evidence. Before considering endoscopic intervention, CT-imaging should differentiate between mechanical obstruction and paralytic ileus/intestinal pseudo-obstruction. Tumor diagnosis and localisation are essential because the latter determines the choice of the decompression procedure. Coecal dilatation of more than 12 cm indicates an increased risk of perforation. In patients with toxic megacolon, dilation of the transverse colon to more than 6 cm is considered critical without much prospective evidence. Endoscopic decompression has a high complication rate and should be performed electively, and not as an emergency procedure, whenever possible. The use of CO2 insufflation rather than ambient air is strongly recommended, as is the availability of fluoroscopy. Prior trans-nasal or oral decompression-tube placement is routinely performed, and tracheobronchial intubation frequently required. In over 90 % of patients with pseudo-obstruction, conservative treatment is successful within 24 to 48 hours, and endoscopic decompression is, therefore, unnecessary. Placement of self-expanding metal stents to decompress a tumor stenosis is considered mostly for the left colon and rectum and burdened with significant risks of perforation and stent migration. Stent impact on oncological outcome is controversial because of possible tumor cell mobilization and increased postoperative cancer recurrence rates. Surgery, as primary intervention, achieves its objective in most cases. Decompression effect by endoscopic suctioning of gas and intestinal fluid is usually transient so that it is combined with transrectal decompression tubes insertion. This paper reviews the advantages and flaws of various decompression procedures in different clinical settings.

Wing-shaped plastic stents vs. self-expandable metal stents for palliative drainage of malignant distal biliary obstruction: a randomized multicenter study.

BACKGROUND AND STUDY AIMS: Previous studies have shown superior patency rates for self-expandable metal stents (SEMS) compared with plastic stents in patients with malignant biliary obstruction. The aim of this study was to compare stent patency, patient survival, and complication rates between a newly designed, wing-shaped, plastic stent and SEMSs in patients with unresectable, malignant, distal, biliary obstruction. PATIENTS AND METHODS: A randomized, multicenter trial was conducted at four tertiary care centers in Germany. A total of 37 patients underwent randomization between March 2010 and January 2013. Patients underwent endoscopic retrograde cholangiography with insertion of either a wing-shaped, plastic stent without lumen or an SEMS.  RESULTS: Stent failure occurred in 10/16 patients (62.5 %) in the winged-stent group vs. 4/18 patients (22.2 %) in the SEMS group (P = 0.034). The median time to stent failure was 51 days (range 2 - 92 days) for the winged stent and 80 days (range 28 - 266 days) for the SEMS (P = 0.002). Early stent failure (< 8 weeks after placement) occurred in 8 patients (50 %) vs. 2 patients (11.1 %), respectively (P = 0.022). After obtaining the results from this interim analysis, the study was discontinued because of safety concerns. CONCLUSIONS: The frequency of stent failure was significantly higher in the winged-stent group compared with the SEMS group. A high incidence of early stent failure within 8 weeks was observed in the winged-stent group. Thus, the winged, plastic stent without central lumen may not be appropriate for mid or long term drainage of malignant biliary obstruction. Study registration ClinicalTrials.gov (NCT01063634).

Biliary metal stents for proximal esophageal or hypopharyngeal strictures.

INTRODUCTION: Endoscopic dilation is the standard of care for stenoses of the cervical esophagus, but refractory strictures require some form of stenting. Most endoscopists avoid the placement of metal stents near the upper esophageal sphincter as they can cause major problems like severe cervical pain and globus sensation. We report our results with the use of biliary SEMS in the upper esophagus, which have a smaller diameter than regular esophageal stents and therefore exert less expansive force. MATERIAL AND METHODS: We retrospectively reviewed all patients in our center between July 2011 and June 2014 who received a biliary metal stent because of a refractory stricture in the cervical esophagus. We implanted biliary SEMS (Wallflex, Boston Scientific) with a diameter of 1 cm and length of 6-8 cm. Technical and clinical success, adverse events and duration of stenting were evaluated. RESULTS: Ten patients were treated with biliary SEMS in the upper esophagus. Strictures were located between 10 and 19 cm from incisor teeth. Stent placement was successful in all (10/10) patients. One stent had to be extracted because of pain and globus sensation. Apart from that stent tolerability was good. All remaining patients (9/9) reported improvement of dysphagia with a decrease in mean dysphagia score from 3.2 to 1.78. Mean duration of stenting was 68 days. DISCUSSION: Because of a high clinical success rate and good tolerability, biliary metal stents are a reasonable alternative for difficult strictures in the cervical esophagus, especially in the palliative setting.

Long-term follow-up after dilation in symptomatic esophageal intramural pseudodiverticulosis: an observational study in 22 cases.

Endoscopic bougienage seems to be the most effective therapy for dysphagia in esophageal intramural pseudodiverticulosis (EIPD), but nothing is known about the long-term success of this treatment option. This report presents long-term results for 21 of 22 patients with EIPD who were treated with bougienage. A total of 103 sessions of bougienage up to a diameter of 18 mm were performed, without major complications and with 100 % clinical success. During follow-up, symptom recurrence with further bougienage occurred in 12 /21 patients (57 %), who had variable symptom-free intervals (range 1.5 - 96 months). Symptom recurrence was associated with concomitant reflux esophagitis. Although this series demonstrates that bougienage is an effective method for relieving dysphagia in EIPD, the long-term effectiveness is limited.

Functional status and quality of life in older patients with advanced esophageal squamous cell cancer receiving second-line nivolumab ± ipilimumab therapy: A post hoc analysis of the phase 2, multicenter RAMONA study.

INTRODUCTION: The phase 2 RAMONA study demonstrated that second-line nivolumab ± ipilimumab immunotherapy was feasible and effective in older patients with advanced esophageal squamous cell cancer (ESCC). Here, we presented results from functional status (FS) and quality-of-life (QoL) analyses. MATERIALS AND METHODS: Patients aged ≥65 years with advanced ESCC and disease progression following first-line therapy were enrolled for study treatment with nivolumab ± ipilimumab. Geriatric assessments (GA) consisting of G8 and GoGo/SlowGo evaluation, and quality of life (QoL) assessments with EORTC QLQ-C30 questionnaires were conducted at baseline and during the treatment. A post hoc analysis was performed to compare therapy efficacy, toxicity, and QoL between age groups (≥70 years vs. <70 years) and functionality groups (G8 > 14 vs. ≤14 and GoGo vs. SlowGo). RESULTS: In 66 treated patients with a median age of 70.5 years, older patients had non-inferior overall survival and tumor response compared to younger patients, with no increased treatment-related adverse events. Fitter patients (G8 > 14, GoGo) had a clinically, yet not statistically significant, survival advantage than less fit patients (G8 ≤ 14, SlowGo) patients. Moreover, FS by G8 and GoGo/SlowGo significantly correlated with QoL. Overall, QoL was impaired at baseline but remained stable in all scales over the course of immunotherapy. DISCUSSION: The administration of nivolumab ± ipilimumab second-line immunotherapy in older patients with ESCC did not show age-dependent effects and maintained QoL. GA could identify functional deficits and limitations of QoL and should be implemented in the context of immunotherapy. CLINICALTRIALS: gov: NCT03416244.

Second-line therapy with nivolumab plus ipilimumab for older patients with oesophageal squamous cell cancer (RAMONA): a multicentre, open-label phase 2 trial.

BACKGROUND: The overall survival of patients with advanced and refractory oesophageal squamous cell carcinoma, mostly aged 65 years and older, is poor. Treatment with PD-1 antibodies showed improved progression-free survival and overall survival. We assessed the safety and efficacy of combined nivolumab and ipilimumab therapy in this population. METHODS: This multicentre, open-label, phase 2 trial done in 32 sites in Germany included patients aged 65 years and older with oesophageal squamous cell carcinoma and disease progression or recurrence following first-line therapy. Patients were treated with nivolumab (240 mg fixed dose once every 2 weeks, intravenously) in the safety run-in phase and continued with nivolumab and ipilimumab (nivolumab 240 mg fixed dose once every 2 weeks and ipilimumab 1 mg/kg once every 6 weeks, intravenously). The primary endpoint was overall survival, which was compared with a historical cohort receiving standard chemotherapy in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03416244. FINDINGS: Between March 2, 2018, and Aug 20, 2020, we screened 75 patients with advanced oesophageal squamous cell carcinoma. We enrolled 66 patients (50 [76%] men and 16 [24%] women; median age 70·5 years [IQR 67·0-76·0]), 44 (67%) of whom received combined nivolumab and ipilimumab therapy and 22 (33%) received nivolumab alone. Median overall survival time at the prespecified data cutoff was 7·2 months (95% CI 5·7-12·4) and significantly higher than in a historical cohort receiving standard chemotherapy (p=0·0063). The most common treatment-related adverse events were fatigue (12 [29%] of 42), nausea (11 [26%]), and diarrhoea (ten [24%]). Grade 3-5 treatment-related adverse events occurred in 13 (20%) of 66 patients. Treatment-related death occurred in one patient with bronchiolitis obliterans while on nivolumab and ipilimumab treatment. INTERPRETATION: Patients aged at least 65 years, with advanced oesophageal squamous cell carcinoma might benefit from combined nivolumab and ipilimumab therapy in second-line treatment. FUNDING: Bristol Myers Squibb.

Determining scope position during colonoscopy without use of ionizing radiation or magnetic imaging: the enhanced mapping ability of the NeoGuide Endoscopy System.

BACKGROUND: Knowledge of the position and shape of the endoscope could overcome many challenges of performing colonoscopy, e.g., loop formation. A novel computer-assisted colonoscope (NeoGuide Endoscopy System) delivers a real-time, three-dimensional map of the tip position and insertion tube shape in addition to the video image of the colon lumen. The aim of this study is to evaluate the mapping capabilities of the NeoGuide Endoscopy System in terms of colonic looping, insertion depth, tip position, and tip angle formation. METHODS: Ten endoscopists with various levels of experience were each shown 70 map images generated by the NeoGuide endoscopy system in a benchtop anatomical colon model. First endoscopists were asked to determine the tip angle based on the map image and the system's corresponding tip positioning aid (20 images). In the second part they had to identify the scope-tip position in the colon model (40 images). In the third part ten images were presented for identification of colonic loops. RESULTS: The tip angle was correctly identified in 99% (198/200) of images. Using only the map images the scope position was accurately determined in 87.5% (350/400). Identification of colonic looping of the scope was appropriate in 99% (99/100). Overall accuracy was 92.4%, and overall positive predictive value was 94.9%. CONCLUSION: Three-dimensional map images generated by the NeoGuide endoscopy system provide accurate information regarding tip position, insertion tube position, and colonic looping.

Nab-paclitaxel plus gemcitabine versus nab-paclitaxel plus gemcitabine followed by FOLFIRINOX induction chemotherapy in locally advanced pancreatic cancer (NEOLAP-AIO-PAK-0113): a multicentre, randomised, phase 2 trial.

BACKGROUND: The optimal preoperative treatment for locally advanced pancreatic cancer is unknown. We aimed to compare the efficacy and safety of nab-paclitaxel plus gemcitabine with nab-paclitaxel plus gemcitabine followed by fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) as multidrug induction chemotherapy regimens in locally advanced pancreatic cancer. METHODS: In this open-label, multicentre, randomised phase 2 study, done at 28 centres in Germany, eligible patients were adults (aged 18-75 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically or cytologically confirmed, treatment-naive locally advanced pancreatic adenocarcinoma, as determined by local multidisciplinary team review. After two cycles of nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (administered intravenously on days 1, 8, and 15 of each 28-day cycle), patients without progressive disease or unacceptable adverse events were randomly assigned (1:1) to receive either two additional cycles of nab-paclitaxel plus gemcitabine (nab-paclitaxel plus gemcitabine group) or four cycles of sequential FOLFIRINOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 180 mg/m2, fluorouracil 400 mg/m2 by intravenous bolus followed by a continuous intravenous infusion of 2400 mg/m2 for 46 h on day 1 of each 14-day cycle; sequential FOLFIRINOX group). Randomisation was done by the clinical research organisation on request of the trial centre using a permuted block design (block size 2 and 4). Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was surgical conversion rate (complete macroscopic tumour resection) in the randomised population by intention-to-treat analysis, which was assessed by surgical exploration in all patients with at least stable disease after completion of induction chemotherapy. This trial is registered with ClinicalTrials.gov, NCT02125136. FINDINGS: Between Nov 18, 2014, and April 27, 2018, 168 patients were registered and 130 were randomly assigned to either the nab-paclitaxel plus gemcitabine group (64 patients) or the sequential FOLFIRINOX group (66 patients). Surgical exploration after completed induction chemotherapy was done in 40 (63%) of 64 patients in the nab-paclitaxel plus gemcitabine group and 42 (64%) of 66 patients in the sequential FOLFIRINOX group. 23 patients in the nab-paclitaxel plus gemcitabine group and 29 in the sequential FOLFIRINOX group had complete macroscopic tumour resection, yielding a surgical conversion rate of 35·9% (95% CI 24·3-48·9) in the nab-paclitaxel plus gemcitabine group and 43·9% (31·7-56·7) in the sequential FOLFIRINOX group (odds ratio 0·72 [95% CI 0·35-1·45]; p=0·38). At a median follow-up of 24·9 months (95% CI 21·8-27·6), median overall survival was 18·5 months (95% CI 14·4-21·5) in the nab-paclitaxel plus gemcitabine group and 20·7 months (13·9-28·7) in the sequential FOLFIRINOX group (hazard ratio 0·86 [95% CI 0·55-1·36]; p=0·53). All other secondary efficacy endpoints, such as investigator-assessed progression-free survival, radiographic response rate, CA 19-9 response rate, and R0 resection rate, were not significantly different between the two treatment groups except for improved histopathological downstaging in evaluable resection specimens from the sequential FOLFIRINOX group (ypT1/2 stage: 20 [69%] of 29 patients in the sequential FOLFIRINOX group vs four [17%] of 23 patients in the nab-paclitaxel plus gemcitabine group, p=0·0003; ypN0 stage: 15 [52%] of 29 patients in the sequential FOLFIRINOX group vs four [17%] of 23 patients in the nab-paclitaxel plus gemcitabine group, p=0·02). Grade 3 or higher treatment-emergent adverse events during induction chemotherapy occurred in 35 (55%) of 64 patients in nab-paclitaxel plus gemcitabine group and in 35 (53%) of 66 patients in the sequential FOLFIRINOX group. The most common of which were neutropenia (18 [28%] in nab-paclitaxel plus gemcitabine group, 16 [24%] in the sequential FOLFIRINOX group), nausea and vomiting (two [3%] in nab-paclitaxel plus gemcitabine group, eight [12%] in the sequential FOLFIRINOX group), and bile duct obstruction with cholangitis (six [9%] in nab-paclitaxel plus gemcitabine group, seven [11%] in the sequential FOLFIRINOX group). No deaths were caused by treatment-related adverse events during the induction chemotherapy phase. INTERPRETATION: Our findings suggest that nab-paclitaxel plus gemcitabine is similarly active and safe as nab-paclitaxel plus gemcitabine followed by FOLFIRINOX as multidrug induction chemotherapy regimens for locally advanced pancreatic cancer. Although conversion to resectability was achieved in about a third of patients, additional evidence is required to determine whether this translates into improved overall survival. FUNDING: Celgene.

PillCamColon2 after incomplete colonoscopy - A prospective multicenter study.

AIM: To evaluate the ability of PillCamColon2 to visualize colonic segments missed by incomplete optical colonoscopy (OC) and to assess the diagnostic yield. METHODS: This prospective multicentre study included 81 patients from nine centres who underwent second-generation colon capsule endoscopy (CCE) following incomplete OC performed by an experienced gastroenterologist (> 1000 colonoscopies). Patients with stenosis were excluded. According to patient preferences, CCE was performed the following day (protocol A) after staying on clear liquids and 0.75 L Moviprep in the morning or within 30 d after new split-dose Moviprep (protocol B). Boosts consisted of 0.75 L and 0.25 L Moviprep, and phospho-soda was given as a rescue if the capsule was not excreted after seven hours. RESULTS: Seventy-four patients were analysed (51% of them in group A; 49% in group B). Bowel cleansing was adequate in 67% of cases, and CCE could visualize colonic segments missed by incomplete colonoscopy in 90% of patients under protocol A and 97% of patients under protocol B (P = 0.35, n.s.). Significant polyps including adenocarcinoma were detected in 24% of cases. Detection rates for all polyps and significant polyps per patient were similar in both protocols. Polyps were found predominantly in the right colon (86%) in segments that were not reached by OC. Extracolonic findings - such as reflux esophagitis, suspected Barrett esophagus, upper GI-bleeding, gastric polyps, gastric erosions and angiectasia - were detected in eight patients. PillCamColon2 capsule was retained in the ileum of one patient (1.4%) without symptoms and removed during an uneventful resection for unknown Crohn's disease that was diagnosed as the cause of anemia, which was the indication for colonoscopy. CCE was well tolerated. One patient suffered from self-limiting vomiting after consuming the phospho-soda. CONCLUSION: Second-generation CCE using a low-volume preparation is useful after incomplete OC, and it allows for the detection of additional relevant findings, but cleansing efficiency could be improved.