Gemcitabine and Paclitaxel Versus Gemcitabine Alone After 5-Fluorouracil, Oxaliplatin, and Irinotecan in Metastatic Pancreatic Adenocarcinoma: A Randomized Phase III PRODIGE 65-UCGI 36-GEMPAX UNICANCER Study.

PURPOSE: GEMPAX was an open-label, randomized phase III clinical trial designed to assess the efficacy and tolerability of gemcitabine plus paclitaxel versus gemcitabine alone as second-line treatment for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously received 5-fluorouracil, oxaliplatin, and irinotecan. METHODS: Patients with histologically or cytologically confirmed mPDAC were randomly assigned (2:1) to receive GEMPAX (paclitaxel 80 mg/m2 + gemcitabine 1,000 mg/m2; IV; once at day (D) 1, D8, and D15/arm A) or gemcitabine (arm B) alone once at D1, D8, and D15 every 28 days until progression, toxicity, or patient's decision. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), quality of life, and safety. RESULTS: Overall, 211 patients (median age, 64 [30-86] years; 62% male) were included. After a median study follow-up for alive patients of 13.4 versus 13.8 months in arm A versus arm B, the median OS (95% CI) was 6.4 (5.2 to 7.4) versus 5.9 months (4.6 to 6.9; hazard ratio [HR], 0.87 [0.63 to 1.20]; P = 0.4095), the median PFS was 3.1 (2.2 to 4.3) versus 2.0 months (1.9 to 2.3; HR, 0.64 [0.47 to 0.89]; P = 0.0067), and the ORR was 17.1% (11.3 to 24.4) versus 4.2% (0.9 to 11.9; P = 0.008) in arm A versus arm B, respectively. Overall, 16.7% of patients in arm A and 2.9% in arm B discontinued their treatment because of adverse events (AEs). One grade 5 AE associated with both gemcitabine and paclitaxel was reported in arm A (acute respiratory distress), and 58.0% versus 27.1% of patients experienced grade ≥3 treatment-related AEs in arm A versus arm B, among which 15.2% versus 4.3% had anemia, 15.9% versus 15.7% had neutropenia, 19.6% versus 4.3% had thrombocytopenia, 10.1% versus 2.9% had asthenia and 12.3% versus 0.0% had neuropathy. CONCLUSION: While GEMPAX did not meet the primary end point of OS versus gemcitabine alone in patients with mPDAC in the second-line setting, both PFS and ORR were significantly improved.

Prevalence and clinical significance of the muscle retracting sign during endoscopic submucosal dissection of large macronodular colorectal lesions (with videos).

BACKGROUND AND AIMS: The muscle retracting sign (MRS) can be present during endoscopic submucosal dissection (ESD) of macronodular colorectal lesions. The prevalence of MRS and its pathologic and clinical implications is unclear. This study evaluated the effect of MRS on the technical and clinical outcomes of ESD. METHODS: All patients referred for ESD of protruding lesions or granular mixed lesions with >10 mm macronodule granular mixed laterally spreading tumors (LST-GMs) in 2 academic centers from January 2017 to October 2022 were prospectively included. Size of the macronodule was analyzed retrospectively. The primary outcome was the curative resection rate according to MRS status. Secondary outcomes were R0 resection, perforation, secondary surgery rate, and risk factors for MRS. RESULTS: Of 694 lesions, 84 (12%) had MRS (MRS+). The curative resection rate was decreased by MRS (MRS+ 41.6% vs lesions without MRS [MRS-] 81.3%), whereas the perforation (MRS+ 22.6% vs MRS- 9.2%), submucosal cancer (MRS+ 34.9% vs MRS- 9.2%), and surgery (MRS+ 45.2% vs MRS- 6%) rates were increased. The R0 resection rate of MRS+ colonic lesions was lower than that of rectal lesions (53% vs 74.3%). In multivariate analysis, protruding lesions (odds ratio, 2.47; 95% confidence interval, 1.27-4.80) and macronodules >4 cm (odds ratio, 4.24; 95% confidence interval, 2.23-8.05) were risk factors for MRS. CONCLUSIONS: MRS reduces oncologic outcomes and increases the perforation rate. Consequently, procedures in the colon should be stopped if MRS is detected, and those in the rectum should be continued due to the morbidity of alternative therapy.

A 3D-printed pedal fixator for connecting different pedal-operated tools reduces the number of mistakes during endoscopic submucosal dissection.

Background and study aims What distinguishes endoscopic submucosal dissection (ESD) from endoscopic mucosal resection is the need for three foot pedals to activate the electrosurgical unit, flushing and knife injection. The lack of connection between the various pedals of different shapes and brands leads to numerous pedals displacements and potential mistakes. The aim of this study was to evaluate an Innovative PEdal FIXator (IPEFIX) to reduce pedal mistakes during ESD. Methods This was a prospective, multicenter, randomized study. Consecutive ESD procedures were randomly assigned to two groups: a control group with the three pedals free and the IPEFIX group in which the three pedals were linked by IPEFIX. The main outcome evaluated was the number of foot mistakes (wrong pedal, foot push beside the pedal). Results A total of 107 ESDs were performed by eight experts in five centers. The median number of mistakes per hour of ESD procedure was 0/h in the IPEFIX group and 1.9/h in the control group ( P <0.001). The mean number of times to look down to control the position of the pedals was 2.2/h the IPEFIX group and 7.7/h in the control group ( P <0.001). Mean replacements of the pedals were 0./h in the IPEFIX group and 1.7/h in the control group ( P <0.001). Similar results were obtained in trainees in simulated ESD on animal models. Conclusions IPEFIX is a simple device to connect different pedals during endoscopic procedures. It helps to reduce the numbers of foot mistakes during ESD and improves operator comfort.

Adjuvant chemotherapy benefit according to T and N stage in small bowel adenocarcinoma: a large retrospective multicenter study.

BACKGROUND: Small bowel adenocarcinoma is a rare cancer, and the role of adjuvant chemotherapy for localized disease is still debated. METHODS: This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for localized small bowel adenocarcinoma between 1996 and 2019 from 3 French cohort studies. Prognostic and predictive factors of adjuvant chemotherapy efficacy were analyzed for disease-free survival and overall survival. The inverse probability of treatment weighting method was applied in the Cox regression model using the propensity score derived from multivariable logistic regression. RESULTS: A total of 354 patients were included: median age, 63.5 years; duodenum location, 53.5%; and tumor stage I, II, and III in 31 (8.7%), 144 (40.7%), and 179 (50.6%) patients, respectively. The adjuvant chemotherapy was administered in 0 (0%), 66 (48.5%), and 143 (80.3%) patients with stage I, II, and III, respectively (P < .0001). In the subgroup analysis by inverse probability of treatment weighting method, a statistically significant disease-free survival and overall survival benefit in favor of adjuvant chemotherapy was observed in high-risk stage II (T4 and/or <8 lymph nodes examined) and III (T4 and/or N2) but not for low-risk stage II (T3 and ≥8 lymph nodes examined) and III (T1-3/N1) tumors (Pinteraction < .05). Furthermore, tumor location in jejunum and ileum was also a statistically significant predictive factor of response to adjuvant chemotherapy in stage II and III tumors (Pinteraction < .05). CONCLUSION: In localized small bowel adenocarcinoma, adjuvant chemotherapy seems to provide a statistically significant survival benefit for high-risk stage II and III tumors and for jejunum and ileum tumor locations.

Surgical rather than endoscopic resection of early-stage colorectal cancers promotes excessive imaging surveillance.

BACKGROUND AND AIMS: Imaging surveillance after curative resection of colorectal cancer (CRC) is debated, particularly in cases of early-stage CRC. The aim of this study was to retrospectively analyze whether and how patients with screened stage 0 and stage 1 CRC were monitored by imaging. METHODS: A cohort of patients with stage 0 (intramucosal) or stage 1 (T1N0) CRC detected from 2003 to 2015 through the French national screening programme was included. All imaging findings were recorded. Statistical analyses were performed for the entire cohort (n = 450) and separately for the two groups (stage 0 n = 268, stage 1 n = 182). Factors associated with imaging surveillance, including the patient's referring gastroenterologist, were determined by logistic regression. RESULTS: A total of 450 patients were followed up for 6.6 ±â€¯3.9 years. Imaging surveillance was performed for 159 (35.3%), more often for those with stage 1 (66.5%) than stage 0 (14.2%) tumours (p < 0.0001). Within the stage 1 group, 17 of the 47 patients (36.2%) treated by local (endoscopic or surgical transanal) resection alone were followed up by imaging monitoring. Factors significantly associated with surveillance in the entire cohort were the gastroenterologist assigned to the patient (p < 0.0001) and surgical vs endoscopic resection (OR = 39.0, p < 0.0001). The histological risk of lymph node metastasis was not significantly associated with imaging monitoring for stage 1 patients. Of the 5 patients who developed distant metastasis during follow-up, one was diagnosed through imaging surveillance. CONCLUSION: This study demonstrates excessive imaging surveillance for early-stage cancers. The use of surgical over endoscopic tumour resection could promote unnecessary surveillance.

Cumulative Exposure to Infliximab, But Not Trough Concentrations, Correlates With Rate of Infection.

BACKGROUND & AIMS: Infliximab increases the risk of infection in patients with inflammatory bowel diseases (IBD), but there is controversy over the relationship between drug concentration and infections. We aimed to assess factors associated with infection in infliximab-treated patients, including pharmacokinetic features. METHODS: We collected data from 209 patients with IBD (102 men; mean age, 39 y; 159 with Crohn's disease; 54 received combination therapy) who received an infliximab maintenance regimen from November 2016 through April 2017 in France. Data were collected from each infusion visit (total of 640 infusions). Infliximab exposure was estimated based on the area under the curve (AUC) of drug concentration in pharmacokinetic models; individual exposures over the 6-month period were estimated based on the sum of the AUC (ΣAUC). RESULTS: The mean infliximab trough level was 5.46 mg/L, and the mean ΣAUC was 3938 ± 1427 mg.d/L. A total of 215 infections were collected from the 640 infusion visits; 123 patients (59%) had at least 1 infection. Factors independently associated with infection after multivariate analysis were smoking (odds ratio [OR], 2.05; P = .046), IBD flare (OR, 2.71; P = .006), and a high ΣAUC of infliximab (above 3234 mg x d/L) (OR, 2.02; P = .02). The ΣAUC was higher in patients with an occurrence of infection (P = .04) and correlated with the number of infections (P = .04). Trough concentration of infliximab alone was not associated with infection. CONCLUSIONS: Almost two-thirds of patients treated with infliximab developed an infection; risk was individually correlated with cumulative increase in drug exposure, but not infliximab trough level.

Reappraisal of the characteristics, management, and prognosis of intramucosal colorectal cancers and their comparison with T1 carcinomas.

BACKGROUND AND AIMS: The recent description of "invasive" forms of intramucosal carcinoma (IMC) has rekindled interest in studying the characteristics, management, and prognosis of IMCs and comparing them with T1 colorectal cancers (CRCs). METHODS: This population-based study included 282 cases of IMC and 207 cases of T1 CRC diagnosed by colonoscopy after a positive fecal blood test through a screening program. RESULTS: IMC presented mainly in the form of pedunculated polyps (68.4%) located in the distal colon (69.9%) ≥20 mm in size (60.6%). IMCs were resected endoscopically in 227 (80.5%) patients and surgically resected in 55 (19.5%) patients. Surgical patients had more right-sided, more sessile, and larger lesions. There was no sign of lymphovascular invasion. Compared with T1 CRCs, IMCs demonstrated lower rates of sessile polyps (31.6% vs 49.8%, P < .0001), primary and ultimate surgical treatment (19.5% vs 39.1% and 19.9% vs 78.7%, P < .0001, respectively), lymph node metastasis in surgical patients (0% vs 9.5%, P = .041), cancer recurrence and cancer-related mortality (0% vs 5.6% and 0% vs 2.5%, respectively), and bleeding after endoscopic resection (1.8% vs 8.7%, P = .001). By multivariate analysis of the pooled cohort (IMC + T1 CRC, n = 489), the factors significantly associated with first-line surgery were shown to be polyp characteristics and the gastroenterologist who performed the colonoscopy. CONCLUSIONS: IMCs account for a quarter of all screening-detected CRCs. They have an excellent prognosis regardless of whether endoscopic or surgical treatment is performed. IMCs differ significantly from T1 carcinomas in terms of management and prognosis.

Incidental anal 18fluorodeoxyglucose uptake: Should we further examine the patient?

BACKGROUND: There are no studies on incidental anal 18F-fluorodeoxyglucose (18FDG) uptake. AIM: To assess the rate and aetiologies of incidental anal 18FDG uptake and to evaluate the correlation between 18FDG positron-emission tomography/computed tomography (PET/CT) parameters and the diagnosis of an anorectal disease. METHODS: The data from patients with incidental anal 18FDG uptake were retrospectively analysed. Patients who underwent anorectal examinations were identified and compared to those who did not undergo examinations. Patients who were offered treatment were then identified and compared to those who did not receive treatment. RESULTS: Among the 43020 18FDG PET/CT scans performed, 197 18FDG PET/CT scans of 146 patients (0.45%) reported incidental anal uptake. Among the 134 patients included, 48 (35.8%) patients underwent anorectal examinations, and anorectal diseases were diagnosed in 33 (69.0%) of these patients and treated in 18/48 (37.5%) patients. Among the examined patients, those with a pathology requiring treatment had significantly smaller metabolic volumes (MV) 30 and MV41 values and higher maximal and mean standardized uptake value measurements than those who did not require treatment. CONCLUSION: Incidental anal 18FDG uptake is rare, but a reliable anorectal diagnosis is commonly obtained when an anorectal examination is performed. The diagnosis of an anorectal disease induces treatment in more than one-third of the patients. These data should encourage practitioners to explore incidental anal 18FDG uptake systematically.

Management of T1 colorectal cancers detected at screening colonoscopy: A study from the French national screening programme.

AIM: The main aim of this study was to examine the management strategies that were used and to determine the outcomes (survival and recurrence rate) of screen-detected T1-CRC. METHODS: Medical records from 207 patients with T1-CRC diagnosed through the French national screening programme in one district from 2003 to 2015 were analysed. The 5-year overall, CRC-specific and CRC-free survival were calculated for the whole cohort and for the 3 groups treated by endoscopic resection (ER) alone, ER followed by subsequent surgery (ERSS), and primary surgery (PS). RESULTS: Of the 207 patients, 81 (39%) underwent PS, and 126 (61%) underwent primary ER, of whom 82 (64%) underwent subsequent surgery. The 5-year overall and cancer-specific survival rates were 95.5% (95% CI, 90.8; 97.9) and 98.8% (95% CI, 95.4; 99.7%), respectively. Long-term cancer-specific mortality and recurrence crude rates were 2.4% and 5.6%, respectively. The 5-year CRC-free survival rate was 96.1% (95% CI, 91.8; 98.1%) and did not differ amongst the 3 groups (ER alone, ERSS and PS). CONCLUSION: This study demonstrates the good prognosis of screen-detected T1-CRC, regardless of the treatment strategy used. But, there is a room to improve the screening programme quality with regard to the management of screen-detected CRC.