Background
TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of ...TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets.
Methods
This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m
2
) was given orally twice daily on days 1–5 and 8–12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety.
Results
Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred.
Conclusions
This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In research settings, circulating tumor DNA (ctDNA) shows promise as a tumor-specific biomarker for pancreatic ductal adenocarcinoma (PDAC). This study aims to perform analytical and clinical ...validation of a
ctDNA assay in a Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathology-certified clinical laboratory.
Digital-droplet PCR was used to detect the major PDAC-associated somatic
mutations (G12D, G12V, G12R, and Q61H) in liquid biopsies. For clinical validation, 290 preoperative and longitudinal postoperative plasma samples were collected from 59 patients with PDAC. The utility of ctDNA status to predict PDAC recurrence during follow-up was assessed.
ctDNA was detected preoperatively in 29 (49%) patients and was an independent predictor of decreased recurrence-free survival (RFS) and overall survival (OS). Patients who had neoadjuvant chemotherapy were less likely to have preoperative ctDNA than were chemo-naïve patients (21% vs. 69%;
< 0.001). ctDNA levels dropped significantly after tumor resection. Persistence of ctDNA in the immediate postoperative period was associated with a high rate of recurrence and poor median RFS (5 months). ctDNA detected during follow-up predicted clinical recurrence sensitivity 90% (95% confidence interval (CI), 74%-98%), specificity 88% (95% CI, 62%-98%) with a median lead time of 84 days (interquartile range, 25-146). Detection of ctDNA during postpancreatectomy follow-up was associated with a median OS of 17 months, while median OS was not yet reached at 30 months for patients without ctDNA (
= 0.011).
Measurement of
ctDNA in a CLIA laboratory setting can be used to predict recurrence and survival in patients with PDAC.
Background and Aim
Colorectal endoscopic submucosal dissection (ESD) is a useful treatment method; however, no index has been established for time for patient to start food ingestion or be discharged ...after ESD. We investigated the potential of a clinical pathway in which patients started food ingestion on day 2 after ESD and were discharged on day 3.
Methods
A total of 382 patients underwent colorectal ESD between 2006 and 2012. A flow chart of a clinical pathway was prepared based on the data obtained, with the aim of shortening hospital stay after ESD.
Results
Mean duration of postoperative hospital stay in the 382 patients was 5.3 ± 1.8 days. The most common cause of extended hospital stay was abnormal blood test finding, as detected in 50 patients in group C (n = 131; 38.2%), followed by careful course observations, as noted in 48 patients in group C (n = 131; 36.6%). Regarding procedural accidents as a result of ESD, intraoperative perforation occurred in 15 patients (3.9%) and post‐ESD bleeding in seven patients (1.8%), which extended the hospital stay. Food ingestion was started on day 2 when no abnormality was noted during ESD or in physical and imaging findings or blood tests on day 1. In the 86 patients who underwent the prepared clinical pathway as a validation study, 68 (79.0%) were discharged on day 3. Duration of postoperative hospital stay was 3.4 ± 1.2 days.
Conclusion
Discharge may be possible 3 days after ESD when no abnormalities are noted during ESD or on post‐ESD day 1.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Construction of a diverting stoma can significantly reduce the onset of severe anastomotic leakage in patients with rectal cancer. High-output stoma is one of the most important potential surgical ...complications after anal function-preserving surgery with ileostomy. Culture-independent techniques have revealed the interaction of the complex intestinal bacterial ecology with various diseases. Our objective was to evaluate the differences in patient characteristics and gut microbiota distribution features in patients with high-output stomas. The cases of 24 consecutive patients who underwent curative resection for rectal cancer at our hospital between November 2016 and June 2018 were reviewed, and the patients were categorized into high-output and low-output groups. Their microbiota were analyzed using next-generation sequencing of ileostomy stool samples collected on postoperative day 7. There was a significant difference in the percentage of Bacteroidetes between the high-output and low-output groups (14.8% vs 0.5%; p=0.01). The percentage of Clostridium butyricum was increased in the low-output group (p=0.01). After the exclusion of those treated with the probiotic Miya-BM, whose principal component is C. butyricum, analyses revealed no significant differences between the high-output and low-output groups. This pilot study provides the first evidence correlating gut microbiota with the pathogenesis of high- output stoma compared with low-output stoma.
Pancreatic intraepithelial neoplasia (PanIN) is a precursor to invasive ductal adenocarcinoma of the pancreas. Observations
made in genetically engineered mouse models suggest that the ...acinar/centroacinar compartment can give rise to ductal neoplasia.
To integrate findings in mice and men, we examined human acinar cells, acinar-ductal metaplasia (ADM) lesions, and PanINs
for KRAS2 gene mutations. Surgically resected pancreata were screened for foci of ADM with or without an associated PanIN lesion. Stromal
cells, acinar cells, ADMs, and PanINs were separately isolated using laser capture microdissection. KRAS2 status was analyzed using genomic DNA isolated from the microdissected tissue. Twelve of these 31 foci of ADM occurred in
isolation, whereas 19 were in the same lobules as a PanIN lesion. All 31 microdissected foci of acinar cells were KRAS2 gene wild-type, as were all 12 isolated ADM lesions lacking an associated PanIN. KRAS2 gene mutations were present in 14 of 19 (74%) PanIN lesions and in 12 of the 19 (63%) foci of ADM associated with these PanINs.
All ADM lesions with a KRAS2 gene mutation harbored the identical KRAS2 gene mutation found in their associated PanIN lesions. Ductal neoplasms of the human pancreas, as defined by KRAS2 gene mutations, do not appear to arise from acinar cells. Isolated AMD lesions are genetically distinct from those associated
with PanINs, and the latter may represent retrograde extension of the neoplastic PanIN cells or less likely are precursors
to PanIN. (Mol Cancer Res 2009;7(2):230–6)
Huge accessory spleen (AS) is a rare condition difficult to diagnose. We recently treated a Japanese woman with a progressive huge AS. She had a history of aortic valve replacement for aortic ...stenosis 1 month prior. At that time, a 4-cm AS had been detected by the preoperative computed tomography (CT). This mass was a progressive tumor which grew to 7 cm over the course of 3 months. Thus, we performed surgery with a preoperative diagnosis of huge AS by CT and positron emission tomography. A laparoscopic resection was performed considering the risk of torsion, spontaneous rupture, or hemorrhage. The final pathological diagnosis was AS. This is the first reported case in the English literature of progressive AS with no symptoms at the initial presentation that was treated with laparoscopic resection.
Perineal hernia (PH) is a rare complication following laparoscopic abdominoperineal resection (APR) for rectal cancer. We present a case report of perineal hernia after laparoscopic APR and discuss ...its management. The patient was a 77‐year‐old man who was diagnosed with lower rectal cancer. He underwent laparoscopic APR and bilateral lateral lymph node dissection. Two months after the surgery, pain and bulging in the perineal region developed, and PH was diagnosed by CT. Repair with a polypropylene mesh was performed using a combination of laparoscopic abdominal and transperineal approaches. Reportedly, the incidence of secondary PH after APR has increased along with the rate of laparoscopic surgery. Treatment of secondary PH with transperineal repair alone may cause injuries to other organs because of adhesion of the pelvic viscera. In the present case, we safely repaired the hernia repair using a laparoscopy‐assisted perineal approach.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Here we report a combined laparoscopic abdominoperineal resection and robotic‐assisted prostatectomy. A 74‐year‐old man was diagnosed with T4b low rectal and prostate cancer. The operation was ...performed after neoadjuvant chemotherapy for the rectal cancer. The procedure used eight ports in total, five for laparoscopic abdominoperineal resection and six for robotic‐assisted prostatectomy. First, laparoscopic total mesorectal excision including division of the inferior mesenteric artery was performed, and then, robotic dissection of the prostate was performed. The en bloc specimen was removed through the perineal wound. Then, robotic urethrovesical anastomosis was performed. An extraperitoneal end colostomy was created to finish the operation. The operating time was 545 min, and blood loss was 170 mL. The postoperative course was uneventful, and the patient discharged on postoperative day 17. The combined laparoscopic abdominoperineal resection and robotic‐assisted prostatectomy were performed safely without any additional technical difficulty, as both procedures shared port settings and patient positions.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Here, we report a case of repeated laparoscopic resection of extra-regional lymph node metastases in a patient after laparoscopic surgery for rectal cancer. A 72-year-old woman was diagnosed with ...upper rectal cancer and underwent laparoscopic low anterior resection and D3 dissection. The pathological stage was considered as T3, N2b, M0, Stage IIIC. Six months after the operation, positron emission tomography-computed tomography (PET-CT) showed fluorodeoxyglucose (FDG) accumulation in the infra-renal para-aortic lymph nodes (PALNs). Systemic chemotherapy was administered; however, chemotherapy was discontinued due to hemoptysis related to her pulmonary disease. Therefore, we performed laparoscopic PALN resection. Pathologically, one lymph node was diagnosed with a metastasis. Three months after the second operation, PET-CT identified FDG accumulation in the left lateral pelvic lymph nodes (LPLNs) and a PALN. Laparoscopic LPLN dissection and PALN resection through minilaparotomy were performed. Pathologically, lymph node metastases were diagnosed in both fields. Sixteen months after the 3rd operation, there is no recurrence.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Human cancer cell lines and xenografts are valuable samples for whole-genome sequencing of human cancer. Tumors can be maintained by serial xenografting in athymic (nude) or severe combined ...immunodeficient (SCID) mice. In the current study, we developed a molecular assay to quantify the relative contributions of human and mouse in mixed DNA samples. The assay was designed based on deletion/insertion variation between human and mouse genomes. The percentage of mouse DNA was calculated according to the relative peak heights of PCR products analyzed by capillary electrophoresis. Three markers from chromosomes 9 and 10 accurately predicted the mouse genome ratio and were combined into a multiplex PCR reaction. We used the assay to quantify the relative DNA amounts of 93 mouse xenografts used for a recently reported integrated genomic analysis of human pancreatic cancer. Of the 93 xenografts, the mean percentage of contaminating mouse DNA was 47%, ranging from 17% to 73%, with 43% of samples having >50% mouse DNA. We then comprehensively compared the human and mouse genomes to identify 370 additional candidate gene loci demonstrating human-mouse length variation. With increasing whole-genome sequencing of human cancers, this assay should be useful to monitor strategies to enrich human cancer cells from mixed human-mouse cell xenografts. Finally, we discuss how contaminating mouse DNA affects next-generation DNA sequencing.
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