Regorafenib has shown survival benefits in metastatic colorectal cancer patients who were exacerbated after all standard therapies. Some patients, however, exhibit severe adverse events (AEs) ...resulting in treatment discontinuation. Therefore, the selection of patients likely to benefit from regorafenib is crucial. Twenty patients were treated with regorafenib for metastatic colorectal cancer; 122 plasma samples were taken from 16 of these patients for monitoring of circulating tumor DNA (ctDNA) in the blood. The treatment response, AEs, overall survival (OS), progression-free survival (PFS) and tumor morphologic changes on CT images were evaluated. KRAS mutant ctDNA was determined using digital PCR. Median PFS and OS were 2.5 and 5.9 months, respectively. Treatment was discontinued because of disease progression (PD) in 10 patients, and AEs in another 10 patients. AEs included hyperbilirubinemia, severe fatigue and skin rash. Hyperbilirubinemia was seen in two patients with multiple bilateral liver metastases, and severe fatigue in another 2 patients with poor performance status (PS). These severe AEs resulted in treatment discontinuation. Ten patients had a median PFS of 2.1 months with AE related discontinuation; PD occurred at 3.5 months (p=0.00334). Four patients exhibited a morphologic response, achieving better PFS times of 3.5, 5.3, 5.6 and 14.2 months. Emergence of the KRAS mutation in ctDNA was observed during anti-EGFR antibody treatment in 3 patients among 11 with KRAS wild-type tumors; it was detectable in the blood prior to radiographic detection of PD. Moreover, the KRAS mutation declined in two patients during regorafenib monotherapy. These patients were re-challenged with anti-EGFR antibody. Patients with extensive multiple liver metastases or poor PS are unlikely to benefit from regorafenib. Patients with a morphologic response will probably benefit from regorafenib with adequate management of other AEs. KRAS monitoring in ctDNA could be useful regarding treatment response and in determining treatment strategy.
Intestinal strangulation caused by a mucocele of the appendix is extremely rare and difficult to diagnose. It is not usually suspected pre-operatively. This report presents a case of intestinal ...strangulation due to a mucous containing cystic lesion that was wrapped around the base of a loop of the small bowel. An 89-year-old female was transferred after an acute onset of abdominal pain. A physical examination revealed severe tenderness with guarding in the right upper quadrant. CT of the abdomen showed a loop of dilated small bowel with edema on the right side of the abdominal cavity suggesting a closed loop obstruction. In addition, a low-density thin-walled mass measuring 5 cm in diameter was also seen in the pelvis. Intestinal strangulation was suspected and emergency laparotomy was thus performed. A loop of terminal ileum 25 cm in length was strangulated by a dilated appendix, and ileocecal resection was performed. The resected appendix measured 9 × 3 cm in size and contained mucus. A histopathological examination showed a mucous containing cystic appendix without mucin-producing, neoplastic epithelial cells. A mucocele of the appendix can present in various ways and it is important to recognize this entity at the time of surgery.
Chemoradiotherapy is considered the standard treatment for patients with localized anal squamous cell carcinoma in western countries. We analyzed the treatment outcomes of six patients with anal ...canal squamous cell carcinoma treated with chemoradiotherapy. The clinical stage was IIIA in one case, IIIB in one case and IIIC in three cases. The stage of the patient when undergoing local resection for tumor prior to chemoradiotherapy was pStage I. The regimens of chemotherapy were fluorouracil plus mitomycin C in four patients and fluorouracil plus cisplatin in two patients. Grade 3 adverse events occurred in three patients. One patient discontinued the second half of the regimen due to adverse events. During the follow-up period, a stoma was created in two patients. The reasons for creating a stoma were bowel obstruction caused by tumor prior to chemoradiotherapy and anal sphincter dysfunction after chemoradiotherapy. The median follow-up period was 49 months. All patients achieved complete response and remain alive without recurrence. Although careful attention should be given to adverse events, chemoradiotherapy is effective for patients with anal canal squamous cell carcinoma.
Introduction
An accurate assessment of the depth of tumor invasion in patients with colon cancer is an important part of the preoperative evaluation. Whether computed tomographic colonography (CTC) ...or optical colonoscopy (OC) is better to accurately determine tumor location and invasion depth has not been definitively determined. The aim of this study was to determine the diagnostic accuracy of tumor localization and tumor invasion depth of colon cancer by preoperative OC alone or combined with CTC.
Methods
Study participants include 143 patients who underwent both preoperative CTC using automated CO2 insufflation and OC from July 2012 to August 2013.
Results
The accuracy of tumor localization was significantly better with CTC than with OC (OC, 90%; CTC, 98%; P < 0.05). No tumor in the descending colon was localized accurately via OC alone. The accuracy of tumor invasion depth was better with CTC plus OC than with OC alone (OC, 55%; CTC, 73%; P < 0.05).
Conclusions
OC combined with CTC provides a more accurate preoperative determination of tumor localization and invasion depth than OC alone.
Background
Anti-epidermal growth factor receptor (EGFR) antibody is widely used for the treatment of patients with metastatic colorectal cancer. Hypomagnesemia is a comparatively frequent adverse ...event of this drug, which is likely overlooked because it occurs later in treatment without symptoms. Furthermore, hypomagnesemia and hypomagnesemia-induced corrected QT (QTc) prolongation may lead to loss of consciousness (LOC), the onset of which is not generally considered associated with the treatment of anti-EGFR antibody because of its rare occurrence. Here, we present a colorectal cancer patient treated with anti-EGFR antibody, who suffered LOC during treatment while severe hypomagnesemia or QTc prolongation was not observed.
Case presentation
A 69-year-old man with metastatic colon cancer was treated with cetuximab (anti-EGFR antibody) plus irinotecan as third-line chemotherapy. His serum magnesium level gradually decreased, and grade 2 hypomagnesemia (a serum magnesium level of 0.9 mg/dL) was observed at the 12th administration of cetuximab. In light of this development, intravenous supplementation of 20 mEq magnesium sulfate began with careful blood monitoring despite the lack of clinical symptoms. Electrocardiogram (ECG) showed prolonged QT or corrected QT (QTc) intervals (grade 1). His serum magnesium level remained at 0.9 mg/dL, and no hypomagnesemia symptoms were observed by the 17th administration of cetuximab. After the treatment, however, he suddenly lost consciousness without symptoms related to infusion or allergic reactions. Circulatory collapse following dermatological reactions and respiratory events were not evident. Intravenous supplementation of magnesium sulfate was administered again. He awakened 2 min after the onset of temporary LOC without any other symptoms related to hypomagnesemia, such as lethargy, tremor, tetany, and seizures. No other etiology outside of the low level of serum magnesium was confirmed in further examinations. Cetuximab was discontinued, and his serum magnesium level returned to a level within the normal range after 6 weeks. Because of tumor progression, regorafenib and TAS-102 (trifluridine tipiracil hydrochloride) were introduced sequentially for 6 months. Five months after the final treatment of TAS-102, he died of his primary disease, which reflected a survival period of 4 years and 6 months since the beginning of treatment.
Conclusions
This case report reminds clinicians that LOC can be induced without severe hypomagnesemia or QTc prolongation, during anti-EGFR antibody treatment for metastatic colorectal cancer even while under carefully monitored magnesium supplementation.
Abstract
Background and study aims
Delayed bleeding is believed to occur less frequently after cold snare polypectomy (CSP), but this has not been validated in clinical trials. This study aimed to ...compare rates of delayed bleeding after CSP and hot snare polypectomy (HSP).
Patients and methods
We conducted a multicenter, randomized controlled trial. Participants scheduled to undergo endoscopic resection of colorectal polyps ≤ 10 mm were enrolled and randomly assigned to CSP or HSP. Prophylactic clipping was performed at the endoscopists’ discretion. The primary outcome was delayed bleeding rate. Secondary outcomes included immediate bleeding rate and clipping rate. Sample size calculation showed that 451 patients were required in each arm.
Results
At the end of the study period decided in advance, 308 participants were recruited and an interim analysis was performed. A total of 273 patients (mean age 62.2 ± 8.8 years; 188 males) were analyzed, with 139 patients allocated to CSP and 134 to HSP. In total, 367 polyps were resected with CSP and 360 polyps with HSP. There were no significant differences in patient demographics or polyp characteristics. In per-patient-based analysis, delayed bleeding rates were 0.7 % after CSP and 0.7 % after HSP. Per-polyp analysis showed similar results (CSP: 0.3 % vs. HSP: 0.6 %). The immediate bleeding rate was significantly higher with CSP vs. HSP (54 % vs.14 %,
P
< 0.0001), while clipping rates were 18 % and 19 %, respectively.
Conclusion
This interim analysis did not demonstrate that delayed bleeding after CSP is less frequent than after HSP. The delayed bleeding rate after HSP was lower than expected.
Meeting presentations: Digestive Disease Week 2017
Background
Lynch syndrome, also referred to as hereditary nonpolyposis colorectal cancer, is the most common form of hereditary colorectal cancer, and is associated with a high incidence of multiple ...primary neoplasms in various organs.
Methods
A 79-year-old woman (patient 1) diagnosed with ascending colon cancer had a history of previous carcinomas of the uterus, stomach, uroepithelial tract, and colon. One year later, she developed a brain tumor (glioblastoma). A 54-year-old female (patient 2) was diagnosed with endometrial cancer and sigmoid colon cancer. Both patients underwent genetic evaluations independently.
Results
No mutations were found in an exon-by-exon analysis of genomic DNA by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR. However, multiplex ligation-dependent probe amplification (MLPA) identified genomic duplication spanning from exon 7 to exon 14 of the
MSH2
gene in both patients. Due to the presence of this characteristic gene duplication, their pedigrees were investigated further, and these showed that they are paternal half-sisters, consistent with paternal inheritance.
Conclusion
Large genomic duplication from intron 6 through intron 14 in
MSH2
is a very rare cause of Lynch syndrome and is difficult to identify with conventional methods. MLPA may be an alternative approach for detecting large-scale genomic rearrangements.
Idiopathic mesenteric phlebosclerosis is a rare entity characterized by chronic intestinal ischemia due to calcification and obstruction of the mesenteric veins. Here, we report a patient with ...idiopathic mesenteric phlebosclerosis treated with laparoscopic subtotal colectomy after evaluation by imaging studies. The patient was a 68‐year‐old Japanese woman with recurrent abdominal pain who had taken a Chinese herbal medicine for more than 20 years. Abdominal CT showed wall thickening of the right colon with calcification of branches of the superior mesenteric vein. Colonoscopy showed cyanotic mucosa from the cecum to the sigmoid colon. The affected area seen on colonoscopy extended to the distal colon. Despite discontinuation of the herbal medicine, her symptoms did not improve. Laparoscopic subtotal colectomy was performed. This report highlights the importance of appropriately evaluating the extent of the affected preoperatively area based on findings from colonoscopy, CT, and contrast enema.
AIM To assess the usefulness of en bloc right hemicolectomy with pancreaticoduodenectomy(RHCPD) for locally advanced right-sided colon cancer(LARCC).METHODS We retrospectively reviewed the database ...of Saitama Medical Center, Jichi Medical University, between January 2009 and December 2016. During this time, 299 patients underwent radical right hemicolectomy for right-sided colon cancer. Among them, 5 underwent RHCPD for LARCC with tumor infiltration to adjacent organs. Preoperative computed tomography(CT) was routinely performed to evaluate local tumor infiltration into adjacent organs. During the operation, we evaluated the resectability and the amount of infiltration into the adjacent organs without dissecting the adherent organs from the cancer. When we confirmed that radical resection was feasible and could lead to R0 resection, we performed RHCPD. The clinical data were carefully reviewed, and the demographic variables, intraoperative data, and postoperative parameters were recorded.RESULTS The median age of the 5 patients who underwent RHCPD for LARCC was 70 years. The tumors were located in the ascending colon(three patients) and transverse colon(two patients). Preoperative CT revealed infiltration of the tumor into the duodenum in all patients, the pancreas in four patients, the superior mesenteric vein(SMV) in two patients, and tumor thrombosis in the SMV in one patient. We performed RHCPD plus SMV resection in three patients. Major postoperative complications occurred in 3 patients(60%) as pancreatic fistula(grade B and grade C, according to International Study Group on Pancreatic Fistula Definition) and delayed gastric empty. None of the patients died during their hospital stay. A histological examination confirmed malignant infiltration into the duodenum and/or pancreas in 4 patients(80%), and no patients showed any malignant infiltration into the SMV. Two patients were histologically confirmed to have tumor thrombosis in the SMV. All of the tumors had clear resection margins(R0). The median follow-up time was 77 mo. During this period, two patients with tumor thrombosis died from liver metastasis. The overall survival rates were 80% at 1 year and 60% at 5 years. All patients with node-negative status(n = 2) survived for more than seven years.CONCLUSION This study showed that the long-term survival is possible for patients with LARCC if RHCPD is performed successfully, particularly in those with node-negative status.
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