Rina Kikugawa

Clinical and molecular assessment of regorafenib monotherapy.

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.

Laparoscopic resection of retroperitoneal ectopic thyroid tissue: Retroperitoneal ectopic thyroid tissue

A 43‐year‐old otherwise healthy woman was found to have a retroperitoneal mass during a routine medical examination and was referred for further evaluation. Abdominal CT scan showed a well‐delineated, low‐density area that exhibited heterogeneous contrast enhancement. The area measured about 20 mm in size and was to the left of the aorta at the level of the inferior mesenteric artery. MRI showed a mass with heterogeneous hypointensity on T1‐weighted images and heterogeneous hyperintensity on T2‐weighted images. PET‐CT scan showed slightly increased 18F‐fluorodeoxyglucose accumulation within the mass. Laparoscopic resection was performed. A smooth, brownish mass was seen in the retroperitoneum and was resected with minimal blood loss. Histopathological examination showed a nodular mass measuring 40 × 26 × 20 mm that was composed solely of ectopic thyroid tissue. This case shows the exceptional development of ectopic thyroid in the infradiaphragmatic retroperitoneum and demonstrates the usefulness of laparoscopy for resecting such masses.

The surgical treatment of acute and severe diversion colitis mimicking ulcerative colitis: a case report

BackgroundDiversion colitis (DC) is characterized by nonspecific inflammation in the remaining colon or rectum, and loss of the fecal stream plays a major role in the disease’s development. Although the majority of patients are asymptomatic, medical and/or surgical treatment is required for those who are symptomatic. There is a particular interest on how to manage patients with acute and severe clinical presentations, but the pathogenesis is not fully understood. We report the rare case of a man with acute and severe DC mimicking ulcerative colitis (UC) with extra-intestinal manifestations that was successfully managed with surgical treatment.Case presentationA 68-year-old man with a history of laparoscopic intersphincteric resection of the rectum with diverting loop ileostomy for lower rectal cancer suffered from anastomotic stenosis requiring repeated endoscopic dilatation. His loop stoma was not reversed because these treatments were unsuccessful. He denied having a history of inflammatory bowel disease. Twelve years postoperatively, he developed a perineal abscess requiring drainage. Subsequently, he developed a high-grade fever, bloody discharge per anus, and skin ulcers in the right ankle and around the stoma. Because culture tests were negative for bacteria, it was deemed that his acute illness reflected an inflammatory response rather than an infectious disease. Colonoscopy revealed anastomotic stenosis, a colonic fistula, and mucosa that hemorrhaged easily, with lacerations. A pathological examination with biopsy revealed inflammatory infiltration without malignancy. After reviewing the patient’s clinical episodes and discussing the case with physicians in multiple specialties, we performed total colectomy with end ileostomy in accordance with the abdominoperineal resection. The postoperative course was uneventful. A resected specimen showed atrophic mucosa with the disappearance of haustra in the distal colon, as well as edematous and dilated mucosa in the proximal colon. The pathological diagnosis was suggestive of UC, including erosion and ulceration in edematous wall, crypt abscess, and inflammatory infiltration into the mucosa. The skin ulcers in the right ankle and around the stoma healed over time.ConclusionsDC can eventuate in a long-term period after fecal diversion surgery, possibly with extra-intestinal manifestations mimicking UC. Surgical treatment seems feasible for patients with acute and severe DC.

Effect of triclosan-coated sutures on the incidence of surgical site infection after abdominal wall closure in gastroenterological surgery: a double-blind, randomized controlled trial in a single center

Background: Surgical site infection is one of the most common postoperative complications after gastroenterologic surgery. This study investigated the effect of triclosan‐coated sutures in decreasing the incidence of surgical site infections after abdominal wall closure in gastroenterologic surgery. Methods: A prospective, double‐blind, randomized, controlled parallel adaptive group‐sequential superiority trial was conducted from March 2014 to March 2017 in a single center. Eligible patients were those who underwent gastroenterologic surgery. Patients were allocated randomly to receive either abdominal wall closure with triclosan‐coated sutures (the study group) or sutures without triclosan (the control group). The primary end point was the incidence of superficial or deep surgical site infections within 30 days after operation. This study was registered with the University Hospital Medical Information Network‐Clinical Trials Registry (http://www.umin.ac.jp/ctr/), identification number UMIN000013054. Results: A total of 1,013 patients (study group, 508 patients; control group, 505 patients) were analyzed by a modified intention‐to‐treat approach. The wounds in 990 (97.7%) of the 1,013 patients were classified as clean‐contaminated. The primary end point (incidence of superficial or deep surgical site infections) was 35 (6.9%) of 508 patients in the study group and 30 (5.9%) of 505 in the control group. The incidence of surgical site infections did not differ markedly between the 2 groups (95% confidence interval: 0.686–2.010, P = .609). Of the 65 infections, 42 (64.6%) were superficial surgical site infections, with similar frequencies in the 2 groups, and 23 (35.4%) were deep surgical site infections, again with similar frequencies in the 2 groups. Conclusion: Triclosan‐coated sutures did not decrease the incidence of surgical site infections after abdominal wall closure in gastroenterologic surgery.

Intussusception secondary to descending colon lipoma presenting with simultaneous acute appendicitis

Abstract We report a patient with a descending colon lipoma presenting with hematochezia who developed intussusception, which was simultaneously accompanied by acute appendicitis. A 43-year-old man presented with hematochezia. Colonoscopy revealed a submucosal tumor with a reddish surface in the descending colon. A solid mass with fat density value measuring 5 cm in diameter was observed in the descending colon on CT. While awaiting elective resection, the patient developed lower abdominal pain. CT demonstrated antegrade colo-colonic intussusception in the descending colon. Simultaneously, the appendix was inflamed with a high density intraluminal lesion suspected to be a fecalith. The diagnosis of simultaneous intussusception and acute appendicitis was made. Appendectomy and partial resection of the descending colon was performed. Histopathological examination was consistent with descending colon lipoma and acute appendicitis. The mechanism for developing hematochezia and the risk for development of colo-colonic intussusception due to large colon lipoma and acute appendicitis were highlighted.

Laparoscopic and percutaneous repair of a large midline incisional hernia extending to the bilateral subcostal region: A case report

Highlights • A hybrid laparoscopic and percutaneous repair for incisional hernia was described.• Percutaneous defect closure can be indicated for large hernia (>10 cm in diameter).• Mesh fixation should be limited below the costal margin in subcostal hernia.• Minimal organ injuries and obtaining more overlap are the advantages.• Postoperative pain is the disadvantage.

Surgical Resection with Neoadjuvant Chemotherapy for Locoregionally Recurrent Appendiceal Cancer Invading the External Iliac Vessels

Recent advancements in multimodal therapy can provide oncologic benefits for patients with recurrent colorectal cancer. This report presents a case of locoregionally recurrent appendiceal cancer treated with neoadjuvant chemotherapy followed by surgical resection with vascular reconstruction. A 68-year-old Japanese woman was diagnosed with appendiceal cancer and underwent ileocecal resection. The pathological evaluation revealed KRAS-mutant adenocarcinoma with the final stage of T4bN1M0. She received oral fluorouracil-based adjuvant chemotherapy. One year later, she was found to have peritoneal dissemination in the pelvic cavity and vaginal metastasis. She received an oxaliplatin-based chemotherapy followed by surgical resection. One year after the second surgery, she developed a locoregional recurrence involving the right external iliac vessels and small intestine. She received an irinotecan-based regimen with bevacizumab as neoadjuvant chemotherapy, followed by surgical resection. At first, a femoro-femoral bypass was made to secure the blood supply to the right lower extremities. Subsequently, an en bloc resection including the recurrent tumor and the external iliac vessels was completed. Surgical resection for recurrent colorectal cancer is often technically challenging because of the tumor location and invasion to adjacent organs. In this case, a surgical approach with persistent chemotherapy achieved oncologic resection of locoregionally recurrent appendiceal cancer.

Sequential administration of XELOX and XELIRI is effective, feasible and well tolerated by patients with metastatic colorectal cancer

Sequential administration of the chemotherapy regimes capecitabine and oxaliplatin (XELOX) and capecitabine and irinotecan (XELIRI) in the first- to second-line treatment setting would allow patients to be managed more easily in an outpatient unit. However, a small number of studies have raised concerns of cumulative adverse events as a consequence of the continuous use of capecitabine. To investigate this, the present study conducted a retrospective review of 81 consecutive metastatic colorectal cancer (mCRC) patients treated with the oxaliplatin, fluorouracil and leucovorin-irinotecan, fluorouracil and leucovorin (FOLFOX-FOFIRI/F-F) regimen (n=40) or the XELOX-XELIRI (X-X) regimen (n=41) in first- to second-line chemotherapy in Saitama Medical Center between 2006 and 2012. The disease control rate (DCR), the progression free survival (PFS), the overall survival (OS) and the time to failure of strategy (TFS) from first to second-line chemotherapy, as well as adverse events, were assessed and compared between patients receiving X-X or F-F. A total of 10 and 20 patients were additionally treated with bevacizumab in the F-F and X-X regimens, respectively, during first or second-line chemotherapy. There was no significant difference in DCR and the median PFS between the two regimens for first or second-line chemotherapy. There was no significant difference in the median OS and TFS between the two regimens (OS=24.5 and TFS=14 months in the F-F vs. 23.2 and 12.0 months in the X-X). Regarding adverse events, 45.0% of patients (18/40) exhibited grade 3-4 neutropenia throughout treatment with F-F. Whilst, 15.0% of patients (6/41) exhibited grade 3 hypertension throughout treatment with X-X, which was effectively controlled by a single antihypertensive drug. The results show that sequential administration of X-X is as effective and feasible as F-F treatment, while additionally reducing the frequency of infusion visits and eliminating the need for a central venous access device or home infusion pump, thereby offering a more convenient treatment option to patients with mCRC.

Significance of the Difference in the Size of Liver Tumors in the Managementof Patients with Colorectal Liver Metastases

Background: The combination of chemotherapy and surgery is currently accepted for the treatment of patients with technically resectable colorectal liver metastases. It is, however, hard to determine which of these modalities should be the forward treatment. In this study, we assessed the usefulness of the difference in tumor size assessed in pretherapeutic imaging in the selection of chemotherapy in these patients. Methods: We present a retrospective review of 80 consecutive colorectal liver metastases without extrahepatic tumors. The relapse-free survival (RFS), progression-free survival (PFS) and overall survival (OS) were evaluated and compared between patients who underwent surgery (n=66) and chemotherapy (n=14) according to clinical features. In particular, we addressed pretherapeutic imaging studies including the distribution and number of metastatic liver tumors. In addition, the ratio of tumor size (largest to smallest tumor) was calculated; two groups classified as R<5 (ratio <5) and R ≥ 5 (ratio ≥ 5) were compared. Results: Univariate analysis was performed in the surgery group; significant differences in RFS were found regarding time of occurrence, the number of tumors and the ratio of tumor diameters. Multivariate analysis showed that the ratio of tumor size, R ≥ 5, was the only independent prognostic risk factor concerning both RFS and OS. We then compared the outcome of patients with prognostic risk factors between surgery and chemotherapy. Surgery achieved significantly better OS than chemotherapy, with the exception of the R ≥ 5 group. No difference in OS, in addition to RFS and PFS, was seen in the R ≥ 5 groups regardless of treatment. Conclusion: CRC patients with resectable liver metastases with R ≥ 5 showed no significant difference in outcome using surgery or chemotherapy. Chemotherapy could be used as an alternative to forward surgery to address oncological concerns such as the presence of latent metastases or poor treatment outcome in these patients.

Successful treatment of recurrent stoma prolapse after Hartmann’s procedure through ileorectal anastomosis: A case report

Highlights • The patient with Parkinson’s disease had stoma prolapse after Hartmann’s procedure.• Local procedure had failed, and stoma reversal was considered to be favorable.• We assumed that stoma reversal alone led to worsening of concomitant constipation.• We performed resection of the remnant colon with ileorectal anastomosis.• It may be an optimal treatment for patients with concomitant colonic motility disorder.