Phase III trial comparing UFT + PSK to UFT + LV in stage IIB, III colorectal cancer (MCSGO-CCTG).

PURPOSE: Oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) is not inferior to standard weekly fluorouracil and folinate for stage II/III colon cancer. However, protein-bound polysaccharide K (PSK) has been evaluated as postoperative adjuvant therapy for colorectal cancer. This report is the first of MCSGO-CCTG, which compared UFT/LV to UFT/PSK as adjuvant chemotherapy for stage IIB or III colorectal cancer in patients who had undergone Japanese D2/D3 lymph node dissection. METHODS: The primary endpoint was the 3-year disease-free survival (DFS). A randomized non-inferiority study compared UFT/LV to UFT/PSK. The overall survival, adverse events, compliance, and quality of life were also investigated as the secondary endpoints. RESULTS: Between March 2006 and December 2010, 357 patients were randomized to UFT/PSK (n = 178) or UFT/LV (n = 179) (median age 65 years, colon/rectum 67.4/32.6%, stage IIB/IIIA/IIIB/IIIC 11.1/15.7/55.0/18.2%). The 3-year DFS rate was 82.3% in those receiving UFT/LV and 72.1% in those receiving UFT/PSK. The non-inferiority of UFT/PSK adjuvant therapy to UFT/LV therapy was not verified (-9.06%, 90% confidence interval -17.06 to -1.06%). The 3-year overall survival rate was 95.4% in those receiving UFT/LV and 90.7% in those receiving UFT/PSK. CONCLUSIONS: As adjuvant chemotherapy for stage IIB and III colorectal cancer patients, UFT/PSK adjuvant therapy was not non-inferior to UFT/LV therapy with respect to the DFS.

[A Case of Rectal Cancer with Multiple Pulmonary and Liver Metastases Could Be Resected through Chemotherapy].

The patient was a 47-year-old man, whose chief complaint was melena. He visited a nearby hospital, and further evaluation showed rectal cancer invading the prostate, with multiple lung and liver metastases. The clinical diagnosis was cT4b(prostate), cN1, cM1b(H2, PUL2), cStage IV . We performed colostomy in the transverse colon prior to chemotherapy. He was administered 1 course of mFOLFOX6 plus bevacizumab and 7 courses of FOLFOXIRI plus bevacizumab. The primary tumor showed PR. The liver metastases were localized and shrunken, while the lung metastases disappeared. Approximately 6 months after the start of chemotherapy, a laparoscopic total pelvic exenteration and ileal conduit were performed following the diagnosis of ycT4b(prostate), ycN1, ycM1a(H2), ycStage IV . About 3 months later, a partial resection of the left liver lobes(S1 and S5/S8)was performed laparoscopically. He has been cancer-free for 8 months.

Neoadjuvant CapeOx therapy followed by sphincter-preserving surgery for lower rectal cancer.

PURPOSE: This retrospective study investigates the safety of neoadjuvant chemotherapy with oxaliplatin capecitabine (CapeOx), followed by laparoscopic surgery, for lower rectal cancer, and its efficacy in preserving the sphincter. METHODS: Ten patients with diagnosed lower rectal cancer received three or four cycles of neoadjuvant CapeOx chemotherapy, prior to undergoing low anterior resection or intersphincteric resection, with total mesorectal excision. The primary outcomes were R0 resection and the rate of sphincter preservation. RESULTS: Nine patients completed CapeOx as scheduled and a partial response was achieved in four; thus, the overall response rate was 40% (n = 4/10). After surgical intervention, 80% of tumors displayed downstaging. Postoperative anastomosis leakage developed in one patient. The distance from the anal verge to the tumor increased by 60% (median 1.5 cm) after CapeOx treatment. The anal sphincter was preserved in all patients and all pathological distal and radial margins were negative (R0 resections). A pathological complete response was achieved in one patient. CONCLUSIONS: Neoadjuvant CapeOx chemotherapy is a promising approach, because it extended the distance from the anus to the tumor. Subsequent laparoscopic intervention for advanced lower rectal cancer could allow for safe preservation of the sphincter.

Single-incision laparoscopic rectopexy (Wells) with simultaneous sigmoidectomy in a case of complete rectal prolapse and a sigmoid tumor: report of a case.

Recently, the technique of single-incision laparoscopic surgery for colorectal disease has rapidly disseminated in association with improvements in instrumentation and procedures, offering a less invasive procedure and excellent cosmetic results. We herein present the case of a 74-year-old female who suffered complete rectal prolapse with a pedunculated polyp (20 mm) in the sigmoid colon; the stalk of the polyp was too thick to perform endoscopic mucosal resection, which is associated with a high risk of bleeding. The patient was successfully managed using single-incision laparoscopic rectopexy (Wells) with simultaneous sigmoidectomy, a procedure that has not been reported in the literature to date. There were no perioperative complications. The patient's constipation caused by the rectal prolapse improved, and no recurrence was observed for 2 months after the operation. This case emphasizes that complete rectal prolapse is a benign disease occurring in elderly patients that is well suited to treatment with minimally invasive single-incision laparoscopic surgery.

Subcuticular sutures versus staples for skin closure after open gastrointestinal surgery: a phase 3, multicentre, open-label, randomised controlled trial.

BACKGROUND: Staples have been widely used for skin closure after open gastrointestinal surgery. The potential advantages of subcuticular sutures compared with staples have not been assessed. We assessed the differences in the frequency of wound complications, including superficial incisional surgical site infection and hypertrophic scar formation, depending on whether subcuticular sutures or staples are used. METHODS: We did a multicentre, open-label, randomised controlled trial at 24 institutions between June 1, 2009, and Feb 28, 2012. Eligible patients aged 20 years or older, with adequate organ function and undergoing elective open upper or lower gastrointestinal surgery, were randomly assigned preoperatively to either staples or subcuticular sutures for skin closure. Randomisation was done via a computer-generated permuted-block sequence, and was stratified by institution, sex, and type of surgery (ie, upper or lower gastrointestinal surgery). Our primary endpoint was the incidence of wound complications within 30 days of surgery. Analysis was done by intention to treat. This study is registered with UMINCTR, UMIN000002480. FINDINGS: 1080 patients were enrolled and randomly assigned in a one to one ratio: 562 to subcuticular sutures and 518 to staples. 1072 were eligible for the primary endpoint and 1058 for the secondary endpoint. Of the 558 patients who received subcuticular sutures, 382 underwent upper gastrointestinal surgery and 176 underwent lower gastrointestinal surgery. Wound complications occurred in 47 of 558 patients (8·4%, 95% CI 6·3-11·0). Of the 514 who received staples, 413 underwent upper gastrointestinal surgery and 101 underwent lower gastrointestinal surgery. Wound complications occurred in 59 of 514 (11·5%, 95% CI 8·9-14·6). Overall, the rate of wound complications did not differ significantly between the subcuticular sutures and staples groups (odds ratio 0·709, 95% CI 0·474-1·062; p=0·12). INTERPRETATION: The efficacy of subcuticular sutures was not validated as an improvement over a standard procedure for skin closure to reduce the incidence of wound complications after open gastrointestinal surgery. FUNDING: Johnson & Johnson.

Phase I Study of the Administration of Low-dose Perioperative Human Atrial Natriuretic Peptide in Patients With Resectable Colorectal Cancer.

BACKGROUND/AIM: The aim of this single center, non-randomized, open-label, uncontrolled, interventional trial was to determine the feasibility of continuous administration of low-dose human atrial natriuretic peptide (hANP) perioperatively during curative operation for colorectal cancer patients without history of acute heart failure. PATIENTS AND METHODS: The study included three males and two females ranging from 27 to 70 years old. Continuous intravenous injection of hANP solution was started before surgery. The primary endpoint was safety of hANP administration, and the secondary endpoints were perioperative changes in ANP, b-type natriuretic peptide, electrocardiogram (ECG), and lung function. RESULTS: The American Society of Anaesthesiologists physical status was 1, 2, and 3 in three, one, and one patient, respectively. Grade 2 hypotension was observed in one case. No marked changes were observed between pre- and post-operation in all cases. CONCLUSION: Perioperative low-dose hANP administration is feasible and safe in patients with curative colorectal cancer.

Prevention of severe pelvic abscess formation following extended radical surgery for locally recurrent rectal cancer.

BACKGROUND: For treatment of locally recurrent rectal cancer (LRRC), extended radical surgery is sometimes required to obtain a negative margin. Such surgery is often associated with severe postoperative pelvic abscess (PA) formation. The aim of this study was to determine the effects of reconstructive surgery using a large rectus abdominis myocutaneous (RAM) flap and anal preservation surgery on the incidence of severe PA. METHOD: Between February 1998 and June 2008, 44 patients underwent extended surgery for LRRC. Patients were divided into the pre-2004 group (n = 15) and the post-2004 group (n = 29). To reduce the risk of infections, we modified the surgical approach after 2004 to include a larger volume of RAM flap (modified RAM flap) and implemented anal preservation surgery. RESULTS: The overall incidence of severe PA was significantly lower in the post-2004 group [6 of 29 (21%)] than the pre-2004 group [9 of 15 (60%), P = 0.017]. The incidence of severe PA was lower in the anal preservation group [1 of 12 (8.3%)] compared with those who did not undergo such surgery [14 of 32 (44%), P = 0.035]. Modified RAM flap reduced the incidence of severe PA, albeit insignificantly (pre-2004 group: 57%, post-2004 group: 23%). All three patients who underwent anal preservation and modified RAM flap reconstruction did not develop severe PA. Multiple logistic analysis identified no anal preservation (Odds ratio [OR] = 10.6) and performing of sacrectomy (OR = 20.0) as risk factors for severe PA. CONCLUSION: Anal preservation surgery is an effective measure against the development of severe PA after radical resection of LRRC.

Safety of Emulsifying Lipid Formulation Containing Omega-3 Polyunsaturated Fatty Acids for Patients with Crohn's Disease.

BACKGROUND/AIM: The efficacy of omega-3 supplementation by oral capsule for patients with Crohn's disease (CD) remains controversial. We investigated the safety and efficacy of an omega-3 emulsified formulation. PATIENTS AND METHODS: Six patients with CD in remission participated in this open-label clinical trial. Patients ingested one bottle (100 ml) of the test formulation (IMARK S®) daily for 28 days. After a 1-month washout period, patients ingested two bottles of the formulation daily for 28 days. Anthropometric and blood tests were performed before and after each intervention. RESULTS: The omega-3 emulsifying formulation was safe with minimal side-effects. Body weight and body-mass index were not altered; however, CD activity index scores tended to decrease after ingested one bottle of formulation. Blood tests revealed no severe adverse effects. CONCLUSION: Supplementation with an omega-3 emulsifying formulation can be safe and useful for maintaining remission in patients with CD and warrants further studies.

Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): a multicentre, randomised, controlled phase 3 trial.

INTRODUCTION: The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin. METHODS: In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT3-receptor antagonist+dexamethasone) or aprepitant group (5-HT3-receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis. RESULTS: A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups. CONCLUSION: The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen.

Laparoscopic surgery for stage IV colorectal cancer.

Laparoscopic surgery (Lap) is a feasible therapy in advanced colorectal cancer (CRC) without distant metastasis. Resection of primary lesion in stage IV CRC is now recognized as part of multimodal therapy. However, technical safety and invasiveness of Lap in stage IV CRC remain controversial. The feasibility of Lap in stage IV CRC was determined. Clinical outcomes were compared in primary colorectal resection using Lap, open surgery (Opn), and radical Lap for stages I to III CRC. No difference was observed regarding estimated blood loss and operative time between procedures. Postoperative recovery time and time to subsequent secondary therapy in the stage IV Lap group were significantly shorter than those in the Opn group. Similar results were observed for the 3-year overall survival rate. Lap for stage IV CRC is feasible and preferable in terms of technical safety and invasiveness. It may be useful in multimodal therapy for stage IV CRC.

Idiopathic granulomatous appendicitis treated surgically with long-term follow-up: report of a case.

Isolated granulomatous inflammation of the appendix is extremely rare, and its etiology is still unknown. Thus, differentiating between idiopathic granulomatous appendicitis and isolated appendiceal Crohn's disease is difficult. We report a case of idiopathic granulomatous appendicitis with long-term follow-up after surgery. A 26-year-old woman was referred to our hospital for investigation of persistent right lower abdominal pain. Abdominal computed tomography showed a mass, suggesting an inflammatory tumor around the appendix; thus, we suspected subacute appendicitis and performed laparoscopically assisted ileocecal resection. Histological examination of the resected specimen revealed several noncaseous epithelioid granulomas in the wall of the appendix, but no foreign bodies, obstructing lesions, or parasites. Stains for acid-fast bacillus and fungi, and serology for yersinia were all negative. The patient has been followed up for 9 years and remains asymptomatic. This clinical course suggests that her isolated granulomatous appendicitis was idiopathic granulomatous appendicitis unrelated to Crohn's disease.