Search

Purpose: We reported in a retrospective study that the presence of micrometastasis in lymph nodes, when assessed by carcinoembryonic antigen (CEA)-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer. The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial.Experimental Design: From November 2001 to December 2005, a total of 419 colorectal cancer cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II colorectal cancer cases were enrolled. After RNA quality check, 304 colorectal cancer cases were analyzed for CEA mRNA in lymph nodes by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method.Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Postoperative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-fluorouracil derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for 1 year, whereas chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (high MMV, n = 95) was an independent poor prognostic factor for 5-year disease-free survival (DFS; P = 0.001) and 5-year overall survival (OS; P = 0.016).Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II colorectal cancer. Clin Cancer Res; 22(13); 3201–8. ©2016 AACR.

LNs were collected within 3 hours after resection of the specimens with a disposable LN sampling kit that was prepared in a RNase-free state. In addition to routine pathological examination of LNs, representative five pericolic nodes adjacent to the tumor were cut into halves and stored in RNA laterTM at -20{degree sign}C. Immediately after pathological tests reported node-negative stage II CRC, RNA was extracted from LNs, checked for RNA quality, and then subjected to conventional RT-PCR for the CEA band and qRT-PCR for CEA mRNA value by the Light CyclerTM. Among seven CRC cases tested, Case No. 3, 4, and 6 were judged positive (Lower panel). Positivity of the CEA band was judged consistently by reference of the simultaneously produced control panel. One microgram of RNA from gastric cancer MKN45 cells and colon cancer LoVo cells was subjected to the RT reaction. Each cDNA was serially diluted at 1x10-1 to 1x10-5. PCR was performed using CEA primers and PBGD primers. A positive CEA band was visible at a 1x10-4 dilution in the MKN45 cells and at a 1x10-3 dilution in the LoVo cells (Upper panel).

The standard curves were plotted using the serial dilution of cDNA from MKN45. We confirmed that the CEA value was reproducibly measured in the range of 1.0x10-1 to 1.0x10-4 with standard deviation < 10% in each dilution.

Of 55 node-negative CRCs (9 stage I and 46 stage II), Micrometastais was positive in 59 of 373 LNs (15.8%) at level 1, 16 of 193 LNs (8.3%) at level 2 and 4 of 86 LNs (4.7%) at level 3 through 5 slides inspection by immunostaining using pan-cytokeratin AE1/AE3 antibody (Dako). As results, 27 CRC cases were positive for micrometastasis in LNs. Micromstastasis was found at pericolic nodes adjacent to the tumor (level 1) in 26 cases of 27 CRCs (96.3%). On the other hand, micrometastasis stayed at intermediate nodes along the course of the main blood vessel, e.g., inferior mesenteric artery (level 2) and at central nodes around the root of the main blood vessel (level 3) in 37.0% and 14.8%, respectively. Level 1, pericolic nodes adjacent to the tumor; Level 2, intermediate nodes along the course of the main blood vessel; Level 3, central nodes around the root of the main blood vessel. Level 1, pericolic nodes adjacent to the tumor; Level 2, intermediate nodes along the course of the main blood vessel; Level 3, central nodes around the root of the main blood vessel.

Figure S5: Impact of chemotherapy in High-MMV group. Post-operative chemotherapy was performed in 29 of 95 High-MMV cases and 2 of 201 Low-MMV cases. Irrespective of chemotherapy applied to High-MMV cases, High-MMV group consistently showed significantly worse 5-year DFS as compared to the Low-MMV group with no treatment (P= 0.009, 0.007). Similar results were observed in analyses for OS (P=0.003, 0.026).; Figure S6:Disease recurrence mode in stage II CRC. Among 296 patients, 51 developed disease recurrence after surgery. The recurrent organ site was 60 in all and are listed here. Like more advanced-stage patients, stage II patients had often hematogenous metastasis to liver and lung.

Figure S8: Survival analyses of the entire CEA　band-positive group.　 Of the entire CEA band-positive cases, 31 cases eventually received post-operative chemotherapy using HCFU for one year, whereas 41 cases had no treatment. There was no significant difference in 5-year DFS and 5-year OS between the two groups.; Figure S9. Survival curves stratified by High CK19 expression and Low CK19 expression. Survival analyses indicated that the High CK19 group (n=96) had a significantly (A) worse 5-year DFS (P= 0.001), (B) 5-year OS (P= 0.020), and (C) OS (P= 0.014) as compared to the Low CK19 group (n=193). A total of 289 cases with residual preserved RNA were analyzed.

MM-free CRC group (group a, n=90) had a considerably favorable prognosis. (A) 5-year DFS: 5-year DSF was 93.3, 86.5, and 74.7% in group a, group b and group c+d (High-MMV), respectively. (B) 5-year OS: 5-year OS was 97.8, 95.5, and 89.5 % in group a, group b, and group c+d (High-MMV), respectively. (C) Final OS: final OS was 97.8, 93.7, and 86.3% in group a, group b, and group c+d (High-MMV), respectively.

Chemotherapy in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of reintroducing modified FOLFOX6 (mFOLFOX6) or CAPOX with or without bevacizumab in recurrent colorectal cancer patients after oxaliplatin adjuvant chemotherapy. Patients that participated in this trial had a medical history of adjuvant chemotherapy, including oxaliplatin with a cumulative dose greater than 400 mg/m2, and recurrence that was diagnosed more six months post adjuvant chemotherapy. Primary endpoints were response rate (RR) and disease control rate (DCR), while key secondary endpoints were time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. A total of 31 patients were enrolled between October 2012 and October 2016. Of the 29 eligible patients, 7 received mFOLFOX6 and 22 received CAPOX. The RR was 62.1% (95% confidence interval 42.3–79.3) and the DCR was 82.8% (95% confidence interval 64.2–94.2). The RR for oxaliplatin-free interval was 100.0% in months 6–12 and 56.0% after 12 months. Median TTF, PFS, and OS were 6.3, 10.8, and 28.7 months, respectively. Grade 3 or worse peripheral sensory neuropathy developed in 6.5%. Allergic reactions occurred in 12.9% of the patients, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. Reintroduction of oxaliplatin was feasible and achieved high RR or DCR in patients after more than 6 months post oxaliplatin adjuvant chemotherapy.

A patient was 70-year-old female. Because unknown fever following operation of left knee in December 20XX-1, abdominal simple CT was performed, diagnosed as cholecystitis and liver abscesses. However, her unknown fever did not improve with antibiotics therapy. Abdominal enhanced CT and MRI revealed to gallbladder cancer with liver invasion and metastases. These lesions were relatively localized in liver S4a/S5 and gallbladder, hepatoduodenal mesentery. Because unknown fever was exhausting, cholecystectomy, S4a+S5 hepatectomy with extrahepatic bile duct resection and lymph node dissemination were performed in January 20XX+1. In these pathological findings, there were moderate to poorly differentiated adenocarcinoma with squamous cell differentiation in almost area of gallbladder, diagnosed as adeno-squamous carcinoma with liver invasion and metastasis(pT3a[SI][H-inf], int, INF-β, ly1, v3, pn1, pN1, pM1, pStage ⅣB). One months after operation, abdominal CT revealed multiple liver metastatic recurrences. She died 7 months after operation. Although gallbladder adeno-squamous carcinoma has a poor prognosis, these many cases had a tendency to local infiltration accompanied with tumor fever. If curative resection might be obtained and the symptoms might be improved, aggressive resection should be performed.

A 69-year-old female underwent a mesh repair for an abdominal incisional hernia 4 years previously in our hospital. She visited local hospital for abdominal pain and fever. Abdominal CT showed a localizes abscess formation above the mesh, then she was taken to our hospital. We suspected mesh infection and performed emergent mesh removal. After the operation, we examined for her anemia. Her colonoscopy and CT findings pointed to transverse colon cancer. We performed right hemicolectomy, and final diagnosis was transverse colon cancer pT4aN0M0, pStage Ⅱb. She underwent adjuvant chemotherapy, and 9 months after surgery, no recurrence was found.

Background Among patients with colorectal cancer (CRC) treated with oxaliplatin (L-OHP)-based chemotherapy, delayed chemotherapy-induced nausea and vomiting (CINV) have not been well controlled. Methods We pooled data from two prospective observational studies in Japan and one phase III clinical trial to assess whether delayed CINV could be controlled with a combination of three antiemetics adding a neurokinin-1 receptor antagonist and identified individual risk factors, using an inverse probability treatment-weighted analysis. Results A total of 661 patients were evaluable in this study (median age: 64 years; 391 male, and 270 female). 3 antiemetics controlled delayed nausea (33.18% vs. 42.25%; p = 0.0510) and vomiting (4.15% vs. 16.08%; p p = 0.0012; 2 antiemetics—OR: 1.485; 95% CI: 1.000–2.204; p = 0.0498) and delayed vomiting (female—OR: 2.735; 95% CI: 1.410–5.304; p = 0.0029; 2 antiemetics—OR: 4.551; 95% CI: 2.116–9.785; p = 0.0001). Conclusions Identifying individual risk factors can facilitate personalized treatments for delayed CINV. We recommend a 3-antiemetic combination prophylaxis for CRC patients treated with L-OHP-based chemotherapy, especially for female patients.

Background Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (FOLFOX) plus panitumumab therapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term administration of oxaliplatin is associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatin after FOLFOX plus panitumumab therapy can maintain efficacy and reduce PN incidence. Patients and methods Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumab as induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab (group A) or to 5-FU/LV plus panitumumab (group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety. Results In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval [CI], 38.1–54.9) and 9.1 months (95% CI, 8.6–11.1) in group A, compared with 47.4% (80% CI, 39.1–55.8) and 9.3 months (95% CI, 6.0–13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%). Conclusion Planned discontinuation of oxaliplatin after six cycles of mFOLFOX6 plus panitumumab is a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab. Trial registration number NCT02337946

To evaluate the efficacy and safety of CAPOX plus bevacizumab as second-line chemotherapy for metastatic colorectal cancer.In this multicenter phase Ⅱ study, the planned number of patients was 48, but owing to poor case accumulation, registration was discontinued for 20 patients. The primary endpoint was the response rate(RR). Secondary endpoints were progression-free survival(PFS), overall survival(OS), disease control rate(DCR), and safety.First-line treatment was combined with irinotecan in 14 cases and bevacizumab in 12 cases. The median number of second- line treatment courses was 7, and the median treatment period was 203 days. The reason for discontinuation of treatment was disease progression in 13 cases, adverse events in 4 cases, and other reasons in 3 cases. The best response was PR in 5 cases, SD in 8 cases, and NE in 4 cases. The RR was 25%, and the DCR was 65%. The median PFS was 7.2 months, and the median OS was 18.6 months. Grade≥3 adverse events were neutropenia in 3 cases and diarrhea and peripheral neuropathy in 2 cases each. There were no treatment-related deaths.CAPOX plus bevacizumab was a safe and effective second-line treatment option for metastatic colorectal cancer.

A 60's woman was admitted to our hospital because of palpitations that occurred with exertion. Coronary angiography computed tomography(CT)of suspected angina detected a tumor in the pancreatic head region. Abdominal CT showed a poorly enhanced 40×32 mm solid tumor in the hepatoduodenal ligament that contained a fatty component and calcification. During surgery, the tumor was located in the hepatoduodenal ligament, adhered to the pancreatic head, common hepatic artery, gastroduodenal artery, portal vein and common bile duct. However, the tumor was resected by preserving them. The tumor contained stratified squamous epithelium, a sebaceous gland, nerve, a pancreatic gland, and an adrenal gland. The histological diagnosis was a mature cystic teratoma. The patient showed no recurrence in 2 years and 10 months post-surgery. Mature teratomas in the hepatoduodenal ligament are extremely rare. Some reports showed that combined resection was performed when the tumor was in contact with the common bile duct, portal vein, and arteries. However, in our case, the tumor was removed relatively safely without combined resection.

A 50-year-old woman was admitted to our hospital due to intermittent epigastric pain and vomiting for 2 months. Contrast enhanced CT scan showed stenosis in the upper jejunum. She was diagnosed with small intestinal ileus. A small enteroscopy revealed a peripheral type 2 lesion in the upper jejunum, approximately 10 cm from the Treitz's ligament. Upon biopsy, she was diagnosed with a well-differentiated adenocarcinoma. A laparoscope-assisted extracorporeal operation was performed due to the ease of raising the umbilical wound. Swollen lymph nodes were found in the mesentery. A surgical margin of 5 cm on the oral side and 20 cm on the anal side was secured. We performed partial resection of the small intestine, including the mesentery with the enlarged lymph nodes. The histopathological diagnosis was a Type 2, 3×2 cm, tub2, pT4aN1aM0, pStage Ⅲb small intestinal cancer. Due to the development of small intestinal ileus, the small bowel cancer was diagnosed preoperatively. Hence, it was slightly we will report including the literature consideration of.

The patient was a 79-year-old woman. In January 20XX, upper gastrointestinal endoscopy revealed a duodenal tumor with bleeding and ulceration. This tumor was diagnosed as a duodenal neuroendocrine tumor(NET)based on biopsy findings. In March 20XX, the patient underwent pancreatoduodenectomy with lymph node dissemination. Based on these pathological findings, the tumor was diagnosed as a duodenal NET(G2)with a lymph node metastasis(T2, N1, M0, Stage Ⅲ). Twenty months after the operation, abdominal CT revealed multiple liver metastases(S4, S7, and S8). After this recurrence, she underwent the subcutaneous somatostatin analogue injection therapy every 28 days, and transarterial chemoembolization( TACE)when these recurrent tumors showed remarkable regrowth, once a year, accounting for her age. She has maintained good disease control for 5 years.

An 84-year-old woman with a chief complaint of right lower abdominal pain was admitted to our hospital in November 20XX. Abdominal CT scan revealed a 9.6×4.1 cm diameter low density area proximal to the 13 mm diameter appendix, which led to perforated appendicitis with a huge abscess. The patient underwent an open appendectomy with partial cecum resection. The appendix was found to be twisted by 540°. The pathological diagnosis was low-grade appendiceal mucinous neoplasm(LAMN). Recent research has found that the use of laparoscopic surgery for the treatment of LAMN has been increasing. Appropriate surgical intervention should be considered for LAMN because it is a borderline malignancy. Careful treatment with laparoscopic surgery might be considered as one of the treatment options for LAMN. We hope to accumulate more cases of LAMN to confirm our results.

A 78-year-old woman had undergone subtotal stomach-preserving pancreatoduodenectomy for acinar cell carcinoma (ACC)of the pancreatic head approximately 2 years before presentation, and the pathological diagnosis had been pT2pN0pM0, fStageⅠB(JPS 7th). Adjuvant chemotherapy was discontinued after 3 months because of side effects. Contrast- enhanced CT and PET-CT 2 years postoperatively revealed a tumor measuring 2 cm with a high concentration of FDG in the minor curvature of the stomach. During laparotomy, a 3 cm large lymph node was palpated in the minor curvature of the stomach, and a small lymph node was found adjacently. We diagnosed the patient with multiple lymph node recurrences and performed gastric lymph node dissection of the minor curvature. The pathological diagnosis was a single 2 cm large ACC lymph node metastasis. The patient did not consent to postoperative adjuvant chemotherapy and showed no recurrence for 1 year and 7 months postoperatively. Pancreatic ACC is a rare pancreatic tumor, and its clinicopathologic features are still largely unknown. In recent years, there have been reports of active resection or long-term survival with anti-cancer drug treatment even in recurrent cases, such as the present case. However, the indication and method of anti-cancer treatment are unclear and might need the accumulation of many more cases.

Introduction Oxaliplatin-induced peripheral neuropathy (OIPN) is a common adverse events that can limit a patient's quality of life during/after chemotherapy. However, no appropriate methods have been established yet for monitoring the risk of progression of OIPN. Methods A simple assessment tool using gem clips, the CLIP test, was established and its performance in predicting the risk of progression to ≥grade 2 peripheral sensory neuropathy (CTCAE ver. 4.0) was investigated in patients receiving chemotherapy with oxaliplatin. Results Among 101 patients included in this study, 71 patients developed CTCAE ≥grade 1 peripheral neuropathy (grade 1, n = 67; grade 2, n = 4) at a median of 63 (range, 14-259) days after the start of treatment. Of the 67 patients with grade 1 peripheral neuropathy, 17 showed progression to ≥grade 2 neuropathy after a median interval of 84 (range, 21-246) days. Of these patients, 27 showed a positive result of the CLIP test at a median of 91 (range, 14-224) days, excluding one patient who already showed a positive result of the test at the baseline. Therefore, the risk ratio for the development of CTCAE ≥grade 2 peripheral neuropathy was 8.3 in the patients who showed a positive result on the CLIP test. Multivariate analysis confirmed that a positive results on the CLIP test was significantly correlated with the risk of future development of CTCAE ≥grade 2 peripheral neuropathy (odds ratio, 9.37; P = 0.002). Conclusion A positive result on the CLIP test predict is predictive of the risk of progression of OIPN during chemotherapy with oxaliplatin.

Oxaliplatin-based adjuvant chemotherapy may be associated with debilitating peripheral sensory neuropathy (PSN) in patients with high-risk stage II colon cancer. This open-label, multicenter, randomized phase III trial was conducted as a prospective pooled analysis to investigate the non-inferiority of 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy.From 12 February 2014 to 31 January 2017, 525 Asian patients with high-risk stage II colon cancer were randomly assigned to 3- and 6-month treatment arms. The treatment consisted of either modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine combined with oxaliplatin (CAPOX). The primary end point was disease-free survival (DFS). The secondary end points were treatment compliance and safety.Of the 525 randomized patients, 11 were not treated. Among the 514 participating patients (255 in the 3-month arm; 259 in the 6-month arm), 432 (84%) received CAPOX, and 184 (36%) presented with T4 as a high-risk factor for recurrence. The 3-year DFS rate was 88.2% in the 3-month arm and 87.9% in the 6-month arm [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.67-1.87]. With CAPOX, the 3-year DFS rate was 88.2% in the 3-month arm and 88.4% in the 6-month arm (HR, 1.13; 95% CI, 0.65-1.96). The discontinuation rate in the 3- and 6-month arms was 10% and 31% for mFOLFOX6 (P = 0.0193), and 15% and 35% for CAPOX (P0.0001), respectively. The incidence of grade ≥2 PSN was significantly lower in the 3-month arm than in the 6-month arm (16% and 43%, respectively, P0.0001).Three months of combination therapy presented significantly less grade ≥2 PSN than the respective 6-month regimen. The shortened therapy duration did not affect the 3-year DFS rate, suggesting that a 3-month course of CAPOX can be an effective treatment option.UMIN Clinical Trials Registry, UMIN000013036 and Japan Registry of Clinical Trials, jRCTs031180128.

In December 20XX-1, abdominal enhanced CT of a 73-year-old female patient showed a 28mm-in-diameter pancreatic tail cancer with splenic venous invasion. She underwent neoadjuvant GEM/TS-1 combination chemotherapy but abandoned this chemotherapy due to melena and exanthema. She underwent a distal pancreatectomy with lymph node dissemination. In these pathological findings, the tumor was diagnosed as a pancreatic tail cancer with splenic venous invasion(T3, N0, M0, Stage ⅡA). She underwent adjuvant GEM chemotherapy, but she abandoned this chemotherapy due to exanthema and was managed with observation. In September 20XX, she had a postoperative bowel obstruction and was treated with natural light. However, she had a postoperative bowel obstruction again in July, 20XX+1. Fluoroscopic images revealed stenosis in the intestine located 170 cm from the nasal cavity. She underwent open surgery to manage the bowel obstruction. There was a peritoneal tumor with adhesion to each intestine serosa in 3 areas located 80 cm, 100 cm, and 150 cm from the Treitz ligament. Therefore, she underwent a small intestine resection and anastomosis 70 cm to 110 cm from the Treitz ligament. Pathological findings showed that there was a 3mm-in-diameter adenocarcinoma in this peritoneal tumor. In these findings, this final diagnosis was an adhesive intestinal obstruction caused by peritoneal metastasis. Curative resection for single peritoneal recurrent metastasis might be useful for prognosis prolongation.

A 57-year-old woman was diagnosed with advanced gastric cancer with bone marrow metastasis(cT4aN1pM1[MAR], pStage Ⅳ). After 18 courses of S-1 and cisplatin and 18 courses of ramucirumab and paclitaxel, the chemotherapy was stopped because of stenosis. We performed endoscopic metallic stent placement, but stenosis reappeared after a month. Subsequently, distal gastrectomy was performed as a palliative surgery. She had no complications and improved appetite, therefore, she resumed chemotherapy after 3 postoperative months and continued for 4 years and 9 months from the first visit. In general, gastric cancer with bone marrow metastasis has a poor prognosis, however, in this case, long-term survival was achieved with palliative surgery.

A 74-year-old man underwent distal gastrectomy for gastric cancer(CY1, fStage Ⅳ). About 18 months after surgery, abdominal CT scans revealed multiple lymph node metastases along the portal vein. Systemic chemotherapy was administered comprising a capecitabine/oxaliplatin(CAPOX)regimen. After 4 courses of chemotherapy, an adverse reaction of Grade 2 diarrhea and peripheral neuropathy occurred, although regression of the lymph node metastasis was confirmed. Ramucirumab was administered as the second-line regimen, but CT imaging revealed lymph node progression after several courses. Although irinotecan(CPT-11)was selected as the third-line chemotherapy, the lymph node progression remained uncontrolled. Nivolumab was selected as the fourth-line chemotherapy. After 23 courses, nivolumab immunotherapy induced a partial response to the lymph node metastasis. Nivolumab immunotherapy continues to be administered until now, 5 years after the operation. We experienced a case of lymph node metastasis from gastric cancer successfully treated with nivolumab chemotherapy.

Fluorouracil monotherapy, instead of the FOLFOX or FOLFIRI regimen, is administered to patients intolerant to oxaliplatin or irinotecan because of their adverse effects. A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan. Screening for potential serum biomarkers to predict early therapeutic responses was conducted. This single-arm, open-label multicenter phase II trial recruited patients with KRAS WT mCRC from 16 institutes between January 2012 and October 2014. Panitumumab (6 mg/kg) was intravenously administered every 2 weeks, combined with fluorouracil monotherapy, in 2-week cycles. The primary objective was overall response rate, and secondary endpoints included disease-control rate, progression-free survival, overall survival, toxicity, and blood-test data. Forty patients (male, 65.0%; median age, 74 years; colon cancer, 72.5%) met eligibility criteria and received 7 cycles (median) of fluorouracil chemotherapy combined with panitumumab. There were no treatment-related deaths. Median time to treatment failure was 3.2 months. 23 (57.5%) patients experienced at least one adverse effect ≥ grade 3. The response rate was 10.0% (95% confidence interval 2.8–23.7%). Median progression-free survival and overall survival were 4.3 and 11.3 months, respectively. Total lactase dehydrogenase (LDH) levels and those of LDH-4 and LDH-5, quickly changed with disease reduction or progression. Fluorouracil monotherapy combined with panitumumab was safely administered to patients with KRAS WT mCRC intolerant to oxaliplatin and irinotecan. Serum LDH levels may predict early responses.

We aimed to determine the recommended dose for bi-weekly XELIRI plus bevacizumab for second-line chemotherapy and examined its safety and efficacy in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy. Irinotecan and bevacizumab were administered as a continuous intravenous infusion on Day 1 at 150 mg/mm2 and 5 mg/kg, respectively. Capecitabine was orally administered in two divided doses on Days 2–8. Each 2-week treatment cycle was defined as a single course of treatment. During Phase I, we determined the recommended dose for capecitabine. In Phase II trials, efficacy and treatment safety was verified (UMIN000003934). The recommended dose of capecitabine was determined to be 2000 mg/m2. Median progression-free survival was 7.8 months [95% confidence interval (CI) 6.1–10.9 months], and median overall survival was 18.9 months (95% CI 11.6–28.4 months). Response rate was 17.4% (95% CI 6.4–28.3%). The most common Grade ≥3 hematotoxic adverse events were anemia (10.9%), neutropenia (10.9%), and leukopenia (8.7%), while the occurrence rate of Grade ≥3 non-hematotoxic adverse events was relatively low (

A70s man was admitted to our hospital complaining of chest discomfort. Endoscopic examination showed mucosal erythema and irregularity and an area unstained by iodine in the middle esophagus 21 to 41 cm from the incisors. The biopsy specimen showed moderately differentiated squamous cell carcinoma. An abdominal computed tomographic(CT)scan revealed swelling of the lymph nodes along the celiac artery and abdominal aorta. The patient was diagnosed with unresectable advanced esophageal cancer(cT2N4M0, cStage Ⅳa). Systemic chemotherapy was initiated using a regimen of 5-FU and cisplatin(FP). After 2 courses of chemotherapy, an abdominal CT scan showed reduction of the lymph node swelling along the abdominal aorta, but the lymph node swelling remained along the celiac artery. Therefore, chemoradiotherapy(CRT; FP plus RT 60 Gy/30 Fr at the main tumor and the swelling of lymph nodes along the celiac artery)was administered. An abdominal CT scan showed reduced swelling of the lymph nodes along the abdominal aorta and the celiac artery after CRT. In addition, FP chemotherapy was also administered. APET -CT scan showed no increased FDG up take in the main tumor and swollen lymph nodes after 2 courses of chemotherapy. The complete response(CR)has been maintained for 30 months without therapy.

A 71-year-old woman complained of melena, and laparoscopic right hemicolectomy was performed for advanced colorec- tal cancer. Pathological examination revealed pStage Ⅲa(RAS-positive)disease. After the operation, UFT/LV was administered. However, peritoneal recurrence was confirmed. We changed the chemotherapeutic regimen to CapeOX plus Bmab and capecitabine plus Bmab. After 5 years and 9 months, pulmonary metastasis was observed. Therefore, we again changed the chemotherapeutic regimen to biweekly XELIRI plus Bmab. After 43 courses, the patient had stable disease. During biweekly XELIRI plus Bmab therapy, Grade 4 neutropenia occurred, so we reduced the CPT-11 dose by 20%. After dose reduction the patient experienced no more Grade 3/4 adverse events. We experienced a case of colorectal cancer wherein biweekly XELIRI plus Bmab therapy contributed to disease control as second-line treatment.

We report a case of primary lymphoma of the breast complicated by heart failure and alcoholic-decompensated hepatic cirrhosis. The patient was a woman in her 60s who noticed a right breast tumor growing 3 months previously. The size of the tumor was approximately 5 cm, and the tumor had infiltrated the skin. There was no metastasis to the axillary lymph node or other organs by CT. We performed right breast mastectomy. Pathology indicated diffuse large B cell lymphoma(DLBCL). We considered chemotherapy, but her general condition was not good because of hepatic cirrhosis, so we administered palliative care. Although chemotherapy is the first choice of treatment for DLBCL, it is necessary to individually consider each patient's circumstances.

4011 Background: The IDEA collaboration for high-risk stage 2 colorectal cancer patients (pts) demonstrated that for CAPOX, 3 months was non-inferior to 6 months treatment, while for FOLFOX, 6 months was superior to 3 months treatment. We investigated the impact of high risk features on disease-free survival (DFS). Methods: ACHIEVE-2, one of the 4 IDEA studies (SCOT, TOSCA, ACHIEVE-2, HORG), was an open-label, multicenter randomized trial for high-risk stage II colon cancer. High risk features are defined as one or more: T4, inadequate nodal harvest < 12, poorly differentiated, clinical sign of obstruction and perforation or vascular invasion. The association of high risk features with DFS were measured by Cox regression analyses. Results: Between 2014 and 2017, ACHIEVE-2 enrolled 525 pts, out of whom 514 pts were the modified ITT (mITT) population; 432 received CAPOX (84.0%) and 82 did mFOLFOX6 (16.0%). High-risk features included 35.8% of T4, 12.8% of inadequate nodal harvest, 11.5% of poorly differentiated, 19.3% of obstruction, 6.4% of perforation and 87.5% of vascular invasion; 47.3% had one features, 35.2% had two, 14.6% had three, and 2.9% had four or more. With a median follow-up of 36.1 months, 3-year DFS rates were 88% in both arms, with a hazard ratio (HR) of 1.12 (95% CI, 0.67-1.87, p=0.67). In multivariate analysis, T4 (HR 3.77 [2.18-6.53], p< 0.0001) and inadequate nodal harvest (HR 2.98 [1.59-5.59], p= 0.0006) remained independent significant negative prognostic factors. The 3-year DFS rates in T4 and Non-T4 diseases were 78% and 94% (p

A patient was 59-year-old female. She presented our hospital with weight loss, anorexia and lower abdominal bloating. Abdominal computed tomography(CT), gastrointestinal endoscopy, colonoscopy and duodenal fistulagram showed duodenal cancer or colon cancer with duodenocolic fistula and ovary metastasis. She underwent subtotal stomach preserving pancreatoduodenectomy and right hemicolectomy. In these pathological findings, tumor was diagnosed as a duodenal cancer with duodenocolic fistula. She was surviving 12 months after the last surgery. In cases of cancer with duodenocolic fistula, pancreatoduodenectomy with right hemicolectomy would be necessary for nutrition improvement and cancer treatment.

We report a case of chemotherapy with FOLFOXIRI plus cetuximab for liver metastasis of sigmoid colon cancer. The patient was a 40's man who was diagnosed with sigmoid colon cancer with liver metastasis. Colonoscopy revealed a type 2 tumor with stenosis in the sigmoid colon. He underwent sigmoidectomy under laparotomy, and after the operation, received 7 courses of chemotherapy with FOLFOXIRI plus cetuximab. The liver tumor was sufficiently reduced, and laparotomy and liver right lobectomy were performed. Histopathology revealed a modified, Grade 2 tumor regression. He has been followed for 1 year 4months after the operation.

The patient was a 66-year-old man. Total abdominal gastrectomy and D2 dissection were performed for gastric cancer (cT3N0M0P0CYXH0, cStage II A). Pathological examination confirmed a diagnosis of Stage III C mucinous adenocarcinoma (pT4pN3pM0, pStage III C). He underwent adjuvant chemotherapy with TS-1(120mg/body). One year after adjuvant chemotherapy, anastomotic stricture was caused. Although it was not possible to point out recurrent lesions on the CT image, we strongly suspected that extrinsic compression around the anastomotic portion was due to peritoneal dissemination recurrence because of symptoms and marked tumor elevation. Therefore, TS-1(120mg/body)plus cisplatin(CDDP 60mg/m2)were administered as first-line therapy for advanced gastric cancer. TS-1 plus CDDP(SP)chemotherapy resulted in marked tumor reduction and improved symptoms. However, after 33 courses of SP chemotherapy, renal function was worse due to cisplatin; thus, docetaxel(DTX 70mg/m2)was administered as second line therapy. After 8 courses of DTX, peritoneal dissemination recurrence was diagnosed, and the patient was treated with irinotecan(CPT-11 150mg/m / 2), ramucirumab(RAM 8 mg/kg) plus paclitaxel(PTX 80mg/m2 day 1, 8, 15). However, the disease worsened. The side effect of SP therapy was renal dysfunction. Nonetheless, we experienced that long-term disease control could be achieved by administering chemotherapy under strict follow-up.

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-HT 3 -receptor antagonist+dexamethasone) or aprepitant group (5-HT 3 -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.

Small-bowel obstruction (SBO) during pregnancy is uncommon and can be difficult to diagnose. Therefore, the condition is associated with significant maternal and fetal mortality. We report a case of successful laparoscopic treatment of SBO in early pregnancy. A 37-year-old woman presented with diffuse abdominal pain and vomiting at 8 weeks of gestation. She had a history of abdominal surgery. Exploratory laparoscopy was performed by a gastrointestinal surgeon because SBO, and specifically strangulated ileus, was strongly suspected. On entry into the abdomen, dilated small bowel was visible in the pelvis; this was attached to the pelvic wall and twisted near the right adnexa. The small bowel initially appeared dark and congested, but after releasing the adhesions, it regained its normal color, was viable, and peristalsis was observed. Therefore, bowel resection was not required. No recurrence was observed after food ingestion, and the patient was discharged 12 days after surgery.

Background The IDEA collaboration, a prospective pooled analysis of four concurrently conducted randomized phase III trials (SCOT, TOSCA, ACHIEVE-2, and HORG) for pts with high-risk stage II CC investigating duration of adj oxaliplatin-based therapy, were presented at ASCO 2019. The results of ACHIEVE-2 trial, the only investigation in Asia, are presented here. Methods ACHIEVE-2 was an open-label, multicenter trial randomizing pts with high-risk stage II CC (T4, inadequate nodal harvest, poorly differentiated, obstruction, perforation or vascular invasion) to receive 3 months (m) or 6m of mFOLFOX6/CAPOX after curative surgery. Choice of regimen was declared before randomization by a site investigator. Primary endpoint was disease-free survival (DFS). No formal hypothesis testing for non-inferiority (NI) was planned in this trial. Results Between Feb 2014 and Jan 2017, 525 pts were randomized. The primary analysis included 514 randomized pts of which 82 had mFOLFOX6 (16.0%) and 432 had CAPOX (84.0%). High-risk features included 35.8% of T4, 12.8% of inadequate nodal harvest, 11.5% of poorly differentiated, 19.3% of obstruction, 6.4% of perforation and 87.5% of vascular invasion. There was significantly less grade 3-5 toxicity with 3m treatment (p = 0.0003). Grade 2 or higher neurotoxicity in 3m was significantly lower than that in 6m (16.5% vs. 42.9%, p Conclusions Shorter duration significantly decreased overall toxicities including neurotoxicity. Our results need to be interpreted within the IDEA combined analysis as well as in terms of the reproducibility of results across all trials. Clinical trial identification UMIN000013036. Legal entity responsible for the study The authors. Funding Japanese Foundation for Multidisciplinary Treatment of Cancer under the contract with Yakult Honsha. Disclosure T. Yoshino: Research grant / Funding (institution): Novartis Pharma K.K; Research grant / Funding (institution): MSD.K.K.; Research grant / Funding (institution): Sumitomo Dainippon Pharma Co., Ltd.; Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Research grant / Funding (institution): Sanofi K.K.; Research grant / Funding (institution): Daiichi Sankyo Company, Limited; Research grant / Funding (institution): Parexel International Inc.; Research grant / Funding (institution): Ono Pharmaceutical Co., Ltd. T. Yamanaka: Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Research grant / Funding (institution): Boehringer-Ingelheim; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): Pfizer; Advisory / Consultancy: Gilead Sciences; Advisory / Consultancy, Research grant / Funding (institution): Daiichi-Sankyo; Advisory / Consultancy: Sysmex; Advisory / Consultancy: Huya Biosciences; Research grant / Funding (institution): Ono; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Eli Lilly. M. Kotaka: Honoraria (self): Yakult Honsha; Honoraria (self): Chugai pharmaceutical. M. Gamoh: Honoraria (self): Taiho; Honoraria (self): Bayer; Honoraria (self): Novartis; Honoraria (self): Ono; Honoraria (self): Shionogi; Honoraria (self): Sanofi; Honoraria (self): Asahikasei; Honoraria (self): Chugai; Honoraria (self): Takeda; Honoraria (self): Daiichisankyo; Honoraria (self): Merck; Honoraria (self): Nipponkayaku; Honoraria (self): Eli Lilly Japan. A. Makiyama: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lily Pharmaceutical; Speaker Bureau / Expert testimony: Chugai; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Takeda. K. Shitara: Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Ono; Advisory / Consultancy, Research grant / Funding (institution): MSD; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Medi Science; Honoraria (self): Novartis; Honoraria (self): AbbVie; Honoraria (self): Yakult. K. Yamazaki: Speaker Bureau / Expert testimony: Chugai; Speaker Bureau / Expert testimony: Yakult. A. Ohtsu: Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self): Chugai; Honoraria (self): Taiho; Honoraria (self): Ono; Honoraria (self): Eisai. Y. Maehara: Research grant / Funding (institution): Yakult; Research grant / Funding (institution): Chugai. All other authors have declared no conflicts of interest.

634 Background: Chemotherapy in relapsed colon cancer patients (pts) treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of re-introducing FOLFOX or XELOX ± bevacizumab therapy for recurrent colorectal cancer pts after adjuvant chemotherapy including oxaliplatin. Methods: Pts with past history of adjuvant chemotherapy including oxaliplatin (FOLFOX, XELOX or SOX) with a cumulative dose of more than 400 mg/m2, and recurrence observed by imaging after more than 6 months post adjuvant chemotherapy participated in this trial. Primary endpoints were response rate (RR) and disease control rate (DCR). Key secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. Results: A total of 31 pts were enrolled between Oct 2012 and Oct 2016. Of 29 eligible pts, 7 received FOLFOX ± bevacizumab, and 22 received XELOX ± bevacizumab. 28 of the pts received bevacizumab. The RR was 66.7% (95% CI, 46.0-83.5) and the DCR was 88.9% (95% CI, 70.8-97.6). The RR for oxaliplatin free-interval was 100.0% (n = 4, 95% CI, 39.8-100.0) in 6 to 12 months, 60.9% (n = 25, 95% CI, 38.5-80.3%) over 12 month, respectively. Median PFS, TTF and OS were 10.9 months (95% CI, 7.0-19.0), 6.3 months (95% CI, 2.8-8.0) and 29.1 months (95% CI, 20.3-53.3). The most common grade 3 or 4 adverse event was hypertension (19.4%). Grade 3 or worse peripheral sensory neuropathy developed only two pts (6.5%). Allergic reactions occurred in 12.9% of the pts, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. Conclusions: Re-introduction of oxaliplatin was feasible and achieved high RR or DCR in after more than 6 months post adjuvant chemotherapy including oxaliplatin. Clinical trial information: UMIN000006523.

Purpose Oxaliplatin-induced peripheral neurotoxicity (OPN) is frequent and potentially severe, but successful treatment of this condition is still an unmet clinical need. We aimed to determine whether treatment with goshajinkigan (TJ-107), a traditional Japanese medicine, is better than placebo in preventing OPN in patients with advanced or recurrent colorectal cancer patients treated with standard FOLFOX regimens. Methods In this phase 2, randomized, double-blind, placebo-controlled study, patients undergoing oxaliplatin-based chemotherapy were randomized to receive either oral TJ-107 (7.5 g) or matching placebo daily. The severity of OPN was assessed according to the Common Toxicity Criteria for Adverse Events at baseline, every 2 weeks until the 8th cycle, and every 4 weeks thereafter until the 26th week. The primary endpoint was the incidence of grade 2 or greater OPN until the 8th cycle of chemotherapy. Results Analyses were done by intention to treat. Eighty-nine patients were randomly assigned to receive either TJ-107 (n = 44) or placebo (n = 45) between May 2009 and March 2010. The incidence of grade 2 or greater OPN until the 8th cycle was 39 and 51 % in the TJ-107 and placebo groups, respectively (relative risk (RR), 0.76; 95 % CI, 0.47–1.21). The incidence of grade 3 OPN was 7 % (TJ-107) vs. 13 % (placebo) (0.51, 0.14–1.92). No concerns regarding toxicity emerged with TJ-107 treatment. Conclusions TJ-107 appears to have an acceptable safety margin and a promising effect in delaying the onset of grade 2 or greater OPN without impairing FOLFOX efficacy.

Pancreatic metastasis of colorectal cancer is uncommon and is often identified in later stages of cancer, thereby making resection more uncommon. We report a case oflong -term survival after resection of metachronous metastasis to the pancreas from primary sigmoid colon cancer. A 50-year-old female patient underwent a sigmoid colon resection and bilateral salpingo-oophorectomy for sigmoid colon cancer and metastatic ovarian cancer in 2007. She underwent partial lung resection for metastatic lung cancer twice. Four years and 11 months after the first operation, an isolated mass was identified in the pancreatic tail, and a distal pancreatectomy, splenectomy, left adrenal gland removal, and regional lymph node dissection were performed. The tumor stained negatively for cytokeratin 7 and positively for cytokeratin 20, resulting in a diagnosis of pancreatic metastatic cancer from sigmoid colon cancer. The patient is alive 3 years and 4 months after distal pancreatectomy. This suggests that curative resection is effective for metastasis of colorectal cancer to the pancreas, similarly to metastases to the liver and lung.

A 35-year-old woman was followed by epilepsy therapy. She was admitted to our hospital because of a 15 kg decrease in weight, bilious vomit, and frequent epileptic seizures because she could not take oral antiepileptic drugs. A primary small intestinal cancer was suspected in the jejunum about 100 cm from the incisor by single-balloon enteroscopy. A single incisional laparoscopic assisted partial jejunectomy that was minimally invasive was performed to improve the symptoms of intestinal obstruction. The histopathological diagnosis was moderately differentiated adenocarcinoma, ly0, v1, pT4(SE), pN0, pM0, pStage II B. A primary small intestinal cancer is a relatively rare disease, accounting for 0.3-1.0%ofall cancers ofthe digestive tract. The primary method oftreatment is surgery, and understanding the positional relationship ofthe tumor is important when performing surgery because most primary small intestinal cancers are located in the vicinity ofthe ligaments ofTreitz. We present a case in which safe and minimally invasive surgery was performed to treat a primary small intestinal cancer in a young woman with intractable epilepsy and a significant decrease in ADL for intestinal obstruction, along with a review of the literature.