Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K-RAS status for unresectable colorectal liver metastasis (BECK study): Long-term results of survival.

BACKGROUND/PURPOSE: To investigate the long-term outcome and entire treatment course of patients with technically unresectable CRLM who underwent conversion hepatectomy and to examine factors associated with conversion to hepatectomy. METHODS: Recurrence and survival data with long-term follow-up were analyzed in the cohort of a multi-institutional phase II trial for technically unresectable colorectal liver metastases (the BECK study). RESULTS: A total of 22/12 patients with K-RAS wild-type/mutant tumors were treated with mFOLFOX6 + cetuximab/bevacizumab. The conversion R0/1 hepatectomy rate was significantly higher in left-sided primary tumors than in right-sided tumors (75.0% vs 30.0%, P = .022). The median follow-up was 72.6 months. The 5-year overall survival (OS) rate in the entire cohort was 48.1%. In patients who underwent R0/1 hepatectomy (n = 21), the 5-year RFS rate and OS rate were 19.1% and 66.3%, respectively. At the final follow-up, seven patients had no evidence of disease, five were alive with disease, and 20 had died from their original cancer. All 16 patients who achieved 5-year survival underwent conversion hepatectomy, and 11 of them underwent further resection for other recurrences (median: 2, range: 1-4). CONCLUSIONS: Conversion hepatectomy achieved a similar long-term survival to the results of previous studies in initially resectable patients, although many of them experienced several post-hepatectomy recurrences. Left-sided primary was found to be the predictor for conversion hepatectomy.

Umbilical resection during laparoscopic surgery for urachal remnants.

INTRODUCTION: Because urachal remnants are rare, no standard therapeutic guidelines have been established for this lesion. In recent years, laparoscopic surgery (LS) has been performed by many surgeons and urologists to treat urachal remnants. The prevention of postoperative umbilical infection and late malignant transformation are major issues in the treatment of urachal remnants. Adequate resection of the urachal epithelial tissue is required, and therefore, umbilical resection (UR) is performed. We retrospectively assessed the feasibility of this modality for urachal remnants by examining cases we have experienced as well as 210 Japanese surgical cases found through literature review. METHODS: From January 1998 to March 2016, we experienced 14 operative cases of urachal remnants who underwent LS at Shimane Prefectural Central Hospital. We examined the types of urachal remnants and patients' ages, symptoms, surgical methods, and pathological findings. RESULTS: We performed UR in 6 of these 14 LS patients to achieve appropriate resection of the urachal epithelial tissue. The main indication for UR was a long history of preoperative therapies for umbilical infection. The average observation period after the operation was 3.95 years, and no patients developed recurrent umbilical infection or cancer. No patients complained about the aesthetic outcome after umbilicoplasty. CONCLUSION: We recommend that UR with LS be performed for urachal remnants to prevent any recurrent umbilical infection or malignant transformation in the future.

A phase II study of neoadjuvant chemotherapy with S-1 and cisplatin for stage III gastric cancer: KUGC03.

OBJECTIVES: A multi-center phase II study was conducted to evaluate the safety and efficacy of neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin for advanced gastric cancer. METHODS: The eligibility criteria were clinical T3/T4 or N2, not Stage IV. Patients received two 35-day cycles of S-1 plus cisplatin, and then underwent D2 gastrectomy. The primary endpoint was 3-year progression free survival (PFS). Secondary endpoints were ratio of R0 resection, response rate, adverse events, and overall survival. A sample size of 49 was determined to have 80% power for detecting 15% improvement in the 3-year PFS over 55% at a one-sided alpha of 0.1. RESULTS: Among 53 patients enrolled, 44 patients completed two cycles of NAC (83%), and 48 patients underwent R0 resection (91%). Postoperative complications occurred in 13 patients (26%). A pathological response was confirmed in 24 patients (45%), including four complete responses. The 3-year PFS was 50.7%, while the 3-year OS was 74.9%. CONCLUSIONS: Although the observed 3-year PFS rate was worse than expected, NAC with S1 plus cisplatin was safe and led to a high rate of R0 resection. A randomized controlled trial is needed to make conclusions about the effectiveness of NAC in Japanese patients undergoing D2 resection.

Long-term survival after resection of pancreatic ductal adenocarcinoma with para-aortic lymph node metastasis: case report.

Pancreatic cancer patients with para-aortic lymph node metastasis have a poor prognosis and patients living longer than 3 years are rare. We had a patient with pancreatic cancer who survived for more than 10 years after removal of the para-aortic lymph node metastasis. A 57-year-old woman was diagnosed with pancreatic head cancer and underwent a pancreaticoduodenectomy with subtotal gastric resection following Whipple reconstruction in 2000. Para-aortic lymph node metastasis was detected during the operation by intraoperative pathological diagnosis and an extended lymphadenectomy was performed with vascular skeletonization of the celiac and superior mesenteric arteries. In 2004, a low-density area was detected around the superior mesenteric artery (SMA) 5 cm from its root and she was treated with gemcitabine, and the area was undetectable after 3 years of treatment. In 2010, computed tomography showed a low-density area around the same lesion with an increased carcinoembryonic antigen level. After 4 months of gemcitabine treatment, we resected the tumor en bloc with the associated superior mesenteric vein and perineural tissue. Histopathological examination of the resected specimen revealed a well-differentiated tubular adenocarcinoma that closely resembled the original primary pancreatic cancer, indicating perineural recurrence 10 years after the initial resection. She had no recurrence around the SMA for more than one year. Although a meta-analysis has not proved the efficacy of preventive radical dissection, this case indicates that a patient with well-differentiated, chemotherapy-responsive pancreatic cancer with para-aortic lymph node metastasis could have a long survival time through extended dissection of the lymph nodes.

The flow angle beneath the gastrojejunostomy predicts delayed gastric emptying in Roux-en-Y reconstruction after distal gastrectomy.

BACKGROUND: Delayed gastric emptying without mechanical obstruction after Roux-en-Y reconstruction has been defined as Roux stasis syndrome. It occurs in 10-30% of patients after such reconstruction. So far, the cause of this stasis has not been completely identified. This study aimed to reduce Roux stasis using surgical techniques. METHODS: From November 2007 to October 2010, we performed 101 distal gastrectomies with Roux-en-Y reconstruction. All the gastrojejunostomies were performed with end-to-end anastomoses. Roux stasis was analyzed with respect to tumor location, extent of the dissection, tumor progression, operation time, antecolic/retrocolic reconstruction, and the shape of the gastrojejunostomy. The shape of the gastrojejunostomy was evaluated by contrast gastroradiography 4 days after the operation. RESULTS: Roux stasis syndrome was observed in 17 of the 101 patients. There was no relationship between the extent of the dissection, tumor progression, or operation time and the occurrence of Roux stasis. There was no difference in the incidence of Roux stasis between antecolic and retrocolic reconstructions. However, the group that displayed a straight anastomotic shape on contrast radiography demonstrated an apparently lower incidence of Roux stasis (p = 0.0003). In addition, Roux-en-Y reconstruction following gastric cancer was more frequently followed by Roux stasis in the antrum than in the midstomach (p = 0.0036). Cases of Roux stasis occurred 11.8 days after surgery on average and resolved within 2 weeks on average. CONCLUSIONS: Our findings demonstrate the substantial benefits of a straight anastomosis of the gastrojejunostomy for the prevention of Roux stasis syndrome.

Evaluation of prognostic significance in extracapsular spread of lymph node metastasis in patients with gastric cancer.

BACKGROUND: Extracapsular spread of lymph node metastasis has been shown as a negative prognostic factor in cancers of several other organs. This study was performed to clarify the prognostic significance of extracapsular spread in patients receiving curative resection for gastric cancer. METHODS: Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the metastatic lymph node. Four hundred and two patients who underwent curative gastrectomy were evaluated. Eight potential prognostic factors, including the International Union Against Cancer (Union International Contra la Cancrum; [UICC]) N stage and nodal status classified by the presence of lymph node metastasis or extracapsular spread, were examined. RESULTS: Three survival curves grouped by nodal status differed significantly, and prognosis of patients with extracapsular spread was significantly worse than for the other groups. Both UICC N stage ( P < .001) and nodal status ( P < .001) were significant prognostic factors by multivariate analysis. UICC N stages were subcategorized by nodal status, and survival was shown to be significantly worse in patients with extracapsular spread in the UICC N1 group ( P = .04). CONCLUSIONS: Extracapsular spread was a significant negative prognostic indicator on multivariate analysis, and may be useful in combination with UICC N stage. Extracapsular spread was regarded as an important indicator to refine the nodal staging system in gastric cancer.

[Efficacy of weekly administration of paclitaxel for advanced or recurrent gastric cancer with peritoneal dissemination].

We report 3 gastric cancer patients with peritoneal dissemination who failed to take TS-1 due to adverse effects and who were successfully treated with weekly paclitaxel administered intravenously. The patients were 2 men and 1 woman from 73 to 82 years in age. The histological types of gastric cancer were undifferentiated adenocarcinoma in all cases. Intravenous infusion of TXL (62-80 mg/m2) after short premedication was continued for 3 weeks followed by 1 week rest. Clinical symptoms, including ascites and intestinal obstruction, improved only after administration of 1 cycle in all patients. Except for 1 event with grade 3 neutropenia, no major adverse reactions were observed. Weekly administration of paclitaxel may be a promising chemotherapy for controlling peritoneal metastasis and improving the quality of life of patients with advanced or recurrent gastric cancer.

[A case of advanced gastric cancer successfully treated with neoadjuvant chemotherapy of combined weekly paclitaxel and doxifluridine (5'-DFUR)].

We report a case of advanced gastric cancer with metastasis to the paraaortic lymph nodes that showed a remarkable response to treatment with a combination of weekly paclitaxel and doxifluridine (5'-DFUR). The patient was a 72-year-old man. Oral chemotherapy of TS-1 was discontinued due to drug induced eruption. Alternatively, we administered weekly paclitaxel/5'-DFUR combination therapy. Paclitaxel was infused at a dose of 100-130 mg after short premedication and continued for 2-3 weeks with a 1 week rest. 5'-DFUR was administered orally at a dose of 800 mg/day for 14-21 consecutive days. After 4 courses of this therapy, the primary carcinoma and lymph nodes decreased in size (PR). Consequently, the patient underwent a total gastrectomy with paraaortic lymph node dissection, which resulted in a curative resection of the cancer cells macroscopically. Except for afebrile neutropenia (grade 4), no major adverse reactions were observed. Histological examination revealed that the cancer cells were degenerated to a moderate extent. Weekly paclitaxel/5'-DFUR combination may be a promising regimen for patients with advanced gastric cancer as preoperative chemotherapy.

A case of chest wall recurrence of breast cancer treated with paclitaxel weekly, 5'-deoxy-5-fluorouridine, arterial embolization and chest wall resection.

Chest wall resection and reconstruction has proved to be a safe surgical procedure for local recurrence of breast cancer. Recently, as second- or third-line chemotherapy for the patients with recurrent breast cancer or ovarian cancer, weekly paclitaxel has provided a significant response rate in those patients, and generated much clinical interest. We report here a case of chest wall recurrence of breast cancer successfully treated by a combination of weekly paclitaxel, 5'-deoxy-5-fluorouridine, arterial embolization, and chest wall resection. A 56-year-old woman presented with a large mass in the left anterior chest. A recurrent tumor developed and enlarged one-and-half years after undergoing modified radical mastectomy for advanced breast cancer (T4N2M0, stage III B) at another hospital. The mass had enlarged while the patient underwent chemotherapy with cyclophosphamide, doxorubicin, 5-fluorouracil, and anastozole, followed by low-dose cisplatin, 5-fluorouracil, and goserelin. To reduce the mass and inflammatory changes of the skin, weekly paclitaxel and 5'-deoxy-5-fluorouridine was given. Furthermore, to obtain hemostasis and promote the mass reduction, arterial embolization of the supply arteries was performed. Chest wall resection, reconstruction of the bony chest wall with polypropylene mesh folded 8 times, and soft tissue reconstruction with a contralateral myocutaneous flap were carried out successfully. The patient was discharged from the hospital ten weeks after the operation without any major morbidity, and remained well for ten months. A multimodal approach with chemotherapy and arterial embolization was effective in this case in treating chest wall recurrence of breast cancer. Reconstruction of the chest wall bone with polypropylene mesh folded 8 times and soft tissue reconstruction with a contralateral myocutaneous flap was a useful procedure after chest wall resection, even after chemotherapy and arterial embolization.

Prognostic effects of dihydropyrimidine dehydrogenase in advanced colorectal cancer after surgery: immunohistochemistry using a new monoclonal antibody.

BACKGROUND: The response rate of 5-FU and its clearance are due to the activity of dihydropyrimidine dehydrogenase (DPD), which is the first and rate-limiting enzyme for the catabolism of 5-FU. Although several studies have evaluated the relationship between DPD expression and chemosensitivity to 5-FU in patients with colorectal cancer (CRC), only a few studies on DPD expression and clinicopathological features have been conducted using immunohistochemical staining since a monoclonal antibody for DPD has not been established. Now, a new monoclonal antibody (2H9-1b) for human DPD is available. PATIENTS AND METHODS: This study included 100 patients whose CRCs were classified into stage II to IV and completely resected surgically in our institute. DPD expression in CRC was evaluated by using immunohistochemical staining with 2H9-1b. The relationship between DPD expression and clinicopathological variables that might have affected the patients' prognosis were evaluated. Survival curves were calculated with the Kaplan-Meier method and differences were evaluated with the log-rank test. The Cox proportional hazards model was used in the univariate and multivariate survival analyses. RESULTS: DPD expression showed a positive correlation with advances in lymphatic invasion (p = 0.066), venous invasion (p = 0.033) and cancer stage (p = 0.033). The patients' survival rates after surgery were significantly (p = 0.018) higher in those DPD-negative than in those DPD-positive. The overall estimated hazard ratio for death in patients with DPD expression was 4.79 according to univariate analysis (p = 0.033). Multivariate analysis showed that DPD expression tended to be a prognostic factor less potent than other variables such as lymph node metastasis and venous invasion. CONCLUSION: With a new sensitive monoclonal antibody to human DPD, the present results indicated that DPD expression is associated with CRC progression and invasion, and closely correlated with poor prognosis in postoperative CRC patients. Moreover, DPD expression is a prognostic factor in CRC patients.

A case of ampullary carcinoma successfully managed with endoscopic snare resection.

Pancreaticoduodenectomy and transduodenal ampullectomy have been the procedures of choice for ampullary cancer in most patients. However, for patients with small ampullary neoplasms or who are unfit for laparotomy or refuse open surgical operations, endoscopic snare ampullectomy may be appropriate. We report here a case of ampullary carcinoma in which endoscopic snare ampullectomy was performed successfully, with long-term survival. The patient was a 77-year-old man with a 30-year history of ulcerative colitis, who presented with epigastric pain and fever. He had a history of four laparotomies. Laboratory studies showed a mild elevation in alkaline phosphatase, serum aspartate aminotransferase, gamma glutamyltransferase, and C-reactive protein values. At endoscopic retrograde cholangiopancreatography, the ampulla was prominent, with granulomatous proliferation. The common bile duct was dilated to approximately 25 mm in diameter. Biopsy specimens of the ampulla showed a well-differentiated adenocarcinoma. Because of extensive adhesions of the peritoneal cavity due to the prior four laparotomies and the patient's refusal of surgery, endoscopic snare ampullectomy was performed. Ten days after the ampullectomy, the patient was discharged from the hospital without any complication. The patient has been well for the 4 years since then, without recurrence of the tumor or jaundice. Endoscopic snare ampullectomy may be considered as a viable alternative to surgery in patients with small ampullary tumors who are unfit for surgery or who prefer a nonsurgical approach.

Prognostic value of thymidine phosphorylase/platelet-derived endothelial cell growth factor in advanced colorectal cancer after surgery: evaluation with a new monoclonal antibody.

BACKGROUND: Thymidine phosphorylase (TP) is an essential enzyme for activation of 5-fluorouracil and its derivatives and identical to platelet-derived endothelial cell growth factor. In colorectal cancer (CRC), previous studies evaluating the relationship between TP expression and clinicopathologic features have yielded inconsistent results. These studies used monoclonal antibody 654-1, which stained CRC cells weakly. Now, a new monoclonal antibody, 1C6-203, more sensitive than 654-1, is available. METHODS: This study included 80 patients whose CRCs were classified into stages II to IV and completely resected surgically in our institute. TP expression in CRC was evaluated by using immunohistochemical staining with 1C6-203. Relationships between TP expression and clinicopathologic variables that might have affected the patients' prognosis were evaluated. Survival curves were calculated with the Kaplan-Meier method, and differences were evaluated with log-rank test. Cox proportional hazards model was used in the univariate and multivariate survival analyses. RESULTS: TP expression showed a positive correlation with advances in histologic differentiation (P =.025), lymph node metastasis (P =.083), lymphatic invasion (P =.049), venous invasion (P =.042), and cancer stage (P =.002). The patients' survival rates after surgery were higher (P =.0041) in those with negative TP than in those with positive TP. The overall estimated hazard ratio for death in patients with TP expression was 6.24 according to univariate analysis (P =.013). Multivariate analysis showed that TP was a significant prognostic factor adjusted for other clinicopathologic variables. CONCLUSIONS: With a new highly sensitive monoclonal antibody to TP, the present results indicated that TP expression is associated with CRC progression and invasion and closely correlated with poor prognosis in postoperative CRC patients. Moreover, TP expression is an independent prognostic factor in CRC patients.