S-1 and CPT-11 Plus Ramucirumab (IRIS+Rmab) as Second-Line Chemotherapy for Patients with Oxaliplatin-Refractory Metastatic Colorectal Cancer (mCRC): A Multicenter Phase II Study in Japan (N-DOCC-F-C-1701).

This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin (L-OHP) containing regimen, in consideration of the result of RAISE, FIRIS and some phase II trials of IRIS+Bevacicizumab (Bmab). The number of patients is set at 38 for the statistical analysis, assuming an expected median PFS of 5.0 months (threshold: 3.0 months). The primary endpoint of the study is the progression free survival (PFS), and the secondary endpoints are the overall response rate (ORR), overall survival (OS), adverse events (AE), quality of life (QOL) and review of nausea and vomiting. This trial is registered in the UMIN Clinical Trials Registry as UMIN000028170. We intend to start conducting the trial in September 1, 2017. If this trial meets the endpoint, IRIS+Rmab might be supported as a new optional standard regimen for mCRC.

The impact of antithrombotic therapy in patients undergoing emergency laparoscopic cholecystectomy for acute cholecystitis - A single center experience.

AIM: The risk of developing hemorrhagic complications during or after surgery in patients receiving antithrombotic therapy remains uncertain. Moreover, the impact of antithrombotic therapy under an acute inflammatory status is unclear. We investigated the impact of antithrombotic therapy in patients undergoing emergency laparoscopic cholecystectomy for acute cholecystitis. METHODS: This record-based retrospective study included patients who underwent emergency laparoscopic cholecystectomy for acute cholecystitis between September 2015 and January 2019. Patients who received elective laparoscopic cholecystectomy, open cholecystectomy, or gallbladder drainage before surgery were excluded. We evaluated the diseases for which antithrombotic therapy was administered, background characteristics, laboratory parameters and perioperative outcomes of patients with acute cholecystitis. The primary outcomes were intraoperative bleeding, blood transfusion requirement, conversion to an open procedure, and postoperative complications, including bleeding. RESULTS: One hundred and twenty-one patients (non-antithrombotic therapy, n = 92; antithrombotic therapy, n = 29) were analyzed. There were differences in age and American Association of Anesthesiologists class (P < .05), but not in the grade of acute cholecystitis (P = .19). There were no differences in the operation time (non-antithrombotic vs antithrombotic therapy: 142 [58-313] vs 146 minutes [65-373], P = .85), bleeding (17.5 mL [1-1400] vs 25 mL [1-1337], P = .58), blood transfusion requirement (n = 3 [3.2%] vs n = 2 [6.9%], P = .59) and the number of cases converted to open surgery (n = 8 [9%] vs n = 2 [7%], P = 1). The rates of postoperative complications, including bleeding, did not differ between the two groups and there was no mortality in either group. CONCLUSION: Emergency laparoscopic cholecystectomy could be planned for patients receiving single antithrombotic therapy, similar to patients who were not receiving antithrombotic therapy.

Acute appendicitis associated with the presence of schistosome eggs in a sailor: a case report.

BACKGROUND: Schistosomiasis is prevalent in tropical and subtropical areas and rarely reported in developed countries. Schistosomiasis often occurs as a chronic illness, which can cause liver and intestinal damage. Appendicitis is an unusual complication of schistosomiasis. We herein present a case of acute appendicitis associated with the presence of schistosome eggs in a sailor from the Philippines. CASE PRESENTATION: A 34-year-old Filipino man who worked as a sailor presented to our hospital with a 2-day history of acute right lower quadrant abdominal pain and fever. A physical examination revealed right lower quadrant abdominal pain with signs of peritoneal irritation, including rebound tenderness. Computed tomography revealed thickening of the appendix associated with mural calcification and fluid collection around the cecum. Based on these findings, the preoperative diagnosis was acute appendicitis. Laparoscopic appendectomy was performed. Swelling of the appendix and contaminated ascites were observed intraoperatively, but there was no evidence of appendiceal perforation. A histopathological examination showed inflammation of the appendix wall and numerous ovoid bodies present within the submucosa, many of which were calcified. Severe infiltration of lymphocytes and fibrosis were recognized around the oval bodies. The numerous oval bodies were morphologically consistent with schistosomiasis. The final diagnosis was acute phlegmonous appendicitis associated with the presence of schistosome eggs. We examined the patient for signs of adult worm activity, but the results of stool ova and parasite examinations performed twice were negative. He was discharged and returned to his country on postoperative day 9. CONCLUSIONS: The incidence of schistosomal appendicitis, which is seldom reported in developed countries, is expected to increase in Japan in the near future. Clinicians should suspect schistosome eggs as a cause of acute appendicitis in patients who have emigrated from or are traveling from endemic areas, and when mural calcification of the appendix is observed on imaging.

The Impact of Low Muscle Mass in Patients Undergoing Emergency Surgery for Colonic Perforation - A Single-center Experience.

AIM: The aim was to analyze the correlation between psoas muscle mass and mortality, as well as postoperative complications in patients treated for colonic perforation. PATIENTS AND METHODS: A total of 46 patients met the study criteria. Patients were classified into an elderly (age, ≥75 years, n=24) and a younger group (age, <75 years, n=22). Background factors, postoperative data (including duration of hospital stay and discharge) were collected. The cross-sectional area of the psoas muscle area (PMA) was measured on the same day of operation. RESULTS: The age/length of stay and PMA were significantly correlated in the younger group (p=0.0015, 0.023, respectively). Fifteen and six patients were discharged to return home, and 8 and 16 patients were transferred to another hospital, in the younger and elderly groups, respectively (p=0.02). Discharge was not correlated with the PMA in either group. CONCLUSION: The total psoas muscle mass would be useful as a quick and convenient measure of sarcopenia in younger patients, but not elderly patients.

Erratum to: Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial.

In the original publication, the article category was published as "Review Article". The correct category should read as "Original Article".

Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial.

BACKGROUND: The use of absorbable sutures in wound closure has been shown to reduce the incidence of surgical site infection (SSI); however, there is no evidence that the intra-abdominal use of absorbable rather than silk sutures reduces the incidence of SSI after gastrointestinal surgery. We report the findings of a phase II trial, designed to evaluate the impact of the intra-abdominal use of absorbable sutures on the incidence of SSI. METHODS: At 19 Japanese hospitals, 1147 patients undergoing elective gastrectomy, colorectal surgery, hepatectomy, or pancreaticoduodenectomy (PD) were randomly assigned to absorbable or silk intra-abdominal suture groups. The primary efficacy endpoint was the incidence of SSI. The secondary efficacy endpoints were the locations of SSI, time to resolution of SSI, length of hospital stay, and the incidence of bile leakage in hepatectomy and pancreatic fistula. RESULTS: The incidence of SSI was 11.3%, 15.5%, 11.3%, and 36.9% after gastrectomy, colorectal surgery, hepatectomy, and PD, respectively. The incidence of SSI was higher in the absorbable suture group than in the silk suture group for all the surgical procedures, but the difference was not significant. CONCLUSION: The intra-abdominal use of absorbable sutures did not have enough of an effect on the reduction of SSI in this phase II trial to justify the planning of a large-scale phase III trial.

Metastasis of colon cancer to the thyroid and cervical lymph nodes: a case report.

The incidence of thyroid metastasis among colorectal cancer patients is extremely rare. We report a case of colonic adenocarcinoma metastasis to the thyroid gland with treatment of lung and liver metastases, in a 61-year-old woman with a history of colon cancer. She showed a thyroid mass related to a 3-month history of hoarseness. Physical and imaging examinations disclosed a diffuse large thyroid mass with swollen cervical lymph nodes. Fine-needle aspiration cytology of the thyroid mass suggested malignancy. The patient underwent total thyroidectomy. Histopathological examination and immunohistochemical staining revealed adenocarcinoma, which was consistent with a diagnosis of metastases from primary colon cancer to the thyroid and cervical lymph nodes. At 2 years after thyroid surgery, the patient has been continuing outpatient chemotherapy for the lung and liver metastases. Thyroidectomy appeared to both relieve the patient and prevent local symptoms.

Gallbladder small cell carcinoma: a case report and literature review.

Gallbladder small cell carcinoma (SCC) comprises only 0.5 % of all gallbladder cancer and consists of aggressive tumors with poor survival outcomes against current treatments. These tumors are most common in elderly females, particularly those with cholecystolithiasis. We report the case of a 79-year-old woman with gallbladder small cell carcinoma. The patient had intermittent right upper quadrant abdominal pain and was admitted to our hospital due to suspected acute cholecystitis. She regularly received medical treatment for diabetes, hypertension, and dyslipidemia. On initial laboratory evaluation, the levels of aspartate aminotransferase (AST), total bilirubin, and C-reactive protein (CRP) were markedly elevated. She underwent computed tomography (CT) for screening. CT images showed a thick-walled gallbladder containing multiple stones and multiple 3-cm-sized round nodular lesions, which were suggestive of metastatic lymph nodes. After percutaneous transhepatic gallbladder drainage was performed, endoscopic ultrasound-guided fine needle aspiration of enlarged lymph nodes resulted in a diagnosis of small cell carcinoma or adenocarcinoma. However, we could not identify the primary lesion before the surgery because of no decisive factors. We performed cholecystectomy because there was a possibility of cholecystitis recurrence risk and also partial liver resection because we suspected tumor invasion. The final pathological diagnosis was neuroendocrine carcinoma of the gallbladder, small cell type. The tumor stage was IVb, T3aN1M1. The patient died 13 weeks after the surgery. In the present paper, we review the current available English-language literature of gallbladder SCC.

Case of plasmablastic lymphoma of the sigmoid colon and literature review.

Plasmablastic lymphoma (PBL) is a rare form of non-Hodgkin's lymphoma that is associated with human immunodeficiency virus (HIV) infection. Although PBL is most commonly observed in the oral cavity of HIV-positive patients, it can also be observed at extra-oral sites in HIV-negative patients. This report represents an unusual case of HIV-negative PBL that occurred in the sigmoid colon. This patient had a history of systemic lupus erythematosus and an underlying immunosuppressive state from long term steroid therapy. The lymphoma cells were positive for CD138, kappa light chain restriction and Epstein-Barr virus and negative for CD20/L26, CD3, CD79a, UCHL1 (CD45RO) and cytokeratin (AE1/AE3). The patient died approximately 2 mo after the operation. In the present paper, we review cases of PBL of the colon in HIV-negative patients.

Endoscopic Sphincterotomy Using the Rendezvous Technique for Choledocholithiasis during Laparoscopic Cholecystectomy: A Case Report.

A 50-year-old male was examined at another hospital for fever, general fatigue and slight abdominal pain. He was treated with antibiotics and observed. However, his symptoms did not lessen, and laboratory tests revealed liver dysfunction, jaundice and an increased inflammatory response. He was then admitted to our hospital and underwent an abdominal computed tomography scan and magnetic resonance cholangiopancreatography (MRCP), which revealed common bile duct (CBD) stones. He was diagnosed with mild acute cholangitis. As the same time, he was admitted to our hospital and an emergency endoscopic retrograde cholangiopancreatography was performed. Vater papilla opening in the third portion of the duodenum and presence of a peripapillary duodenal diverticulum made it difficult to perform cannulation of the CBD. In addition, MRCP revealed that the CBD was extremely narrow (diameter 5 mm). We therefore performed laparoscopic cholecystectomy and endoscopic sphincterotomy using the rendezvous technique for choledocholithiasis simultaneously rather than laparoscopic CBD exploration. After the operation, the patient was discharged with no complications. Although the rendezvous technique has not been very commonly used because several experts in the technique and a large operating room are required, this technique is a very attractive and effective approach for treating choledocholithiasis, for which endoscopic treatment is difficult.

Management of peripheral neuropathy induced by nab-paclitaxel treatment for breast cancer.

Nanoparticle albumin-bound paclitaxel (nab-PTX) is a key drug used in breast cancer treatment which often causes chemotherapy-induced peripheral neuropathy (CIPN). No effective approach for CIPN control has been established to date. This study assessed a new approach to CIPN integrating two concepts: compression therapy using stockings and sleeves, and medication therapy using selected prophylactic drugs, including goshajinkigan, which we named the "3S" approach. Fourteen breast cancer patients were divided into a 3S group (n=7) and a control group (n=7), and were treated with 260 mg/m(2) of nab-PTX once every three weeks. CIPN initially developed in five control-group patients and one 3S-group patient (p=0.03). Across all cycles, the CIPN grades, as determined by the Common Terminology Criteria for Adverse Events (CTCAE), were significantly lower in the 3S group than in the control group (p<0.001). The mean nab-PTX dose in the 3S group was 77.1 mg/m(2)/week versus 64.7 mg/m(2)/week in the control group (p<0.01). By controlling the development and severity of CIPN, 3S treatment appears to support the use of the recommended nab-PTX dosing for breast cancer patients.

Suppression of reactive oxygen species develops lymph node metastasis in colorectal cancer.

BACKGROUND/AIMS: Recent evidence indicates that reactive oxygen species (ROS) can induce a wide type of cellular responses from proliferation to senescence and cell death. ROS may not be an absolute carcinogenic factor or cancer suppressor. The aim of this study was to assess the biological paradox of ROS in colorectal cancer cells. METHODOLOGY: Blood specimens were obtained from the drainage vein of the tumor during operation in 135 patients with colorectal cancer. Serum ROS levels were measured using the derivatives of reactive oxygen metabolites (d-ROM) test. RESULTS: Serum ROS levels increased significantly in tumor size larger than 40mm (p<0.01). On the other hand, serum ROS levels decreased significantly in patients with lymph node metastasis (p<0.01). Multiple linear regression models showed a significant association of serum ROS levels with serum carcinoembryonic antigen (CEA) levels (p<0.01) and lymph node metastasis (p=0.026). CONCLUSIONS: In colorectal cancer cells, the increase of intracellular ROS is first associated with cell growth and invasion. However, a further increase inhibits cancer cell proliferation, whereas any decrease in ROS concentration needs to stimulate lymph node metastasis. Thus, a precise understanding how ROS are generated and involved in lymph node metastasis will help us to design better therapeutic strategies.

The serum level of carcinoembryonic antigen in drainage venous blood is not a sensitive predictor of metachronous hepatic metastasis for patients with colorectal cancer.

PURPOSE: To establish whether the serum levels of carcinoembryonic antigen (CEA) in drainage venous blood (d-CEA) is a better predictor of prognosis or survival than the preoperative CEA level in peripheral venous blood (p-CEA), and how these two CEA levels compare as predictive factors for metachronous hepatic metastasis. METHODS: We examined specimens of peripheral and drainage venous blood from 119 patients with colorectal cancer. RESULTS: There was a strong positive correlation between p-CEA and d-CEA levels. The 5-year survival rates were 81.5% and 80.2% for patients with normal p-CEA and d-CEA levels (< or =5 ng/ml), respectively, and 68.4% and 71.1% for those with abnormal p-CEA and d-CEA levels (>5 ng/ml). The p-CEA and d-CEA levels were both normal in seven of ten patients with metachronous hepatic metastasis. The CEA gradient between the d-CEA and p-CEA levels (d-p CEA gradient) was not a significant predictive factor for hepatic metastases. CONCLUSIONS: There was virtually no change between preoperative p-CEA and d-CEA levels. These findings suggest that the d-CEA level is not a predictor for metachronous hepatic metastasis and that measuring p-CEA levels is sufficient in the surveillance of colorectal cancer.

MRI can determine the adequate area for debridement in the case of Fournier's gangrene.

A 57-year-old man was transferred to our hospital because of gluteal pain. His right buttock had flare and swelling. Complete blood count showed leukocytosis, and renal failure was evident. Pelvic computed tomography (CT) revealed that the abscess, including gas, was widespread into the hypodermal tissue of the right buttock. Fournier's gangrene had been suspected, and immediate drainage was performed on the right buttock. The symptom and the condition improved rapidly, but on the day after the operation, the patient became drowsy and fell into endotoxic shock. Magnetic resonance imaging (MRI) revealed strong inflammation along the entire fascia of the right femur and necrotizing fasciitis. MRI was very useful for identification of the necrotic range. Immediately, an emergency operation was performed; 3 wide incisions were made on the right thigh and crus for drainage. The patient was cared for intensively under a sedated condition, and irrigation and debridement were repeated every day. Culture of the pus revealed mixed infection of Escherichia coli and anaerobic bacteria, and a large quantity of antimicrobial drug was used. The inflammatory reaction decreased, and the patient's general condition tentatively improved. With Fournier's gangrene, initiating adequate surgical and medical treatment is essential. Therefore, MRI should be used in the early exact diagnosis of this disease to obtain knowledge of the extent of necrosis and to determine the adequate area for debridement.

Oxidative stress and tumor progression in colorectal cancer.

BACKGROUND/AIMS: Elevated oxidative status has been found in many types of cancer cells. Recent studies have shown that the enzymatic product of thymidine phosphorylase (TP) generated reactive oxygen species (ROS) within cancer cells. The aim of this study was thus to evaluate the signal transduction pathway and the role of ROS in colorectal cancer. METHODOLOGY: Blood specimens were obtained from the drainage vein of the tumor during operation in 76 patients with colorectal cancer. Serum ROS levels were measured using the derivative-Reactive Oxygen Metabolites (d-ROM) test and serum TP levels were examined by a highly sensitive ELISA method. RESULTS: There was no significant correlation between serum levels of ROS and TP. Serum ROS levels were elevated in proportion to tumor invasion and had a significant positive correlation with tumor size (p < 0.05). However, they did not increase in patients with liver metastasis. CONCLUSIONS: These findings suggest that ROS are independent of TP-triggered signaling transduction and are associated with increased tumor invasion, but not liver metastasis in patients with colorectal cancer. From this point of view, new strategies related to ROS may provide improved therapeutic results as well as a preventative effect on carcinogenesis of the colorectum.

Prognostic significance of the serum thymidine phosphorylase levels in venous blood drainage specimens in patients with colorectal cancer.

BACKGROUND/AIMS: We investigated whether the serum Thymidine phosphorylase (TP) levels in venous blood drainage specimens were associated with the prognosis and risk of liver metastasis in patients with resectable colorectal cancer. METHODOLOGY: From 88 patients with colorectal cancer, specimens of venous blood drainage were obtained during operation. The serum TP levels were measured by a highly sensitive Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULTS: Subsequently, 88 patients were divided into two groups based on the levels of TP. The dividing line was determined to be 55ng/mL. The TP-high group (> 55ng/mL) had a significantly shorter overall survival than the TP-low group (< 55ng/mL). A multivariate analysis indicated that the serum TP level in venous blood drainage specimens to be a better prognostic factor independent of the traditional pathologic parameters. The serum TP levels of 3 patients with metachronous liver metastasis were high (> 55ng/mL). CONCLUSIONS: These findings suggest that the serum TP levels in venous blood drainage specimens reflect the prognosis of patients with colorectal cancer undergoing curative resection, particularly the risk of liver metastasis.

Obturator hernia in an ageing society.

INTRODUCTION: Obturator hernia is an important cause of small bowel obstruction and is associated with difficult diagnosis and high mortality. MATERIALS AND METHODS: We reviewed 22 cases of intestinal obstruction due to obturator hernia that necessitated surgical intervention over the last 17 years and evaluated the changes in the number of patients based on the census data. RESULTS: All cases were elderly females. The Howship-Romberg sign was present in 15 patients (68%). Computed tomography (CT) correctly diagnosed 13/15 (87%) of cases in which it was performed prospectively. The median time to surgery was 7.5+/-5.2 days for those patients with bowel resection, compared to 0.8+/-1.3 days for those without (P <0.05). The number of patients with obturator hernia has increased with an ageing society. CONCLUSIONS: The rising incidence of obturator hernia is probably linked to an ageing society. CT of the pelvis was helpful in obtaining the correct diagnosis. The shorter the delay between admission and surgery, the lower the bowel resection rate. Laparotomy at an early stage is recommended in such patients as it leads to reduced morbidity and mortality.

Gastric wall-covering method for the prevention of pancreatic fistula after pancreatic resection.

A pancreatic fistula is one of the most frequent complications and is still responsible for most mortality after pancreatic surgery. We propose a gastric wall-covering method, a new and novel surgical technique in pancreatic surgery for the prevention of pancreatic fistula, in which the pancreatic cutting surface is covered completely with the gastric wall. Ten patients underwent our new surgical technique, gastric wall-covering method, in 7 patients with distal pancreatectomy and in 3 with partial resection of the head of the pancreas. There were no episodes of pancreatic fistula or any complications. Our novel technique is simple, technically feasible, and useful for the prevention of the pancreatic leakage following pancreatic surgery.