[A Case of Advanced Gastric Cancer Treated Effectively with Combination Chemotherapy of Paclitaxel plus Ramucirumab].

A 74-year-old man was referred to our hospital because of a gastric tumor. A Borrmann type 2 gastric tumor was found on upper gastrointestinal endoscopy, but tissue biopsy indicated only necrotic tissue and the preoperative diagnosis was difficult. Contrast CT and FDG-PET revealed lymphadenopathy at multiple sites accompanied by high accumulation of FDG in the perigastric lymph nodes, left upper collarbicular fossa, bilateral hilar ganglia, and longitudinal cauda. Because the tumor was strongly suspected to be gastric cancer or malignant lymphoma, distal gastrectomy was performed. The tumor was finally diagnosed as a poorly differentiated adenocarcinoma with multiple lymph node metastasis. S-1 plus cisplatin therapy was administered as first-line chemotherapy, and paclitaxel(PTX)plus ramucirumab(RAM)therapy was administered as secondline chemotherapy. PTX plus RAM therapy was effective, and the patient achieved complete remission(CR), as observed on imaging. However, because adverse events such as numbness in the periphery of the limbs were noted, PTX plus RAM therapy was discontinued per the patient's request. Currently, 13 months since the interruption of treatment, the CR has been maintained, as determined on imaging.

Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer.

Purpose Opioid-induced constipation (OIC) is a frequent and debilitating adverse effect (AE) of opioids-common analgesics for cancer pain. We investigated the efficacy and safety of a peripherally acting µ-opioid receptor antagonist, naldemedine (S-297995), for OIC, specifically in patients with cancer. Patients and Methods This phase III trial consisted of a 2-week, randomized, double-blind, placebo-controlled study (COMPOSE-4) and an open-label, 12-week extension study (COMPOSE-5). In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned on a 1:1 basis to receive once-daily oral naldemedine 0.2 mg or placebo. The primary end point was the proportion of spontaneous bowel movement (SBM) responders (≥ 3 SBMs/week and an increase of ≥ 1 SBM/week from baseline). The primary end point of COMPOSE-5 was safety. Results In COMPOSE-4, 193 eligible patients were randomly assigned to naldemedine (n = 97) or placebo (n = 96). The proportion of SBM responders in COMPOSE-4 was significantly greater with naldemedine than with placebo (71.1% [69 of 97 patients] v 34.4% [33 of 96 patients]; P < .0001). A greater change from baseline was observed with naldemedine than with placebo in the frequency of SBMs/week (5.16 v 1.54; P < .0001), SBMs with complete bowel evacuation/week (2.76 v 0.71; P < .0001), and SBMs without straining/week (3.85 v 1.17; P = .0005). In COMPOSE-4, more patients treated with naldemedine than with placebo reported treatment-emergent AEs (TEAEs) (44.3% [43 of 97 patients] v 26.0% [25 of 96 patients]; P = .01); in COMPOSE-5, 105 (80.2%) of 131 of patients reported TEAEs. Diarrhea was the most frequently reported TEAE in COMPOSE-4 (19.6% [19 of 97 patients] v 7.3% [seven of 96 patients] with naldemedine v placebo) and COMPOSE-5 (18.3% [24 of 131 patients] with naldemedine). Naldemedine was not associated with signs or symptoms of opioid withdrawal and had no notable impact on opioid-mediated analgesia. Conclusion Once-daily oral naldemedine 0.2 mg effectively treated OIC and was generally well tolerated in patients with OIC and cancer.

Multidisciplinary management of small cell carcinoma of the breast: a case report.

We report a case of primary small cell carcinoma (SCC) of the breast in a 59-year-old female. To the best of our knowledge, there are only 44 cases of this disease reported in the English literature. The patient also had regional nodal metastases, but no distant metastases. She underwent neoadjuvant chemotherapy according to a regimen of pulmonary SCC, and combination of cisplatin and etoposide (CDDP+VP16). The tumor partially responded to neoadjuvant chemotherapy. The treatment was followed by modified radical mastectomy and adjuvant chemotherapy, i.e., EC therapy (epirubicin and cyclophosphamide). She was also administered in total 50 Gy of radiation treatment to the chest wall. At this writing, the patient has evidenced no recurrence 36 months after her diagnosis.

An awareness survey of surgeons involved in breast cancer treatment regarding their patients returning to work.

Surgeons focus on the period of absence from work during the initial treatment of breast cancer. The aim of this study was to determine surgeons' perceptions and awareness regarding the necessary period of absence from work during breast cancer treatment. We created a questionnaire for all surgeons involved in breast cancer treatment who are affiliated with the Department of Surgery at the Nagoya University Graduate School of Medicine and its associated facilities. The necessary leave of absence period for each treatment was considered, and the decision regarding whether patients should return to work was examined. The surgeons were instructed to assume that a 'heavy load worker' was a nurse or caregiver and that a 'light load worker' was a medical office worker. This study included 184 surgeons (response rate: 96.8%). More than half of the surgeons considered that light load workers could return to work within 2 weeks; 89.8% after conservative resection, 71.6% after total mastectomy, 50.3% after axillary dissection. In contrast, more than half of the surgeons considered that heavy load worker should wait returning to work more than 3 weeks; 49.4% after conservative resection, 73.3% after total mastectomy, 85.7% after axillary dissection. For patients treated with chemotherapy, three-quarters of the surgeons indicated that it would be difficult to work while receiving anthracycline regimens. The results suggest that surgeons can predict the approximate period of absence from work for patients who receive an initial treatment of breast cancer.

[A case of spindle cell carcinoma of the breast, in which irinotecan was effective against respiratory failure due to pulmonary metastases].

We present our experience with chemotherapy using irinotecan for lung metastases of spindle cell carcinoma of the breast. The patient is a 50-year-old female, who consulted our hospital due to a large breast tumor about 7 cm in diameter. Although computed tomography revealed invasion to the chest wall, no distant metastases were confirmed. Chemotherapy (FEC100 followed by paclitaxel) was not effective for down-staging. To improve her quality of life, standard radical mastectomy with combined partial resection of the chest wall was performed. The tumor was histologically diagnosed as spindle cell carcinoma. After the operation, multiple lung metastases appeared, and she had severe dyspnea. Thereafter irinotecan was administered. One week after the administration, metastatic lesions were reduced so that her dyspnea was remarkably relieved. The patient continued to receive irinotecan weekly until she died on the 49th day of treatment with irinotecan.

Efficacy of preoperative dexamethasone in patients with laparoscopic cholecystectomy: a prospective randomized double-blind study.

BACKGROUND/PURPOSE: Dexamethasone has been reported to reduce postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy (LC). However, its effect on other surgical outcomes such as pain and fatigue have been unclear. The purpose of this clinical study was to evaluate the efficacy of preoperative dexamethasone in ameliorating postoperative symptoms after LC. METHODS: In this prospective, double-blind, placebo-controlled study, 80 patients scheduled for LC were analyzed after randomization to intravenous dexamethasone (8 mg) or placebo. All patients underwent standardized procedures for general anesthesia and surgery, and were recommended to remain in hospital for 3 postoperative days. Episodes of PONV, and pain and fatigue scores on a visual analogue scale (VAS) were recorded. Analgesic and antiemetic requirements were also recorded. RESULTS: There were no apparent side effects of the study drug. Seven patients (18%) in the dexamethasone group reported nausea, compared with 16 (40%) in the placebo group (p = 0.026). One patient (3%) in the dexamethasone group and 7 (18%) in the placebo group reported vomiting (p = 0.025). Dexamethasone significantly reduced the postoperative VAS pain score (p = 0.030) and VAS fatigue score (p = 0.023). The mean number of patients requiring diclofenac sodium 50 mg was 0.9 +/- 1.3 in the dexamethasone group and 2.2 +/- 2.5 in the placebo group (p = 0.002). CONCLUSIONS: The regimen we employed is safe and without apparent side effects. These results suggest that preoperative dexamethasone (8 mg) significantly reduces the incidence of PONV, pain, and fatigue after LC.

Side-to-end anastomosis in a colostomy for acute malignant large-bowel obstruction: side-to-end anastomosis with a colostomy (STEC procedure).

This report describes the use of side-to-end anastomosis in a colostomy for an acute malignant large-bowel obstruction. A 59-year-old man presented with a colonic obstruction due to advanced descending colon cancer. The preoperative imaging studies revealed a complete obstruction of the descending colon at the site of the splenic flexure, a remarkably dilated transverse colon, and no other metastatic lesions. Side-to-end anastomosis was performed with the colostomy because of the high comorbidity associated with such cases. When the patient's general condition improved, a stoma closure was performed under local anesthesia. In conclusion, a side-to-end anastomosis with a colostomy (STEC procedure) was found to be a simple, useful, and cost-effective technique for an acute malignant large-bowel obstruction, particularly in a high-risk patient.

A case of anaplastic carcinoma of the pancreas producing granulocyte-colony stimulating factor.

We report a case of anaplastic carcinoma of the pancreas with production of granulocyte-colony stimulating factor (G-CSF) in a 59-year-old male. He was referred to our hospital with a chief complaint of epigastralgia and suffered from leukocytosis. Differential diagnosis included pancreatic tumors and submucosal tumor of the stomach, but definite preoperative diagnosis could not be made. He underwent distal pancreactomy, total gastrectomy with Roux-en-Y reconstruction and splenectomy. He recovered uneventfully postoperatively and was discharged from hospital on the 14th postoperative day. Histological examination showed anaplastic carcinoma of the pancreas. Since the peripheral leukocyte count was sharply decreased after the operation, we suspected the tumor would be producing G-CSF. Then immunohistochemistry showed a positive stain in the tumor. Therefore, we diagnosed the tumor as anaplastic carcinoma of the pancreas producing G-CSF. Three months after the resection, local recurrence was detected by abdominal computed tomography. The patient died of hemorrhagic shock due to tumor invasion of the intestine 8 months after the operation.

[Evaluation of weekly low-dose CPT-11 combined with 5-FU/l-LV therapy for advanced and recurrent colorectal cancer--preliminary study].

In Japan, cancer chemotherapy for advanced and recurrent colorectal cancer has not been adequately developed in comparison with the USA and Europe. However, the number of patients with advanced colorectal cancer has increased dramatically in this decade. Therefore, effective and feasible regimens against colorectal cancer are urgently needed. We designed a new regimen to evaluate the efficacy and feasibility of weekly low dose CPT-11 combined with 5-FU/l-LV therapy based on an RPMI regimen against advanced and recurrent colorectal cancer. Twenty patients were enrolled in this study. Weekly administration (CPT-11; 60 mg/m(2) div for 1st-line chemotherapy, 40 mg/m(2) div for 2nd-or 3rd-line chemotherapy, l-LV; 200 mg/m(2) div, 5-FU; 500 mg/m(2) iv, 3 consecutive weeks, 1-week break) was performed on an ambulatory basis. The treatment cycles were repeated every 4 weeks until disease progression and/or severe toxic events occurred. The overall response rate was 31.6% with 5.3% complete response and 26.3% partial response in addition to 42.1% with no changes beyond 3 months. These results suggested that the clinical benefit was shown in 73.7% of patients. Furthermore, median TTF (time to failure) of this regimen was 6.5 months and MST was 20.4 months, respectively. On the other hand, adverse events were restricted to grade 3 with 30.0% neutorocytopenia and 5.0% thrombocytopenia. Therefore, weekly low-dose CPT-11 combined with 5-FU/l-LV therapy seems to be extremely useful, with excellent anti-tumor effect and tolerable adverse reactions, for the treatment of advanced and recurrent colorectal cancer on an ambulatory basis.

[Experience of weekly paclitaxel combined with orally administered doxifluridine therapy for advanced and recurrent gastric cancer-preliminary study].

We designed a new regimen to evaluate the efficacy and feasibility of weekly paclitaxel combined with orally administered 5'-DFUR therapy against advanced and recurrent gastric cancer. Nine patients were enrolled. Weekly paclitaxel administration (PTX 60 mg/m2, 2 consecutive weeks, 1-week break) and oral administration of 5'-DFUR (460 mg/m2, 14 consecutive days) were performed on an ambulatory basis. This was repeated every 3 weeks until disease progression and/or severe toxic events occurred. The overall response rate was 44.4% with 22.2% complete response and 22.2% partial response in addition to 44.4% no changes beyond 3 months. In NC criteria, 3 patients showed clinical improvements, such as decreasing tumor markers, releasing from the ileus, and improvement of liver dysfunction. These results suggested that clinical benefits in 89% of patients. On the other hand, toxic events were restricted to grade 3 with 11.1% general fatigue and 11.1% appetite loss. Therefore, the weekly administration of PTX in conjunction with daily oral administration of 5'-DFUR therapy seems to be extremely useful, with excellent anti-tumor effect and tolerable adverse reactions for the treatment of recurrent gastric cancer on an ambulatory basis.

[Weekly paclitaxel administration and intraabdominal CBDCA injection possibly beneficial treatment for recurrent breast cancer associated with metastatic ovarian cancer and peritoneal dissemination after operation--a case report].

A 46-year-old woman who had received mastectomy for breast cancer 6 years earlier complained of abdominal distension. Computed tomography and ultrasonography revealed massive ascites and ovarian swelling of both sides. She was diagnosed as having primary ovarian cancer and peritoneal dissemination, and underwent a total hysterectomy as well as ovarectomy on both sides. After surgery, she received a sequential chemotherapy, ie, intraabdominal injection of carboplatin (CBDCA 300 mg/m2) and div administration of paclitaxel (PTX 180 mg/m2) as a standard regimen for advanced ovarian cancer. However, detailed histological examinations showed that the ovarian cancer had metastasized from her breast cancer. It is well-known that breast cancer easily metastasizes to the bone, liver, pleura and lymph node, but rarely to the ovarium or peritoneum when chemotherapy is conducted. Therefore, no standard therapy has been established for breast cancer metastasizing to the ovarium. Our patient received 4 cycles of weekly administration of PTX (PTX 80 mg/m2, 3 consecutive weeks, 1-week break), followed by oral administration of doxifluridine+anastrozole on an outpatient basis. No evidence of recurrence of breast cancer has been noted 1 year after surgery. This result suggests that weekly administration of PTX and intraabdominal injection of CBDCA might be beneficial in the treatment of recurrent breast cancer associated with metastatic ovarian cancer and peritoneal dissemination after operation.

[Weekly administration of paclitaxel might be beneficial against TS-1-resistant recurrent gastric cancer--a case report].

At one year after postoperative adjuvant therapy consisting of TS-1, UFT, and PSK, lymph-node metastasis and recurrent suprarenal metastasis were confirmed in a patient with Stage IV gastric cancer. Despite TS-1 therapy (120 mg/body, 4 consecutive weeks, 2-week break), the therapeutic effect remained PR, and the severity of adverse reactions, such as skin symptoms, leukopenia, and diarrhea, ranged from grade 1 to 3. Although this therapy was continued intermittently, the therapeutic effect worsened to PD and, as a result, the therapy was discontinued. Next, in accordance with the treatment of recurrent and advanced breast cancer, weekly paclitaxel (PTX 80 mg/m2, 3 consecutive weeks, 1-week break) administration was performed on an outpatient basis. CR was achieved after 4 cycles. In addition, no adverse reactions were seen. Therefore, the weekly administration of PTX for the treatment of recurrent gastric cancer resistant to 5-FU anticancer agents is extremely useful, as the antitumor effect of this therapy was great, no adverse reactions were seen, and it can be performed on an outpatient basis.

Therapeutic significance of Y-27632, a Rho-kinase inhibitor, on the established liver fibrosis.

BACKGROUND: Recently, we demonstrated that Y-27632, a Rho-kinase inhibitor, inhibited hepatic stellate cells (HSCs) activation in terms of cellular morphology, improved the progression of carbon tetrachloride (CCl(4))-induced rat liver fibrosis. The objective of the present study was to investigate the effects of Y-27632 on the established liver fibrosis. METHODS AND METHODS: Liver cirrhosis was induced by intragastric administration of CCl(4) once a week for 12 weeks. After the first 6 weeks of CCl(4) injection, Y-27632 (30 mg/kg body weight) or saline was continuously administered to the rats via an intraperitoneally implanted osmotic pump during the final 6 weeks of CCl(4) injection. Two days after the last CCl(4) injection, 70% hepatectomy was performed. RESULTS: Y-27632 prevented the development of CCl(4)-induced liver fibrosis and improved the fibrotic changes, hydroxyproline content, and serum hyaluronic acid level in the liver. Moreover, Y-27632 reduced the number of smooth muscle alpha-actin- and transforming growth factor beta1-positive cells, and inhibited the expression of Na(+)/Ca(2+) exchanger mRNA which was reported to be an indicator of HSCs activation and liver fibrosis. Further, the Y-27632-treated group showed markedly increased survival rate after hepatectomy. CONCLUSIONS: These findings indicated that Y-27632 may be useful therapeutically in liver cirrhosis.

P53 labeling index in cholangioscopic biopsies is useful for determining spread of bile duct carcinomas.

BACKGROUND: Preoperative biopsy specimens obtained by means of percutaneous transhepatic cholangioscopy are useful for planning curative resection of bile duct carcinoma in an effort to improve survival. However, tissue diagnosis is sometimes difficult. This study evaluated the usefulness of p53 immunostaining of cholangioscopic specimens for determination of tumor spread. METHODS: A total of 107 biopsy specimens from 28 patients with bile duct carcinoma was selected. Before surgery, these specimens were diagnosed histopathologically (hematoxylin and eosin staining) as positive or negative for carcinoma. After definitive surgery, specimens were immunostained with anti-p53 antibody. RESULTS: Eighteen of 28 cases (64%) were positive for p53. Among these, 86% obtained from the main carcinomatous lesion or an area of superficial spread of the carcinoma exhibited a p53 labeling index (LI) over 25% as opposed to a p53 LI under 25% for all specimens obtained from noncarcinomatous lesions. Twelve specimens from 8 cases were classified before surgery as indeterminate (hematoxylin and eosin staining). The criterion of p53 LI over 25% was applicable in 11 of the 12 specimens. CONCLUSION: The p53 immunostaining of biopsy specimens obtained by means of percutaneous transhepatic cholangioscopy is helpful in determining tumor spread in bile duct carcinoma.

Heparin accelerates liver regeneration following portal branch ligation in normal and cirrhotic rats with increased plasma hepatocyte growth factor levels.

BACKGROUND/AIMS: Heparin is widely used as a general anticoagulant, and has been recently reported to elevate plasma hepatocyte growth factor (HGF) levels by releasing HGF sequestrated in the extracellular matrix. Therefore, we investigated the effects of heparin administration on liver regeneration following portal branch ligation (PBL) in normal and cirrhotic rats. METHODS: Dimethylnitrosamine-induced cirrhotic rats and control rats underwent portal ligation of the left lateral and median branches, followed by intraperitoneal heparin injections, every 12 h. To examine the feasibility of an extensive hepatectomy in the cirrhotic livers, cirrhotic rats with or without heparin treatment underwent resection of occluded lobes at 72 h after the PBL. RESULTS: Heparin injections significantly augmented liver regeneration after PBL in both normal and cirrhotic rats, following an increase in hepatocellular DNA synthesis at 24 h after the PBL. The plasma HGF concentrations were elevated by heparin treatment in both groups. In addition, heparin administration dramatically improved the survival rate after an extensive hepatectomy in the cirrhotic rats. CONCLUSIONS: Heparin treatment significantly accelerated liver regeneration following the PBL, with an increase in the plasma HGF levels in both normal and cirrhotic rats. Heparin administration may make an extensive hepatectomy clinically feasible even for cirrhotic livers.

Pseudoaneurysm of the cystic artery with hemobilia treated by arterial embolization and elective cholecystectomy.

Pseudoaneurysm of the cystic artery is a rare cause of hemobilia, with only 11 cases having been reported in the English literature. We report this unusual condition in a 62-year-old Japanese man whose chief complaint was repeated upper abdominal pain. A liver function test showed obstructive jaundice, and endoscopy revealed a small amount of blood coming from the papilla of Vater. We diagnosed him as having hemobilia, and immediate angiography was performed. The results demonstrated a pseudoaneurysm arising in the cystic artery. Selective embolization of the cystic artery then followed. Ten days later the patient underwent elective cholecystectomy and had a good postoperative course. Microscopically, the resected specimen revealed caliculous cholecystitis and an organized pseudoaneurysm perforating the lumen of the gallbladder. We supposed that this pseudoaneurysm was associated with the inflammatory reaction seen with the acute cholecystitis. This case emphasizes the need for a high level of awareness of hemobilia whenever bleeding is associated with signs of biliary disorders. Immediate angiography and embolization of the pseudoaneurysm followed by radical surgery may be the preferred strategy. We believe this is the first reported case of successful "two-step" treatment of such a pseudoaneurysm.