Impact of Second-line Chemotherapy on Prognosis: Response of Advanced Gastric Cancer to Taxanes Plus Ramucirumab.

BACKGROUND/AIM: The impact of clinical response to taxanes plus ramucirumab (RAM) on overall survival (OS) has not been clarified for advanced gastric cancer (AGC), although this type of therapy is already in use as second-line chemotherapy (CTx). This study aimed to investigate the prognostic impact of the clinical response to taxanes plus ramucirumab (RAM) for AGC patients. PATIENTS AND METHODS: This study included AGC patients treated with paclitaxel (PTX) or nab-paclitaxel (nab-PTX) and RAM. A retrospective analysis of response and survival rates in consecutive medical records of patients was performed. RESULTS: Forty-two patients were enrolled. Median progression-free survival and OS were 5.4 months [95% confidence interval (CI)=4.440-6.361] and 11.8 months (95% CI=8.648-15.019), respectively. In Cox-hazard multivariate analysis, peritoneal metastasis [hazard ratio (HR)=2.830; 95% CI=1.320-6.067; p=0.008], and disease control rate (HR=0.310; 95% CI=0.129-0.741; p=0.008) were independent factors. CONCLUSION: The response to taxanes plus RAM CTx had an impact on the survival of patients with AGC.

Ligation and Fibrin Glue Spraying for Intractable Chylous Ascites after Radical Gastrectomy for Gastric Cancer: Case Report and Literature Review.

Chylous ascites associated with radical resection of gastric cancer is a serious clinical condition. Lymph node dissection is indispensable during gastrectomy for gastric cancer. However, postoperative chylous ascites prolongs the hospital stay and re-operation. There are few reports on this subject. Most cases of chylous ascites resolve without treatment, but the condition can result in substantial morbidity. The definition of chylous ascites is ambiguous and varies in the English literature. In this report, we discuss a case of chylous ascites in a 68-year-old man who underwent distal gastrectomy for early gastric cancer at our hospital. He was admitted 8 months after surgery with a main complaint of abdominal swelling. Abdominal puncture helped to diagnose chylous ascites with marked elevation of triglyceride level. The patient received a hypercaloric infusion through a central line, and octreotide acetate, but did not improve. After assessment of lymph outflow by lymph scintigraphy, surgical ligation of the lymph vessels was performed through laparotomy. The volume of milky-white ascites in the abdominal cavity was 3,000 mL. Macroscopically, the fluid was confirmed as flowing from behind the common hepatic artery. Thus, ligation was performed. Chylous ascites has not recurred at 12 months after the re-operation. In summary, a case of chylous ascites after radical gastrectomy for gastric cancer was successfully treated by surgery. We review and discuss the relevant literature.

Preoperatively diagnosed gastric collision tumor with mixed adenocarcinoma and gastrointestinal stromal tumor: a case report and literature review.

Reports of gastric collision tumors, comprising adenocarcinoma and gastrointestinal stromal tumor, are extremely rare. Here, we report the case of a 68-year-old male who was diagnosed with a lower-body, moderately differentiated, tubular-type adenocarcinoma and submucosal tumor and underwent an elective D2 distal gastrectomy. The tumor cells of the gastrointestinal stromal tumor were positive for H-caldesmon and CD117, weakly positive for smooth muscle actin and DOG-1, and negative for desmin, S-100 protein, CD31, and AE1/AE3. The tumor had grown into a mixed form of adenocarcinoma and gastrointestinal stromal tumor. Thus, we report the first case of a preoperatively diagnosed collision tumor in the stomach consisting of adenocarcinoma and gastrointestinal stromal tumor.

An advanced case of gastric histiocytic sarcoma treated with chemotherapy and gastrectomy: a case report and review of literature.

Histiocytic sarcoma is a relatively new disease category and the gastrointestinal origin is sporadic. We report a case of a 74-year-old woman who underwent chemotherapy and proximal gastrectomy for extremely rare, advanced gastric histiocytic sarcoma. The resected specimen was subjected to numerous immunostainings to meet the diagnostic criteria of histiocytic sarcoma and was positive for the histiocyte markers' cluster of differentiation 68 and lysozyme. The markers of Langerhans cells, follicular dendritic cells, and myelocyte were all negative. Six reports of surgical resection of histiocytic sarcoma originating in the stomach exist, including our case. We reviewed the clinical course and the histological and immunohistochemical diagnostic features of surgically resected gastric histiocytic sarcoma.

Rat gastric banding model for bariatric surgery.

BACKGROUND: Adjustable gastric banding is a surgical approach to weight reduction. In this study we created a gastric banding model in rats to better understand the mechanism of body weight loss. METHODS: Male Sprague-Dawley rats weighing 260 to 280 g were subjected to gastric banding (band group) (n=8) or to a sham operation (control group) (n=8). Body weights were monitored for 14 days, and daily food and water intake and nitrogen balance were monitored for 7 days. RESULTS: Two rats in the band group died of malnutrition due to gastric stomal stenosis and obstruction caused by the gastric banding. Body weight gain during the 14 days after the operation was less in the band group than in the control group (p<0.01). Food intake during the 7 days after the operation was significantly less in the band group than in the control group (p<0.01), and water intake during the 7 days after the operation was significantly less in the band group than in the control group (p<0.01). Cumulative nitrogen balance was significantly less in the band group than in the control group (p<0.01). CONCLUSION: Gastric banding decreased the body weight gain of rats by decreasing the amount of food intake because of the creation of a small gastric pouch.

Factor XIII therapy of anastomotic leak, and circulating growth factors.

Wound healing is far more rapid in the gastrointestinal tract than in the skin. Once dehiscence of a surgical anastomosis in the gastrointestinal tract occurs, the high collagenase activity in the gastrointestinal tract may delay wound healing and promote the formation of a nonhealing fistula. Because factor XIII promotes cross-linking of fibrin during the early phase of wound healing, we investigated the effect of factor XIII concentrate on 16 anastomotic leaks and a nonhealing fistula. A 240-U dose of factor XIII concentrate (Fibrogammin P) was administrated intravenously for 5 days. Factor XIII activity and plasma levels of epidermal growth factor (EGF), transforming growth factor (TGF)-beta, and interleukin-6 were measured before treatment and 1 day and 7 days after the end of treatment. Clinical outcomes were evaluated on the basis of the findings of contrast radiography, computed tomography, and drainage volume. Improvement relevant to the therapy was observed in 15 cases (88.2%). Factor XIII activity increased to more than 70% of the normal value in 11 cases (64.7%) but remained at 40% to 70% of the normal value in 6 cases (35.3%). Plasma EGF and TGF-betalevels increased in patients with improvement but were unchanged in patients without improvement. Our findings suggest that factor XIII significantly accelerates wound healing of anastomotic leaks and nonhealing fistulas by increasing circulating growth factors after systemic administration.

Laparoscopic surgery for gastric cancer: 5 years' experience.

The purpose of this study was to clarify the safety and value of laparoscopic surgery for gastric cancer. This retrospective study involved 101 patients with gastric cancer treated with laparoscopic surgery at the Nippon Medical School Hospital from February 2001 through July 2005. The following variables were evaluated: age, sex, comorbid conditions, tumor size, location, gross type, histological type, depth of wall invasion, and presence or absence of lymph node metastasis. The surgical variables investigated included operating time, blood loss, postoperative complications, and length of postoperative stay. Mean tumor diameter was 24.1 +/- 18.4 mm, and most tumors were located in the lower third of the stomach. Endoscopic examination revealed that 98 of the tumors were early gastric cancers. The mean operation time was 255 +/- 74 min, and mean blood loss was 128 +/- 162 g. Local gastrectomy without lymphadenectomy was performed in 13 cases, and pylorus-preserving gastrectomy with perigastric lymphadenectomy was performed in 16 cases. Distal gastrectomy with systemic lymphadenectomy was performed in 56 cases. Proximal or total gastrectomy with lymph node dissection for tumors located in the upper half of the stomach was performed in 16 cases. The mean postoperative hospital stay was 13.3 +/- 7.6 days. No patients died during the admission. Postoperative surgical complications occurred in 10 patients (10%) and consisted of anastomotic bleeding in 3 patients, pneumohypoderma in 1 patient, and remote infection in 6 patients. The only medical complication was a stroke in 1 patient. We conclude that laparoscopy-assisted gastrectomy is a safe and useful operation for most early gastric cancers. If patients are selected properly, laparoscopy-assisted gastrectomy can be a curative and minimally invasive treatment for gastric cancer.

Inflammation of the gastric remnant after gastrectomy: mucosal erythema is associated with bile reflux and inflammatory cellular infiltration is associated with Helicobacter pylori infection.

BACKGROUND: Controversy exists concerning the role of bile reflux and Helicobacter pylori ( H. pylori) infection in the development of inflammation of the gastric remnant after gastrectomy. This study was designed to investigate association of bile reflux and H. pylori infection or both with inflammatory changes in the gastric remnant. METHODS: A questionnaire on GI symptoms was returned by 200 gastrectomy patients, and 24-h bilirubin monitoring in the gastric remnant was performed on 55 patients with Bilitec 2000. Upper GI endoscopy evaluated reflux gastritis in the gastric remnant, and the presence of H. pylori infection and chronic, active inflammatory cellular infiltration in the biopsy specimens were examined microscopically with the updated Sydney system. RESULTS: No difference in the incidence of GI symptoms was observed among individual gastrectomy patients. Bile reflux was lower in patients who had undergone a gastrectomy with jejunal interposition, a pylorus-preserving gastrectomy, and a gastrectomy with Roux-Y anastomosis than those who had undergone a Billroth-II (B-II) anastomosis ( P < 0.05). Endoscopy showed positive correlation between mucosal erythema and bile reflux ( P < 0.001). No correlation was observed between the mucosal erythema and chronic and active inflammatory cellular infiltration. Infection of H. pylori correlated with chronic and active inflammatory cellular infiltration ( P < 0.001). Bile reflux did not correlate with the severity of chronic and active inflammatory cellular infiltration or H. pylori infection. CONCLUSIONS: Bile reflux into the gastric remnant was observed by Bilitec 2000. Mucosal erythema and chronic, active inflammatory cell infiltration in the gastric remnant after gastrectomy may be caused by bile reflux or H. pylori infection, respectively.

Surgical outcome of 483 patients with early gastric cancer: prognosis, postoperative morbidity and mortality, and gastric remnant cancer.

BACKGROUND/AIMS: The aim of this retrospective study was to evaluate the characteristics, treatment, postoperative morbidity, mortality, and prognosis of early gastric cancer patients as well as the incidence of gastric remnant cancer after curative surgery based on an analysis of the surgical results of Nippon Medical School Hospital over the past 10 years (1991-2000). METHODOLOGY: Out of 1057 patients with gastric cancer (all stages), 483 patients (301 males and 182 females; mean age 60.9 years) underwent surgery for early gastric cancer. Early gastric cancer, defined as that invading the m or sm layer regardless of lymph node metastasis, was classified according to the Japanese Classification of Gastric Carcinoma. The survival rate was calculated using the Kaplan-Meier method. RESULTS: The stages of the 483 patients were as follows: stage Ia patients, 443 cases; stage Ib, 29 cases; stage II, 7 cases; and stage IV, 4 cases. The overall 5- and 10-year survival rates were 95.9% and 95.9% for stage Ia, 82.9% and 80.2% for stage Ib, 73.2% and 68.6% for stage II and 0% for stage IV, respectively. No difference was observed in the 5- and 10-year survival rates between patients with D1 and D2 dissections in cases without lymph node metastasis. In patients with n1 positive sm cancer, however, the 5-year survival rate of the patients who underwent D2 dissection was 91.0% while that of those who underwent D1 dissection was 80.0% (P<0.05). The incidences of postoperative morbidity from various cancers included 4.2% from surgical site infections, 1.6% from anastomotic dehiscence, 1.6% from intestinal obstructions, and 3.9% from respiratory and/or heart dysfunction. Three patients (0.6%) died of multiple organ failure. Five patients who had undergone gastrectomy for early gastric cancer were diagnosed as having early cancer in the gastric remnant during a periodic follow-up endoscopy and underwent regastrectomy. CONCLUSIONS: The prognosis of early gastric cancer is usually excellent, and the morbidity and mortality rates are satisfactory. D2 lymph node dissection is necessary in patients with n1 positive sm cancer. Periodic follow-up endoscopies in gastrectomized patients may be useful for the early detection of gastric remnant cancer.

Implementation of the diagnosis procedure combination in specific-function hospitals.

A Nobel medical payment system, the Diagnosis Procedure Combination (DPC), was implemented in Nippon Medical School Hospital and 81 other specific-function hospitals in 2003. This payment system depends on the length of hospital stay and diagnosis and medical procedures, and differs from the existing payment system, which depends on a piece rate. The daily payment differs for among almost 2,500 groups of DPC defined by the International Statistical Classification of Diseases and Related Health Problems (ICD-10), and procedures, such as operations (K and J codes of the existing payment system). One of the most important outcomes may be a decrease in lengths of hospital stay, because the range of mean lengths of stay in specific-function hospitals has been officially stated to be 14 to 30 days, and the difference between the longest and shortest mean is almost double. The new medical payment system should stimulate competition among hospitals. In order to decrease the length of stay, we developed clinical pathways for patients undergoing surgery, such as laparoscopic cholecystectomy, gastrectomy, and inguinal hernia operations, as well as clinical protocols for the surgical procedures, such as percutaneous transhepatic cholangiodrainage (PTCD) and percutaneous endoscopic gastrostomy (PEG). Health care is undergoing a challenging transition, and we must improve patient care and clinical practice.

A case report of duodenal carcinoid tumor associated with early gastric cancer.

A rare case of carcinoid tumor in the duodenal bulb associated with early gastric carcinoma is reported. An 85-year-old asymptomatic male was admitted to our hospital, referred by his neighboring doctor because of early gastric carcinoma shown by endoscopic examination. X-ray studies of the upper gastrointestinal tract showed irregular lesser curvature of the gastric antrum and a filling defect (phi1 cm) at the duodenal bulb. Gastric biopsy revealed the histological findings of Group V. Distal gastrectomy including the duodenal bulb with D2 lymph node dissection was performed. A resected specimens showed superficial depressed type carcinoma at the lesser curvature of the antrum, and an isolated submucosal tumor of 7x7 mm in size at the duodenal bulb. Histological examination disclosed papillary adenocarcinoma in the gastric mucosa and a carcinoid tumor of the duodenal bulb in the submucosal layer without high malignant findings. The patient has been well for 5 years since the surgery. In conclusion, we discussed 46 collected cases of carcinoid tumor of the duodenum associated with gastric carcinoma in Japan. Preoperative diagnosis of carcinoid tumor of the duodenum is very difficult, and thorough examinations are needed for submucosal lesion.

[Surgical treatment of gastric remnant-stump cancer].

The aim of this study was to evaluate the characteristics, and treatment of gastric remnant cancer based on an analysis of the surgical results of Nippon Medical School over the past 18 years. Thirty seven patients (27 males and 10 females, mean age 60 years) underwent surgery for gastric remnant cancer. Patients who had undergone gastrectomy with Billroth II anastomosis for benign disorder underwent re-gastrectomy for the cancer of gastric remnant 20 years after the first gastrectomy. While, patients who had undergone gastrectomy with Billroth I anastomosis for malignant disorder underwent re-gastrectomy within 10 years after the first gastrectomy. Early-type gastric remnant cancers were not observed in the suture line or gastric stump region, while advanced-type cancers were observed in the anastomotic region. Surgical treatment was carried out by the method of total gastrectomy with Roux-en-Y esophago-jejunal anastomosis. The 5 year survival rates were 77%for early cancer and 14%for advanced cancer. Periodic follow-up endoscopies in gastrectomized patients may be useful for the early detection of gastric remnant cancer after operations for gastric cancer.

[Pharmacoeconomical evaluation of clinical pathway in gastrectomy patients].

The aim of the present study was to ascertain the pharmacoeconomical efficacy of a clinical pathway (CP) employing medication management and instruction tasks (i. e. pharmaceutical care and counseling for inpatients) in gastrectomy patients. Pharmaceutical services of a uniform quality were provided. These included a CP check sheet, medication management, and a history of the drugs chiefly prescribed by pharmacists. As a result, the average number of hospitalized days among the patients who were offered pharmaceutical care compared with those who were not was significantly shortened from 35.4 days to 26.1 days (P<0.001). Moreover, the average cost of medication was also significantly reduced from 270,631 yen to 190,331 yen (P<0.05). These data provide the first evidence that a CP employing medication management and instruction tasks for gastrectomy patients may play a substantial role in saving on medical costs.

[Clinical significance of a standardized clinical pathway in gastrectomy patients].

UNLABELLED: In traditional practice patterns, physicians take care of all clinical decisions, such as diagnosis, treatment, and recovery. In the Nippon Medical School Hospital a clinical pathway for distal gastrectomy patients, recorded as a post-operative care map, was introduced in August 2000. In January 2001 the post-operative management was analyzed and standardization of practice was carried out with printed order sets, such as drugs and infusion solutions. The aim of this study was to evaluate the clinical significance of the clinical pathway for gastrectomy patients by employing standardized postoperative management and printed order sets. PATIENTS AND METHODS: From January 2001 to December 2001, 87 patients underwent distal (43), total (28), proximal (7) and partial gastrectomy (9) for gastric cancer (stage IA: 47, IB: 9, II: 7, IIIA: 8, IIIB 2, IV: 10) and gastrointestinal stromal tumor (4). These patients were randomly assigned to either the main building or the east building of our hospital. In the main building 38 patients were looked after using traditional practice (control group). In the east building 47 patients were looked after according to the clinical pathway (path group) and 2 patients were excluded from the path group because of neo-adjuvant chemotherapy and severe heart failure. Aspects of the patients' outcomes, including length of stay, the first day of the diet, morbidity, and medical costs, were compared between the path group and the control group. All data were expressed as means+/-standard deviation. Statistical analyses were made using Student t-test, Mann-Whitney U-test, and chi(2) test, and the 5%level was chosen for statistical significance. RESULTS: The length of the hospital stay was 27.1+/-10.0 and 40.8+/-26.1 days (p<0.005) and the length of post-operative stay was 18.1+/-9.5 and 28.2+/-22.3 days (p<0.01) in the path group and the control group, respectively. The post-operative day when the diet was started for the path and control groups was 6.8+/-8.9 and 8.2+/-7.2, respectively; however, the length of the intravenous infusion for the two groups was 11.8+/-1.1 and 16.5+/-1.2 days (p<0.01), respectively. There was no statistically significant difference in the morbidity rate between the path group (3/47) and the control group (5/38). The total cost was 1,502,587 yen +/-41,650 in the path group and 1,932,197 yen +/-131,030 in the control (p<0.001). CONCLUSION: A clinical pathway for gastrectomy patients proved useful to optimize their postoperative care, including medication management and diet education. It is suggested that the implementation of a standardized clinical pathway for gastrectomy patients reduced the length of the hospital stay and the medical costs.

[Comparison of the effects of prophylactic antibiotic therapy and cost-effectiveness between cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway].

The present study was designed to investigate the effects of prophylactic antibiotic therapy and the cost-effectiveness of Cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway. 157 patients (62 in the CEZ group and 95 in the SBT/ABPC group), who underwent surgery for gastric cancer at the First Department of Surgery of our hospital, were investigated. There was no significant difference between the groups with regard to sex, age, incidence of complication, stage of cancer, surgical method, operative time and blood loss, length of hospitalization, the appearance of systemic inflammatory response syndrome (SIRS), changes body temperature, white blood cell count (WBC), C-reactive protein (CRP), or clinical outcome of postoperative care by a nurse during post-operation for 7 days. The prophylactic effect of infection was also no different between the CEZ (69.4%) and SBT/ABPC (69.5%) groups. In contrast, decision analysis strongly indicated that the anticipate cost of antibiotics was higher in the latter group (yen 20402) than in the CEZ group (yen 15556), suggesting that the prophylactic effect of CEZ may be more cost-effective. Thus, evaluations of pharmacotherapy from the aspect of cost may be one of the important responsibility of hospital pharmacists in the future.

[Pilot study of TS-1 combined with lentinan in patients with unresectable or recurrent advanced gastric cancer].

TS-1, an anticancer, antimetabolis agent, has shown clinically superior antitumor activity against unresectable advanced or recurrent gastric cancer (UARG). A biological response modifier, lentinan (LNT) prolonged the survival period of patients with UARG when combined with tegafur (FT). To assess the efficacy, the safety and prognostic factors of chemo-immunotherapy using TS-1, a FT derivative, and LNT, we conducted a multi-institutional pilot study in patients with UARG. Patients were treated with TS-1 at 80 mg/m2/day (bid) for 4-weeks, and LNT was given at 2 mg/body (i.v.) in a week, followed by a 2-week rest for 4 cycles. Twenty-two patients were entered from 4 institutes and 19 patients were eligible. The median survival time in eligible patients was 400 days. The incidence of hematological toxicity (grade 2 leukopenia), and non-hematological toxicity (grade 3 nausea or fatigue) was 5.3% (1/19) and no grade 4 toxicity was observed. The response ratio was 37.5% in 8 patients who had been administered the planned dose of TS-1. In subset analyses, the survival period of the patients with normal (< 500 micrograms/ml) serum immunosuppressive acidic protein level was significantly (p < 0.0001) better than that of the higher one. The survival period for those patients whose granulocytes/lymphocytes ratio was not more than 2 tended to be better. From the prolonged survival periods, chemo-immunotherapy using TS-1 combined with LNT would seem to have a benefit against UARG, and reduced toxicity. Future clinical trials are warranted to confirm its potency.

[An economic evaluation on the clinical pathway for gastrectomy].

OBJECTIVE: To analyze the costs of gastrectomy patients treated with the clinical pathway. PATIENTS AND METHODS: Seventy-six patients (path group 44, control 32) had undergone gastrectomy in our hospital in 2001. The clinical pathway included the same care map. Treatment costs were estimated from medical cost receipt data. The economical analysis was performed from the point of the direct cost payer's view. RESULTS: The length of hospital stay in the path group was 27.1 +/- 5.9 days and decreased 8.3 days in comparison with the control(p < 0.001). The cost of the path group was 145.290 +/- 23.773 points and 19.278 points less than the control(p < 0.005). In the path group the operation case per bed was increased 30% and the cost per bed was also increased 15% more than the control. CONCLUSIONS: The implementation of the clinical pathway decreased the length and the cost of hospital stay. The clinical pathway is effective to use the hospital resources, such as bed.