Operative treatment for metachronous pulmonary metastasis from esophageal carcinoma.

BACKGROUND: The clinical significance of operative treatment for metachronous pulmonary metastasis from esophageal carcinoma is unclear. METHODS: We retrospectively reviewed 23 consecutive patients who underwent operative resection for metachronous pulmonary metastasis from esophageal carcinoma from 1991 to 2008. Patient baseline characteristics, survival probability, and prognostic factors were analyzed. The median follow-up period was 31 months for surviving patients. RESULTS: There were 19 men and 4 women, with a median age of 66 years at the time of pulmonary resection. The median disease-free interval was 15.5 months. Cervical or mediastinal lymph node metastases preceded pulmonary metastases in 4 patients. Seven patients (30.4%) had multiple metastases with a maximum number of 4. The median operative time and blood loss were 94.5 minutes and 18 mL, respectively. The median length of postoperative stay was 12.5 days. The predicted 1-, 3-, and 5-year survival rates using the Kaplan-Meier method were 73.9%, 43.5%, and 43.5%, respectively, with a median survival time of 28.7 months. Univariate analysis revealed that an extrapulmonary metastasis as the initial recurrence site was an unfavorable prognostic factor (P = .0411). Multivariate analyses, however, did not identify the initial recurrence site as an independent prognostic factor (P = .0542). CONCLUSION: Operative resection for metachronous pulmonary metastasis from esophageal carcinoma is an acceptable treatment. This study of a limited number of patients may have created a constitutional selection bias. An antecedent extrapulmonary metastasis was found to be an unfavorable prognostic factor.

[Evaluation of hepatic resection for synchronous liver metastasis from gastric cancer].

To evaluate the effect of hepatic resection for synchronous liver metastasis from gastric cancer, the clinicopathological factors of gastric cancer, the size and number of liver metastasis and surgical procedures for liver metastasis were studied. Between 1977 and 2006, a total of 49 patients (38 men and 11 women) underwent hepatic resections and gastrectomy. The median age was 70 years old (range 41-81). As for pathological type, intestinal/diffuse was 26/23. T1/T2/T3/T4 was 4/14/23/8. For lymph node metastasis, N0/N1/N2/N3 was 4/15/18/12. The number of liver metastasis: 27 patients had 1 lesion, 9 patients had 2 lesions, and 13 patients had more than 3 lesions. A partial resection was performed for 37 patients. MST was 663 days. The 5-year survival rate was 19.7%. Univariate analysis pointed out several prognostic factors such as histological type of primary lesion, T-factor, lymph node metastasis, the number and size of liver metastasis and the procedures for hepatic resection. Multivariate analysis revealed that two factors of N0 or N1 in lymph node metastasis and partial resection of liver metastasis were favorable independent prognostic factors (p=0.0108 and p=0.0192). In conclusion, N0 and N1 state and partial resection of the liver metastasis would be good candidates for gastrectomy and synchronous resection of liver metastatic lesions.

Prognostic factors for radical resection of middle and distal bile duct cancer.

BACKGROUND/AIMS: Prognostic factors after radical operation for middle and distal bile duct cancer are not fully understood. The aim of this study is to identify prognostic factors for patients undergoing radical operation for middle and distal bile duct cancer. METHODOLOGY: The records of 57 patients with middle (n=22) and distal (n=35) bile duct cancer who had undergone radical surgery were reviewed (pancreaticoduodenectomy in 46 patients, extrahepatic bile duct resection in 6, and major hemihepatectomy in 5). The clinicopathological prognostic factors affecting survival were examined. RESULTS: The 5 years survival rate was 36% (median survival time, 34 months). Significant prognostic factors according to univariate analysis include pT classification, papillary type, number of metastatic lymph node, positive radial margin, pancreatic invasion, lymphatic invasion, venous invasion, common hepatic node metastasis, paraaortic node metastasis, and combined vascular resection. Independent significant prognostic factors according to multivariate analysis include the number of metastatic lymph nodes (5 or more), positive radial margin, and common hepatic node metastasis. CONCLUSIONS: The number of metastatic lymph nodes, common hepatic node metastasis, and positive radial margin are independent prognostic factors for middle and distal bile duct cancer. The surgical treatment of middle and bile duct cancer should achieve a negative radial margin for a favorable outcome.

A phase II trial of chemoradiotherapy for stage I esophageal squamous cell carcinoma: Japan Clinical Oncology Group Study (JCOG9708).

OBJECTIVE: The study objective was to evaluate the efficacy and toxicity of chemoradiotherapy with 5-fluorouracil (5-FU) plus cisplatin in patients with Stage I esophageal squamous cell carcinoma (ESCC). The primary endpoint was proportion of complete response (%CR). METHODS: Patients with Stage I (T1N0M0) ESCC, aged 20-75 years, without indication of endoscopic mucosal resection were eligible. Treatment consisted of cisplatin 70 mg/m(2) (day 1) and 5-FU 700 mg/m(2)/day (days 1-4) combined with 30 Gy radiotherapy (2 Gy/day, 5 days/week, days 1-21). The cycle was repeated twice with 1-week split. Salvage surgery was recommended for residual tumor or local recurrence. RESULTS: From December 1997 to June 2000, 72 patients were enrolled. No ineligible patient or major protocol violation was observed. There were 63 CRs for %CR of 87.5% [95% confidence interval (CI): 77.6-94.1]. Six patients with residual tumor successfully underwent esophagectomy. There was no Grade 4 toxicity. Four-year survival proportion was 80.5% (95% CI: 71.3-89.7), and 4-year major relapse-free survival proportion was 68% (95% CI: 57.3-78.8) (mucosal recurrence removed by endoscopy was not counted as an event). CONCLUSIONS: High CR proportion and survival proportion with mild toxicity suggest that this regimen could be considered as a candidate of new standard treatment to be compared with surgery in patients with Stage I ESCC.

[Examination of s-1 therapy for adjuvant chemotherapy in patients with advanced gastric cancer].

PURPOSE: In our department, S-1 has been administered for 1 year as postoperative adjuvant chemotherapy for advanced gastric cancer since 2000. It was started by a standard dosage of 4-week administration with 2 weeks rest since 2000(A group). However, since 2002, it was changed with the expectation of the reduction of side effects by 2-week administration with a one-week rest(B group). Treatment continuity, adverse events and efficacy in both A and B groups were examined. SUBJECTS: The subjects were 96 patients with fStage II, III A and III B who were treated with S-1 after curative operation between 2000 and 2006. RESULTS: The percentage of patients who complied with the dosing instructions completely during a 1-year period was 70.2% in the A group and 77.6% in the B group. The incidence of Grade 3 and 4 toxicity was 1 nausea, 2 appetite loss, 1 neutropenia, 1 liver dysfunction in the A group and 1 nausea, 3 neutropenia in the B group, against, 76.6% in the A group and 44.9% in the B group, respectively, in the case of discontinuation, Thus, the trend in significantly high incidence in the A group was recognized. The 3-year survival rates in cases with a case of over 3 years were 88.5% in the A group and 87.5% in the B group, i. e., no difference. CONCLUSION: Though the difference was not recognized in continuation rate, efficacy and adverse events in both A and B groups, there were significantly few withdrawal cases in the B group, and it seemed to be an effective medication method.

[Three cases of complete response after treatment with UFT and leucovorin for recurrent colorectal cancer].

We report three cases of complete response (CR) after treatment with UFT/LV for recurrent colorectal cancer. Case 1: A 44-year-old man was diagnosed with multiple liver metastases after resection of cecal cancer. UFT (500 mg/day)/Leucovorin (75 mg/day) was administered. Metastatic lesions of the liver completely disappeared on computed tomography(CT)one month after chemotherapy. Grade 2 hyperbilirubinemia and grade 1 diarrhea, pigmentation and rash were recognized. No signs of recurrence were observed for 35 months. Case 2: A 66-year-old man who underwent left colectomy and partial hepatectomy for transverse colon cancer and descending colon cancer with liver metastasis was determined to have multiple lung metastases. UFT/LV therapy was started. The lung lesions became only scars 7 months later. Adverse events were not seen. No other recurrence was found over 20 months. Case 3: A 66- year-old woman was detected with a lymph node recurrence after surgery for rectal cancer. CT revealed the disappearance of the tumor after 7 courses of UFT/LV therapy. Grade 2 hyperbilirubinemia appeared. Recurrence was not observed for 22 months, and the treatment has been discontinued.

[A case of advanced gastric cancer responding to neoadjuvant S-1/CDDP therapy].

A 77-year-old male had complaints of epigastralgia. Gastrointestinal endoscopic examination revealed type 2 advanced gastric cancer. Computed tomography revealed metastatic Bulkey group 2 lymph nodes. The diagnosis was sStage IIIB gastric cancer (sT3 sN2sH0 sP0 CY0) at staging laparoscopy. S-1 (100 mg/body/day) was orally administered for 3 weeks followed by a drug-free 2 weeks, and CDDP (74 mg/body/day) was given intravenously on day 8. After 3 courses of chemotherapy, the primary lesion and the regional lymph nodes were significantly reduced in size. He was judged as clinical PR, followed by total gastrectomy, splenectomy and lymph node dissection. The pathological findings showed that there were very few cancer cells in the primary lesion, and lymph nodes had become scarred and fibrous. The final diagnosis was T2N0 H0 P0, fStageIB and curability A.

Probiotics reduce infectious complications after pancreaticoduodenectomy.

BACKGROUND/AIMS: Postoperative morbidity is a significant problem associated with pancreaticoduodenectomy. The clinical value of probiotics in surgical patients remains unclear. This study investigated the effect of probiotics on surgical outcome after pancreaticoduodenectomy. METHODOLOGY: Seventy patients with pancreaticobiliary diseases were randomly allocated to two groups before pancreaticoduodenectomy, one of which received probiotics perioperatively and the other served as controls. Postoperative infectious complications were recorded. RESULTS: Of the 70 patients, 64 completed the trial (30 receiving probiotics and 34 controls). The probiotics used in the study contained Enterococcus faecalis T-110, Clostridium butyricum TO-A, and Bacillus mesentericus TO-A. The probiotics were first administered immediately after admission, 3 to 15 days before the operation, and then reintroduced on the second postoperative day. They were continued until hospital discharge. Infectious complications occurred after pancreaticoduodenectomy in 25 patients (39%). The incidence of infectious complications in the probiotics group (23%, 7/30) was significantly lower than in controls (53%, 18/34) (P = 0.02). Mortality amongst all patients was 1.6% (1 patient in the control group). CONCLUSIONS: The use of perioperative probiotics reduced postoperative infectious complications after pancreaticoduodenectomy, making it a promising potential adjunct therapy for patients undergoing high-risk hepato, biliary, and pancreatic surgery.

[Advanced gastric cancer responding to pathological CR after neoadjuvant TS-1 combined with CDDP therapy--report of a case].

A 54-year-old woman with advanced gastric cancer was referred to our hospital. Because it was the yearend, we selected neoadjuvant TS-1 combined with CDDP therapy. TS-1 (60 mg bid) was administered orally for 21 consecutive days, and CDDP (60 mg/m(2)) was infused intravenously on day 8. One course was completed without serious toxicities. The primary tumor revealed partial response (PR) with no lymph node metastasis judged from barium meal study and upper GI endoscopic findings. After 3 weeks, a simple total gastrectomy with lymph node dissection was performed. The pathological diagnosis proved that there were no cancer cells in the primary lesion or regional lymph nodes, suggesting a complete response (CR) to chemotherapy. The postoperative course was uneventful, and she has been fine as an outpatient.

Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study--JCOG9204.

PURPOSE: We performed a multicenter randomized controlled trial to determine whether postoperative adjuvant chemotherapy improves outcome in patients with esophageal squamous cell carcinoma undergoing radical surgery. PATIENTS AND METHODS: Patients undergoing transthoracic esophagectomy with lymphadenectomy between July 1992 and January 1997 at 17 institutions were randomly assigned to receive surgery alone or surgery plus chemotherapy including two courses of cisplatin (80 mg/m2 of body-surface area x 1 day) and fluorouracil (800 mg/m2 x 5 days) within 2 months after surgery. Adaptive stratification factors were institution and lymph node status (pN0 versus pN1). The primary end point was disease-free survival. RESULTS: Of the 242 patients, 122 were assigned to surgery alone, and 120 to surgery plus chemotherapy. In the surgery plus chemotherapy group, 91 patients (75%) received both full courses of chemotherapy; grade 3 or 4 hematologic or nonhematologic toxicities were limited. The 5-year disease-free survival rate was 45% with surgery alone, and 55% with surgery plus chemotherapy (one-sided log-rank, P =.037). The 5-year overall survival rate was 52% and 61%, respectively (P =.13). Risk reduction by postoperative chemotherapy was remarkable in the subgroup with lymph node metastasis. CONCLUSION: Postoperative adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent relapse in patients with esophageal cancer than surgery alone.

[Evaluation of TS-1 combined with cisplatin for neoadjuvant chemotherapy in patients with advanced gastric cancer].

We performed a critical evaluation of neoadjuvant chemotherapy (NAC) with TS-1 and cisplatin (CDDP) for advanced gastric cancer patients. Since October 2000, 37 patients with far advanced or non-curative resectable gastric cancer received NAC, together with TS-1 and CDDP after informed consent was obtained. TS-1 (80 mg/m2/day) was administrated for 21 consecutive days followed by 14 days rest as one course, and CDDP (50 mg/m2) was infused over 2 hours on day 8. After at least 2 courses of treatment, the patients underwent gastrectomy with lymphadenectomy. The median number of courses administered was 3 (range 2-7), and 6 cases were treated on an outpatient basis only. The overall response rate was 62.2% (no CR, but 23 PR), and the individual response rates were 67.6% for the primary lesion, 90.5% for lymph node metastasis including para-aortic region, 50.0% for liver metastasis and 14.3% for peritoneal dissemination, respectively. Toxicities were generally mild, no treatment-related death and no serious adverse reactions were observed. There were only 2 grade 4 anemia (5.4%), and leucopenia, neutropenia, anemia, thrombocytopenia of grade 3 were observed in one (2.7%), 3 (8.1%), 6 (16.2%), and 2 (5.4%) patients respectively at hematological toxicity. Appetite loss and diarrhea of grade 3 were observed in only one (2.7%) patient at nonhematological toxicity. Twenty-four cases had undergone surgical treatment, and resection was performed in all cases. Seventeen of the 24 (70.8%) patients underwent curative resection. There was no major morbidity following surgery. The patients were favorable both for operation time (229 min) and bleeding volume (365 ml). The mean duration of hospitalization after surgery was 23.5 days and the only complications were one leakage, ileus and 2 pancreatitis. Two-year survival rate was 46.8% and MST was 523 days. In conclusion, a combination of TS-1 and CDDP for NAC appears to be an effective treatment modality for far advanced gastric cancer patients in view of toxicities, antitumor effects and QOL of the patients.

[A case of advanced gastric cancer responding to neoadjuvant TS-1/CDDP therapy].

A 62-year-old advanced gastric cancer patient with bulky N2 lymph node metastases was treated by neoadjuvant chemotherapy with TS-1 and CDDP. TS-1 (100 mg/body/day) was orally administered for 3 weeks followed by a drug-free 2-week period as 1 course, and 75 mg/body/day of CDDP was administered by intravenous drip on day 8. After the first course, the primary lesion and the regional lymph node metastases showed partial response in terms of size. No serious drug adverse reaction was observed. During the second course, urgent total gastrectomy with distal pancreatectomy and splenectomy was performed for massive bleeding from a deep gastric peptic ulcer. The histopathological findings showed complete response of the carcinoma as primary lesion except for two sites of minimal lymphatic permeation and one lymph node (No. 8a) metastasis. The combined use of TS-1 and CDDP is useful as neoadjuvant chemotherapy for advanced gastric cancer.

[Evaluation of hepatic resection for metachronous liver metastases from gastric cancer].

To evaluate the effect of hepatic resection for metachronous liver metastases after resection of gastric cancer, the clinicopathological factors of gastric cancer, state of liver metastasis, surgical procedures for liver metastasis, and remote survival were studied. Between 1989 and 2001, 30 consecutive patients underwent hepatic resections (36 resections) for metachronous liver metastases. The patients included 25 men and 5 women, and the median age was 60 years old (range 46-86 years old). As for curability, curative A/curative B was 10/20, and H0/H1/H2 was 25/3/2. The mean period from initial surgery to the liver resection was 19.3 months (range 6.3-65.2 months), and the liver metastatic conditions were H1 for 27 patients and H2 for 9 patients. By number of liver metastases, 27 patients had 1 lesion, 24 patients had 2, and 5 patients had more than 3 lesions. Twenty-nine patients were negative and 7 were positive for lymph node metastasis. A partial resection was performed for 13 patients, a subsegmentectomy for 3 patients, a segmentectomy for 7 patients, a lobectomy for 8 patients, and an extended lobectomy for 5 patients. For all patients except those who had other causes of death, the overall mean survival time was 702 days and the 5-year survival rate was 26.4%. There were four 5-year survivors after hepatic resection. In conclusion, the main prognostic factor after resection of metachronous liver metastases was the existence of lymph node metastasis, and the remote survival of patients with abdominal para-aortic lymph node recurrence was poor. The type of liver resection was not a predictor of survival. The resection of liver recurrence was evaluated clinically, but we should maintain strict criteria and select adequate surgical procedures.

[A complete response after neoadjuvant chemotherapy for advanced gastric cancer with esophageal invasion].

The patient was a 65-year-old woman with type 3 gastric cancer (por) in the upper third of the stomach invading esophagus. Because of No. 16 lymph node swelling on abdominal CT examination, she was treated with FLP (5-fluorouracil + Leucovorin + cisplatin) as a neoadjuvant chemotherapy (NAC). The activities of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in the primary tumors upon endoscopic examination were 2.72 pmol/g tissue and 129.1 pmol/mg/min, respectively. After the second course, we carried out lower esophagectomy and spleno-total gastrectomy with D3 including the No. 16 lymph nodes. Histopathological examination of resected specimens showed dense fibrosis and xanthogranulomatous inflammation with foamy cells and giant cells. No residual carcinoma was seen (complete response). The patient is still alive with no sign of recurrence 1 year after surgery. NAC by combination of FLP is thought to be effective for the treatment of highly advanced gastric cancer, especially in cases with locally advanced disease and lymph node metastasis such as the present. Although no relations were seen between NAC effects and TS, DPD activities and TSIR in primary tumors in 12 gastric cancer patients, the survival rate of a low DPD activity group was significantly better than a high group in 106 cases undergoing adjuvant chemotherapy including 5-FU after surgery.

Neoadjuvant chemotherapy in advanced gastric cancer with non-curative factors: a Phase II study with 5-fluorouracil, leucovorin, and cisplatin.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has recently received increasing attention in an attempt to increase the rate of complete tumor resections, reduce systemic metastases, and prolong survival in patients with advanced gastric cancer.METHODS: Since 1993, 21 patients with unresectable or non-curative resectable gastric cancer received NAC, consisting of 5-fluorouracil, leucovorin, and cisplatin (FLP) with at least two cycles before surgery.RESULTS: All except 2 patients underwent surgical treatment, and resection was performed in 18 (85.7%). There were no deaths and no major morbidity following operation. There was no complete response (CR), but 12 patients (57.1%) had a partial response (PR), the response rate was 47.6% for the primary region, 64.7% for abdominal para-aortic (No.16) lymph node metastasis, 40.0% for liver metastasis, and 11.1% for peritoneal dissemination. One-year survival of the 21 patients was 40.5%, and median survival time (MST) was 322 days. MST in the responders was 571 days, and that in non-responders was 199 days ( P < 0.01). MST was 835 days in patients who underwent curative resection and 310 days in those who underwent non-curative surgery ( P < 0.01). There was no grade 4 toxicity, but grade 3 leukopenia occurred in 4 patients (19.0%), grade 3 anemia occurred in 3 patients (14.3%), and grade 3 stomatitis in 2 patients (9.5%). There were no serious renal disorders and no treatment-related death.CONCLUSIONS: The combination of FLP for NAC was feasible and useful for tumor reduction, especially for No.16 lymph node metastasis. There was a survival benefit in patients whose tumor had PR or who had had curative resection. We should confirm the effect and survival benefit of FLP for NAC by a prospectively randomized clinical controlled study.